WO2024054972A2 - Composition radionucléidique et procédé d'utilisation associée pour la détection de cellules tumorales - Google Patents

Composition radionucléidique et procédé d'utilisation associée pour la détection de cellules tumorales Download PDF

Info

Publication number
WO2024054972A2
WO2024054972A2 PCT/US2023/073725 US2023073725W WO2024054972A2 WO 2024054972 A2 WO2024054972 A2 WO 2024054972A2 US 2023073725 W US2023073725 W US 2023073725W WO 2024054972 A2 WO2024054972 A2 WO 2024054972A2
Authority
WO
WIPO (PCT)
Prior art keywords
alkyl
independently
alkylaryl
co2h
aryl
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US2023/073725
Other languages
English (en)
Other versions
WO2024054972A3 (fr
Inventor
Jacob HOUGHTON
Vilma JALLINOJA
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Research Foundation of the State University of New York
Original Assignee
Research Foundation of the State University of New York
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Research Foundation of the State University of New York filed Critical Research Foundation of the State University of New York
Priority to CN202380075881.0A priority Critical patent/CN120129539A/zh
Priority to EP23864036.1A priority patent/EP4583928A2/fr
Priority to CA3266257A priority patent/CA3266257A1/fr
Priority to AU2023338487A priority patent/AU2023338487A1/en
Priority to JP2025514746A priority patent/JP2025530298A/ja
Priority to KR1020257010933A priority patent/KR20250065366A/ko
Priority to IL319424A priority patent/IL319424A/en
Publication of WO2024054972A2 publication Critical patent/WO2024054972A2/fr
Publication of WO2024054972A3 publication Critical patent/WO2024054972A3/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D255/00—Heterocyclic compounds containing rings having three nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D249/00 - C07D253/00
    • C07D255/02—Heterocyclic compounds containing rings having three nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D249/00 - C07D253/00 not condensed with other rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6891—Pre-targeting systems involving an antibody for targeting specific cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
    • A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
    • A61K51/04—Organic compounds
    • A61K51/0404—Lipids, e.g. triglycerides; Polycationic carriers
    • A61K51/0406—Amines, polyamines, e.g. spermine, spermidine, amino acids, (bis)guanidines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
    • A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
    • A61K51/04—Organic compounds
    • A61K51/0495—Pretargeting
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
    • A61K51/12—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by a special physical form, e.g. emulsion, microcapsules, liposomes, characterized by a special physical form, e.g. emulsions, dispersions, microcapsules
    • A61K51/1268—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by a special physical form, e.g. emulsion, microcapsules, liposomes, characterized by a special physical form, e.g. emulsions, dispersions, microcapsules host-guest, closed hollow molecules, inclusion complexes, e.g. with cyclodextrins, clathrates, cavitates, fullerenes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D257/00—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms
    • C07D257/02—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F17/00—Metallocenes
    • C07F17/02—Metallocenes of metals of Groups 8, 9 or 10 of the Periodic Table
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
    • A61K47/555—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound pre-targeting systems involving an organic compound, other than a peptide, protein or antibody, for targeting specific cells

Definitions

  • Pretargeted positron emission tomography provides quantitative, non-invasive whole- body in vivo profile of macromolecules with an overall lower total body radiation dose compared to directly radiolabeled macromolecules (Altai, 2017 and Jallinoja, 2021).
  • Pretargeting is a two-step strategy that involves the administration of a target binding macromolecule which accumulates at the target site over several days while the unbound macromolecule excretes from non-target tissue.
  • a bioorthogonal small molecule radioligand is administered.
  • Figure 1 The low molecular weight of the radioligand allows its target accumulation and excretion to occur faster than that of the initial macromolecule.
  • the present invention harnesses a host-guest complex formation as the specific pretargeting interaction between the macromolecule and the radioligand. It was hypothesized that due to the high in vivo stability, modularity and low immunogenicity, the chosen host-guest pair, cucurbit[7]uril- adamantane (CB7-Adma, Ka ⁇ 10 14 M -1 ) makes an ideal interaction pair for pretargeted PET (Assaf KI, 2015, Shetty D, 2015 and Wanka L, 2013).
  • the strong complex between the two molecules forms when the Adma guest with an adjacent positively charged moiety binds to the carbonyl framed cavity of the macrocyclic CB7 host molecule via multiple van der Waals and ion-dipole interactions. So far, the medical imaging applications utilizing host-guest chemistry have been limited to pre-formed host-guest complexes to increase stability and/or sensitivity of imaging agents (Zhao, 2022, Sembo-Backonly, 2021 and Wu 2021). In nuclear medicine, the high affinity non-covalent binding between CB7 and Adma molecules has remained minimally explored (Strebl MG, 2018).
  • the present invention provides a compound having the structure: wherein Y 1 , Y 2 , Y 3 are each, independently, -H, alkyl-N-(CO 2 R 4 ) 2 , alkyl-N-(alkyl-CO 2 R 4 ) 2 , alkylheteroaryl, alkyl-CO 2 H, alkylaryl-CO 2 H, alkylheteroaryl-CO 2 H, alkyl-CO 2 R 4 , alkylaryl-NH-CO 2 R 4, alkylaryl-CO 2 R 4 , alkylheteroaryl-CO 2 R 4 , alkyl-OH, alkylaryl-OH, alkylheteroaryl-OH, alkyl-N(alkylaryl) 2 , alkyl- N(alkylaryl-CO 2 H) 2 , alkyl-N(alkylheteroaryl-CO 2 H) 2 , alkyl-N(alkylheteroaryl-CO 2 H)
  • the present invention provides a compound having the structure: wherein Y1, Y2, Y3 , Y4 are each, independently, -H, alkyl-N-(CO2R4)2, alkyl-N-(alkyl-CO2R4)2 , alkylheteroaryl, alkyl-CO2H, alkylaryl-CO2H, alkylheteroaryl-CO2H, alkyl-CO2R4, alkylaryl-NH-CO2R4, alkylaryl-CO2R4, alkylheteroaryl-CO2R4, alkyl-OH, alkylaryl-OH, alkylheteroaryl-OH, alkyl- N(alkylaryl)2, alkyl-N(alkylaryl-CO2H)2, alkyl-N(alkylheteroaryl-CO2H)2, alkyl-N(alkylaryl-CO2R4)2, alkyl-N(alkylheteroaryl-CO2 , al
  • the present invention provides a compound having the structure: wherein Y1, Y2, Y3 , Y4 are each, independently, -H, alkyl-N-(CO2R4)2, alkyl-N-(alkyl-CO2R4)2 , alkylheteroaryl, alkyl-CO2H, alkylaryl-CO2H, alkylheteroaryl-CO2H, alkyl-CO2R4, alkylaryl-NH-CO2R4, alkylaryl-CO2R4, alkylheteroaryl-CO2R4, alkyl-OH, alkylaryl-OH, alkylheteroaryl-OH, alkyl- N(alkylaryl)2, alkyl-N(alkylaryl-CO2H)2, alkyl-N(alkylheteroaryl-CO2H)2, alkyl-N(alkylaryl-CO2R4)2, alkyl-N(alkylheteroaryl-CO2 , al
  • Figure 1A and 1B An illustration of the two-step cucurbit[7]uril-adamantane pretargeting approach.
  • Figure 2 The chemical structure of the [ 64 Cu]Cu-NOTA-Adma (1), [ 64 Cu]Cu-NOTA-PEG 3 - Adma (2) and [ 64 Cu]Cu-NOTA-PEG 7 -Adma (3) and their respective distribution coefficient (log D) and blood half-lives (A).
  • the in vitro stability of 1-3 in phosphate buffer saline (PBS pH 7.4) and in bovine plasma at 37°C and their plasma protein binding.
  • bovine plasma 37°C and their plasma protein binding.
  • Figure 7 The reaction scheme for the synthesis of 6 and 7. I. triethylamine, methanol; II. sodium triacetoxyborohydride; III. iodomethane, sodium hydroxide, triethylamine; IV. trifluoroacetic acid, dichloromethane; V. p-SCN-Bn-NOTA x 3 HCl, N,N-diisopropylethylamine, dimethyl sulfoxide.
  • Figure 8. The reaction scheme for the synthesis of 8 and 9. I.
  • UV-Vis HPLC chromatograph of NOTA-PEG 7 -Adma (9) monitoring absorption of wavelength 254 nm.
  • Figure 12 Radio-HPLC chromatograph of [ 64 Cu]Cu-NOTA-Adma (1).
  • Figure 13 Radio-HPLC chromatograph of [ 64 Cu]Cu-NOTA-PEG 3 -Adma (2).
  • Figure 14. Radio-HPLC chromatograph of [ 64 Cu]Cu-NOTA-PEG 7 -Adma (3).
  • Figure 16 The percentage of internalized and membrane bound [ 64 Cu]CuCl2 and [ 64 Cu]Cu- NOTA-PEG3-Adma (2) of total added activity over 6 hours in BxPC3 cells. [0026] Figure 17. The two-phase decay curves are based on the %ID/g of the blood samples as a function of time. [ 64 Cu]Cu-NOTA-Adma (A), [ 64 Cu]Cu-NOTA-PEG3-Adma (B) and [ 64 Cu]Cu-NOTA-PEG7-Adma (C). [0027] Figure 18. Western Blotting of carcinoembryonic antigen (CEA) in BxPC3 and MIAPaCa-2 cell lysates.
  • CEA carcinoembryonic antigen
  • the present invention provides a compound having the structure: wherein Y 1 , Y 2 , Y 3 are each, independently, -H, alkyl-N-(CO 2 R 4 ) 2 , alkyl-N-(alkyl-CO 2 R 4 ) 2 , alkylheteroaryl, alkyl-CO 2 H, alkylaryl-CO 2 H, alkylheteroaryl-CO 2 H, alkyl-CO 2 R 4 , alkylaryl-NH-CO 2 R 4, alkylaryl-CO 2 R 4 , alkylheteroaryl-CO 2 R 4 , alkyl-OH, alkylaryl-OH, alkylheteroaryl-OH, alkyl-N(alkylaryl) 2 , alkyl- N(alkylaryl-CO 2 H) 2 , alkyl-N(alkylheteroaryl-CO 2 H) 2 , alkyl-N(alkylheteroaryl-CO 2 H)
  • the present invention provides a compound having the structure: wherein Y1, Y2, Y3 , Y4 are each, independently, -H, alkyl-N-(CO2R4)2, alkyl-N-(alkyl-CO2R4)2 , alkylheteroaryl, alkyl-CO2H, alkylaryl-CO2H, alkylheteroaryl-CO2H, alkyl-CO2R4, alkylaryl-NH-CO2R4, alkylaryl-CO2R4, alkylheteroaryl-CO2R4, alkyl-OH, alkylaryl-OH, alkylheteroaryl-OH, alkyl- N(alkylaryl)2, alkyl-N(alkylaryl-CO2H)2, alkyl-N(alkylheteroaryl-CO2H)2, alkyl-N(alkylaryl-CO2R4)2, alkyl-N(alkylheteroaryl-CO2 , al
  • the present invention provides a compound having the structure: wherein Y1, Y2, Y3 are each, independently, -H, alkyl-N-(CO2R4)2, alkyl-N-(alkyl-CO2R4)2 , alkylheteroaryl, alkyl-CO2H, alkylaryl-CO2H, alkylheteroaryl-CO2H, alkyl-CO2R4, alkylaryl-NH-CO2R4, alkylaryl-CO2R4, alkylheteroaryl-CO2R4, alkyl-OH, alkylaryl-OH, alkylheteroaryl-OH, alkyl-N(alkylaryl)2, alkyl- N(alkylaryl-CO2H)2, alkyl-N(alkylheteroaryl-CO2H)2, alkyl-N(alkylaryl-CO2R4)2, alkyl- N(alkylheteroaryl-CO2R4)2, alkyl- N
  • A is substituted with -OH, -NH 2 , halogen, alkyl, -O-alkyl, -alkyl-NH 2 , - NH-alkyl, -CHF 2 , -CF 3 , -OCHF 2 , -OCF 3 .
  • A is substituted with -NH 2 , -alkyl-NH 2 , -NH-alkyl, or alkyl.
  • n and m are each independently 0, 1, 2, 3, 4, 5, or 6.
  • n and m are each independently 1, 2, or 3.
  • n and m are each independently 1. [0037] In some embodiments, n is 1, 2, or 3. [0038] In some embodiments, m is 1, 2, or 3. [0039] In some embodiments, n is 1 or 2. [0040] In some embodiments, m is 1 or 2. [0041] In some embodiments, n is 1. [0042] In some embodiments, m is 1. [0043] In some embodiments, n and m are the same. [0044] In some embodiments, n and m are different.
  • R1 and R2 are each independently H, halogen, alkyl, alkenyl, alkynyl, - OH, -O-(alkyl), -CHF2, -CF3, -OCHF2 or -OCF3.
  • R1 and R2 are each independently H, halogen, C1-C6 alkyl, C1-C6 alkenyl, or C1-C6 alkynyl.
  • R1 and R2 are each independently, C1-C6 alkyl or C1-C6 alkenyl.
  • R1 and R2 are each independently C1-C6 alkyl.
  • R1 and R2 are C1-5 alkyl. [0050] In some embodiments, R1 and R2 are C1-3 alkyl. [0051] In some embodiments, R1 and R2 are methyl. [0052] In some embodiments, R1 and R2 are ethyl. [0053] In some embodiments, X is alkyl-aryl-thiourea, alkyl-heteroaryl-thiourea, alkyl-cycloalkyl- thiourea, alkenyl-aryl-thiourea, or alkenyl -heteroaryl-thiourea.
  • X is alkyl-aryl-thiourea, alkyl-heteroaryl-thiourea, or alkyl-cycloalkyl- thiourea. [0055] In some embodiments, X is alkyl-aryl-thiourea, or alkyl-heteroaryl-thiourea. [0056] In some embodiments, X is alkyl-aryl-thiourea.
  • the chemical linker L is an alkyl, alkenyl, alkynyl, alkylether, alkylthioether, alkylamino, alkylamido, alkylester, alkylaryl, alklyheteroaryl, polyethylene glycol (PEG), aryl, heteroaryl, a natural amino acid, an unnatural amino acid, a disulfide or thioether containing linker or combinations thereof.
  • the chemical linker L is an alkyl linker, an alkyne linker, alkynal linker or a polyethylene glycol (PEG) or combinations thereof.
  • the chemical linker L is an alkyl or a PEG or combinations thereof. [0060] In some embodiments, the chemical linker L is a PEG. [0061] In some embodiments, the chemical linker L has the following structure: , wherein m is 1, 2, 3, 4, 5, 6, [0062] In some embodiments of chemical linker L, m is 1, 2, 3, 4, 5, 6, or 7. [0063] In some embodiments of chemical linker L, m is 1, 3, or 7. [0064] In some embodiments of chemical linker L, m is 3.
  • the chemical linker L has the following structure: , wherein m is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 3, 4, 5, 6, or 7; more preferably, m is 1, 3, or 7. [0066] In some embodiments of chemical linker L, m is 1, 3 or 7. [0067] In some embodiments of chemical linker L, m is 3.
  • each occurrence of R 4 is independently, -H, -OH, -NH 2 , halogen, alkyl, - O-alkyl, -NH-alkyl, -CHF 2 , -CF 3 , -OCHF 2 , -OCF 3 , amide, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF 3 , or -Si(alkyl) 3 .
  • each occurrence of R 4 is independently, -H, -OH, -NH 2 , halogen, alkyl, - O-alkyl, -NH-alkyl, amide, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF 3 , or - Si(alkyl) 3 .
  • each occurrence of R 4 is independently, -OH, -NH 2 , alkyl, -O-alkyl, -NH- alkyl, amide, aryl, heteroaryl, or alkyl-CF 3 .
  • each occurrence of R4 is independently, -OH, -NH2, alkyl, -O-alkyl, -NH- alkyl, amide.
  • each occurrence of R4 is independently, -OH, -NH2, alkyl, -O-alkyl, -NH- alkyl.
  • R4 is -OH.
  • R4 is -NH2.
  • Y1, Y2, Y3, Y4 are each independently alkyl-CO2H, , alkyl-N-(CO2R4)2, alkyl-N-(alkyl-CO2R4)2, alkylaryl-CO2H, alkylheteroaryl-CO2H, alkyl-CO2R4, alkylaryl-NH-CO2R4, alkylaryl-CO2R4, alkylheteroaryl-CO2R4, alkyl-N(alkylaryl-CO2H)2, alkyl-N(alkylheteroaryl-CO2H)2, alkyl-N(alkylaryl-CO2R4)2, alkyl-N(alkylheteroaryl-CO2R4)2, alkyl-N(alkylheteroaryl-CO2R4)2, alkyl-N(alkyl-CO2H)2, alkyl-N(alkylaryl-OH)(alkyl-CO2H), alkyl-Nalkylhe
  • Y1, Y2, Y3, Y4 are each independently alkyl-CO2H, , alkyl-N-(CO2R4)2, alkyl-N-(alkyl-CO2R4)2, alkylaryl-CO2H, alkylheteroaryl-CO2H, alkyl-N(alkylaryl-CO2H)2, alkyl- N(alkylheteroaryl-CO2H)2, alkyl-N(alkyl-CO2H)2, alkyl-N(alkylaryl-OH)(alkyl-CO2H), alkyl- N(alkylheteroaryl-OH)(alkyl-CO2H), or alkylheteroaryl- P(O)(OH)2.
  • Y1, Y2, Y3, Y4 are each independently alkyl-CO2H, or alkyl-CO2NH2, or alkyl-N(alkyl-CO2H)2. [0078] In some embodiments, at least one of Y1, Y2, Y3, Y4 is alkyl-CO2H. [0079] In some embodiments, at least one of Y1, Y2, Y3, Y4 is alkyl-CO2NH2. [0080] In some embodiments, at least one of Y 1 , Y 2 , Y 3 , Y 4 is alkyl-N(alkyl-CO 2 H) 2 .
  • At least one of Y 1 , Y 2 , Y 3 , Y 4 is -CH 2 -CO 2 H. [0082] In some embodiments, at least one of Y 1 , Y 2 , Y 3 , Y 4 is -CH 2 -CO 2 NH 2 . [0083] In some embodiments, at least one of Y 1 , Y 2 , Y 3 , Y 4 is -CH 2 -N(alkyl-CO 2 H) 2 [0084] In some embodiments, at least two of Y 1 , Y 2 , Y 3 , Y 4 are the same.
  • At least three of Y 1 , Y 2 , Y 3 , Y 4 are the same. [0086] In some embodiments, Y 1 , Y 2 , Y 3 , Y 4 are the same. [0087] In some embodiments, at least one of Y 1 , Y 2 , Y 3 and Y 4 is H. [0088] In some embodiments, none of Y 1 , Y 2 , Y 3 and Y 4 are H.
  • Y 1 , Y 2 , Y 3 are each independently alkyl-CO 2 H, , alkyl-N-(CO 2 R 4 ) 2 , alkyl- N-(alkyl-CO 2 R 4 ) 2 , alkylaryl-CO 2 H, alkylheteroaryl-CO 2 H, alkyl-CO 2 R 4 , alkylaryl-NH-CO 2 R 4, alkylaryl- CO2R4, alkylheteroaryl-CO2R4, alkyl-N(alkylaryl-CO2H)2, alkyl-N(alkylheteroaryl-CO2H)2, alkyl- N(alkylaryl-CO2R4)2, alkyl-N(alkylheteroaryl-CO2R4)2, alkyl-N(alkylheteroaryl-CO2R4)2, alkyl-N(alkyl-CO2H)2, alkyl-N(alkylaryl- OH)(alkyl-CO
  • Y1, Y2, Y3 are each independently alkyl-CO2H, , alkyl-N-(CO2R4)2, alkyl- N-(alkyl-CO2R4)2, alkylaryl-CO2H, alkylheteroaryl-CO2H, alkyl-N(alkylaryl-CO2H)2, alkyl- N(alkylheteroaryl-CO2H)2, alkyl-N(alkyl-CO2H)2, alkyl-N(alkylaryl-OH)(alkyl-CO2H), alkyl- N(alkylheteroaryl-OH)(alkyl-CO2H), or alkylheteroaryl- P(O)(OH)2.
  • Y1, Y2, Y3 are each independently alkyl-CO2H, or alkyl-CO2NH2, or alkyl- N(alkyl-CO2H)2. [0092] In some embodiments, at least one of Y1, Y2, Y3 is alkyl-CO2H. [0093] In some embodiments, at least one of Y1, Y2, Y3 is alkyl-CO2NH2. [0094] In some embodiments, at least one of Y1, Y2, Y3 is alkyl-N(alkyl-CO2H)2. [0095] In some embodiments, at least one of Y1, Y2, Y3 is -CH2-CO2H.
  • At least one of Y1, Y2, Y3 is -CH2-CO2NH2. [0097] In some embodiments, at least one of Y1, Y2, Y3 is -CH2-N(alkyl-CO2H)2 [0098] In some embodiments, at least two of Y1, Y2 and Y3 are the same. [0099] In some embodiments, Y1, Y2 and Y3 are the same. [0100] In some embodiments, at least one of Y1, Y2, and Y3 is H. [0101] In some embodiments, none of Y1, Y2, and Y3 are H.
  • Y 1 , Y 2 , Y 3 , Y 4 are each independently - , In some embodiments, Y1, Y2, Y3, Y4 are each , , [0103] In some embodiments, Y 1 , Y 2 , Y 3 , Y 4 are each independent , . [0104] In some embodiments, Y1, Y2, Y3, Y4 are each , . [0105] In some embodiments, Y 1 , Y 2 , Y 3 , Y 4 are each , . [0106] In some embodiments, Y 1 andY 3 .
  • the guest molecule A is substituted or unsubstituted adamantane, 4,9- diamino diamantane, ferrocene, bicyclo[2.2.2]octane, iceane, diamantane, triamantane, isotetramantane, pentamantane, or cyclohexamantane.
  • the guest molecule A is substituted or unsubstituted adamantane, diamantane, 4,9-diamino diamantane or ferrocene.
  • the guest molecule A is substituted or unsubstituted adamantane or diamantane.
  • the guest molecule A is substituted with halogen, alkyl, alkenyl, alkynyl, -OH, -O-(alkyl), -N-(alkyl), -CHF 2 , -CF 3 , -OCHF 2 or -OCF 3 .
  • the guest molecule A is substituted with halogen, alkyl, -O-(alkyl), -N- (alkyl).
  • the guest molecule A is substituted or unsubstituted adamantane.
  • the guest molecule A is substituted or unsubstituted diamantane.
  • the guest molecule A is substituted or unsubstituted ferrocene. [0116] In some embodiments, the guest molecule A is unsubstituted adamantane. [0117] In some embodiments, the guest molecule A is substituted adamantane. [0118] In some embodiments, the guest molecule A is 4,9-diamino diamantane. [0119] In some embodiments, the guest molecule A is unsubstituted ferrocene. [0120] In some embodiments, the guest molecule A is unsubstituted diamantane. [0121] In some embodiments, the guest molecule A is substituted diamantane.
  • the substituted diamantane having the following structure: . [0123] In some embodiments, the guest substituted ferrocene. [0124] In some embodiments, the substituted ferrocene is substituted with C1-C6 alkyl, -alkyl-N-(C1-C6 alkyl), -OH, -O-(C1-C6 alkyl), -NH-(C1-C6 alkyl), -CHF2, -CF3, -OCHF2, or -OCF3.
  • the substituted ferrocene is substituted with C1-C6 alkyl, -alkyl-N-(C1-C6 alkyl), -OH, -O-(C1-C6 alkyl), -NH-(C1-C6 alkyl).
  • the substituted ferrocene is substituted with C 1 -C 6 alkyl, -alkyl-N-(C 1 -C 6 alkyl).
  • the substituted ferrocene is substituted with -alkyl-N-(C 1 -C 6 alkyl).
  • the substituted ferrocene having the following structure: .
  • the present invention provides a compound having the structure: wherein n and m are each n and m are each independently 1, 2, or 3; more preferably, n and m are 1; wherein o is 0, 1, 2, 3, 4, 5, or 6; preferably o is 1, 2, or 3; more preferably, o is 1; wherein Y 1 , Y 2 , Y 3 are each, independently, -H, alkyl-N-(CO 2 R 4 ) 2 , alkyl-N-(alkyl-CO 2 R 4 ) 2 , alkylheteroaryl, alkyl-CO 2 H, alkylaryl-CO 2 H, alkylheteroaryl-CO 2 H, alkyl-CO 2 R 4 , alkylaryl-NH-CO 2 R 4, alkylaryl-CO 2 R 4 , alkylheteroaryl-CO 2 R 4 , alkylaryl-NH-CO 2 R 4, alky
  • the present invention provides a compound having the structure: wherein n and m are each n and m are each independently 1, 2, or 3; more preferably, n and m are 1; wherein o is 0, 1, 2, 3, 4, 5, or 6; preferably o is 1, 2, or 3; more preferably, o is 1; wherein Y1, Y2, Y3 are each, independently, -H, alkyl-N-(CO2R4)2, alkyl-N-(alkyl-CO2R4)2 , alkylheteroaryl, alkyl-CO2H, alkylaryl-CO2H, alkylheteroaryl-CO2H, alkyl-CO2R4, alkylaryl-NH-CO2R4, alkylaryl-CO2R4, alkylheteroaryl-CO2R4, alkyl-OH, alkylaryl-OH, alkylheteroaryl-OH, alkyl-N(alkylaryl)2, alky
  • A is substituted with -OH, -NH 2 , halogen, alkyl, -O-alkyl, -alkyl-NH 2 , - NH-alkyl, -CHF 2 , -CF 3 , -OCHF 2 , -OCF 3 .
  • A is substituted with -NH2, -alkyl-NH2, -NH-alkyl, or alkyl.
  • the compound is other than . 0, 1, 2, 3, 4, 5, or 6.
  • n and m are each independently 1, 2, or 3.
  • n and m are 1.
  • n is 1, 2, or 3.
  • m is 1, 2, or 3.
  • n is 1 or 2.
  • n is 1.
  • m is 1.
  • n and m are the same.
  • n and m are different.
  • o is 0, 1, 2, 3, 4, 5, or 6.
  • o is 0, 1, 2, or 3.
  • o is 1 or 2.
  • o is 1.
  • R 1 and R 2 are each independently H, halogen, alkyl, alkenyl, alkynyl, - OH, -O-(alkyl), -CHF 2 , -CF 3 , -OCHF 2 or -OCF 3 .
  • R 1 and R 2 are each independently H, halogen, C 1 -C 6 alkyl, C 1 -C 6 alkenyl, or C 1 -C 6 alkynyl.
  • R1 and R2 are each independently, C1-C6 alkyl or C1-C6 alkenyl.
  • R1 and R2 are each independently C1-C6 alkyl. [0153] In some embodiments, R1 and R2 are C1-5 alkyl. [0154] In some embodiments, R1 and R2 are C1-3 alkyl. [0155] In some embodiments, R1 and R2 are methyl. [0156] In some embodiments, R1 and R2 are ethyl.
  • each occurrence of R4 is independently, -H, -OH, -NH2, halogen, alkyl, - O-alkyl, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3, amide, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3.
  • each occurrence of R4 is independently, -H, -OH, -NH2, halogen, alkyl, - O-alkyl, -NH-alkyl, amide, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or - Si(alkyl)3.
  • each occurrence of R4 is independently, -OH, -NH2, alkyl, -O-alkyl, -NH- alkyl, amide, aryl, heteroaryl, or alkyl-CF3.
  • each occurrence of R4 is independently, -OH, -NH2, alkyl, -O-alkyl, -NH- alkyl, amide. [0161] In some embodiments, each occurrence of R4 is independently, -OH, -NH2, alkyl, -O-alkyl, -NH- alkyl. [0162] In some embodiments, R4 is -OH. [0163] In some embodiments, R 4 is -NH 2 .
  • Y 1 , Y 2 , Y 3 are each independently alkyl-CO 2 H, , alkyl-N-(CO 2 R 4 ) 2 , alkyl- N-(alkyl-CO 2 R 4 ) 2 , alkylaryl-CO 2 H, alkylheteroaryl-CO 2 H, alkyl-CO 2 R 4 , alkylaryl-NH-CO 2 R 4, alkylaryl- CO 2 R 4 , alkylheteroaryl-CO 2 R 4 , alkyl-N(alkylaryl-CO 2 H) 2 , alkyl-N(alkylheteroaryl-CO 2 H) 2 , alkyl- N(alkylaryl-CO 2 R 4 ) 2 , alkyl-N(alkylheteroaryl-CO 2 R 4 ) 2 , alkyl-N(alkylheteroaryl-CO 2 R 4 ) 2 , alkyl-N(alkyl-CO 2 H) 2
  • Y 1 , Y 2 , Y 3 are each independently alkyl-CO 2 H, , alkyl-N-(CO 2 R 4 ) 2 , alkyl- N-(alkyl-CO 2 R 4 ) 2 , alkylaryl-CO 2 H, alkylheteroaryl-CO 2 H, alkyl-N(alkylaryl-CO 2 H) 2 , alkyl- N(alkylheteroaryl-CO 2 H) 2 , alkyl-N(alkyl-CO 2 H) 2 , alkyl-N(alkylaryl-OH)(alkyl-CO 2 H), alkyl- N(alkylheteroaryl-OH)(alkyl-CO2H), or alkylheteroaryl- P(O)(OH)2.
  • Y1, Y2, Y3 are each independently alkyl-CO2H, or alkyl-CO2NH2, or alkyl- N(alkyl-CO2H)2. [0167] In some embodiments, at least one of Y1, Y2, Y3 is alkyl-CO2H. [0168] In some embodiments, at least one of Y1, Y2, Y3 is alkyl-CO2NH2. [0169] In some embodiments, at least one of Y1, Y2, Y3 is alkyl-N(alkyl-CO2H)2. [0170] In some embodiments, at least one of Y1, Y2, Y3 is -CH2-CO2H.
  • At least one of Y1, Y2, Y3 is -CH2-CO2NH2. [0172] In some embodiments, at least one of Y1, Y2, Y3 is -CH2-N(alkyl-CO2H)2 [0173] In some embodiments, at least two of Y1, Y2 and Y3 are the same. [0174] In some embodiments, Y1, Y2 and Y3 are the same. [0175] In some embodiments, at least one of Y1, Y2, Y3 and Y4 is H. [0176] In some embodiments, none of Y1, Y2, Y3 and Y4 are H.
  • Y 1 , Y 2 , Y 3 , Y 4 are each independently , , , . [0180] In some embodiments, Y 1 , Y 2 , Y 3 , Y 4 are each , . [0181] In some embodiments, Y 1 , Y 2 , Y 3 , Y 4 are each , . [0182] In some embodiments, Y 1 andY 3 is , Y 2 and/or Y 4 is .
  • the L is an alkyl, alkenyl, alkynyl, alkylether, alkylthioether, alkylamino, alkylamido, alkylester, alkylaryl, alklyheteroaryl, polyethylene glycol (PEG), aryl, heteroaryl, a natural amino acid, an unnatural amino acid, a disulfide or thioether containing linker or combinations thereof.
  • the chemical linker L is an alkyl linker, an alkyne linker, alkynal linker or a polyethylene glycol (PEG) or combinations thereof.
  • the chemical linker L is an alkyl or a PEG or combinations thereof. [0186] In some embodiments, the chemical linker L is a PEG. [0187] In some embodiments, the chemical linker L has the following structure: , wherein m is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; preferably m is 1, 2, 3, 4, 5, 6, or 7; more preferably, m is 1, 3, or 7. [0188] In some embodiments, the chemical linker L has the following structure: , wherein m is 1, 2, 3, 4, 5, 6, 7, 8, 9, or m 3, 4, 5, 6, or 7; more preferably, m is 1, 3, or 7. [0189] In some embodiments of chemical linker L, m is 1, 3 or 7.
  • each occurrence of R4 is independently, -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3, amide, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3.
  • each occurrence of R4 is independently, -H, -OH, -NH2, halogen, alkyl, - O-alkyl, -NH-alkyl, amide, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF 3 , or - Si(alkyl)3.
  • each occurrence of R4 is independently, -OH, -NH2, alkyl, -O-alkyl, -NH- alkyl, amide, aryl, heteroaryl, or alkyl-CF 3 .
  • each occurrence of R 4 is independently, -OH, -NH 2 , alkyl, -O-alkyl, -NH- alkyl, amide. [0195] In some embodiments, each occurrence of R 4 is independently, -OH, -NH 2 , alkyl, -O-alkyl, -NH- alkyl. [0196] In some embodiments, R 4 is -OH. [0197] In some embodiments, R 4 is -NH 2 .
  • A is substituted with -OH, -NH 2 , halogen, alkyl, -O-alkyl, -alkyl-NH 2 , - NH-alkyl, -CHF 2 , -CF 3 , -OCHF 2 , -OCF 3 .
  • A is substituted with -NH 2 , -alkyl-NH 2 , -NH-alkyl, or alkyl.
  • the guest molecule A is substituted or unsubstituted adamantane, diamantane, ferrocene, bicyclo[2.2.2]octane, buckminsterfullerene (C60), iceane, triamantane, isotetramantane, ferrocene-modified peracetic acid, pentamantane, or cyclohexamantane.
  • the guest molecule A is substituted or unsubstituted adamantane, ferrocene, bicyclo[2.2.2]octane, iceane, diamantane, triamantane, isotetramantane, pentamantane, or cyclohexamantane.
  • the guest molecule A is substituted or unsubstituted adamantane, 4,9- diamino diamantane, ferrocene, bicyclo[2.2.2]octane, iceane, diamantane, triamantane, isotetramantane, pentamantane, or cyclohexamantane. [0203] In some embodiments, the guest molecule A is substituted or unsubstituted adamantane, diamantane , 4,9-diamino diamantane or ferrocene.
  • the guest molecule A is substituted or unsubstituted adamantane or diamantane.
  • the guest molecule A is substituted with halogen, alkyl, alkenyl, alkynyl, -OH, -O-(alkyl), -N-(alkyl), -CHF2, -CF3, -OCHF2 or -OCF3.
  • the guest molecule A is substituted with halogen, alkyl, -O-(alkyl), -N- (alkyl).
  • the guest molecule A is substituted or unsubstituted adamantane.
  • the guest molecule A is substituted or unsubstituted diamantane. [0209] In some embodiments, the guest molecule A is substituted or unsubstituted ferrocene. [0210] In some embodiments, the guest molecule A is unsubstituted adamantane. [0211] In some embodiments, the guest molecule A is substituted adamantane. [0212] In some embodiments, the guest molecule A is 4,9-diamino diamantane. [0213] In some embodiments, the guest molecule A is unsubstituted ferrocene. [0214] In some embodiments, the guest molecule A is unsubstituted diamantane.
  • the guest molecule A is substituted diamantane.
  • the substituted diamantane having the following structure: .
  • the guest molecule A is substituted ferrocene.
  • the substituted ferrocene is substituted with C1-C6 alkyl, -alkyl-N-(C1-C6 alkyl), -OH, -O-(C1-C6 alkyl), -NH-(C1-C6 alkyl), -CHF2, -CF3, -OCHF2, or -OCF3.
  • the substituted ferrocene is substituted with C1-C6 alkyl, -alkyl-N-(C1-C6 alkyl), -OH, -O-(C1-C6 alkyl), -NH-(C1-C6 alkyl).
  • the substituted ferrocene is substituted with C1-C6 alkyl, -alkyl-N-(C1-C6 alkyl).
  • the substituted ferrocene is substituted with -alkyl-N-(C1-C6 alkyl).
  • the substituted ferrocene having the following structure: .
  • the a compound having the structure wherein n and m are each n and m are each independently 1, 2, or 3; more preferably, n and m are wherein o is 0, 1, 2, 3, 4, 5, or 6; preferably o is 1, 2, or 3; more preferably, o is 1; wherein Y 1 , Y 2 , Y 3 , Y 4 are each, independently, -H, alkyl-N-(CO 2 R 4 ) 2 , alkyl-N-(alkyl-CO 2 R 4 ) 2 , alkylheteroaryl, alkyl-CO 2 H, alkylaryl-CO 2 H, alkylheteroaryl-CO 2 H, alkyl-CO 2 R 4 , alkylaryl-NH-CO 2 R 4, alkylaryl-CO 2 R 4 , alkylheteroaryl-CO 2 R 4 , alkyl-OH, alkylaryl-OH, alkylheteroary
  • n and m are each independently 0, 1, 2, 3, 4, 5, or 6. [0225] In some embodiments, n and m are each independently 1, 2, or 3. [0226] In some embodiments, n and m are 1. [0227] In some embodiments, n is 1, 2, or 3. [0228] In some embodiments, m is 1, 2, or 3. [0229] In some embodiments, n is 1 or 2. [0230] In some embodiments, m is 1 or 2. [0231] In some embodiments, n is 1. [0232] In some embodiments, m is 1. [0233] In some embodiments, n and m are the same. [0234] In some embodiments, n and m are different.
  • o is 0, 1, 2, 3, 4, 5, or 6.
  • o is 0, 1, 2, or 3.
  • o is 1 or 2.
  • o is 1.
  • R1 and R2 are each independently H, halogen, alkyl, alkenyl, alkynyl, - OH, -O-(alkyl), -CHF2, -CF3, -OCHF2 or -OCF3.
  • R1 and R2 are each independently H, halogen, C1-C6 alkyl, C1-C6 alkenyl, or C1-C6 alkynyl.
  • R1 and R2 are each independently, C1-C6 alkyl or C1-C6 alkenyl. [0242] In some embodiments, R1 and R2 are each independently C1-C6 alkyl. [0243] In some embodiments, R1 and R2 are C1-5 alkyl. [0244] In some embodiments, R1 and R2 are C1-3 alkyl. [0245] In some embodiments, R1 and R2 are methyl.
  • each occurrence of R4 is independently, -H, -OH, -NH2, halogen, alkyl, - O-alkyl, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3, amide, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3.
  • each occurrence of R4 is independently, -H, -OH, -NH2, halogen, alkyl, - O-alkyl, -NH-alkyl, amide, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or - Si(alkyl)3.
  • each occurrence of R4 is independently, -OH, -NH2, alkyl, -O-alkyl, - NH-alkyl, amide, aryl, heteroaryl, or alkyl-CF3.
  • each occurrence of R4 is independently, -OH, -NH2, alkyl, -O-alkyl, - NH-alkyl, or amide.
  • each occurrence of R 4 is independently, -OH, -NH 2 , alkyl, -O-alkyl, - or NH-alkyl.
  • R 4 is -OH.
  • R 4 is -NH 2 .
  • Y 1 , Y 2 , Y 3, Y 4 are each independently alkyl-CO 2 H, , alkyl-N-(CO 2 R 4 ) 2 , alkyl-N-(alkyl-CO 2 R 4 ) 2 , alkylaryl-CO 2 H, alkylheteroaryl-CO 2 H, alkyl-CO 2 R 4 , alkylaryl-NH-CO 2 R 4, alkylaryl-CO 2 R 4 , alkylheteroaryl-CO 2 R 4 , alkyl-N(alkylaryl-CO 2 H) 2 , alkyl-N(alkylheteroaryl-CO 2 H) 2 , alkyl-N(alkylaryl-CO 2 R 4 ) 2 , alkyl-N(alkylheteroaryl-CO 2 R 4 ) 2 , alkyl-N(alkylheteroaryl-CO 2 R 4 ) 2 , alkyl-N(alkylhetero
  • Y1, Y2, Y3, Y4 are each independently alkyl-CO2H, , alkyl-N-(CO2R4)2, alkyl-N-(alkyl-CO2R4)2, alkylaryl-CO2H, alkylheteroaryl-CO2H, alkyl-N(alkylaryl-CO2H)2, alkyl- N(alkylheteroaryl-CO2H)2, alkyl-N(alkyl-CO2H)2, alkyl-N(alkylaryl-OH)(alkyl-CO2H), alkyl- N(alkylheteroaryl-OH)(alkyl-CO2H), or alkylheteroaryl- P(O)(OH)2.
  • Y1, Y2, Y3, Y4 are each independently alkyl-CO2H, or alkyl-CO2NH2, or alkyl-N(alkyl-CO2H)2. [0256] In some embodiments, at least one of Y1, Y2, Y3, Y4 is alkyl-CO2H. [0257] In some embodiments, at least one of Y1, Y2, Y3, Y4 is alkyl-CO2NH2. [0258] In some embodiments, at least one of Y1, Y2, Y3, Y4 is alkyl-N(alkyl-CO2H)2.
  • At least one of Y1, Y2, Y3, Y4 is -CH2-CO2H.
  • at least one of Y1, Y2, Y3, Y4 is -CH2-CO2NH2.
  • at least one of Y1, Y2, Y3 , Y4 is -CH2-N(alkyl-CO2H)2
  • at least two of Y1, Y2 and Y3, Y4 are the same.
  • at least three of Y1, Y2, Y3 and Y4 are the same.
  • At least one of Y1, Y2, Y3 and Y4 is H. [0265] In some embodiments, none of Y1, Y2, Y3 and Y4 are H. [0266] In some embodiments, Y1, Y2 Y3, and Y4 are the same. [0267] In some embodiments, at least one of Y1, Y2, Y3 and Y4 is H. [0268] In some embodiments, none of Y 1 , Y 2 , Y 3 and Y 4 are H.
  • Y 1 , Y 2 , Y 3 , Y 4 are each independently - , , , , or [0272] In some embodiments, Y 1 , Y 2 , Y 3 , Y 4 are each , . [0273] In some embodiments, Y1, Y2, Y3, Y4 are each or . [0274] In some embodiments, Y 1 andY 3 is , Y 2 and/or Y 4 is .
  • alkylether alkylthioether, alkylamino, glycol (PEG), aryl, heteroaryl, a natural amino acid, an unnatural amino acid, a disulfide or thioether containing linker or combinations thereof.
  • the chemical linker L is an alkyl linker, an alkyne linker, alkynal linker or a polyethylene glycol (PEG) or combinations thereof.
  • the chemical linker L is an alkyl or a PEG or combinations thereof.
  • the chemical linker L is a PEG.
  • the chemical linker L has the following structure: , wherein m is 1, 2, 3, 4, 5, 6, or m or 7; more preferably, m is 1, 3, or 7. [0280] In some embodiments, the chemical linker L has the following structure: , wherein m is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 3, 4, 5, 6, or 7; more preferably, m is 1, 3, or 7. [0281] In some embodiments of chemical linker L, m is 1, 3 or 7. [0282] In some embodiments of chemical linker L, m is 3.
  • A is substituted with -OH, -NH2, halogen, alkyl, -O-alkyl, -alkyl-NH2, - NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3.
  • A is substituted with -NH 2 , -alkyl-NH 2 , -NH-alkyl, or alkyl.
  • the guest molecule A is substituted or unsubstituted adamantane, diamantane, ferrocene, bicyclo[2.2.2]octane, buckminsterfullerene (C60), iceane, triamantane, isotetramantane, ferrocene-modified peracetic acid, pentamantane, or cyclohexamantane.
  • the guest molecule A is substituted or unsubstituted adamantane, ferrocene, bicyclo[2.2.2]octane, iceane, diamantane, triamantane, isotetramantane, pentamantane, or cyclohexamantane.
  • the guest molecule A is substituted or unsubstituted adamantane, 4,9- diamino diamantane, ferrocene, bicyclo[2.2.2]octane, iceane, diamantane, triamantane, isotetramantane, pentamantane, or cyclohexamantane.
  • the guest molecule A is substituted or unsubstituted adamantane, diamantane, 4,9-diamino diamantane or ferrocene.
  • the guest molecule A is substituted or unsubstituted adamantane or diamantane.
  • the guest molecule A is substituted with halogen, alkyl, alkenyl, alkynyl, -OH, -O-(alkyl), -N-(alkyl), -CHF 2 , -CF 3 , -OCHF 2 or -OCF 3 .
  • the guest molecule A is substituted with halogen, alkyl, -O-(alkyl), -N- (alkyl).
  • the guest molecule A is substituted or unsubstituted adamantane.
  • the guest molecule A is substituted or unsubstituted diamantane.
  • the guest molecule A is substituted or unsubstituted ferrocene. [0295] In some embodiments, the guest molecule A is unsubstituted adamantane. [0296] In some embodiments, the guest molecule A is substituted adamantane. [0297] In some embodiments, the guest molecule A is 4,9-diamino diamantane . [0298] In some embodiments, the guest molecule A is unsubstituted ferrocene. [0299] In some embodiments, the guest molecule A is unsubstituted diamantane. [0300] In some embodiments, the guest molecule A is substituted diamantane.
  • the substituted diamantane having the following structure: .
  • the guest substituted ferrocene is substituted with C1-C6 alkyl, -alkyl-N-(C1-C6 alkyl), -OH, -O-(C1-C6 alkyl), -NH-(C1-C6 alkyl), -CHF2, -CF3, -OCHF2, or -OCF3.
  • the substituted ferrocene is substituted with C1-C6 alkyl, -alkyl-N-(C1-C6 alkyl), -OH, -O-(C1-C6 alkyl), -NH-(C1-C6 alkyl).
  • the substituted ferrocene is substituted with C 1 -C 6 alkyl, -alkyl-N-(C 1 -C 6 alkyl).
  • the substituted ferrocene is substituted with -alkyl-N-(C 1 -C 6 alkyl).
  • the substituted ferrocene having the following structure: .
  • the present invention provides a compound having the structure: wherein L is a chemical linker; wherein n and m are each independently 0, 1, 2, 3, 4, 5, or 6; wherein A is a guest molecule which is substituted or unsubstituted adamantane, ferrocene, diamantane , 4,9-diamino diamantane , bicyclo[2.2.2]octane, iceane, triamantane, isotetramantane, pentamantane cyclohexamantane, super-adamantane, 1,3,5,7-tetramethyl-1,3,5,7-tetrasilaadamantane, adamanzane, antimony trioxide, arsenic trioxide, 2,4,6-trioxa-1,3,5,7-tetraarsaadamantane, diamondoi
  • the present invention provides a compound having the structure: wherein L is a chemical linker; wherein n and m are each independently 0, 1, 2, 3, 4, 5, or 6; wherein A is a guest molecule which is substituted or unsubstituted adamantane, ferrocene, diamantane , 4,9-diamino diamantane , bicyclo[2.2.2]octane, iceane, triamantane, isotetramantane, pentamantane cyclohexamantane, super-adamantane, 1,3,5,7-tetramethyl-1,3,5,7-tetrasilaadamantane, adamanzane, antimony trioxide, arsenic trioxide, 2,4,6-trioxa-1,3,5,7-tetraarsaadamantane, diamondoid, hexamethylenetetramine, phosphorus pentasulfide,
  • each occurrence of R 4 is independently, -H, -OH, -NH 2 , halogen, alkyl, - O-alkyl, -NH-alkyl, -CHF 2 , -CF 3 , -OCHF 2 , -OCF 3 , amide, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF 3 , or -Si(alkyl) 3 .
  • each occurrence of R 4 is independently, -H, -OH, -NH 2 , halogen, alkyl, - O-alkyl, -NH-alkyl, amide, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF 3 , or - Si(alkyl) 3 .
  • each occurrence of R 4 is independently, -OH, -NH 2 , alkyl, -O-alkyl, -NH- alkyl, amide, aryl, heteroaryl, or alkyl-CF 3 .
  • each occurrence of R 4 is independently, -OH, -NH 2 , alkyl, -O-alkyl, - NH-alkyl, amide.
  • each occurrence of R 4 is independently, -OH, -NH 2 , alkyl, -O-alkyl, or - NH-alkyl.
  • R 4 is -OH.
  • R 4 is -NH 2 .
  • the compound is other than .
  • n and m are each n and m are each independently 1, 2, or 3; more preferably, n and wherein o is 0, 1, 2, 3, 4, 5, or 6; preferably o is 1, 2, or 3; more preferably, o is 1; wherein each occurrence of R 4 is independently, -H, -OH, -NH 2 , halogen, alkyl, -O-alkyl, -NH- alkyl, -CHF 2 , -CF 3 , -OCHF 2 , -OCF 3 , amide, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF 3 , or -Si(alkyl) 3 ; wherein X is alkyl-aryl-thiourea, alkyl-heteroaryl-thiourea, alkyl-cycloalkyl-thiourea, alkenyl-
  • each occurrence of R4 is independently, -H, -OH, -NH2, halogen, alkyl, - O-alkyl, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3, amide, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3.
  • each occurrence of R4 is independently, -H, -OH, -NH2, halogen, alkyl, - O-alkyl, -NH-alkyl, amide, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or - Si(alkyl)3.
  • each occurrence of R4 is independently, -OH, -NH2, alkyl, -O-alkyl, -NH- alkyl, amide, aryl, heteroaryl, or alkyl-CF3.
  • each occurrence of R4 is independently, -OH, -NH2, alkyl, -O-alkyl, -NH- alkyl, or amide. [0323] In some embodiments, each occurrence of R4 is independently, -OH, -NH2, alkyl, -O-alkyl, or - NH-alkyl. [0324] In some embodiments, R 4 is -OH. [0325] In some embodiments, R 4 is -NH 2 .
  • the present invention provides a compound having the structure: wherein n and m are each independently 0, 1, 2, 3, 4, 5, or 6; preferably, n and m are each independently 1, 2, or 3; more preferably, n and m are 1; wherein o is 0, 1, 2, 3, 4, 5, or 6; preferably o is 1, 2, or 3; more preferably, o is 1; wherein each occurrence of R 4 is independently, -H, -OH, -NH 2 , halogen, alkyl, -O-alkyl, -NH- alkyl, -CHF 2 , -CF 3 , -OCHF 2 , -OCF 3 , amide, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF 3 , or -Si(alkyl) 3 ; wherein X is alkyl-aryl-thiourea, alkyl-hetero
  • each occurrence of R4 is independently, -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3, amide, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3.
  • each occurrence of R 4 is independently, -H, -OH, -NH 2 , halogen, alkyl, -O-alkyl, -NH-alkyl, amide, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF 3 , or - Si(alkyl) 3 .
  • each occurrence of R 4 is independently, -OH, -NH 2 , alkyl, -O-alkyl, - NH-alkyl, amide, aryl, heteroaryl, or alkyl-CF 3 .
  • each occurrence of R 4 is independently, -OH, -NH 2 , alkyl, -O-alkyl, - NH-alkyl, or amide. [0331] In some embodiments, each occurrence of R 4 is independently, -OH, -NH 2 , alkyl, -O-alkyl, or - NH-alkyl. [0332] In some embodiments, R4 is -OH. [0333] In some embodiments, R4 is -NH2.
  • the present invention provides a compound having the structure: wherein n and m are each independently 0, 1, 2, 3, 4, 5, or 6; wherein A is a guest molecule which is substituted or unsubstituted adamantane, ferrocene, diamantane , 4,9-diamino diamantane , bicyclo[2.2.2]octane, iceane, triamantane, isotetramantane, pentamantane cyclohexamantane, super-adamantane, 1,3,5,7-tetramethyl-1,3,5,7-tetrasilaadamantane, adamanzane, antimony trioxide, arsenic trioxide, 2,4,6-trioxa-1,3,5,7-tetraarsaadamantane, diamondoid, hexamethylenetetramine, phosphorus pentasulfide, phosphorus pentoxide, phosphorus pentoxid
  • the present invention provides a compound having the structure: wherein n m are or n m are independently 1, 2, or 3; more preferably, n and m are 1; wherein o is 0, 1, 2, 3, 4, 5, or 6; preferably o is 1, 2, or 3; more preferably, o is 1; wherein each occurrence of R4 is independently, -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH- alkyl, -CHF2, -CF3, -OCHF2, -OCF3, amide, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3; wherein X is alkyl-aryl-thiourea, alkyl-heteroaryl-thiourea, alkyl-cycloalkyl-thiourea, alkenyl-ary
  • the present invention provides a compound having the structure: wherein n and m are each independently 0, 1, 2, 3, 4, 5, or 6; preferably, n and m are each independently 1, 2, or 3; more preferably, n and m are 1; wherein o is 0, 1, 2, 3, 4, 5, or 6; preferably o is 1, 2, or 3; more preferably, o is 1; wherein each occurrence of R 4 is independently, -H, -OH, -NH 2 , halogen, alkyl, -O-alkyl, -NH- alkyl, -CHF 2 , -CF 3 , -OCHF 2 , -OCF 3 , amide, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF 3 , or -Si(alkyl) 3 ; wherein X is alkyl-aryl-thiourea, alkyl-hetero
  • each occurrence of R 4 is independently, -H, -OH, -NH 2 , halogen, alkyl, - O-alkyl, -NH-alkyl, -CHF 2 , -CF 3 , -OCHF 2 , -OCF 3 , amide, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF 3 , or -Si(alkyl) 3 .
  • each occurrence of R 4 is independently, -H, -OH, -NH 2 , halogen, alkyl, - O-alkyl, -NH-alkyl, amide, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF 3 , or - Si(alkyl) 3 .
  • each occurrence of R 4 is independently, -OH, -NH 2 , alkyl, -O-alkyl, -NH- alkyl, amide, aryl, heteroaryl, or alkyl-CF 3 .
  • each occurrence of R4 is independently, -OH, -NH2, alkyl, -O-alkyl, -NH- alkyl, or amide. [0341] In some embodiments, each occurrence of R4 is independently, -OH, -NH2, alkyl, -O-alkyl, or - NH-alkyl. [0342] In some embodiments, R4 is -OH. [0343] In some embodiments, R4 is -NH2.
  • A is substituted with -OH, -NH2, halogen, alkyl, -O-alkyl, -alkyl-NH2, - NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3.
  • A is substituted with -NH2, -alkyl-NH2, -NH-alkyl, or alkyl.
  • the present invention provides a compound having the structure: wherein L is alkyl, alkenyl, alkylester, alkylaryl, alklyheteroaryl,or wherein n and m are each independently 0, 1, 2, or 3; wherein A is a guest molecule which is substituted or unsubstituted adamantane, ferrocene, diamantane, 4,9-diamino diamantane, bicyclo[2.2.2]octane, iceane, triamantane, isotetramantane, pentamantane cyclohexamantane, super-adamantane, 1,3,5,7-tetramethyl-1,3,5,7-tetrasilaadamantane; and wherein each occurrence of R 4 is independently, -H, -OH, -NH 2 , halogen, alkyl, -O-alkyl, -NH- alkyl, -CHF 2 ,
  • the compound is other than .
  • the present invention provides a compound having the structure: alklyheteroaryl,or polyethylene glycol (PEG); wherein n and m are each independently 0, 1, 2, or 3; wherein A is a guest molecule which is substituted or unsubstituted adamantane, ferrocene, diamantane , 4,9-diamino diamantane , bicyclo[2.2.2]octane, iceane, triamantane, isotetramantane, pentamantane cyclohexamantane, super-adamantane, 1,3,5,7-tetramethyl-1,3,5,7-tetrasilaadamantane; and wherein each occurrence of R 4 is independently, -H, -OH, -NH 2 , halogen, alkyl, -O-alkyl, -NH-alkyl, - CHF
  • each occurrence of R4 is independently, -H, -OH, -NH2, halogen, alkyl, - O-alkyl, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3, amide, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3.
  • each occurrence of R4 is independently, -H, -OH, -NH2, halogen, alkyl, - O-alkyl, -NH-alkyl, amide, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or - Si(alkyl)3.
  • each occurrence of R4 is independently, -OH, -NH2, alkyl, -O-alkyl, -NH- alkyl, amide, aryl, heteroaryl, or alkyl-CF3.
  • each occurrence of R4 is independently, -OH, -NH2, alkyl, -O-alkyl, -NH- alkyl, or amide.
  • each occurrence of R4 is independently, -OH, -NH2, alkyl, -O-alkyl, or - NH-alkyl.
  • R4 is -OH.
  • R4 is -NH2.
  • n and m are each independently 1, 2, or 3.
  • n and m are 1.
  • n is 1, 2, or 3.
  • n is 1, 2, or 3.
  • n is 1 or 2.
  • m is 1 or 2.
  • n is 1.
  • m is 1.
  • R 1 and R 2 are each independently H, halogen, alkyl, alkenyl, alkynyl, - OH, -O-(alkyl), -CHF 2 , -CF 3 , -OCHF 2 or -OCF 3 .
  • R 1 and R 2 are each independently H, halogen, C 1 -C 6 alkyl, C 1 -C 6 alkenyl, or C 1 -C 6 alkynyl. [0368] In some embodiments, R 1 and R 2 are each independently, C 1 -C 6 alkyl or C 1 -C 6 alkenyl. [0369] In some embodiments, R1 and R2 are each independently C1-C6 alkyl. [0370] In some embodiments, R1 and R2 are C1-5 alkyl. [0371] In some embodiments, R1 and R2 are C1-3 alkyl. [0372] In some embodiments, R1 and R2 are methyl.
  • alkyl is C1-6 alkyl. [0374] In some embodiments, alkyl is C1-3 alkyl. [0375] In some embodiments, alkyl is methyl. [0376] In some embodiments, aryl is phenyl, p-toluenyl (4-methylphenyl), naphthyl, tetrahydronaphthyl; indanyl, biphenyl, phenanthryl, anthryl or acenaphthyl. [0377] In some embodiments, aryl is phenyl, p-toluenyl (4-methylphenyl), or naphthyl.
  • aryl is phenyl.
  • the chemical linker L is an alkyl, alkenyl, alkynyl, alkylether, alkylthioether, alkylamino, alkylamido, alkylester, alkylaryl, alklyheteroaryl, polyethylene glycol (PEG), aryl, heteroaryl, a natural amino acid, an unnatural amino acid, a disulfide or thioether containing linker or combinations thereof.
  • the chemical linker L is an alkyl linker, an alkyne linker, alkynal linker or a polyethylene glycol (PEG) or combinations thereof.
  • the chemical linker L is an alkyl or a PEG or combinations thereof. [0382] In some embodiments, the chemical linker L is a PEG. [0383] In some embodiments, the chemical linker L has the following structure: , wherein m is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; preferably m is 1, 2, 3, 4, 5, 6, or 7; more preferably, m is 1, 3, or 7. [0384] In some embodiments, the chemical linker L has the following structure: , wherein m is 1, 2, 3, 4, 5, 6, 7, 8, 9, or m 3, 4, 5, 6, or 7; more preferably, m is 1, 3, or 7. [0385] In some embodiments of chemical linker L, m is 1, 3 or 7.
  • m is 3.
  • the guest molecule A is substituted or unsubstituted adamantane, diamantane, ferrocene, bicyclo[2.2.2]octane, buckminsterfullerene (C60), iceane, triamantane, isotetramantane, ferrocene-modified peracetic acid, pentamantane, or cyclohexamantane.
  • the guest molecule A is substituted or unsubstituted adamantane, ferrocene, bicyclo[2.2.2]octane, iceane, diamantane, triamantane, isotetramantane, pentamantane, or cyclohexamantane.
  • the guest molecule A is substituted or unsubstituted adamantane, 4,9- diamino diamantane , ferrocene, bicyclo[2.2.2]octane, iceane, diamantane, triamantane, isotetramantane, pentamantane, or cyclohexamantane.
  • the guest molecule A is substituted with halogen, alkyl, alkenyl, alkynyl, -OH, -O-(alkyl), -N-(alkyl), -CHF 2 , -CF 3 , -OCHF 2 or -OCF 3 .
  • A is substituted with -OH, -NH 2 , halogen, alkyl, -O-alkyl, -alkyl-NH 2 , - NH-alkyl, -CHF 2 , -CF 3 , -OCHF 2 , -OCF 3 .
  • A is substituted with -NH 2 , -alkyl-NH 2 , -NH-alkyl, or alkyl.
  • the guest molecule A is substituted with halogen, alkyl, -O-(alkyl), or -N- (alkyl).
  • the guest molecule A is substituted or unsubstituted adamantane, diamantane , 4,9-diamino diamantane or ferrocene. [0395] In some embodiments, the guest molecule A is substituted or unsubstituted adamantane or diamantane. [0396] In some embodiments, the guest molecule A is substituted or unsubstituted adamantane. [0397] In some embodiments, the guest molecule A is substituted or unsubstituted diamantane. [0398] In some embodiments, the guest molecule A is substituted or unsubstituted ferrocene.
  • the guest molecule A is unsubstituted adamantane.
  • the guest molecule A is substituted adamantane.
  • the guest molecule A is 4,9-diamino diamantane .
  • the guest molecule A is unsubstituted ferrocene.
  • the guest molecule A is unsubstituted diamantane.
  • the guest molecule A is substituted diamantane.
  • the substituted diamantane having the following structure: .
  • the guest substituted ferrocene is substituted with C1-C6 alkyl, -alkyl-N-(C1-C6 alkyl), -OH, -O-(C1-C6 alkyl), -NH-(C1-C6 alkyl), -CHF2, -CF3, -OCHF2, or -OCF3.
  • the substituted ferrocene is substituted with C1-C6 alkyl, -alkyl-N-(C1-C6 alkyl), -OH, -O-(C1-C6 alkyl), or -NH-(C1-C6 alkyl).
  • the substituted ferrocene is substituted with C1-C6 alkyl, or -alkyl-N-(C1- C6 alkyl).
  • the substituted ferrocene is substituted with -alkyl-N-(C1-C6 alkyl).
  • the substituted ferrocene having the following structure: .
  • the present invention provides a compound having the structure: wherein L is alkyl, alkenyl, ; wherein n and m are each independently 1, 2, or 3; wherein A is a guest molecule which is adamantane, ferrocene, or diamantane ; and wherein R4 is -OH, -O-(C1-C6 alkyl), or NH-(C1-C6 alkyl), more preferably R4 is -OH.
  • the compound is other than .
  • L is alkyl, alkenyl, alkynyl, alkylether, or polyethylene glycol (PEG); wherein n and m are each independently 1, 2, or 3; wherein A is a guest molecule which is adamantane, ferrocene, or diamantane; and wherein R 4 is -OH, -O-(C 1 -C 6 alkyl), or NH-(C 1 -C 6 alkyl), more preferably R 4 is -OH.
  • n and m are each independently 1, 2, or 3.
  • n and m are 1.
  • n is 1, 2, or 3.
  • n is 1, 2, or 3.
  • n is 1 or 2.
  • m is 1 or 2.
  • n is 1.
  • m is 1.
  • R 1 and R 2 are each independently H, halogen, alkyl, alkenyl, alkynyl, - OH, -O-(alkyl), -CHF 2 , -CF 3 , -OCHF 2 or -OCF 3 .
  • R 1 and R 2 are each independently H, halogen, C 1 -C 6 alkyl, C 1 -C 6 alkenyl, or C 1 -C 6 alkynyl.
  • R1 and R2 are each independently, C1-C6 alkyl or C1-C6 alkenyl.
  • R1 and R2 are each independently C1-C6 alkyl.
  • R1 and R2 are C1-5 alkyl.
  • R 1 and R 2 are C 1-3 alkyl.
  • R 1 and R 2 are methyl.
  • R 1 and R 2 are ethyl.
  • the present invention provides compound having the structure: , , or .
  • the present invention provides a metal complex comprising the compound described in the invention, wherein the compound coordinates to a metal.
  • the present invention provides a metal complex having the structure: , wherein M is the metal; wherein Y1, Y2, Y3 are each, independently, -H, alkyl-N-(CO2R4)2, alkyl-N-(alkyl-CO2R4)2 , alkylheteroaryl, alkyl-CO2H, alkylaryl-CO2H, alkylheteroaryl-CO2H, alkyl-CO2R4, alkylaryl-NH-CO2R4, alkylaryl-CO2R4, alkylheteroaryl-CO2R4, alkyl-OH, alkylaryl-OH, alkylheteroaryl-OH, alkyl-N(alkylaryl)2, alkyl- N(alkylaryl-CO2H)2, alkyl-N(alkylheteroaryl-CO2H)2, alkyl-N(alkylaryl-CO2R4)2, alkyl- N(alkylheteroaryl-
  • the present invention provides a metal complex having the structure: wherein M is the metal; wherein Y 1 , Y 2 , Y 3 , Y 4 are each, independently, -H, alkyl-N-(CO 2 R 4 ) 2 , alkyl-N-(alkyl-CO 2 R 4 ) 2 , alkylheteroaryl, alkyl-CO 2 H, alkylaryl-CO 2 H, alkylheteroaryl-CO 2 H, alkyl-CO 2 R 4 , alkylaryl-NH-CO 2 R 4, alkylaryl-CO 2 R 4 , alkylheteroaryl-CO 2 R 4 , alkyl-OH, alkylaryl-OH, alkylheteroaryl-OH, alkyl- N(alkylaryl) 2 , alkyl-N(alkylaryl-CO 2 H) 2 , alkyl-N(alkylheteroaryl-CO 2 H) 2 , alkyl-N(
  • the present invention provides a metal complex having the structure: , wherein M is the metal; wherein Y1, Y2, Y3 are each, independently, -H, alkyl-N-(CO2R4)2, alkyl-N-(alkyl-CO2R4)2 , alkylheteroaryl, alkyl-CO2H, alkylaryl-CO2H, alkylheteroaryl-CO2H, alkyl-CO2R4, alkylaryl-NH-CO2R4, alkylaryl-CO2R4, alkylheteroaryl-CO2R4, alkyl-OH, alkylaryl-OH, alkylheteroaryl-OH, alkyl-N(alkylaryl)2, alkyl- N(alkylaryl-CO2H)2, alkyl-N(alkylheteroaryl-CO2H)2, alkyl-N(alkylaryl-CO2R4)2, alkyl- N(alkylheteroaryl-
  • the metal complex is other than . 0, 1, 2, 3, 4, 5, or 6.
  • n and m are each independently 1, 2, or 3.
  • n and m are 1.
  • n is 1, 2, or 3.
  • m is 1, 2, or 3.
  • n is 1 or 2.
  • n is 1.
  • m is 1.
  • n and m are the same.
  • n and m are different.
  • R1 and R2 are each independently H, halogen, alkyl, alkenyl, alkynyl, - OH, -O-(alkyl), -CHF2, -CF3, -OCHF2 or -OCF3.
  • R1 and R2 are each independently H, halogen, C1-C6 alkyl, C1-C6 alkenyl, or C1-C6 alkynyl.
  • R 1 and R 2 are each independently, C 1 -C 6 alkyl or C 1 -C 6 alkenyl.
  • R 1 and R 2 are each independently C 1 -C 6 alkyl.
  • R 1 and R 2 are C 1-5 alkyl. [0455] In some embodiments, R 1 and R 2 are C 1-3 alkyl. [0456] In some embodiments, R 1 and R 2 are methyl. [0457] In some embodiments, R 1 and R 2 are ethyl.
  • each occurrence of R 4 is independently, -H, -OH, -NH 2 , halogen, alkyl, - O-alkyl, -NH-alkyl, -CHF 2 , -CF 3 , -OCHF 2 , -OCF 3 , amide, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3.
  • each occurrence of R4 is independently, -H, -OH, -NH2, halogen, alkyl, - O-alkyl, -NH-alkyl, amide, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or - Si(alkyl)3.
  • each occurrence of R4 is independently, -OH, -NH2, alkyl, -O-alkyl, -NH- alkyl, amide, aryl, heteroaryl, or alkyl-CF3.
  • each occurrence of R4 is independently, -OH, -NH2, alkyl, -O-alkyl, -NH- alkyl, amide.
  • each occurrence of R4 is independently, -OH, -NH2, alkyl, -O-alkyl, -NH- alkyl.
  • R4 is -OH.
  • R4 is -NH2.
  • X is alkyl-aryl-thiourea, alkyl-heteroaryl-thiourea, alkyl-cycloalkyl- thiourea, alkenyl-aryl-thiourea, or alkenyl -heteroaryl-thiourea.
  • X is alkyl-aryl-thiourea, alkyl-heteroaryl-thiourea, or alkyl-cycloalkyl- thiourea.
  • X is alkyl-aryl-thiourea, or alkyl-heteroaryl-thiourea.
  • X is alkyl-aryl-thiourea.
  • Y1, Y2, Y3, Y4 are each independently alkyl-CO2H, , alkyl-N-(CO2R4)2, alkyl-N-(alkyl-CO 2 R 4 ) 2 , alkylaryl-CO 2 H, alkylheteroaryl-CO 2 H, alkyl-CO 2 R 4 , alkylaryl-NH-CO 2 R 4, alkylaryl-CO 2 R 4 , alkylheteroaryl-CO 2 R 4 , alkyl-N(alkylaryl-CO 2 H) 2 , alkyl-N(alkylheteroaryl-CO 2 H) 2 , alkyl-N(alkylaryl-CO 2 R 4 ) 2 , alkyl-N(alkylaryl-CO 2 R 4 ) 2 , alkyl-N(alkylaryl-CO 2 R 4 ) 2 , alkyl-N(alkylheter
  • Y 1 , Y 2 , Y 3, Y 4 are each independently alkyl-CO 2 H, , alkyl-N-(CO 2 R 4 ) 2 , alkyl-N-(alkyl-CO 2 R 4 ) 2 , alkylaryl-CO 2 H, alkylheteroaryl-CO 2 H, alkyl-N(alkylaryl-CO 2 H) 2 , alkyl- N(alkylheteroaryl-CO 2 H) 2 , alkyl-N(alkyl-CO 2 H) 2 , alkyl-N(alkylaryl-OH)(alkyl-CO 2 H), alkyl- N(alkylheteroaryl-OH)(alkyl-CO 2 H), or alkylheteroaryl- P(O)(OH) 2 .
  • Y 1 , Y 2 , Y 3, Y 4 are each independently alkyl-CO 2 H, or alkyl-CO 2 NH 2 , or alkyl-N(alkyl-CO 2 H) 2 .
  • at least one of Y1, Y2, Y3, Y4 is alkyl-CO2H.
  • at least one of Y1, Y2, Y3, Y4 is alkyl-CO2NH2.
  • at least one of Y1, Y2, Y3, Y4 is alkyl-N(alkyl-CO2H)2.
  • At least one of Y1, Y2, Y3, Y4 is -CH2-CO2H.
  • at least one of Y1, Y2, Y3, Y4 is -CH2-CO2NH2.
  • at least one of Y1, Y2, Y3 , Y4 is -CH2-N(alkyl-CO2H)2
  • at least two of Y1, Y2 and Y3, Y4 are the same.
  • at least three of Y1, Y2, Y3 and Y4 are the same.
  • Y1, Y2 Y3, and Y4 are the same. [0481] In some embodiments, at least one of Y1, Y2, Y3 and Y4 is H. [0482] In some embodiments, none of Y1, Y2, Y3 and Y4 are H. In Y4 - , , . [0484] In some embodiments, Y1, Y2, Y3, Y4 are each , , [0485] In some embodiments, Y1, Y2, Y3, Y4 are each , or [0486] In some embodiments, Y 1 , Y 2 , Y 3 , Y 4 are each independentl , .
  • Y 1 , Y 2 , Y 3 , Y 4 are each independently . some an alkynyl, alkylether, alkylthioether, alkylamino, alkylamido, alkylester, alkylaryl, alklyheteroaryl, polyethylene glycol (PEG), aryl, heteroaryl, a natural amino acid, an unnatural amino acid, a disulfide or thioether containing linker or combinations thereof.
  • the chemical linker L is an alkyl linker, an alkyne linker, alkynal linker or a polyethylene glycol (PEG) or combinations thereof.
  • the chemical linker L is an alkyl or a PEG or combinations thereof. [0492] In some embodiments, the chemical linker L is a PEG. [0493] In some embodiments, the chemical linker L has the following structure: , wherein m is 1, 2, 3, 4, 5, 6, or 7; more preferably, m is 1, 3, or 7. [0494] In some embodiments, the chemical linker L has the following structure: , wherein m is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; preferably m is 1, 2, 3, 4, 5, 6, or 7; more preferably, m is 1, 3, or 7. [0495] In some embodiments of chemical linker L, m is 1, 3 or 7.
  • m is 3.
  • the guest molecule A is adamantane, diamantane, ferrocene, bicyclo[2.2.2]octane, buckminsterfullerene (C60), iceane, triamantane, isotetramantane, ferrocene- modified peracetic acid, pentamantane, or cyclohexamantane.
  • the guest molecule A is adamantane, ferrocene, bicyclo[2.2.2]octane, iceane, diamantane, triamantane, isotetramantane, pentamantane, or cyclohexamantane.
  • the guest molecule A is substituted or unsubstituted adamantane, 4,9- diamino diamantane, ferrocene, bicyclo[2.2.2]octane, iceane, diamantane, triamantane, isotetramantane, pentamantane, or cyclohexamantane.
  • the guest molecule A is substituted or unsubstituted adamantane, diamantane, 4,9-diamino diamantane or ferrocene.
  • the guest molecule A is substituted with halogen, alkyl, alkenyl, alkynyl, -OH, -O-(alkyl), -N-(alkyl), -CHF2, -CF3, -OCHF2 or -OCF3.
  • the guest molecule A is substituted with halogen, alkyl, -O-(alkyl), -N- (alkyl).
  • the guest molecule A is substituted or unsubstituted adamantane or diamantane. [0504] In some embodiments, the guest molecule A is substituted or unsubstituted adamantane. [0505] In some embodiments, the guest molecule A is substituted or unsubstituted diamantane. [0506] In some embodiments, the guest molecule A is substituted or unsubstituted ferrocene. [0507] In some embodiments, the guest molecule A is unsubstituted adamantane. [0508] In some embodiments, the guest molecule A is substituted adamantane.
  • the guest molecule A is 4,9-diamino diamantane. [0510] In some embodiments, the guest molecule A is unsubstituted ferrocene. [0511] In some embodiments, the guest molecule A is unsubstituted diamantane. [0512] In some embodiments, the guest molecule A is substituted diamantane. [0513] In some embodiments, the substituted diamantane having the following structure: . [0514] In some embodiments, the guest molecule A is substituted ferrocene.
  • the substituted ferrocene is substituted with C1-C6 alkyl, -alkyl-N-(C1-C6 alkyl), -OH, -O-(C1-C6 alkyl), -NH-(C1-C6 alkyl), -CHF2, -CF3, -OCHF2, or -OCF3.
  • the substituted ferrocene is substituted with C1-C6 alkyl, -alkyl-N-(C1-C6 alkyl), -OH, -O-(C1-C6 alkyl), -NH-(C1-C6 alkyl).
  • the substituted ferrocene is substituted with C1-C6 alkyl, -alkyl-N-(C1-C6 alkyl). [0518] In some embodiments, the substituted ferrocene is substituted with -alkyl-N-(C1-C6 alkyl). [0519] In some embodiments, the substituted ferrocene having the following structure: .
  • the a metal complex having the structure: wherein M is the metal; wherein Y1, Y2, Y3 are each, independently, -H, alkyl-N-(CO2R4)2, alkyl-N-(alkyl-CO2R4)2 , alkylheteroaryl, alkyl-CO2H, alkylaryl-CO2H, alkylheteroaryl-CO2H, alkyl-CO2R4, alkylaryl-NH-CO2R4, alkylaryl-CO2R4, alkylheteroaryl-CO2R4, alkyl-OH, alkylaryl-OH, alkylheteroaryl-OH, alkyl-N(alkylaryl)2, alkyl- N(alkylaryl-CO2H)2, alkyl-N(alkylheteroaryl-CO2H)2, alkyl-N(alkylaryl-CO2R4)2, alkyl- N(alkylheteroaryl, alkyl-N
  • the present invention provides a metal complex having the structure: wherein M is the metal; wherein Y1, Y2, Y3 are each, independently, -H, alkyl-N-(CO2R4)2, alkyl-N-(alkyl-CO2R4)2 , alkylheteroaryl, alkyl-CO2H, alkylaryl-CO2H, alkylheteroaryl-CO2H, alkyl-CO2R4, alkylaryl-NH-CO2R4, alkylaryl-CO2R4, alkylheteroaryl-CO2R4, alkyl-OH, alkylaryl-OH, alkylheteroaryl-OH, alkyl-N(alkylaryl)2, alkyl- N(alkylaryl-CO2H)2, alkyl-N(alkylheteroaryl-CO2H)2, alkyl-N(alkylaryl-CO2R4)2, alkyl- N(alkyl-N(alkylaryl-
  • In complex is other than some occurrence -H, -OH, -NH 2 , halogen, alkyl, - O-alkyl, -NH-alkyl, -CHF 2 , -CF 3 , -OCHF 2 , -OCF 3 , amide, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF 3 , or -Si(alkyl) 3 .
  • each occurrence of R 4 is independently, -H, -OH, -NH 2 , halogen, alkyl, - O-alkyl, -NH-alkyl, amide, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF 3 , or - Si(alkyl) 3 .
  • each occurrence of R 4 is independently, -OH, -NH 2 , alkyl, -O-alkyl, -NH- alkyl, amide, aryl, heteroaryl, or alkyl-CF3.
  • each occurrence of R4 is independently, -OH, -NH2, alkyl, -O-alkyl, -NH- alkyl, amide. [0527] In some embodiments, each occurrence of R4 is independently, -OH, -NH2, alkyl, -O-alkyl, -NH- alkyl. [0528] In some embodiments, R4 is -OH. [0529] In some embodiments, R4 is -NH2. [0530] In some embodiments, n and m are each independently 0, 1, 2, 3, 4, 5, or 6. [0531] In some embodiments, n and m are each independently 1, 2, or 3. [0532] In some embodiments, n and m are 1.
  • n is 1, 2, or 3.
  • m is 1, 2, or 3.
  • n is 1 or 2.
  • n is 1.
  • m is 1.
  • n and m are the same.
  • n and m are different.
  • o is 0, 1, 2, 3, 4, 5, or 6.
  • o is 0, 1, 2, or 3.
  • o is 1 or 2.
  • o is 1.
  • R1 and R2 are each independently H, halogen, alkyl, alkenyl, alkynyl, - OH, -O-(alkyl), -CHF2, -CF3, -OCHF2 or -OCF3.
  • R1 and R2 are each independently H, halogen, C1-C6 alkyl, C1-C6 alkenyl, or C1-C6 alkynyl.
  • R1 and R2 are each independently, C1-C6 alkyl or C1-C6 alkenyl.
  • R1 and R2 are each independently C1-C6 alkyl.
  • R1 and R2 are C1-5 alkyl.
  • R1 and R2 are C1-3 alkyl.
  • R1 and R2 are methyl.
  • Y1, Y2, Y3 are each independently alkyl-CO2H, , alkyl-N-(CO2R4)2, alkyl- N-(alkyl-CO2R4)2, alkylaryl-CO2H, alkylheteroaryl-CO2H, alkyl-CO2R4, alkylaryl-NH-CO2R4, alkylaryl- CO2R4, alkylheteroaryl-CO2R4, alkyl-N(alkylaryl-CO2H)2, alkyl-N(alkylheteroaryl-CO2H)2, alkyl- N(alkylaryl-CO2R4)2, alkyl-N(alkylheteroaryl-CO2R4)2, alkyl-N(alkylheteroaryl-CO2R4)2, alkyl-N(alkyl
  • Y1, Y2, Y3 are each independently alkyl-CO2H, , alkyl-N-(CO2R4)2, alkyl- N-(alkyl-CO 2 R 4 ) 2 , alkylaryl-CO 2 H, alkylheteroaryl-CO 2 H, alkyl-N(alkylaryl-CO 2 H) 2 , alkyl- N(alkylheteroaryl-CO 2 H) 2 , alkyl-N(alkyl-CO 2 H) 2 , alkyl-N(alkylaryl-OH)(alkyl-CO 2 H), alkyl- N(alkylheteroaryl-OH)(alkyl-CO 2 H), or alkylheteroaryl- P(O)(OH) 2 .
  • Y 1 , Y 2 , Y 3 are each independently alkyl-CO 2 H, or alkyl-CO 2 NH 2 , or alkyl- N(alkyl-CO 2 H) 2 .
  • at least one of Y 1 , Y 2 , Y 3 is alkyl-CO 2 H.
  • at least one of Y 1 , Y 2 , Y 3 is alkyl-CO 2 NH 2 .
  • at least one of Y 1 , Y 2 , Y 3 is alkyl-N(alkyl-CO 2 H) 2 .
  • At least one of Y 1 , Y 2 , Y 3 is -CH 2 -CO 2 H.
  • at least one of Y1, Y2, Y3 is -CH2-CO2NH2.
  • at least one of Y1, Y2, Y3 is -CH2-N(alkyl-CO2H)2
  • at least two of Y1, Y2 and Y3 are the same.
  • at least three of Y1, Y2, Y3 and Y4 are the same.
  • Y1, Y2 and Y3 are the same.
  • At least one of Y1, Y2, and Y3 is H. [0565] In some embodiments, none of Y1, Y2, and Y3 are H. , , [0567] In some embodiments, Y 1 , Y 2 , Y 3 , Y 4 are each independentl , , [0568] In some embodiments, Y1, Y2, Y3, Y4 are each , or [0569] In some embodiments, Y1, Y2, Y3, Y4 are each , . some embodiments, Y 1 , Y 2 , Y 3 , Y 4 are each independentl or .
  • Y1 andY3 , Y2 and/or Y4 is .
  • the chemical linker L is an alkyl, alkenyl, alkynyl, alkylether, alkylthioether, alkylamino, alkylamido, alkylester, alkylaryl, alklyheteroaryl, polyethylene glycol (PEG), aryl, heteroaryl, a natural amino acid, an unnatural amino acid, a disulfide or thioether containing linker or combinations thereof.
  • the chemical linker L is an alkyl linker, an alkyne linker, alkynal linker or a polyethylene glycol (PEG) or combinations thereof.
  • the chemical linker L is an alkyl or a PEG or combinations thereof.
  • the chemical linker L is a PEG.
  • the chemical linker L has the following structure: , wherein m is 1, 2, 3, 4, 5, 6, or 7; more preferably, m is 1, 3, or 7.
  • the chemical linker L has the following structure: , wherein m is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 3, 4, 5, 6, or 7; more preferably, m is 1, 3, or 7. [0578] In some embodiments of chemical linker L, m is 1, 3 or 7. [0579] In some embodiments, of chemical linker L, m is 3. [0580] In some embodiments, A is substituted with -OH, -NH 2 , halogen, alkyl, -O-alkyl, -alkyl-NH 2 , - NH-alkyl, -CHF 2 , -CF 3 , -OCHF 2 , -OCF 3 .
  • A is substituted with -NH 2 , -alkyl-NH 2 , -NH-alkyl, or alkyl.
  • the guest molecule A is adamantane, diamantane, ferrocene, bicyclo[2.2.2]octane, buckminsterfullerene (C60), iceane, triamantane, isotetramantane, ferrocene- modified peracetic acid, pentamantane, or cyclohexamantane.
  • the guest molecule A is adamantane, ferrocene, bicyclo[2.2.2]octane, iceane, diamantane, triamantane, isotetramantane, pentamantane, or cyclohexamantane.
  • the guest molecule A is substituted or unsubstituted adamantane, 4,9- diamino diamantane, ferrocene, bicyclo[2.2.2]octane, iceane, diamantane, triamantane, isotetramantane, pentamantane, or cyclohexamantane.
  • the guest molecule A is substituted or unsubstituted adamantane, diamantane, 4,9-diamino diamantane or ferrocene.
  • the guest molecule A is substituted with halogen, alkyl, alkenyl, alkynyl, -OH, -O-(alkyl), -N-(alkyl), -CHF2, -CF3, -OCHF2 or -OCF3.
  • the guest molecule A is substituted with halogen, alkyl, -O-(alkyl), -N- (alkyl).
  • the guest molecule A is substituted or unsubstituted adamantane or diamantane. [0589] In some embodiments, the guest molecule A is substituted or unsubstituted adamantane. [0590] In some embodiments, the guest molecule A is substituted or unsubstituted diamantane. [0591] In some embodiments, the guest molecule A is substituted or unsubstituted ferrocene. [0592] In some embodiments, the guest molecule A is unsubstituted adamantane. [0593] In some embodiments, the guest molecule A is substituted adamantane.
  • the guest molecule A is 4,9-diamino diamantane. [0595] In some embodiments, the guest molecule A is unsubstituted ferrocene. [0596] In some embodiments, the guest molecule A is unsubstituted diamantane. [0597] In some embodiments, the guest molecule A is substituted diamantane. [0598] In some embodiments, the substituted diamantane having the following structure: . [0599] In some embodiments, the guest molecule A is substituted ferrocene.
  • the substituted ferrocene is substituted with C 1 -C 6 alkyl, -alkyl-N-(C 1 -C 6 alkyl), -OH, -O-(C 1 -C 6 alkyl), -NH-(C 1 -C 6 alkyl), -CHF 2 , -CF 3 , -OCHF 2 , or -OCF 3 .
  • the substituted ferrocene is substituted with C1-C6 alkyl, -alkyl-N-(C1-C6 alkyl), -OH, -O-(C1-C6 alkyl), -NH-(C1-C6 alkyl).
  • the substituted ferrocene is substituted with C1-C6 alkyl, -alkyl-N-(C1-C6 alkyl). [0603] In some embodiments, the substituted ferrocene is substituted with -alkyl-N-(C1-C6 alkyl). [0604] In some embodiments, the substituted ferrocene having the following structure: . [0605] In some embodiments, the a metal complex having the structure:
  • M is the metal; wherein Y 1 , Y 2 , Y 3 , Y 4 are each, independently, --H, alkyl-N-(CO 2 R 4 ) 2 , alkyl-N-(alkyl-CO 2 R 4 ) 2 , alkylheteroaryl, alkyl-CO 2 H, alkylaryl-CO 2 H, alkylheteroaryl-CO 2 H, alkyl-CO 2 R 4 , alkylaryl-NH-CO 2 R 4, alkylaryl-CO 2 R 4 , alkylheteroaryl-CO 2 R 4 , alkyl-OH, alkylaryl-OH, alkylheteroaryl-OH, alkyl- N(alkylaryl) 2 , alkyl-N(alkylaryl-CO 2 H) 2 , alkyl-N(alkylheteroaryl-CO 2 H) 2 , alkyl-N(alkylaryl-CO 2 R 4 ) 2 ,
  • each occurrence of R 4 is independently, -H, -OH, -NH 2 , halogen, alkyl, - O-alkyl, -NH-alkyl, -CHF 2 , -CF 3 , -OCHF 2 , -OCF 3 , amide, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF 3 , or -Si(alkyl) 3 .
  • each occurrence of R 4 is independently, -H, -OH, -NH 2 , halogen, alkyl, - O-alkyl, -NH-alkyl, amide, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF 3 , or - Si(alkyl) 3 .
  • each occurrence of R 4 is independently, -OH, -NH 2 , alkyl, -O-alkyl, -NH- alkyl, amide, aryl, heteroaryl, or alkyl-CF 3 .
  • each occurrence of R4 is independently, -OH, -NH2, alkyl, -O-alkyl, -NH- alkyl, amide.
  • each occurrence of R4 is independently, -OH, -NH2, alkyl, -O-alkyl, -NH- alkyl.
  • R4 is -OH.
  • R4 is -NH2.
  • n and m are each independently 0, 1, 2, 3, 4, 5, or 6.
  • n and m are each independently 1, 2, or 3.
  • n and m are 1.
  • n is 1, 2, or 3.
  • m is 1, 2, or 3.
  • n is 1 or 2.
  • n is 1.
  • m is 1.
  • n and m are the same.
  • n and m are different.
  • o is 0, 1, 2, 3, 4, 5, or 6.
  • o is 0, 1, 2, or 3.
  • o is 1 or 2. [0627] In some embodiments, o is 1.
  • R 1 and R 2 are each independently H, halogen, alkyl, alkenyl, alkynyl, - OH, -O-(alkyl), -CHF 2 , -CF 3 , -OCHF 2 or -OCF 3 .
  • R 1 and R 2 are each independently H, halogen, C 1 -C 6 alkyl, C 1 -C 6 alkenyl, or C 1 -C 6 alkynyl.
  • R 1 and R 2 are each independently, C 1 -C 6 alkyl or C 1 -C 6 alkenyl.
  • R 1 and R 2 are each independently C 1 -C 6 alkyl. [0632] In some embodiments, R 1 and R 2 are C 1-5 alkyl. [0633] In some embodiments, R1 and R2 are C1-3 alkyl. [0634] In some embodiments, R1 and R2 are methyl.
  • Y1, Y2, Y3, Y4 are each independently alkyl-CO2H, alkylaryl-CO2H, alkylheteroaryl-CO2H, alkyl-CO2R4, alkylaryl-NH-CO2R4, alkylaryl-CO2R4, alkylheteroaryl-CO2R4, alkyl- N(alkylaryl-CO2H)2, alkyl-N(alkylheteroaryl-CO2H)2, alkyl-N(alkylaryl-CO2R4)2, alkyl- N(alkylheteroaryl-CO2R4)2, alkyl-N(alkyl-CO2H)2, alkyl-N(alkylaryl-OH)(alkyl-CO2H), alkyl- Nalkylheteroaryl-OH)(alkyl-CO2H), or alkylheteroaryl- P(O)(OH)2.
  • Y1, Y2, Y3, Y4 are each independently alkyl-CO2H, alkylaryl-CO2H, alkylheteroaryl-CO2H, alkyl-N(alkylaryl-CO2H)2, alkyl-N(alkylheteroaryl-CO2H)2, alkyl-N(alkyl-CO2H)2, alkyl-N(alkylaryl-OH)(alkyl-CO2H), alkyl-N(alkylheteroaryl-OH)(alkyl-CO2H), or alkylheteroaryl- P(O)(OH)2.
  • Y1, Y2, Y3, Y4 are each independently alkyl-CO2H, , alkyl-N-(CO2R4)2, alkyl-N-(alkyl-CO2R4)2, alkylaryl-CO2H, alkylheteroaryl-CO2H, alkyl-CO2R4, alkylaryl-NH-CO2R4, alkylaryl-CO2R4, alkylheteroaryl-CO2R4, alkyl-N(alkylaryl-CO2H)2, alkyl-N(alkylheteroaryl-CO2H)2, alkyl-N(alkylaryl-CO2R4)2, alkyl-N(alkylheteroaryl-CO2R4)2, alkyl-N(alkylheteroaryl-CO2R4)2, alkyl-N(alkyl-CO2H)2, alkyl-N(alkylaryl-OH)(alkyl-CO2H), alkyl-Nalkylhe
  • Y1, Y2, Y3, Y4 are each independently alkyl-CO2H, , alkyl-N-(CO2R4)2, alkyl-N-(alkyl-CO2R4)2, alkylaryl-CO2H, alkylheteroaryl-CO2H, alkyl-N(alkylaryl-CO2H)2, alkyl- N(alkylheteroaryl-CO2H)2, alkyl-N(alkyl-CO2H)2, alkyl-N(alkylaryl-OH)(alkyl-CO2H), alkyl- N(alkylheteroaryl-OH)(alkyl-CO 2 H), or alkylheteroaryl- P(O)(OH) 2 .
  • Y 1 , Y 2 , Y 3, Y 4 are each independently alkyl-CO 2 H, or alkyl-CO 2 NH 2 , or alkyl-N(alkyl-CO 2 H) 2 .
  • at least one of Y 1 , Y 2 , Y 3, Y 4 is alkyl-CO 2 H.
  • at least one of Y 1 , Y 2 , Y 3, Y 4 is alkyl-CO 2 NH 2 .
  • at least one of Y 1 , Y 2 , Y 3, Y 4 is alkyl-N(alkyl-CO 2 H) 2 .
  • At least one of Y 1 , Y 2 , Y 3, Y 4 is -CH 2 -CO 2 H. [0644] In some embodiments, at least one of Y 1 , Y 2 , Y 3, Y 4 is -CH 2 -CO 2 NH 2 . [0645] In some embodiments, at least one of Y 1 , Y 2 , Y 3 , Y 4 is -CH 2 -N(alkyl-CO 2 H) 2 [0646] In some embodiments, at least two of Y 1 , Y 2 and Y 3, Y 4 are the same.
  • Y1, Y2 Y3, and Y4 are the same. , , . [0651] In some embodiments, Y1, Y2, Y3, Y4 are each independently , . . linker L is an alkyl, alkenyl, alkynyl, alkylether, alkylaryl, alklyheteroaryl, polyethylene glycol (PEG), aryl, heteroaryl, a natural amino acid, an unnatural amino acid, a disulfide or thioether containing linker or combinations thereof.
  • PEG polyethylene glycol
  • the chemical linker L is an alkyl linker, an alkyne linker, alkynal linker or a polyethylene glycol (PEG) or combinations thereof.
  • the chemical linker L is an alkyl or a PEG or combinations thereof.
  • the chemical linker L is a PEG.
  • the chemical linker L has the following structure: , wherein m is 1, 2, 3, 4, 5, 6, or 7; more preferably, m is 1, 3, or 7.
  • the chemical linker L has the following structure: , wherein m is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 3, 4, 5, 6, or 7; more preferably, m is 1, 3, or 7. [0660] In some embodiments of chemical linker L, m is 1, 3 or 7. [0661] In some embodiments, of chemical linker L, m is 3.
  • the guest molecule A is adamantane, diamantane, ferrocene, bicyclo[2.2.2]octane, buckminsterfullerene (C60), iceane, triamantane, isotetramantane, ferrocene- modified peracetic acid, pentamantane, or cyclohexamantane.
  • the guest molecule A is adamantane, ferrocene, bicyclo[2.2.2]octane, iceane, diamantane, triamantane, isotetramantane, pentamantane, or cyclohexamantane.
  • the guest molecule A is substituted or unsubstituted adamantane, 4,9- diamino diamantane, ferrocene, bicyclo[2.2.2]octane, iceane, diamantane, triamantane, isotetramantane, pentamantane, or cyclohexamantane.
  • the guest molecule A is substituted or unsubstituted adamantane, diamantane, 4,9-diamino diamantane or ferrocene.
  • the guest molecule A is substituted with halogen, alkyl, alkenyl, alkynyl, -OH, -O-(alkyl), -N-(alkyl), -CHF 2 , -CF 3 , -OCHF 2 or -OCF 3 .
  • A is substituted with -OH, -NH 2 , halogen, alkyl, -O-alkyl, -alkyl-NH 2 , - NH-alkyl, -CHF 2 , -CF 3 , -OCHF 2 , -OCF 3 .
  • A is substituted with -NH 2 , -alkyl-NH 2 , -NH-alkyl, or alkyl.
  • the guest molecule A is substituted with halogen, alkyl, -O-(alkyl), -N- (alkyl).
  • the guest molecule A is substituted or unsubstituted adamantane or diamantane.
  • the guest molecule A is substituted or unsubstituted adamantane.
  • the guest molecule A is substituted or unsubstituted diamantane.
  • the guest molecule A is substituted or unsubstituted ferrocene. [0674] In some embodiments, the guest molecule A is unsubstituted adamantane. [0675] In some embodiments, the guest molecule A is substituted adamantane. [0676] In some embodiments, the guest molecule A is 4,9-diamino diamantane. [0677] In some embodiments, the guest molecule A is unsubstituted ferrocene. [0678] In some embodiments, the guest molecule A is unsubstituted diamantane. [0679] In some embodiments, the guest molecule A is substituted diamantane.
  • the substituted diamantane having the following structure: .
  • the guest substituted ferrocene is substituted with C1-C6 alkyl, -alkyl-N-(C1-C6 alkyl), -OH, -O-(C1-C6 alkyl), -NH-(C1-C6 alkyl), -CHF2, -CF3, -OCHF2, or -OCF3.
  • the substituted ferrocene is substituted with C1-C6 alkyl, -alkyl-N-(C1-C6 alkyl), -OH, -O-(C1-C6 alkyl), -NH-(C1-C6 alkyl).
  • the substituted ferrocene is substituted with C 1 -C 6 alkyl, -alkyl-N-(C 1 -C 6 alkyl).
  • the substituted ferrocene is substituted with -alkyl-N-(C 1 -C 6 alkyl).
  • the substituted ferrocene having the following structure: .
  • the present invention provides a metal complex having the structure: wherein M is the metal; wherein L is a chemical linker; wherein n and m are each independently 0, 1, 2, 3, 4, 5, or 6; preferably, n and m are each independently 1, 2, or 3; more preferably, n and m are 1; wherein A is a guest molecule which is substituted or unsubstituted adamantane, ferrocene, diamantane, 4,9-diamino diamantane, bicyclo[2.2.2]octane, iceane, triamantane, isotetramantane, pentamantane cyclohexamantane, super-adamantane, 1,3,5,7-tetramethyl-1,3,5,7-tetrasilaadamantane, adamanzane, antimony trioxide, arsen
  • the present invention provides a metal complex having the structure: wherein M is the metal; wherein L is a chemical linker; wherein n and m are each independently 0, 1, 2, 3, 4, 5, or 6; preferably, n and m are each independently 1, 2, or 3; more preferably, n and m are 1; wherein A is a guest molecule which is substituted or unsubstituted adamantane, ferrocene, diamantane, 4,9-diamino diamantane, bicyclo[2.2.2]octane, iceane, triamantane, isotetramantane, pentamantane cyclohexamantane, super-adamantane, 1,3,5,7-tetramethyl-1,3,5,7-tetrasilaadamantane, adamanzane, antimony trioxide, arsenic trioxide, 2,4,6-trioxa-1,3,5,7-tetraars
  • M is the metal; wherein L is an alkyl linker, an alkyne linker, alkynal linker or a polyethylene glycol (PEG) or combinations thereof; wherein n and m are each independently 0, 1, 2, 3, 4, 5, or 6; preferably, n and m are each independently 1, 2, or 3; more preferably, n and m are 1; wherein A is a guest molecule which is adamantane, ferrocene, diamantane; and wherein each occurrence of R4 is independently, -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, - CHF2, -CF3, -OCHF2, -OCF3, amide, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl- CF3, or -Si(alkyl)3; preferably, R4 is -
  • each occurrence of R4 is independently, -H, -OH, -NH2, halogen, alkyl, - O-alkyl, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3, amide, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3.
  • each occurrence of R4 is independently, -H, -OH, -NH2, halogen, alkyl, - O-alkyl, -NH-alkyl, amide, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or - Si(alkyl)3.
  • each occurrence of R4 is independently, -OH, -NH2, alkyl, -O-alkyl, -NH- alkyl, amide, aryl, heteroaryl, or alkyl-CF3.
  • each occurrence of R4 is independently, -OH, -NH2, alkyl, -O-alkyl, -NH- alkyl, or amide.
  • each occurrence of R4 is independently, -OH, -NH2, alkyl, -O-alkyl, or - NH-alkyl.
  • R 4 is -OH.
  • R 4 is -NH 2 .
  • n and m are each independently 0, 1, 2, 3, 4, 5, or 6.
  • n and m are each independently 1, 2, or 3.
  • n and m are 1. [0700] In some embodiments, n is 1, 2, or 3. [0701] In some embodiments, m is 1, 2, or 3. [0702] In some embodiments, n is 1 or 2. [0703] In some embodiments, m is 1 or 2. [0704] In some embodiments, n is 1. [0705] In some embodiments, m is 1. [0706] In some embodiments, n and m are the same. [0707] In some embodiments, n and m are different.
  • R1 and R2 are each independently H, halogen, C1-C6 alkyl, C1-C6 alkenyl, or C1-C6 alkynyl. [0709] In some embodiments, R1 and R2 are each independently, C1-C6 alkyl or C1-C6 alkenyl. [0710] In some embodiments, R1 and R2 are each independently C1-C6 alkyl. [0711] In some embodiments, R1 and R2 are C1-5 alkyl. [0712] In some embodiments, R1 and R2 are C1-3 alkyl. [0713] In some embodiments, R1 and R2 are methyl.
  • the chemical linker L is an alkyl, alkenyl, alkynyl, alkylether, alkylthioether, alkylamino, alkylamido, alkylester, alkylaryl, alklyheteroaryl, polyethylene glycol (PEG), aryl, heteroaryl, a natural amino acid, an unnatural amino acid, a disulfide or thioether containing linker or combinations thereof.
  • the chemical linker L is an alkyl linker, an alkyne linker, alkynal linker or a polyethylene glycol (PEG) or combinations thereof.
  • the chemical linker L is an alkyl or a PEG or combinations thereof. [0717] In some embodiments, the chemical linker L is a PEG. [0718] In some embodiments, the chemical linker L has the following structure: , wherein m is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; preferably m is 1, 2, 3, 4, 5, 6, or 7; more preferably, m is 1, 3, or 7. [0719] In some embodiments, the chemical linker L has the following structure: , wherein m is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; preferably m is 1, 2, 3, 4, 5, 6, or 7; more preferably, m is 1, 3, or 7.
  • m is 1, 3 or 7.
  • m is 3.
  • alkyl is C1-6 alkyl.
  • alkyl is C1-3 alkyl.
  • alkyl is methyl.
  • aryl is phenyl, p-toluenyl (4-methylphenyl), naphthyl, tetrahydronaphthyl; indanyl, biphenyl, phenanthryl, anthryl or acenaphthyl.
  • aryl is phenyl, p-toluenyl (4-methylphenyl), or naphthyl. [0727] In some embodiments, aryl is phenyl. [0728] In some embodiments, the guest molecule A is adamantane, diamantane, ferrocene, bicyclo[2.2.2]octane, buckminsterfullerene (C60), iceane, triamantane, isotetramantane, ferrocene- modified peracetic acid, pentamantane, or cyclohexamantane.
  • the guest molecule A is adamantane, ferrocene, bicyclo[2.2.2]octane, iceane, diamantane, triamantane, isotetramantane, pentamantane, or cyclohexamantane.
  • the guest molecule A is substituted or unsubstituted adamantane, 4,9- diamino diamantane, ferrocene, bicyclo[2.2.2]octane, iceane, diamantane, triamantane, isotetramantane, pentamantane, or cyclohexamantane.
  • the guest molecule A is substituted or unsubstituted adamantane, diamantane, 4,9-diamino diamantane or ferrocene.
  • the guest molecule A is substituted with halogen, alkyl, alkenyl, alkynyl, -OH, -O-(alkyl), -N-(alkyl), -CHF 2 , -CF 3 , -OCHF 2 or -OCF 3 .
  • the guest molecule A is substituted with halogen, alkyl, -O-(alkyl), -N- (alkyl).
  • the guest molecule A is substituted or unsubstituted adamantane or diamantane. [0735] In some embodiments, the guest molecule A is substituted or unsubstituted adamantane. [0736] In some embodiments, the guest molecule A is substituted or unsubstituted diamantane. [0737] In some embodiments, the guest molecule A is substituted or unsubstituted ferrocene. [0738] In some embodiments, the guest molecule A is unsubstituted adamantane. [0739] In some embodiments, the guest molecule A is substituted adamantane.
  • the guest molecule A is 4,9-diamino diamantane. [0741] In some embodiments, the guest molecule A is unsubstituted ferrocene. [0742] In some embodiments, the guest molecule A is unsubstituted diamantane. [0743] In some embodiments, the guest molecule A is substituted diamantane. [0744] In some embodiments, the substituted diamantane having the following structure: . [0745] In some embodiments, the guest substituted ferrocene.
  • the substituted ferrocene is substituted with C1-C6 alkyl, -alkyl-N-(C1-C6 alkyl), -OH, -O-(C1-C6 alkyl), -NH-(C1-C6 alkyl), -CHF2, -CF3, -OCHF2, or -OCF3.
  • the substituted ferrocene is substituted with C1-C6 alkyl, -alkyl-N-(C1-C6 alkyl), -OH, -O-(C1-C6 alkyl), -NH-(C1-C6 alkyl).
  • the substituted ferrocene is substituted with C1-C6 alkyl, -alkyl-N-(C1-C6 alkyl). [0749] In some embodiments, the substituted ferrocene is substituted with -alkyl-N-(C1-C6 alkyl). [0750] In some embodiments, the substituted ferrocene having the following structure: .
  • the present invention provides a metal complex having the structure: wherein M is the metal; wherein L is a chemical linker; wherein n and m are each independently 1, 2, or 3; wherein A is a guest molecule which is adamantane, ferrocene, or diamantane; and wherein R4 is -OH, -NH2, -O-(C1-C6 alkyl), or NH-(C1-C6 alkyl), more preferably R4 is -OH or -NH2.
  • the present invention provides a metal complex having the structure: wherein is the metal; wherein n and m are each independently 0, 1, 2, 3, 4, 5, or 6; preferably, n and m are each independently 1, 2, or 3; more preferably, n and m are 1; wherein o is 0, 1, 2, 3, 4, 5, or 6; preferably o is 1, 2, or 3; more preferably, o is 1; wherein each occurrence of R 4 is independently, -H, -OH, -NH 2 , halogen, alkyl, -O-alkyl, -NH- alkyl, -CHF 2 , -CF 3 , -OCHF 2 , -OCF 3 , amide, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF 3 , or -Si(alkyl) 3 ; wherein X is alkyl-aryl-thiourea,
  • the present invention provides a metal complex having the structure: wherein is the metal; wherein n and m are each independently 0, 1, 2, 3, 4, 5, or 6; preferably, n and m are each independently 1, 2, or 3; more preferably, n and m are 1; wherein o is 0, 1, 2, 3, 4, 5, or 6; preferably o is 1, 2, or 3; more preferably, o is 1; wherein each occurrence of R 4 is independently, -H, -OH, -NH 2 , halogen, alkyl, -O-alkyl, -NH- alkyl, -CHF 2 , -CF 3 , -OCHF 2 , -OCF 3 , amide, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF 3 , or -Si(alkyl) 3 ; wherein X is alkyl-aryl-thiourea,
  • the present invention provides a metal complex having the structure: wherein L is a chemical linker; wherein n and m are each independently 1, 2, or 3; wherein A is a guest molecule which is adamantane, ferrocene, or diamantane; and wherein each occurrence of R 4 is independently -OH, -NH 2, -O-(C 1 -C 6 alkyl), or NH-(C 1 -C 6 alkyl), more preferably R 4 is -OH or -NH 2 .
  • the present invention provides a metal complex having the structure: 1, 2, or 3; more preferably, n and m are 1; wherein o is 0, 1, 2, 3, 4, 5, or 6; preferably o is 1, 2, or 3; more preferably, o is 1; wherein R 4 is independently, -H, alkyl, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl- CF 3 , or -Si(alkyl) 3 ; wherein X is alkyl-aryl-thiourea, alkyl-heteroaryl-thiourea, alkyl-cycloalkyl-thiourea, alkenyl-aryl- thiourea, alkenyl -heteroaryl-thiourea, alkenyl -cycloalkyl-thiourea, alkynyl-aryl-thiourea, alkynyl- heteroourea
  • the present invention provides metal complex having the structure: wherein n independently 1, 2, or 3; more preferably, n and m are 1; wherein o is 0, 1, 2, 3, 4, 5, or 6; preferably o is 1, 2, or 3; more preferably, o is 1; wherein each occurrence of R4 is independently -OH, -NH2, -O-(C1-C6 alkyl), or NH-(C1-C6 alkyl), more preferably R4 is -OH or -NH2 ; wherein X is alkyl-aryl-thiourea, alkyl-heteroaryl-thiourea, alkyl-cycloalkyl-thiourea, alkenyl-aryl- thiourea, alkenyl -heteroaryl-thiourea, alkenyl -cycloalkyl-thiourea, alkynyl-aryl-thiourea, alkynyl- heteroaryl-thiourea,
  • A is substituted with -OH, -NH 2 , halogen, alkyl, -O-alkyl, -alkyl-NH 2 , - NH-alkyl, -CHF 2 , -CF 3 , -OCHF 2 , -OCF 3 .
  • A is substituted with -NH 2 , -alkyl-NH 2 , -NH-alkyl, or alkyl.
  • each occurrence of R 4 is independently, -H, -OH, -NH 2 , halogen, alkyl, - O-alkyl, -NH-alkyl, -CHF 2 , -CF 3 , -OCHF 2 , -OCF 3 , amide, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF 3 , or -Si(alkyl) 3 .
  • each occurrence of R 4 is independently, -H, -OH, -NH 2 , halogen, alkyl, - O-alkyl, -NH-alkyl, amide, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or - Si(alkyl)3.
  • each occurrence of R4 is independently, -OH, -NH2, alkyl, -O-alkyl, -NH- alkyl, amide, aryl, heteroaryl, or alkyl-CF3.
  • each occurrence of R4 is independently, -OH, -NH2, alkyl, -O-alkyl, -NH- alkyl, or amide.
  • each occurrence of R4 is independently, -OH, -NH2, alkyl, -O-alkyl, or - NH-alkyl.
  • the present invention provides a metal complex having the structure: or , wherein the metal.
  • the metal is Copper-62 ( 62 Cu), Copper-64 ( 64 Cu), Copper-67 ( 67 Cu), Gallium-68 ( 68 Ga) Scandium-44 ( 44 Sc), Scandium-47 ( 47 Sc), Scandium-43 ( 43 Sc), Lead-203 ( 203 Pb), Lead- 212 ( 212 Pb), Lanthanum-132 ( 132 La), Lanthanum-135 ( 135 La), Yttrium-86 ( 86 Y), Yttrium-90 ( 90 Y), Lutetium 177 ( 177 Lu), Terbium -149 ( 149 Tb), Terbium-152 ( 152 Tb), Terbium-155 ( 155 Tb) or Terbium-161 ( 161 Tb).
  • the metal is Copper-62 ( 62 Cu), Copper-64 ( 64 Cu), Copper-67 ( 67 Cu), Scandium-44 ( 44 Sc), Scandium-47 ( 47 Sc), or Scandium-43 ( 43 Sc). [0767] In some embodiments, the metal is Copper-64 ( 64 Cu).
  • the present invention provides a pharmaceutical composition comprising the metal complex described in the invention and a marker attached to a host molecule. [0769] In some embodiments, the marker is a biological marker. [0770] In some embodiments, the marker is modified. [0771] In some embodiments, the marker is un-modified. [0772] In some embodiments, the marker is a tumor marker or a cancer marker.
  • the tumor marker is a prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), cancer antigen 125 (CA 125), carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), human chorionic gonadotropin (HCG), cancer antigen 19-9 (CA 19-9), cancer antigen 15-3 (CA 15- 3), cancer antigen 27-29 (CA 27-29), lactate dehydrogenase (LDH), or neuron-specific enolase (NSE).
  • PSA prostate-specific antigen
  • PAP prostatic acid phosphatase
  • CA 125 cancer antigen 125
  • CEA carcinoembryonic antigen
  • AFP alpha-fetoprotein
  • HCG human chorionic gonadotropin
  • HCG human chorionic gonadotropin
  • CA 19-9 cancer antigen 19-9
  • cancer antigen 15-3 CA 15- 3
  • cancer antigen 27-29 CA 27-29
  • LDH lactate dehydrogenas
  • the tumor marker is prostate-specific antigen (PSA), cancer antigen 125 (CA 125), carcinoembryonic antigen (CEA), cancer antigen 19-9 (CA 19-9), cancer antigen 15-3 (CA 15- 3), or cancer antigen 27-29 (CA 27-29).
  • PSA prostate-specific antigen
  • CEA carcinoembryonic antigen
  • the tumor marker is a carcinoembryonic antigen (CEA).
  • the host molecule comprises cucurbit[5]uril, cucurbit[6]uril, cucurbit[7]uril, cucurbit[8]uril, cucurbit[10]uril, cucurbit[14]uril, cyclodextrin, or calix-[5]-arenes. [0778] In some embodiments, the host molecule comprises cucurbit[5]uril, cucurbit[6]uril, cucurbit[7]uril, cucurbit[8]uril, or cucurbit[10]uril.
  • the host molecule comprises cucurbit[5]uril, cucurbit[6]uril, cucurbit[7]uril, or cucurbit[8]uril. [0780] In some embodiments, the host molecule comprises cucurbit[7]uril, or cucurbit[8]uril. [0781] In some embodiments, the host molecule is cucurbit[7]uril. [0782] In some embodiments, the interaction between the host and the guest molecule is a non-covalent interaction.
  • the non-covalent interaction is ion-ion interaction, ion-dipole interaction, dipole-dipole interaction, hydrogen bonding, cation- ⁇ interaction, ⁇ - ⁇ interaction, van der Waals interaction or hydrophobic interaction.
  • the non-covalent interaction is ion-ion interaction, or an der Waals interaction.
  • the metal complex described in the invention and the host molecule described in the invention form a high affinity host-guest complex.
  • the present invention provides a method of detecting cells in a subject comprises administering an effective amount of metal complex having the structure: , wherein M is the metal; wherein Y1, Y2, Y3 are each, independently, -H, alkyl-N-(CO2R4)2, alkyl-N-(alkyl-CO2R4)2 , alkylheteroaryl, alkyl-CO2H, alkylaryl-CO2H, alkylheteroaryl-CO2H, alkyl-CO2R4, alkylaryl-NH-CO2R4, alkylaryl-CO2R4, alkylheteroaryl-CO2R4, alkyl-OH, alkylaryl-OH, alkylheteroaryl-OH, alkyl-N(alkylaryl)2, alkyl- N(alkylaryl-CO 2 H) 2 , alkyl-N(alkylheteroaryl-CO 2 H) 2 , alkyl-N(alkyl-CO
  • the present invention provides a method of detecting cells in a subject comprises administering an effective amount of metal complex having the structure: wherein M is the metal; wherein Y 1 , Y 2 , Y 3 , Y 4 are each, independently, -H, alkyl-N-(CO 2 R 4 ) 2 , alkyl-N-(alkyl-CO 2 R 4 ) 2 , alkylheteroaryl, alkyl-CO 2 H, alkylaryl-CO 2 H, alkylheteroaryl-CO 2 H, alkyl-CO 2 R 4 , alkylaryl-NH-CO 2 R 4, alkylaryl-CO 2 R 4 , alkylheteroaryl-CO 2 R 4 , alkyl-OH, alkylaryl-OH, alkylheteroaryl-OH, alkyl- N(alkylaryl) 2 , alkyl-N(alkylaryl-CO 2 H) 2 , alkyl-N(alkyl) 2
  • the present invention provides a method of detecting cells in a subject comprises administering an effective amount of metal complex having the structure: , wherein M is the metal; wherein Y1, Y2, Y3 are each, independently, -H, alkyl-N-(CO2R4)2, alkyl-N-(alkyl-CO2R4)2 , alkylheteroaryl, alkyl-CO2H, alkylaryl-CO2H, alkylheteroaryl-CO2H, alkyl-CO2R4, alkylaryl-NH-CO2R4, alkylaryl-CO2R4, alkylheteroaryl-CO2R4, alkyl-OH, alkylaryl-OH, alkylheteroaryl-OH, alkyl-N(alkylaryl)2, alkyl- N(alkylaryl-CO2H)2, alkyl-N(alkylheteroaryl-CO2H)2, alkyl-N(alkylaryl-CO2H)
  • the metal complex is other than . some with -OH, -NH 2 , halogen, alkyl, -O-alkyl, -alkyl-NH 2 , -NH-alkyl, -CHF 2 , -CF 3 , -OCHF 2 , -OCF 3 .
  • A is substituted with -NH 2 , -alkyl-NH 2 , -NH-alkyl, or alkyl.
  • each occurrence of R 4 is independently, -H, -OH, -NH 2 , halogen, alkyl, -O-alkyl, -NH-alkyl, -CHF 2 , -CF 3 , -OCHF 2 , -OCF 3 , amide, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF 3 , or -Si(alkyl) 3 .
  • each occurrence of R 4 is independently, -H, -OH, -NH 2 , halogen, alkyl, -O-alkyl, -NH-alkyl, amide, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3.
  • each occurrence of R4 is independently, -OH, -NH2, alkyl, -O-alkyl, -NH-alkyl, amide, aryl, heteroaryl, or alkyl-CF3.
  • each occurrence of R4 is independently, -OH, -NH2, alkyl, -O-alkyl, -NH-alkyl, amide.
  • each occurrence of R4 is independently, -OH, -NH2, alkyl, -O-alkyl, -NH-alkyl.
  • Y1, Y2, Y3 are each independently alkyl-CO2H, , alkyl-N- (CO2R4)2, alkyl-N-(alkyl-CO2R4)2, alkylaryl-CO2H, alkylheteroaryl-CO2H, alkyl-CO2R4, alkylaryl-NH- CO2R4, alkylaryl-CO2R4, alkylheteroaryl-CO2R4, alkyl-N(alkylaryl-CO2H)2, alkyl-N(alkylheteroaryl- CO 2 H) 2 , alkyl-N(alkylaryl-CO 2 R 4 ) 2 , alkyl-N(alkylheteroaryl-CO 2 R 4 ) 2 , alkyl-N(alkyl-CO 2 H) 2 , alkyl- N(alkylaryl-OH)(alkyl-CO 2 H), alkyl-Nalkylhe
  • Y 1 , Y 2 , Y 3 are each independently alkyl-CO 2 H, , alkyl-N- (CO 2 R 4 ) 2 , alkyl-N-(alkyl-CO 2 R 4 ) 2 , alkylaryl-CO 2 H, alkylheteroaryl-CO 2 H, alkyl-N(alkylaryl-CO 2 H) 2 , alkyl-N(alkylheteroaryl-CO 2 H) 2 , alkyl-N(alkyl-CO 2 H) 2 , alkyl-N(alkylaryl-OH)(alkyl-CO 2 H), alkyl- N(alkylheteroaryl-OH)(alkyl-CO 2 H), or alkylheteroaryl- P(O)(OH) 2 .
  • Y 1 , Y 2 , Y 3 are each independently alkyl-CO 2 H, or alkyl- CO 2 NH 2 , or alkyl-N(alkyl-CO 2 H) 2 .
  • at least one of Y1, Y2, Y3 is alkyl-CO2H.
  • at least one of Y1, Y2, Y3 is alkyl-CO2NH2.
  • at least one of Y1, Y2, Y3 is alkyl-N(alkyl-CO2H)2.
  • At least one of Y1, Y2, Y3 is -CH2-CO2H.
  • at least one of Y1, Y2, Y3 is -CH2-CO2NH2.
  • at least one of Y1, Y2, Y3 is -CH2-N(alkyl-CO2H)2
  • at least two of Y1, Y2 and Y3 are the same.
  • Y1, Y2, and Y3 are the same.
  • Y1, Y2, Y3 and Y4 are H. [0809] In some embodiments of the method, none of Y1, Y2, Y3 and Y4 are H. [0810] In some embodiments of the method, Y1, Y2, Y3, Y4 are each independently alkyl-CO2H, , alkyl- N-(CO2R4)2, alkyl-N-(alkyl-CO2R4)2, alkylaryl-CO2H, alkylheteroaryl-CO2H, alkyl-CO2R4, alkylaryl-NH- CO2R4, alkylaryl-CO2R4, alkylheteroaryl-CO2R4, alkyl-N(alkylaryl-CO2H)2, alkyl-N(alkylheteroaryl- CO2H)2, alkyl-N(alkylaryl-CO2R4)2, alkyl-N(alkylheteroaryl-CO2R4)2, alkyl-N(alky
  • Y1, Y2, Y3, Y4 are each independently alkyl-CO2H, , alkyl- N-(CO2R4)2, alkyl-N-(alkyl-CO2R4)2, alkylaryl-CO2H, alkylheteroaryl-CO2H, alkyl-N(alkylaryl-CO2H)2, alkyl-N(alkylheteroaryl-CO2H)2, alkyl-N(alkyl-CO2H)2, alkyl-N(alkylaryl-OH)(alkyl-CO2H), alkyl- N(alkylheteroaryl-OH)(alkyl-CO2H), or alkylheteroaryl- P(O)(OH)2.
  • Y 1 , Y 2 , Y 3, Y 4 are each independently alkyl-CO 2 H, or alkyl- CO 2 NH 2 , or alkyl-N(alkyl-CO 2 H) 2 .
  • at least one of Y 1 , Y 2 , Y 3 , Y 4 is alkyl-CO 2 H.
  • at least one of Y 1 , Y 2 , Y 3 , Y 4 is alkyl-CO 2 NH 2 .
  • At least one of Y 1 , Y 2 , Y 3 , Y 4 is alkyl-N(alkyl-CO 2 H) 2 .
  • at least one of Y 1 , Y 2 , Y 3 , Y 4 is -CH 2 -CO 2 H.
  • at least one of Y 1 , Y 2 , Y 3 , Y 4 is -CH 2 -CO 2 NH 2 .
  • At least one of Y 1 , Y 2 , Y 3 , Y 4 is -CH 2 -N(alkyl-CO 2 H) 2 [0819] In some embodiments of the method, at least two of Y 1 , Y 2 , Y 3 , Y 4 are the same. [0820] In some embodiments of the method, at least three of Y 1 , Y 2 , Y 3 , Y 4 are the same. [0821] In some embodiments of the method, Y1, Y2, Y3, Y4 are the same. [0822] In some embodiments of the method, at least one of Y1, Y2, Y3 and Y4 is H.
  • none of Y1, Y2, Y3 and Y4 are H.
  • Y1, Y2, Y3, Y4 are each independently - , , or [0825]
  • Y1, Y2, Y3, Y4 are each independently , , [0826]
  • Y 1 , Y 2 , Y 3 , Y 4 are each , , , .
  • Y1, Y2, Y3, Y4 are each independentl , .
  • n and m are each independently 0, 1, 2, 3, 4, 5, or 6.
  • n and m are each independently 1, 2, or 3.
  • n and m are 1.
  • n is 1, 2, or 3.
  • m is 1, 2, or 3.
  • n is 1 or 2.
  • n is 1.
  • m is 1.
  • n and m are the same. [0840] In some embodiments of the method, n and m are different. [0841] In some embodiments of the method, R 1 and R 2 are each independently H, halogen, alkyl, alkenyl, alkynyl, -OH, -O-(alkyl), -CHF 2 , -CF 3 , -OCHF 2 or -OCF 3 , wherein n is 1, 2, 3, 4, 5, or 6.
  • R 1 and R 2 are each independently H, halogen, C 1 -C 6 alkyl, C 1 -C 6 alkenyl, or C 1 -C 6 alkynyl. [0843] In some embodiments of the method, R 1 and R 2 are each independently, C 1 -C 6 alkyl or C 1 -C 6 alkenyl. [0844] In some embodiments of the method, R 1 and R 2 are each independently C 1 -C 6 alkyl. [0845] In some embodiments of the method, R1 and R2 are C1-5 alkyl. [0846] In some embodiments of the method, R1 and R2 are C1-3 alkyl.
  • R1 and R2 are methyl.
  • R 1 and R 2 are ethyl.
  • X is alkyl-aryl-thiourea, alkyl-heteroaryl-thiourea, alkyl- cycloalkyl-thiourea, alkenyl-aryl-thiourea, or alkenyl -heteroaryl-thiourea.
  • X is alkyl-aryl-thiourea, alkyl-heteroaryl-thiourea, or alkyl- cycloalkyl-thiourea. [0851] In some embodiments of the method, X is alkyl-aryl-thiourea, or alkyl-heteroaryl-thiourea. [0852] In some embodiments of the method, X is alkyl-aryl-thiourea. [0853] In some embodiments of the method, alkyl is C 1-6 alkyl. [0854] In some embodiments of the method, alkyl is C1-3 alkyl.
  • alkyl is methyl.
  • alkyl is ethyl.
  • aryl is phenyl, p-toluenyl (4-methylphenyl), naphthyl, tetrahydronaphthyl; indanyl, biphenyl, phenanthryl, anthryl or acenaphthyl.
  • aryl is phenyl, p-toluenyl (4-methylphenyl), or naphthyl.
  • aryl is phenyl.
  • the chemical linker L is an alkyl, alkenyl, alkynyl, alkylether, alkylthioether, alkylamino, alkylamido, alkylester, alkylaryl, alklyheteroaryl, polyethylene glycol (PEG), aryl, heteroaryl, a natural amino acid, an unnatural amino acid, a disulfide or thioether containing linker or combinations thereof.
  • the chemical linker L is an alkyl linker, an alkyne linker, alkynal linker or a polyethylene glycol (PEG) or combinations thereof.
  • the chemical linker L is an alkyl or a PEG or combinations thereof. [0863] In some embodiments of the method, the chemical linker L is a PEG. [0864] In some embodiments of the method, the chemical linker L has the following structure: , wherein m is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; preferably m is 1, 2, 3, 4, 5, 6, or 7; more preferably, m is 1, 3, or 7. [0865] In some embodiments of the method, the chemical linker L has the following structure: , wherein m is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; preferably m is 1, 2, 3, 4, 5, 6, or 7; more preferably, m is 1, 3, or 7.
  • m is 1, 3 or 7. [0867] In some embodiments of the method of the chemical linker L, m is 3. [0868] In some embodiments of the method, A is substituted with -OH, -NH2, halogen, alkyl, -O-alkyl, -alkyl-NH2, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3. [0869] In some embodiments the method, A is substituted with -NH2, -alkyl-NH2, -NH-alkyl, or alkyl.
  • the guest molecule A is substituted or unsubstituted adamantane, diamantane, ferrocene, bicyclo[2.2.2]octane, buckminsterfullerene (C60), iceane, triamantane, isotetramantane, ferrocene-modified peracetic acid, pentamantane, or cyclohexamantane.
  • the guest molecule A is substituted or unsubstituted adamantane, ferrocene, bicyclo[2.2.2]octane, iceane, diamantane, triamantane, isotetramantane, pentamantane, or cyclohexamantane.
  • the guest molecule A is substituted or unsubstituted adamantane, 4,9-diamino diamantane, ferrocene, bicyclo[2.2.2]octane, iceane, diamantane, triamantane, isotetramantane, pentamantane, or cyclohexamantane.
  • the guest molecule A is substituted or unsubstituted adamantane, diamantane, 4,9-diamino diamantane or ferrocene.
  • the guest molecule A is substituted or unsubstituted adamantane or diamantane. [0875] In some embodiments of the method, the guest molecule A is substituted or unsubstituted adamantane. [0876] In some embodiments of the method, the guest molecule A is substituted or unsubstituted diamantane. [0877] In some embodiments of the method, the guest molecule A is substituted with halogen, alkyl, alkenyl, alkynyl, -OH, -O-(alkyl), -N-(alkyl), -CHF 2 , -CF 3 , -OCHF 2 or -OCF 3 .
  • the guest molecule A is substituted with halogen, alkyl, - O-(alkyl), -N-(alkyl). [0879] In some embodiments of the method, the guest molecule A is substituted or unsubstituted ferrocene. [0880] In some embodiments of the method, the guest molecule A is unsubstituted adamantane. [0881] In some embodiments of the method, the guest molecule A is substituted adamantane. [0882] In some embodiments of the method, the guest molecule A is 4,9-diamino diamantane.
  • the guest molecule A is unsubstituted ferrocene.
  • the guest molecule A is unsubstituted diamantane.
  • the guest molecule A is substituted diamantane.
  • the substituted diamantane having the following structure: .
  • the substituted ferrocene In some embodiments of the method, the molecule A is substituted ferrocene.
  • the substituted ferrocene is substituted with C1-C6 alkyl, - alkyl-N-(C1-C6 alkyl), -OH, -O-(C1-C6 alkyl), -NH-(C1-C6 alkyl), -CHF2, -CF3, -OCHF2, or -OCF3.
  • the substituted ferrocene is substituted with C1-C6 alkyl, - alkyl-N-(C1-C6 alkyl), -OH, -O-(C1-C6 alkyl), -NH-(C1-C6 alkyl).
  • the substituted ferrocene is substituted with C1-C6 alkyl, - alkyl-N-(C1-C6 alkyl). [0891] In some embodiments of the method, the substituted ferrocene is substituted with -alkyl-N-(C1- C6 alkyl). [0892] In some embodiments of the method, the substituted ferrocene having the following structure: .
  • the metal complex having the structure: wherein M is the metal; wherein Y1, Y2, Y3 are each, independently, -H, alkyl-N-(CO2R4)2, alkyl-N-(alkyl-CO2R4)2 , alkylheteroaryl, alkyl-CO2H, alkylaryl-CO2H, alkylheteroaryl-CO2H, alkyl-CO2R4, alkylaryl-NH-CO2R4, alkylaryl-CO2R4, alkylheteroaryl-CO2R4, alkyl-OH, alkylaryl-OH, alkylheteroaryl-OH, alkyl-N(alkylaryl)2, alkyl- N(alkylaryl-CO 2 H) 2 , alkyl-N(alkylheteroaryl-CO 2 H) 2 , alkyl-N(alkylaryl-CO 2 R 4 ) 2 , alkyl
  • the metal complex is other than .
  • n and m are each independently 1, 2, or 3.
  • n and m are 1.
  • n is 1, 2, or 3.
  • m is 1, 2, or 3.
  • 0900 In some embodiments of the method, n is 1 or 2.
  • n is 1.
  • m is 1.
  • n and m are the same. [0905] In some embodiments of the method, n and m are different. [0906] In some embodiments of the method, R1 and R2 are each independently H, halogen, alkyl, alkenyl, alkynyl, -OH, -O-(alkyl), -CHF2, -CF3, -OCHF2 or -OCF3, wherein n is 1, 2, 3, 4, 5, or 6. [0907] In some embodiments of the method, R 1 and R 2 are each independently H, halogen, C 1 -C 6 alkyl, C 1 -C 6 alkenyl, or C 1 -C 6 alkynyl.
  • R 1 and R 2 are each independently, C 1 -C 6 alkyl or C 1 -C 6 alkenyl. [0909] In some embodiments of the method, R 1 and R 2 are each independently C 1 -C 6 alkyl. [0910] In some embodiments of the method, R 1 and R 2 are C 1-5 alkyl. [0911] In some embodiments of the method, R 1 and R 2 are C 1-3 alkyl. [0912] In some embodiments of the method, R 1 and R 2 are methyl. [0913] In some embodiments of the method, R1 and R2 are ethyl.
  • each occurrence of R4 is independently, -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3, amide, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3.
  • each occurrence of R4 is independently, -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, amide, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3.
  • each occurrence of R4 is independently, -OH, -NH2, alkyl, -O-alkyl, -NH-alkyl, amide, aryl, heteroaryl, or alkyl-CF3.
  • each occurrence of R4 is independently, -OH, -NH2, alkyl, -O-alkyl, -NH-alkyl, or amide.
  • each occurrence of R4 is independently, -OH, -NH2, alkyl, -O-alkyl, or -NH-alkyl.
  • Y1, Y2, Y3 are each independently alkyl-CO2H, , alkyl-N- (CO2R4)2, alkyl-N-(alkyl-CO2R4)2, alkylaryl-CO2H, alkylheteroaryl-CO2H, alkyl-CO2R4, alkylaryl-NH- CO2R4, alkylaryl-CO2R4, alkylheteroaryl-CO2R4, alkyl-N(alkylaryl-CO2H)2, alkyl-N(alkylheteroaryl- CO2H)2, alkyl-N(alkylaryl-CO2R4)2, alkyl-N(alkylheteroaryl-CO2R4)2, alkyl-N(alkylheteroaryl-CO2R4)2, alkyl-N(alkyl-CO2H)2, alkyl- N(alkylaryl-OH)(alkyl-CO2H), alkyl-Nalkylheteroary
  • Y1, Y2, Y3 are each independently alkyl-CO2H, , alkyl-N- (CO 2 R 4 ) 2 , alkyl-N-(alkyl-CO 2 R 4 ) 2 , alkylaryl-CO 2 H, alkylheteroaryl-CO 2 H, alkyl-N(alkylaryl-CO 2 H) 2 , alkyl-N(alkylheteroaryl-CO 2 H) 2 , alkyl-N(alkyl-CO 2 H) 2 , alkyl-N(alkylaryl-OH)(alkyl-CO 2 H), alkyl- N(alkylheteroaryl-OH)(alkyl-CO 2 H), or alkylheteroaryl- P(O)(OH) 2 .
  • Y 1 , Y 2 , Y 3 are each independently alkyl-CO 2 H, or alkyl- CO 2 NH 2 , or alkyl-N(alkyl-CO 2 H) 2 .
  • at least one of Y 1 , Y 2 , Y 3 is alkyl-CO 2 H.
  • at least one of Y 1 , Y 2 , Y 3 is alkyl-CO 2 NH 2 .
  • at least one of Y 1 , Y 2 , Y 3 is alkyl-N(alkyl-CO 2 H) 2 .
  • At least one of Y 1 , Y 2 , Y 3 is -CH 2 -CO 2 H.
  • at least one of Y 1 , Y 2 , Y 3 is -CH 2 -CO 2 NH 2 .
  • at least one of Y 1 , Y 2 , Y 3 is -CH 2 -N(alkyl-CO 2 H) 2
  • at least two of Y1, Y2 and Y3 are the same.
  • At least three of Y1, Y2, Y3 and Y4 are the same.
  • Y1, Y2 and Y3 are the same.
  • at least one of Y1, Y2, Y3 and Y4 is H.
  • none of Y1, Y2, Y3 and Y4 are H.
  • Y 1 , Y 2 , Y 3 , Y 4 are each independently -H, , , or , , [0934] In some embodiments of the method, Y 1 , Y 2 , Y 3 , Y 4 are each , , , . [0936] In some embodiments of the method, Y1, Y2, Y3, Y4 are each independentl , . [0937] In some embodiments of the method, Y1 andY3 .
  • X is alkyl-aryl-thiourea, alkyl-heteroaryl-thiourea, alkyl- cycloalkyl-thiourea, alkenyl-aryl-thiourea, or alkenyl -heteroaryl-thiourea.
  • X is alkyl-aryl-thiourea, alkyl-heteroaryl-thiourea, or alkyl- cycloalkyl-thiourea.
  • X is alkyl-aryl-thiourea, or alkyl-heteroaryl-thiourea.
  • X is alkyl-aryl-thiourea.
  • alkyl is C 1-6 alkyl.
  • alkyl is C 1-3 alkyl.
  • alkyl is methyl.
  • alkyl is ethyl.
  • aryl is phenyl, p-toluenyl (4-methylphenyl), naphthyl, tetrahydronaphthyl; indanyl, biphenyl, phenanthryl, anthryl or acenaphthyl.
  • aryl is phenyl, p-toluenyl (4-methylphenyl), or naphthyl.
  • aryl is phenyl.
  • the chemical linker L is an alkyl, alkenyl, alkynyl, alkylether, alkylthioether, alkylamino, alkylamido, alkylester, alkylaryl, alklyheteroaryl, polyethylene glycol (PEG), aryl, heteroaryl, a natural amino acid, an unnatural amino acid, a disulfide or thioether containing linker or combinations thereof.
  • the chemical linker L is an alkyl linker, an alkyne linker, alkynal linker or a polyethylene glycol (PEG) or combinations thereof.
  • the chemical linker L is an alkyl or a PEG or combinations thereof. [0952] In some embodiments of the method, the chemical linker L is a PEG. [0953] In some embodiments of the method, the chemical linker L has the following structure: , wherein m is 1, 2, 3, 4, 5, 6, or m or 7; more preferably, m is 1, 3, or 7. [0954] In some embodiments of the method, the chemical linker L has the following structure: , wherein m is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 3, 4, 5, 6, or 7; more preferably, m is 1, 3, or 7. [0955] In some embodiments of the method of chemical linker L, m is 1, 3 or 7.
  • m is 3.
  • A is substituted with -OH, -NH2, halogen, alkyl, -O-alkyl, -alkyl-NH2, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3.
  • A is substituted with -NH 2 , -alkyl-NH 2 , -NH-alkyl, or alkyl.
  • the guest molecule A is substituted or unsubstituted adamantane, diamantane, ferrocene, bicyclo[2.2.2]octane, buckminsterfullerene (C60), iceane, triamantane, isotetramantane, ferrocene-modified peracetic acid, pentamantane, or cyclohexamantane.
  • the guest molecule A is substituted or unsubstituted adamantane, ferrocene, bicyclo[2.2.2]octane, iceane, diamantane, triamantane, isotetramantane, pentamantane, or cyclohexamantane.
  • the guest molecule A is substituted or unsubstituted adamantane, 4,9-diamino diamantane, ferrocene, bicyclo[2.2.2]octane, iceane, diamantane, triamantane, isotetramantane, pentamantane, or cyclohexamantane.
  • the guest molecule A is substituted or unsubstituted adamantane, diamantane, 4,9-diamino diamantane or ferrocene.
  • the guest molecule A is substituted with halogen, alkyl, alkenyl, alkynyl, -OH, -O-(alkyl), -N-(alkyl), -CHF 2 , -CF 3 , -OCHF 2 or -OCF 3 .
  • the guest molecule A is substituted with halogen, alkyl, -O- (alkyl), -N-(alkyl).
  • the guest molecule A is substituted or unsubstituted adamantane or diamantane.
  • the guest molecule A is substituted or unsubstituted adamantane.
  • the guest molecule A is substituted or unsubstituted diamantane.
  • the guest molecule A is substituted or unsubstituted ferrocene.
  • the guest molecule A is unsubstituted adamantane.
  • the guest molecule A is substituted adamantane.
  • the guest molecule A is 4,9-diamino diamantane.
  • the guest molecule A is unsubstituted ferrocene.
  • the guest molecule A is unsubstituted diamantane.
  • the guest molecule A is substituted diamantane.
  • the substituted diamantane having the following structure: .
  • the substituted ferrocene In some embodiments of the method, the molecule A is substituted ferrocene.
  • the substituted ferrocene is substituted with C1-C6 alkyl, - alkyl-N-(C1-C6 alkyl), -OH, -O-(C1-C6 alkyl), -NH-(C1-C6 alkyl), -CHF2, -CF3, -OCHF2, or -OCF3.
  • the substituted ferrocene is substituted with C 1 -C 6 alkyl, - alkyl-N-(C 1 -C 6 alkyl), -OH, -O-(C 1 -C 6 alkyl), -NH-(C 1 -C 6 alkyl).
  • the substituted ferrocene is substituted with C 1 -C 6 alkyl, - alkyl-N-(C 1 -C 6 alkyl). [0980] In some embodiments of the method, the substituted ferrocene is substituted with -alkyl-N-(C 1 - C 6 alkyl). [0981] In some embodiments of the method, the substituted ferrocene having the following structure: .
  • M is the metal; wherein Y 1 , Y 2 , Y 3 , Y 4 are each, independently, -H, alkyl-N-(CO 2 R 4 ) 2 , alkyl-N-(alkyl-CO 2 R 4 ) 2 , alkylheteroaryl, alkyl-CO 2 H, alkylaryl-CO 2 H, alkylheteroaryl-CO 2 H, alkyl-CO 2 R 4 , alkylaryl-NH-CO 2 R 4, alkylaryl-CO 2 R 4 , alkylheteroaryl-CO 2 R 4 , alkyl-OH, alkylaryl-OH, alkylheteroaryl-OH, alkyl- N(alkylaryl) 2 , alkyl-N(alkylaryl-CO 2 H) 2 , alkyl-N(alkylheteroaryl-CO 2 H) 2 , alkyl-N(alkylheteroaryl-CO 2 H) 2
  • the metal complex having the structure: wherein M is the metal; wherein Y 1 , Y 2 , Y 3 are each, independently, -H, alkyl-N-(CO 2 R 4 ) 2 , alkyl-N-(alkyl-CO 2 R 4 ) 2 , alkylheteroaryl, alkyl-CO 2 H, alkylaryl-CO 2 H, alkylheteroaryl-CO 2 H, alkyl-CO 2 R 4 , alkylaryl-NH-CO 2 R 4, alkylaryl-CO 2 R 4 , alkylheteroaryl-CO 2 R 4 , alkyl-OH, alkylaryl-OH, alkylheteroaryl-OH, alkyl-N(alkylaryl) 2 , alkyl- N(alkylaryl-CO 2 H) 2 , alkyl-N(alkylheteroaryl-CO 2 H) 2 , alkyl-N(alkylheteroaryl-CO
  • each occurrence of R4 is independently, -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3, amide, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF 3 , or -Si(alkyl) 3 .
  • each occurrence of R 4 is independently, -H, -OH, -NH 2 , halogen, alkyl, -O-alkyl, -NH-alkyl, amide, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF 3 , or -Si(alkyl) 3 .
  • each occurrence of R 4 is independently, -OH, -NH 2 , alkyl, -O-alkyl, -NH-alkyl, amide, aryl, heteroaryl, or alkyl-CF 3 .
  • each occurrence of R 4 is independently, -OH, -NH 2 , alkyl, -O-alkyl, -NH-alkyl, amide.
  • each occurrence of R 4 is independently, -OH, -NH 2 , alkyl, -O-alkyl, -NH-alkyl.
  • R 4 is -OH.
  • R 4 is -NH 2 .
  • n and m are each independently 0, 1, 2, 3, 4, 5, or 6.
  • n and m are each independently 1, 2, or 3.
  • n and m are 1.
  • n is 1, 2, or 3.
  • m is 1, 2, or 3.
  • n is 1 or 2.
  • m is 1 or 2.
  • n is 1.
  • m is 1.
  • n and m are the same. [1001] In some embodiments of the method, n and m are different.
  • R1 and R2 are each independently H, halogen, alkyl, alkenyl, alkynyl, -OH, -O-(alkyl), -CHF2, -CF3, -OCHF2 or -OCF3, wherein n is 1, 2, 3, 4, 5, or 6.
  • R1 and R2 are each independently H, halogen, C1-C6 alkyl, C1-C6 alkenyl, or C1-C6 alkynyl.
  • R1 and R2 are each independently, C1-C6 alkyl or C1-C6 alkenyl.
  • R1 and R2 are each independently C1-C6 alkyl. [1006] In some embodiments of the method, R1 and R2 are C1-5 alkyl. [1007] In some embodiments of the method, R 1 and R 2 are C 1-3 alkyl. [1008] In some embodiments of the method, R 1 and R 2 are methyl. [1009] In some embodiments of the method, R 1 and R 2 are ethyl.
  • Y 1 , Y 2 , Y 3 , Y 4 are each independently alkyl-CO 2 H, , alkyl- N-(CO 2 R 4 ) 2 , alkyl-N-(alkyl-CO 2 R 4 ) 2 , alkylaryl-CO 2 H, alkylheteroaryl-CO 2 H, alkyl-CO 2 R 4 , alkylaryl-NH- CO 2 R 4, alkylaryl-CO 2 R 4 , alkylheteroaryl-CO 2 R 4 , alkyl-N(alkylaryl-CO 2 H) 2 , alkyl-N(alkylheteroaryl- CO 2 H) 2 , alkyl-N(alkylaryl-CO 2 R 4 ) 2 , alkyl-N(alkylheteroaryl-CO 2 R 4 ) 2 , alkyl-N(alkylheteroaryl-CO 2 R 4 ) 2 , alkyl-N(alkylhe
  • Y1, Y2, Y3, Y4 are each independently alkyl-CO2H, , alkyl- N-(CO2R4)2, alkyl-N-(alkyl-CO2R4)2, alkylaryl-CO2H, alkylheteroaryl-CO2H, alkyl-N(alkylaryl-CO2H)2, alkyl-N(alkylheteroaryl-CO2H)2, alkyl-N(alkyl-CO2H)2, alkyl-N(alkylaryl-OH)(alkyl-CO2H), alkyl- N(alkylheteroaryl-OH)(alkyl-CO2H), or alkylheteroaryl- P(O)(OH)2.
  • Y1, Y2, Y3, Y4 are each independently alkyl-CO2H, or alkyl- CO2NH2, or alkyl-N(alkyl-CO2H)2. [1013] In some embodiments of the method, at least one of Y1, Y2, Y3, Y4 is alkyl-CO2H. [1014] In some embodiments of the method, at least one of Y1, Y2, Y3, Y4 is alkyl-CO2NH2. [1015] In some embodiments of the method, at least one of Y1, Y2, Y3, Y4 is alkyl-N(alkyl-CO2H)2.
  • At least one of Y1, Y2, Y3, Y4 is -CH2-CO2H.
  • at least one of Y1, Y2, Y3, Y4 is -CH2-CO2NH2.
  • at least one of Y1, Y2, Y3, Y4 is -CH2-N(alkyl-CO2H)2
  • at least two of Y1, Y2, Y3, Y4 are the same.
  • at least three of Y1, Y2, Y3, Y4 are the same.
  • Y1, Y2, Y3, Y4 are the same. [1022] In some embodiments of the method, at least one of Y1, Y2, Y3 and Y4 is H. [1023] In some embodiments of the method, none of Y1, Y2, Y3 and Y4 are H.
  • Y1, Y2, Y3, Y4 are each independently , , or , , [1026] In some embodiments of the method, Y1, Y2, Y3, Y4 are each independently , , [1027] In some embodiments of the method, Y 1 , Y 2 , Y 3 , Y 4 are each , . [1028] In some embodiments of the method, Y 1 , Y 2 , Y 3 , Y 4 are each independently , . [1029] In some embodiments of the method, Y1 andY3 is Y2 and/or Y4 is .
  • X is alkyl- cycloalkyl-thiourea, alkenyl-aryl-thiourea, or alkenyl - [1031] In some embodiments of the method, X is alkyl-aryl-thiourea, alkyl-heteroaryl-thiourea, or alkyl- cycloalkyl-thiourea. [1032] In some embodiments of the method, X is alkyl-aryl-thiourea, or alkyl-heteroaryl-thiourea. [1033] In some embodiments of the method, X is alkyl-aryl-thiourea.
  • alkyl is C 1-6 alkyl. [1035] In some embodiments of the method, alkyl is C 1-3 alkyl. [1036] In some embodiments of the method, alkyl is methyl. [1037] In some embodiments of the method, alkyl is ethyl. [1038] In some embodiments of the method, aryl is phenyl, p-toluenyl (4-methylphenyl), naphthyl, tetrahydronaphthyl; indanyl, biphenyl, phenanthryl, anthryl or acenaphthyl.
  • aryl is phenyl, p-toluenyl (4-methylphenyl), or naphthyl. [1040] In some embodiments of the method, aryl is phenyl. [1041] In some embodiments of the method, the chemical linker L is an alkyl, alkenyl, alkynyl, alkylether, alkylthioether, alkylamino, alkylamido, alkylester, alkylaryl, alklyheteroaryl, polyethylene glycol (PEG), aryl, heteroaryl, a natural amino acid, an unnatural amino acid, a disulfide or thioether containing linker or combinations thereof.
  • PEG polyethylene glycol
  • the chemical linker L is an alkyl linker, an alkyne linker, alkynal linker or a polyethylene glycol (PEG) or combinations thereof.
  • the chemical linker L is an alkyl or a PEG or combinations thereof.
  • the chemical linker L is a PEG.
  • the chemical linker L has the following structure: , wherein m is 1, 2, 3, 4, 5, 6, or 7; more preferably, m is 1, 3, or 7.
  • the chemical linker L has the following structure: , wherein m is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 3, 4, 5, 6, or 7; more preferably, m is 1, 3, or 7. [1047] In some embodiments of the method of chemical linker L, m is 1, 3 or 7. [1048] In some embodiments of the method chemical linker L, m is 3. [1049] In some embodiments of the method, A is substituted with -OH, -NH 2 , halogen, alkyl, -O-alkyl, -alkyl-NH 2 , -NH-alkyl, -CHF 2 , -CF 3 , -OCHF 2 , -OCF 3 .
  • the method is substituted with -NH 2 , -alkyl-NH 2 , -NH-alkyl, or alkyl.
  • the guest molecule A is substituted or unsubstituted adamantane, diamantane, ferrocene, bicyclo[2.2.2]octane, buckminsterfullerene (C60), iceane, triamantane, isotetramantane, ferrocene-modified peracetic acid, pentamantane, or cyclohexamantane.
  • A is substituted with -OH, -NH 2 , halogen, alkyl, -O-alkyl, -alkyl-NH2, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3.
  • A is substituted with -NH2, -alkyl-NH2, -NH-alkyl, or alkyl.
  • the guest molecule A is substituted or unsubstituted adamantane, ferrocene, bicyclo[2.2.2]octane, iceane, diamantane, triamantane, isotetramantane, pentamantane, or cyclohexamantane.
  • the guest molecule A is substituted or unsubstituted adamantane, 4,9-diamino diamantane, ferrocene, bicyclo[2.2.2]octane, iceane, diamantane, triamantane, isotetramantane, pentamantane, or cyclohexamantane.
  • the guest molecule A is substituted or unsubstituted adamantane, diamantane, 4,9-diamino diamantane or ferrocene.
  • the guest molecule A is substituted or unsubstituted adamantane or diamantane. [1058] In some embodiments of the method, the guest molecule A is substituted or unsubstituted adamantane. [1059] In some embodiments of the method, the guest molecule A is substituted or unsubstituted diamantane. [1060] In some embodiments of the method, the guest molecule A is substituted or unsubstituted ferrocene.
  • the guest molecule A is substituted with halogen, alkyl, alkenyl, alkynyl, -OH, -O-(alkyl), -N-(alkyl), -CHF 2 , -CF 3 , -OCHF 2 or -OCF 3 .
  • the guest molecule A is substituted with halogen, alkyl, - O-(alkyl), -N-(alkyl).
  • the guest molecule A is unsubstituted adamantane.
  • the guest molecule A is substituted adamantane. [1065] In some embodiments of the method, the guest molecule A is 4,9-diamino diamantane. [1066] In some embodiments of the method, the guest molecule A is unsubstituted ferrocene. [1067] In some embodiments of the method, the guest molecule A is unsubstituted diamantane. [1068] In some embodiments of the method, the guest molecule A is substituted diamantane. [1069] In some embodiments of the method, the substituted diamantane having the following structure: . [1070] In some embodiments of the molecule A is substituted ferrocene.
  • the substituted ferrocene is substituted with C1-C6 alkyl, - alkyl-N-(C1-C6 alkyl), -OH, -O-(C1-C6 alkyl), -NH-(C1-C6 alkyl), -CHF2, -CF3, -OCHF2, or -OCF3.
  • the substituted ferrocene is substituted with C1-C6 alkyl, - alkyl-N-(C1-C6 alkyl), -OH, -O-(C1-C6 alkyl), -NH-(C1-C6 alkyl).
  • the substituted ferrocene is substituted with C1-C6 alkyl, - alkyl-N-(C1-C6 alkyl). [1074] In some embodiments of the method, the substituted ferrocene is substituted with -alkyl-N-(C1- C6 alkyl). [1075] In some embodiments of the method, the substituted ferrocene having the following structure: .
  • the metal complex having the structure: wherein M is the metal; wherein L is a chemical linker; wherein n and m are each independently 1, 2, or 3; wherein A is a guest molecule which is substituted and unsubstituted adamantane, ferrocene, diamantane, bicyclo[2.2.2]octane, iceane, triamantane, isotetramantane, pentamantane cyclohexamantane, super- adamantane, 1,3,5,7-tetramethyl-1,3,5,7-tetrasilaadamantane, adamanzane, antimony trioxide, arsenic trioxide, 2,4,6-trioxa-1,3,5,7-tetraarsaadamantane, diamondoid, hexamethylenetetramine, phosphorus pentasulfide, phosphorus pentoxide
  • each occurrence of R4 is independently, -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3, amide, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3.
  • each occurrence of R4 is independently, -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, amide, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF 3 , or -Si(alkyl) 3 .
  • each occurrence of R 4 is independently, -OH, -NH 2 , alkyl, -O-alkyl, -NH-alkyl, amide, aryl, heteroaryl, or alkyl-CF 3 .
  • each occurrence of R 4 is independently, -OH, -NH 2 , alkyl, -O-alkyl, -NH-alkyl, or amide.
  • each occurrence of R 4 is independently, -OH, -NH 2 , alkyl, -O-alkyl, or -NH-alkyl.
  • R 4 is -OH.
  • R 4 is -NH 2 .
  • the metal complex having the structure: wherein M is the metal; wherein L is a chemical linker; wherein n and m are each independently 1, 2, or 3; wherein A is a guest molecule which is substituted and unsubstituted adamantane, ferrocene, diamantane, bicyclo[2.2.2]octane, iceane, triamantane, isotetramantane, pentamantane cyclohexamantane, super- adamantane, 1,3,5,7-tetramethyl-1,3,5,7-tetrasilaadamantane, adamanzane, antimony trioxide, arsenic trioxide, 2,4,6-trioxa-1,3,5,7-tetraarsaadamantane, diamondoid, hexamethylenetetramine, phosphorus pentasulfide, phosphorus pentoxide
  • the metal complex having the structure: wherein M is the metal; wherein L is a chemical linker; wherein n and m are each independently 1, 2, or 3; wherein A is a guest molecule which is substituted and unsubstituted adamantane, ferrocene, diamantane, bicyclo[2.2.2]octane, iceane, triamantane, isotetramantane, pentamantane cyclohexamantane, super- adamantane, 1,3,5,7-tetramethyl-1,3,5,7-tetrasilaadamantane, adamanzane, antimony trioxide, arsenic trioxide, 2,4,6-trioxa-1,3,5,7-tetraarsaadamantane, diamondoid, hexamethylenetetramine, phosphorus pentasulfide, phosphorus pentoxide
  • each occurrence of R4 is independently, -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3, amide, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3.
  • each occurrence of R4 is independently, -H, -OH, -NH2, halogen, alkyl, -O-alkyl, -NH-alkyl, amide, alkenyl, alkynyl, alkyl-aryl, alkyl-heteroaryl, aryl, heteroaryl, alkyl-CF3, or -Si(alkyl)3.
  • each occurrence of R4 is independently, -OH, -NH2, alkyl, -O-alkyl, -NH-alkyl, amide, aryl, heteroaryl, or alkyl-CF 3 .
  • each occurrence of R 4 is independently, -OH, -NH 2 , alkyl, -O-alkyl, -NH-alkyl, or amide.
  • each occurrence of R 4 is independently, -OH, -NH 2 , alkyl, -O-alkyl, or -NH-alkyl.
  • R 4 is -OH.
  • R 4 is -NH 2 .
  • alkyl is C 1-6 alkyl.
  • alkyl is C 1-3 alkyl. [1095] In some embodiments of the method, alkyl is methyl. [1096] In some embodiments of the method, alkyl is ethyl. [1097] In some embodiments of the method, aryl is phenyl, p-toluenyl (4-methylphenyl), naphthyl, tetrahydronaphthyl; indanyl, biphenyl, phenanthryl, anthryl or acenaphthyl.
  • the chemical linker L is an alkyl, alkenyl, alkynyl, alkylether, alkylthioether, alkylamino, alkylamido, alkylester, alkylaryl, 125lkylheteroaryl, polyethylene glycol (PEG), aryl, heteroaryl, a natural amino acid, an unnatural amino acid, a disulfide or thioether containing linker or combinations thereof.
  • the chemical linker L is an alkyl linker, an alkyne linker, alkynal linker or a polyethylene glycol (PEG) or combinations thereof.
  • the chemical linker L is an alkyl or a PEG or combinations thereof. [1101] In some embodiments of the method, the chemical linker L is a PEG. [1102] In some embodiments of the method, the chemical linker L has the following structure: , wherein m is 1, 2, 3, 4, 5, 6, or 7; more preferably, m is 1, 3, or 7. [1103] In some embodiments of the method, the chemical linker L has the following structure: , wherein m is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; preferably m is 1, 2, 3, 4, 5, 6, or 7; more preferably, m is 1, 3, or 7.
  • m is 1, 3 or 7.
  • m is 3.
  • A is substituted with -OH, -NH2, halogen, alkyl, -O-alkyl, -alkyl-NH2, -NH-alkyl, -CHF2, -CF3, -OCHF2, -OCF3.
  • A is substituted with -NH2, -alkyl-NH2, -NH-alkyl, or alkyl.
  • the guest molecule A is substituted or unsubstituted adamantane, diamantane, ferrocene, bicyclo[2.2.2]octane, buckminsterfullerene (C60), iceane, triamantane, isotetramantane, ferrocene-modified peracetic acid, pentamantane, or cyclohexamantane.
  • the guest molecule A is substituted or unsubstituted adamantane, 4,9-diamino diamantane, ferrocene, bicyclo[2.2.2]octane, iceane, diamantane, triamantane, isotetramantane, pentamantane, or cyclohexamantane.
  • the guest molecule A is substituted or unsubstituted adamantane, diamantane, 4,9-diamino diamantane or ferrocene.
  • the guest molecule A is substituted or unsubstituted adamantane or diamantane.
  • A is substituted with -OH, -NH2, halogen, alkyl, -O-alkyl, -alkyl-NH 2 , -NH-alkyl, -CHF 2 , -CF 3 , -OCHF 2 , -OCF 3 .
  • A is substituted with -NH 2 , -alkyl-NH 2 , -NH-alkyl, or alkyl.
  • the guest molecule A is substituted with halogen, alkyl, alkenyl, alkynyl, -OH, -O-(alkyl), -N-(alkyl), -CHF 2 , -CF 3 , -OCHF 2 or -OCF 3 .
  • the guest molecule A is substituted with halogen, alkyl, - O-(alkyl), or -N-(alkyl).
  • the guest molecule A is substituted or unsubstituted adamantane.
  • the guest molecule A is substituted or unsubstituted diamantane.
  • the guest molecule A is substituted or unsubstituted ferrocene.
  • the guest molecule A is unsubstituted adamantane.
  • the guest molecule A is substituted adamantane.
  • the guest molecule A is 4,9-diamino diamantane.
  • the guest molecule A is unsubstituted ferrocene.
  • the guest molecule A is unsubstituted diamantane.
  • the guest molecule A is substituted diamantane.
  • the substituted diamantane having the following structure: .
  • the molecule A is substituted ferrocene.
  • the substituted ferrocene is substituted with C1-C6 alkyl, - alkyl-N-(C1-C6 alkyl), -OH, -O-(C1-C6 alkyl), -NH-(C1-C6 alkyl), -CHF2, -CF3, -OCHF2, or -OCF3.
  • the substituted ferrocene is substituted with C1-C6 alkyl, - alkyl-N-(C1-C6 alkyl), -OH, -O-(C1-C6 alkyl), or -NH-(C1-C6 alkyl).
  • the substituted ferrocene is substituted with C1-C6 alkyl, or -alkyl-N-(C1-C6 alkyl).
  • the substituted ferrocene having the following structure: .
  • the metal complex having the structure: wherein is the metal; wherein L is alkyl, alkenyl, alkynyl, alkylether, alkylthioether, alkylamino, alkylamido, alkylester, alkylaryl, alklyheteroaryl,or polyethylene glycol (PEG); wherein n and m are each independently 1, 2, or 3; wherein A is a guest molecule which is substituted or unsubstituted adamantane, ferrocene, diamantane, bicyclo[2.2.2]octane, iceane, triamantane, isotetramantane, pentamantane cyclohexamantane, super- adamantane, 1,3,5,7-tetramethyl-1,3,5,7-tetrasilaadamantane; and wherein each occurrence of R4 is independently, -H, -OH,
  • the metal complex having the structure: wherein the metal; wherein L is alkyl, alkenyl, alkynyl, alkylether, alkylthioether, alkylamino, alkylamido, alkylester, alkylaryl, alklyheteroaryl,or polyethylene glycol (PEG); wherein n and m are each independently 1, 2, or 3; wherein A is a guest molecule which is substituted or unsubstituted adamantane, ferrocene, diamantane, bicyclo[2.2.2]octane, iceane, triamantane, isotetramantane, pentamantane cyclohexamantane, super- adamantane, 1,3,5,7-tetramethyl-1,3,5,7-tetrasilaadamantane; and wherein each occurrence of R 4 is independently, -H, -OH, -
  • the metal complex having the structure: , wherein is the metal; wherein chemical linker; wherein n and m are each independently 1, 2, or 3; wherein A is a guest molecule which is adamantane, ferrocene, or diamantane, wherein R 4 is -OH, -NH 2, -O-(C 1 -C 6 alkyl), or NH-(C 1 -C 6 alkyl), more preferably R 4 is -OH or -NH 2 .
  • the metal complex having the structure: wherein L is a chemical linker; wherein n and m are each independently 1, 2, or 3; wherein A is a guest molecule which is adamantane, ferrocene, or diamantane; and wherein R 4 is -OH, -O-(C 1 -C 6 alkyl), or NH-(C 1 -C 6 alkyl), more preferably R 4 is -OH.
  • the metal complex having the structure: wherein is the metal; wherein L is alkyl, alkenyl, alkynyl, alkylether, or polyethylene glycol (PEG); wherein n and m are each independently 1, 2, or 3; wherein A is a guest molecule which is adamantane, ferrocene, or diamantane; and wherein R 4 is -OH, -NH 2, -O-(C 1 -C 6 alkyl), or NH-(C 1 -C 6 alkyl), more preferably R 4 is -OH or -NH 2 .
  • the metal complex having the structure: wherein L is alkyl, alkenyl, alkynyl, alkylether, or polyethylene glycol (PEG); wherein n and m are each independently 1, 2, or 3; wherein A is a guest molecule which is adamantane, ferrocene, or diamantane; and wherein R 4 is -OH, -NH 2, -O-(C 1 -C 6 alkyl), or NH-(C 1 -C 6 alkyl), more preferably R 4 is -OH or -NH 2 .
  • the metal complex having the structure [1137] In some embodiments of the method, the metal complex having the structure: [1138] In some embodiments of the method, the metal complex having the structure: or , wherein the metal. [1139] In some embodiments of the method, the metal is Copper-62 ( 62 Cu), Copper-64 ( 64 Cu), Copper- 67 ( 67 Cu), Gallium-68 ( 68 Ga) Scandium-44 ( 44 Sc), Scandium-47 ( 47 Sc), Scandium-43 ( 43 Sc), Lead-203 ( 203 Pb), Lead-212 ( 212 Pb), Lanthanum-132 ( 132 La), Lanthanum-135 ( 135 La), Yttrium-86 ( 86 Y), Yttrium-90 ( 90 Y), Lutetium 177 ( 177 Lu), Terbium -149 ( 149 Tb), Terbium-152 ( 152 Tb), Terbium-155 ( 155 Tb) or Terbium- 161 ( 161 Tb).
  • the metal is Copper-62 ( 62 Cu), Copper-64 ( 64 Cu), Copper- 67 ( 67 Cu), Scandium-44 ( 44 Sc), Scandium-47 ( 47 Sc), or Scandium-43 ( 43 Sc).
  • the metal is Copper-64 ( 64 Cu).
  • the present invention provides a method of detecting cells in a subject comprises administering an effective amount of a pharmaceutical composition comprising the metal complex described in the invention and a marker attached to a host molecule.
  • the marker is a biological marker.
  • the marker is a tumor marker or a cancer marker.
  • the tumor marker is prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), cancer antigen 125 (CA 125), carcinoembryonic antigen (CEA), alpha- fetoprotein (AFP), human chorionic gonadotropin (HCG), cancer antigen 19-9 (CA 19-9), cancer antigen 15-3 (CA 15-3), cancer antigen 27-29 (CA 27-29), lactate dehydrogenase (LDH), or neuron-specific enolase (NSE).
  • PSA prostate-specific antigen
  • PAP prostatic acid phosphatase
  • CA 125 cancer antigen 125
  • CEA carcinoembryonic antigen
  • AFP alpha- fetoprotein
  • HCG human chorionic gonadotropin
  • CA 19-9 cancer antigen 19-9
  • cancer antigen 15-3 CA 15-3
  • cancer antigen 27-29 CA 27-29
  • LDH lactate dehydrogenase
  • NSE neuron-specific enolase
  • the tumor marker is prostate-specific antigen (PSA), cancer antigen 125 (CA 125), carcinoembryonic antigen (CEA), cancer antigen 19-9 (CA 19-9), cancer antigen 15-3 (CA 15-3), or cancer antigen 27-29 (CA 27-29).
  • PSA prostate-specific antigen
  • CEA carcinoembryonic antigen
  • the tumor marker is carcinoembryonic antigen (CEA).
  • the host molecule comprises cucurbit[5]uril, cucurbit[6]uril, cucurbit[7]uril, cucurbit[8]uril, cucurbit[10]uril, cucurbit[14]uril, cyclodextrin, calix-[5]- arenes.
  • the host molecule comprises cucurbit[5]uril, cucurbit[6]uril, cucurbit[7]uril, cucurbit[8]uril, or cucurbit[10]uril.
  • the host molecule comprises cucurbit[5]uril, cucurbit[6]uril, cucurbit[7]uril, or cucurbit[8]uril. [1152] In some embodiments of the method, the host molecule comprises cucurbit[7]uril, or cucurbit[8]uril. [1153] In some embodiments of the method, the host molecule is cucurbit[7]uril. [1154] In some embodiments of the method, the interaction between the host and the guest molecule is a non-covalent interaction.
  • the non-covalent interaction is ion-ion interaction, ion- dipole interaction, dipole-dipole interaction, hydrogen bonding, cation- ⁇ interaction, ⁇ - ⁇ interaction, van der Waals interaction or hydrophobic interaction.
  • the non-covalent interaction is ion-ion interaction, or van der Waals interaction.
  • the metal complex described in the invention and the host molecule described in the invention form a high affinity host-guest complex.
  • the present invention provides a method of detecting cells in a subject comprises administering an effective amount of the modified marker with a host molecule described in the invention to the subject who contains a guest molecule.
  • the present invention provides a method of detecting cells in a subject comprising administering an effective amount of the pharmaceutical composition described in the invention to the subject and imaging the subject with a molecular imaging device to detect the composition in the subject.
  • the present invention provides a method of imaging cells in a subject comprising: 1) administering to the subject an effective amount of the composition described in the invention, wherein the composition specifically accumulates at the cells in the subject; 2) detecting in the subject the location of the composition; and 3) obtaining an image of the cells in the subject based on the location of the composition in the subject.
  • the present invention provides a method of detecting the presence of cells in a subject which comprises determining if an amount of the composition described in the invention is present in the subject at a period of time after administration of the composition to the subject, thereby detecting the presence of the cells based on the amount of the composition determined to be present in the subject.
  • the metal complex and the host molecule are applied concurrently, or wherein the host molecule is applied first, and the metal complex is applied after a period of time.
  • the period of time is 24 hours, 48 hours, 72, hours, 96 hours, 120 hours, or 144 hours.
  • the period of time is 72 hours.
  • the cells are cancer cells or tumor cells.
  • the cancer cells or tumor cells have elevated levels of proteins or antigens, or both.
  • the cancer is lung cancer, breast cancer, prostate cancer, cervical cancer, pancreatic cancer, colon cancer, ovarian cancer, stomach cancer, esophagus cancer, skin cancer, heart cancer, liver cancer, bronchial cancer, testicular cancer, kidney cancer, bladder cancer, spleen cancer, thymus cancer, thyroid cancer, brain cancer, or gall bladder cancer.
  • the cancer is pancreatic cancer.
  • the tumor is bone tumor, brain tumor, malignant soft tissue tumor, organ tumor, ovarian germ cell tumor, gland tumor, lymphatic tumor, or skin tumor.
  • the subject is a mammal.
  • the subject is a human.
  • the molecular imaging device is a PET imaging device.
  • the present invention provides a use of an effective amount of metal complex described in the invention to detect cells within a subject, wherein the subject contains a host molecule.
  • the present invention provides a use of an effective amount of a marker attached to a host molecule described in the invention to detect cells in a subject, wherein the subject contains a guest molecule.
  • the present invention provides a use of an effective amount of the composition described in the invention to image a subject with a molecular imaging device to detect cells in a subject.
  • the compounds of the present invention include all hydrates, solvates, and complexes of the compounds used by this invention. If a chiral center or another form of an isomeric center is present in a compound of the present invention, all forms of such isomer or isomers, including enantiomers and diastereomers, are intended to be covered herein.
  • Compounds containing a chiral center may be used as a racemic mixture, an enantiomerically enriched mixture, or the racemic mixture may be separated using well-known techniques and an individual enantiomer may be used alone.
  • the compounds described in the present invention are in racemic form or as individual enantiomers.
  • PCT/US2023/064637 can be used to attach to a guest molecule as disclosed in the subject application for PET imaging in a subject.
  • the contents of U.S. Patent Application Publication No. 2021/0276971 A1, International Application No. US/2022/078389, and International Application No. PCT/US2023/064637 are hereby incorporated by reference.
  • the compounds of the subject invention may have spontaneous tautomeric forms. In cases wherein compounds may exist in tautomeric forms, such as keto-enol tautomers, each tautomeric form is contemplated as being included within this invention whether existing in equilibrium or predominantly in one form.
  • Isotopes include those atoms having the same atomic number but different mass numbers.
  • isotopes of hydrogen include tritium and deuterium.
  • isotopes of carbon include C-13 and C-14.
  • any notation of a carbon in structures throughout this application when used without further notation, are intended to represent all isotopes of carbon, such as 12 C, 13 C, or 14 C.
  • any compounds containing 13 C or 14 C may specifically have the structure of any of the compounds disclosed herein.
  • any notation of a hydrogen in structures throughout this application when used without further notation, are intended to represent all isotopes of hydrogen, such as 1 H, 2 H, or 3 H. Furthermore, any compounds containing 2 H or 3 H may specifically have the structure of any of the compounds disclosed herein.
  • Isotopically-labeled compounds can generally be prepared by conventional techniques known to those skilled in the art using appropriate isotopically-labeled reagents in place of the non-labeled reagents employed.
  • the substituents may be substituted or unsubstituted, unless specifically defined otherwise.
  • alkyl, heteroalkyl, monocycle, bicycle, aryl, heteroaryl and heterocycle groups can be further substituted by replacing one or more hydrogen atoms with alternative non-hydrogen groups.
  • substituents and substitution patterns on the compounds used in the method of the present invention can be selected by one of ordinary skill in the art to provide compounds that are chemically stable and that can be readily synthesized by techniques known in the art from readily available starting materials.
  • a substituent is itself substituted with more than one group, it is understood that these multiple groups may be on the same carbon or on different carbons, so long as a stable structure results.
  • substituents i.e. R1, R2, etc. are to be chosen in conformity with well- known principles of chemical structure connectivity.
  • biological marker refers to a broad subcategory of medical signs – that is, objective indications of medical state observed from outside the patient – which can be measured accurately and reproducibly. Medical signs stand in contrast to medical symptoms, which are limited to those indications of health or illness perceived by patients themselves.
  • biomarker as “a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention.”
  • WHO World Health Organization
  • a biomarker as “any substance, structure, or process that can be measured in the body or its products and influence or predict the incidence of outcome or disease”.
  • An even broader definition takes into account not just incidence and outcome of disease, but also the effects of treatments, interventions, and even unintended environmental exposure, such as to chemicals or nutrients.
  • biomarkers In their report on the validity of biomarkers in environment risk assessment, the WHO has stated that a true definition of biomarkers includes “almost any measurement reflecting an interaction between a biological system and a potential hazard, which may be chemical, physical, or biological. The measured response may be functional and physiological, biochemical at the cellular level, or a molecular interaction.” Examples of biomarkers include everything from pulse and blood pressure through basic chemistries to more complex laboratory tests of blood and other tissues. [1195] As used herein, the term “Guest-Host” refers to host guest interactions involving two molecules or materials that can form complexes through unique structural relationships and noncovalent binding.
  • PSA Prostate-specific antigen
  • BPH benign prostatic hyperplasia
  • PAP Prostatic acid phosphatase
  • ovarian cancer is the most common cause of elevated CA 125, but cancers of the uterus, cervix, pancreas, liver, colon, breast, lung, and digestive tract can also raise CA 125 levels. Several noncancerous conditions can also elevate CA 125. CA 125 is mainly used to monitor the treatment of ovarian cancer.
  • Carcinoembryonic antigen (CEA) is normally found in small amounts in the blood. Colorectal cancer is the most common cancer that raises this tumor marker.
  • AFP Alpha-fetoprotein
  • HCG Human chorionic gondadotropin
  • HCG may indicate cancer in the testis, ovary, liver, stomach, pancreas, and lung. Marijuana use can also raise HCG levels.
  • CA 19-9 marker is associated with cancers in the colon, stomach, and bile duct. Elevated levels of CA 19-9 may indicate advanced cancer in the pancreas, but it is also associated with noncancerous conditions, including gallstones, pancreatitis, cirrhosis of the liver, and cholecystitis.
  • CA 15-3 is most useful in evaluating the effect of treatment for women with advanced breast cancer.
  • Elevated levels of CA 15-3 are also associated with cancers of the ovary, lung, and prostate, as well as noncancerous conditions such as benign breast or ovarian disease, endometriosis, pelvic inflammatory disease, and hepatitis. Pregnancy and lactation also can raise CA 15-3 levels.
  • CA 27-29 marker, like CA 15-3, is used to follow the course of treatment in women with advanced breast cancer. Cancers of the colon, stomach, kidney, lung, ovary, pancreas, uterus, and liver may also raise CA 27-29 levels. Noncancerous conditions associated with this substance are first trimester pregnancy, endometriosis, ovarian cysts, benign breast disease, kidney disease, and liver disease.
  • LDH lactate dyhydrogenase
  • NSE Neuron-specific enolase
  • alkyl is intended to include both branched and straight-chain saturated aliphatic hydrocarbon groups having the specified number of carbon atoms.
  • C1-Cn as in “C1–Cn alkyl” is defined to include groups having 1, 2ising, n-1 or n carbons in a linear or branched arrangement, and specifically includes methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, isopropyl, isobutyl, sec-butyl and so on.
  • An embodiment can be C1-C12 alkyl, C2-C12 alkyl, C3-C12 alkyl, C4-C12 alkyl and so on.
  • alkenyl refers to a non-aromatic hydrocarbon radical, straight or branched, containing at least 1 carbon to carbon double bond, and up to the maximum possible number of non-aromatic carbon- carbon double bonds may be present.
  • C 2 -C n alkenyl is defined to include groups having 1, 2...., n-1 or n carbons.
  • C 2 -C 6 alkenyl means an alkenyl radical having 2, 3, 4, 5, or 6 carbon atoms, and at least 1 carbon-carbon double bond, and up to, for example, 3 carbon-carbon double bonds in the case of a C 6 alkenyl, respectively.
  • Alkenyl groups include ethenyl, propenyl, butenyl and cyclohexenyl. As described above with respect to alkyl, the straight, branched or cyclic portion of the alkenyl group may contain double bonds and may be substituted if a substituted alkenyl group is indicated. An embodiment can be C 2 -C 12 alkenyl, C 3 -C 12 alkenyl, C 4 -C 12 alkenyl and so on. [1209]
  • alkynyl refers to a hydrocarbon radical straight or branched, containing at least 1 carbon to carbon triple bond, and up to the maximum possible number of non-aromatic carbon-carbon triple bonds may be present.
  • C 2 -C n alkynyl is defined to include groups having 1, 2...., n-1 or n carbons.
  • C 2 -C 6 alkynyl means an alkynyl radical having 2 or 3 carbon atoms, and 1 carbon-carbon triple bond, or having 4 or 5 carbon atoms, and up to 2 carbon-carbon triple bonds, or having 6 carbon atoms, and up to 3 carbon-carbon triple bonds.
  • Alkynyl groups include ethynyl, propynyl and butynyl. As described above with respect to alkyl, the straight or branched portion of the alkynyl group may contain triple bonds and may be substituted if a substituted alkynyl group is indicated.
  • An embodiment can be a C2- Cn alkynyl.
  • An embodiment can be C2-C12 alkynyl, C3-C12 alkynyl, C4-C12 alkynyl and so on.
  • Alkylene”, “alkenylene” and “alkynylene” shall mean, respectively, a divalent alkane, alkene and alkyne radical, respectively. It is understood that an alkylene, alkenylene, and alkynylene may be straight or branched. An alkylene, alkenylene, and alkynylene may be unsubstituted or substituted.
  • heteroalkyl includes both branched and straight-chain saturated aliphatic hydrocarbon groups having the specified number of carbon atoms and at least 1 heteroatom within the chain or branch.
  • heterocycle or “heterocyclyl” as used herein is intended to mean a 5- to 10- membered nonaromatic ring containing from 1 to 4 heteroatoms selected from the group consisting of O, N and S, and includes bicyclic groups.
  • Heterocyclyl therefore includes, but is not limited to the following: imidazolyl, piperazinyl, piperidinyl, pyrrolidinyl, morpholinyl, thiomorpholinyl, tetrahydropyranyl, dihydropiperidinyl, tetrahydrothiophenyl and the like. If the heterocycle contains a nitrogen, it is understood that the corresponding N-oxides thereof are also encompassed by this definition.
  • cycloalkyl shall mean cyclic rings of alkanes of three to eight total carbon atoms, or any number within this range (i.e., cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl).
  • “monocycle” includes any stable polyatomic carbon ring of up to 10 atoms and may be unsubstituted or substituted. Examples of such non-aromatic monocycle elements include but are not limited to: cyclobutyl, cyclopentyl, cyclohexyl, and cycloheptyl.
  • aromatic monocycle elements examples include but are not limited to: phenyl.
  • “bicycle” includes any stable polyatomic carbon ring of up to 10 atoms that is fused to a polyatomic carbon ring of up to 10 atoms with each ring being independently unsubstituted or substituted.
  • non-aromatic bicycle elements examples include but are not limited to: decahydronaphthalene.
  • aromatic bicycle elements examples include but are not limited to: naphthalene.
  • aryl is intended to mean any stable monocyclic, bicyclic or polycyclic carbon ring of up to 10 atoms in each ring, wherein at least one ring is aromatic, and may be unsubstituted or substituted.
  • aryl elements include phenyl, p-toluenyl (4-methylphenyl), naphthyl, tetrahydro-naphthyl, indanyl, biphenyl, phenanthryl, anthryl or acenaphthyl.
  • the aryl substituent is bicyclic and one ring is non-aromatic, it is understood that attachment is via the aromatic ring.
  • polycyclic refers to unsaturated or partially unsaturated multiple fused ring structures, which may be unsubstituted or substituted.
  • arylalkyl refers to alkyl groups as described above wherein one or more bonds to hydrogen contained therein are replaced by a bond to an aryl group as described above. It is understood that an “arylalkyl” group is connected to a core molecule through a bond from the alkyl group and that the aryl group acts as a substituent on the alkyl group.
  • arylalkyl moieties include, but are not limited to, benzyl (phenylmethyl), p-trifluoromethylbenzyl (4-trifluoromethylphenylmethyl), 1-phenylethyl, 2- phenylethyl, 3-phenylpropyl, 2-phenylpropyl and the like.
  • heteroaryl represents a stable monocyclic, bicyclic or polycyclic ring of up to 10 atoms in each ring, wherein at least one ring is aromatic and contains from 1 to 4 heteroatoms selected from the group consisting of O, N and S.
  • Bicyclic aromatic heteroaryl groups include phenyl, pyridine, pyrimidine or pyridizine rings that are (a) fused to a 6-membered aromatic (unsaturated) heterocyclic ring having one nitrogen atom; (b) fused to a 5- or 6-membered aromatic (unsaturated) heterocyclic ring having two nitrogen atoms; (c) fused to a 5-membered aromatic (unsaturated) heterocyclic ring having one nitrogen atom together with either one oxygen or one sulfur atom; or (d) fused to a 5- membered aromatic (unsaturated) heterocyclic ring having one heteroatom selected from O, N or S.
  • Heteroaryl groups within the scope of this definition include but are not limited to: benzoimidazolyl, benzofuranyl, benzofurazanyl, benzopyrazolyl, benzotriazolyl, benzothiophenyl, benzoxazolyl, carbazolyl, carbolinyl, cinnolinyl, furanyl, indolinyl, indolyl, indolazinyl, indazolyl, isobenzofuranyl, isoindolyl, isoquinolyl, isothiazolyl, isoxazolyl, naphthpyridinyl, oxadiazolyl, oxazolyl, oxazoline, isoxazoline, oxetanyl, pyranyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridopyridinyl, pyridazinyl, pyridyl, pyr
  • heteroaryl substituent is bicyclic and one ring is non-aromatic or contains no heteroatoms, it is understood that attachment is via the aromatic ring or via the heteroatom containing ring, respectively. If the heteroaryl contains nitrogen atoms, it is understood that the corresponding N-oxides thereof are also encompassed by this definition.
  • alkylheteroaryl refers to alkyl groups as described above wherein one or more bonds to hydrogen contained therein are replaced by a bond to an heteroaryl group as described above.
  • alkylheteroaryl is connected to a core molecule through a bond from the alkyl group and that the heteroaryl group acts as a substituent on the alkyl group.
  • alkylheteroaryl moieties include, but are not limited to, -CH2-(C5H4N), -CH2-CH2-(C5H4N) and the like.
  • heterocycle or “heterocyclyl” refers to a mono- or poly-cyclic ring system which can be saturated or contains one or more degrees of unsaturation and contains one or more heteroatoms. Preferred heteroatoms include N, O, and/or S, including N-oxides, sulfur oxides, and dioxides.
  • the ring is three to ten-membered and is either saturated or has one or more degrees of unsaturation.
  • the heterocycle may be unsubstituted or substituted, with multiple degrees of substitution being allowed.
  • Such rings may be optionally fused to one or more of another "heterocyclic" ring(s), heteroaryl ring(s), aryl ring(s), or cycloalkyl ring(s).
  • heterocycles include, but are not limited to, tetrahydrofuran, pyran, 1,4-dioxane, 1,3-dioxane, piperidine, piperazine, pyrrolidine, morpholine, thiomorpholine, tetrahydrothiopyran, tetrahydrothiophene, 1,3-oxathiolane, and the like.
  • the alkyl, alkenyl, alkynyl, aryl, heteroaryl and heterocyclyl substituents may be substituted or unsubstituted, unless specifically defined otherwise.
  • alkyl, alkenyl, alkynyl, aryl, heterocyclyl and heteroaryl groups can be further substituted by replacing one or more hydrogen atoms with alternative non-hydrogen groups.
  • non-hydrogen groups include, but are not limited to, halo, hydroxy, mercapto, amino, carboxy, cyano and carbamoyl.
  • halogen refers to F, Cl, Br, and I.
  • substitution refers to a functional group as described above in which one or more bonds to a hydrogen atom contained therein are replaced by a bond to non- hydrogen or non-carbon atoms, provided that normal valencies are maintained and that the substitution results in a stable compound.
  • Substituted groups also include groups in which one or more bonds to a carbon(s) or hydrogen(s) atom are replaced by one or more bonds, including double or triple bonds, to a heteroatom.
  • substituent groups include the functional groups described above, and halogens (i.e., F, Cl, Br, and I); alkyl groups, such as methyl, ethyl, n-propyl, isopropryl, n-butyl, tert-butyl, and trifluoromethyl; hydroxyl; alkoxy groups, such as methoxy, ethoxy, n-propoxy, and isopropoxy; aryloxy groups, such as phenoxy; arylalkyloxy, such as benzyloxy (phenylmethoxy) and p- trifluoromethylbenzyloxy (4-trifluoromethylphenylmethoxy); heteroaryloxy groups; sulfonyl groups, such as trifluoromethanesulfonyl, methanesulfonyl, and p-toluenesulfonyl; nitro, nitrosyl; mercapto; sulfanyl groups, such as
  • the substituted compound can be independently substituted by one or more of the disclosed or claimed substituent moieties, singly or pluraly.
  • independently substituted it is meant that the (two or more) substituents can be the same or different.
  • substituents and substitution patterns on the compounds of the instant invention can be selected by one of ordinary skill in the art to provide compounds that are chemically stable and that can be readily synthesized by techniques known in the art, as well as those methods set forth below, from readily available starting materials. If a substituent is itself substituted with more than one group, it is understood that these multiple groups may be on the same carbon or on different carbons, so long as a stable structure results.
  • the compounds used in the method of the present invention may be prepared by techniques described in Vogel’s Textbook of Practical Organic Chemistry, A.I. Vogel, A.R. Tatchell, B.S. Furnis, A.J. Hannaford, P.W.G. Smith, (Prentice Hall) 5 th Edition (1996), March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, Michael B. Smith, Jerry March, (Wiley-Interscience) 5 th Edition (2007), and references therein, which are incorporated by reference herein. However, these may not be the only means by which to synthesize or obtain the desired compounds.
  • a pharmaceutical composition comprising the compound of the present invention and a pharmaceutically acceptable carrier.
  • pharmaceutically active agent means any substance or compound suitable for administration to a subject and furnishes biological activity or other direct effect in the treatment, cure, mitigation, diagnosis, or prevention of disease, or affects the structure or any function of the subject.
  • Pharmaceutically active agents include, but are not limited to, substances and compounds described in the Physicians’ Desk Reference (PDR Network, LLC; 64th edition; November 15, 2009) and “Approved Drug Products with Therapeutic Equivalence Evaluations” (U.S.
  • compositions which have pendant carboxylic acid groups may be modified in accordance with the present invention using standard esterification reactions and methods readily available and known to those having ordinary skill in the art of chemical synthesis. Where a pharmaceutically active agent does not possess a carboxylic acid group, the ordinarily skilled artisan will be able to design and incorporate a carboxylic acid group into the pharmaceutically active agent where esterification may subsequently be carried out so long as the modification does not interfere with the pharmaceutically active agent’s biological activity or effect.
  • the compounds used in the method of the present invention may be in a salt form.
  • a “salt” is a salt of the instant compounds which has been modified by making acid or base salts of the compounds.
  • the salt is pharmaceutically acceptable.
  • pharmaceutically acceptable salts include, but are not limited to, mineral or organic acid salts of basic residues such as amines; alkali or organic salts of acidic residues such as phenols.
  • the salts can be made using an organic or inorganic acid.
  • Such acid salts are chlorides, bromides, sulfates, nitrates, phosphates, sulfonates, formates, tartrates, maleates, malates, citrates, benzoates, salicylates, ascorbates, and the like.
  • Phenolate salts are the alkaline earth metal salts, sodium, potassium or lithium.
  • pharmaceutically acceptable salt in this respect, refers to the relatively non-toxic, inorganic and organic acid or base addition salts of compounds of the present invention.
  • salts can be prepared in situ during the final isolation and purification of the compounds of the invention, or by separately reacting a purified compound of the invention in its free base or free acid form with a suitable organic or inorganic acid or base, and isolating the salt thus formed.
  • Representative salts include the hydrobromide, hydrochloride, sulfate, bisulfate, phosphate, nitrate, acetate, valerate, oleate, palmitate, stearate, laurate, benzoate, lactate, phosphate, tosylate, citrate, maleate, fumarate, succinate, tartrate, napthylate, mesylate, glucoheptonate, lactobionate, and laurylsulphonate salts and the like. (See, e.g., Berge et al. (1977) "Pharmaceutical Salts", J. Pharm. Sci.66:1-19).
  • the compounds of the present invention may also form salts with basic amino acids such a lysine, arginine, etc. and with basic sugars such as N-methylglucamine, 2-amino-2-deoxyglucose, etc. and any other physiologically non-toxic basic substance.
  • “administering” an agent may be performed using any of the various methods or delivery systems well known to those skilled in the art.
  • the administering can be performed, for example, orally, parenterally, intraperitoneally, intravenously, intraarterially, transdermally, sublingually, intramuscularly, rectally, transbuccally, intranasally, liposomally, via inhalation, vaginally, intraoccularly, via local delivery, subcutaneously, intraadiposally, intraarticularly, intrathecally, into a cerebral ventricle, intraventicularly, intratumorally, into cerebral parenchyma or intraparenchchymally.
  • the compounds used in the method of the present invention may be administered in various forms, including those detailed herein.
  • the treatment with the compound may be a component of a combination therapy or an adjunct therapy, i.e.
  • a "pharmaceutically acceptable carrier” is a pharmaceutically acceptable solvent, suspending agent or vehicle, for delivering the instant compounds to the animal or human.
  • the carrier may be liquid or solid and is selected with the planned manner of administration in mind.
  • Liposomes are also a pharmaceutically acceptable carrier as are slow-release vehicles.
  • a dosage unit of the compounds used in the method of the present invention may comprise a single compound or mixtures thereof with additional antitumor agents.
  • the compounds can be administered in oral dosage forms as tablets, capsules, pills, powders, granules, elixirs, tinctures, suspensions, syrups, and emulsions.
  • the compounds may also be administered in intravenous (bolus or infusion), intraperitoneal, subcutaneous, or intramuscular form, or introduced directly, e.g. by injection, topical application, or other methods, into or topically onto a site of disease or lesion, all using dosage forms well known to those of ordinary skill in the pharmaceutical arts.
  • the compounds used in the method of the present invention can be administered in admixture with suitable pharmaceutical diluents, extenders, excipients, or in carriers such as the novel programmable sustained-release multi-compartmental nanospheres (collectively referred to herein as a pharmaceutically acceptable carrier) suitably selected with respect to the intended form of administration and as consistent with conventional pharmaceutical practices.
  • the unit will be in a form suitable for oral, nasal, rectal, topical, intravenous or direct injection or parenteral administration.
  • the compounds can be administered alone or mixed with a pharmaceutically acceptable carrier.
  • This carrier can be a solid or liquid, and the type of carrier is generally chosen based on the type of administration being used.
  • the active agent can be co-administered in the form of a tablet or capsule, liposome, as an agglomerated powder or in a liquid form.
  • suitable solid carriers include lactose, sucrose, gelatin and agar. Capsule or tablets can be easily formulated and can be made easy to swallow or chew; other solid forms include granules, and bulk powders.
  • Tablets may contain suitable binders, lubricants, diluents, disintegrating agents, coloring agents, flavoring agents, flow-inducing agents, and melting agents.
  • suitable liquid dosage forms include solutions or suspensions in water, pharmaceutically acceptable fats and oils, alcohols or other organic solvents, including esters, emulsions, syrups or elixirs, suspensions, solutions and/or suspensions reconstituted from non-effervescent granules and effervescent preparations reconstituted from effervescent granules.
  • Such liquid dosage forms may contain, for example, suitable solvents, preservatives, emulsifying agents, suspending agents, diluents, sweeteners, thickeners, and melting agents.
  • Oral dosage forms optionally contain flavorants and coloring agents.
  • Parenteral and intravenous forms may also include minerals and other materials to make them compatible with the type of injection or delivery system chosen.
  • Techniques and compositions for making dosage forms useful in the present invention are described in the following references: 7 Modern Pharmaceutics, Chapters 9 and 10 (Banker & Rhodes, Editors, 1979); Pharmaceutical Dosage Forms: Tablets (Lieberman et al., 1981); Ansel, Introduction to Pharmaceutical Dosage Forms 2nd Edition (1976); Remington's Pharmaceutical Sciences, 17th ed. (Mack Publishing Company, Easton, Pa., 1985); Advances in Pharmaceutical Sciences (David Ganderton, Trevor Jones, Eds., 1992); Advances in Pharmaceutical Sciences Vol. 7.
  • Tablets may contain suitable binders, lubricants, disintegrating agents, coloring agents, flavoring agents, flow-inducing agents, and melting agents.
  • the active drug component can be combined with an oral, non-toxic, pharmaceutically acceptable, inert carrier such as lactose, gelatin, agar, starch, sucrose, glucose, methyl cellulose, magnesium stearate, dicalcium phosphate, calcium sulfate, mannitol, sorbitol and the like.
  • Suitable binders include starch, gelatin, natural sugars such as glucose or beta-lactose, corn sweeteners, natural and synthetic gums such as acacia, tragacanth, or sodium alginate, carboxymethylcellulose, polyethylene glycol, waxes, and the like.
  • Lubricants used in these dosage forms include sodium oleate, sodium stearate, magnesium stearate, sodium benzoate, sodium acetate, sodium chloride, and the like.
  • Disintegrators include, without limitation, starch, methyl cellulose, agar, bentonite, xanthan gum, and the like.
  • the compounds used in the method of the present invention may also be administered in the form of liposome delivery systems, such as small unilamellar vesicles, large unilamellar vesicles, and multilamellar vesicles.
  • Liposomes can be formed from a variety of phospholipids such as lecithin, sphingomyelin, proteolipids, protein-encapsulated vesicles or from cholesterol, stearylamine, or phosphatidylcholines.
  • the compounds may be administered as components of tissue-targeted emulsions.
  • the compounds used in the method of the present invention may also be coupled to soluble polymers as targetable drug carriers or as a prodrug.
  • Such polymers include polyvinylpyrrolidone, pyran copolymer, polyhydroxylpropylmethacrylamide-phenol, polyhydroxyethylasparta-midephenol, or polyethyleneoxide-polylysine substituted with palmitoyl residues.
  • the compounds may be coupled to a class of biodegradable polymers useful in achieving controlled release of a drug, for example, polylactic acid, polyglycolic acid, copolymers of polylactic and polyglycolic acid, polyepsilon caprolactone, polyhydroxy butyric acid, polyorthoesters, polyacetals, polydihydropyrans, polycyanoacylates, and crosslinked or amphipathic block copolymers of hydrogels.
  • Gelatin capsules may contain the active ingredient compounds and powdered carriers, such as lactose, starch, cellulose derivatives, magnesium stearate, stearic acid, and the like. Similar diluents can be used to make compressed tablets. Both tablets and capsules can be manufactured as immediate release products or as sustained release products to provide for continuous release of medication over a period of hours. Compressed tablets can be sugar-coated or film-coated to mask any unpleasant taste and protect the tablet from the atmosphere, or enteric coated for selective disintegration in the gastrointestinal tract. [1246] For oral administration in liquid dosage form, the oral drug components are combined with any oral, non-toxic, pharmaceutically acceptable inert carrier such as ethanol, glycerol, water, and the like.
  • any oral, non-toxic, pharmaceutically acceptable inert carrier such as ethanol, glycerol, water, and the like.
  • liquid dosage forms examples include solutions or suspensions in water, pharmaceutically acceptable fats and oils, alcohols or other organic solvents, including esters, emulsions, syrups or elixirs, suspensions, solutions and/or suspensions reconstituted from non-effervescent granules and effervescent preparations reconstituted from effervescent granules.
  • Such liquid dosage forms may contain, for example, suitable solvents, preservatives, emulsifying agents, suspending agents, diluents, sweeteners, thickeners, and melting agents.
  • Liquid dosage forms for oral administration can contain coloring and flavoring to increase patient acceptance.
  • parenteral solutions In general, water, asuitable oil, saline, aqueous dextrose (glucose), and related sugar solutions and glycols such as propylene glycol or polyethylene glycols are suitable carriers for parenteral solutions.
  • Solutions for parenteral administration preferably contain a water soluble salt of the active ingredient, suitable stabilizing agents, and if necessary, buffer substances.
  • Antioxidizing agents such as sodium bisulfite, sodium sulfite, or ascorbic acid, either alone or combined, are suitable stabilizing agents.
  • citric acid and its salts and sodium EDTA are also used.
  • parenteral solutions can contain preservatives, such as benzalkonium chloride, methyl- or propyl-paraben, and chlorobutanol.
  • Suitable pharmaceutical carriers are described in Remington's Pharmaceutical Sciences, Mack Publishing Company, a standard reference text in this field.
  • the compounds used in the method of the present invention may also be administered in intranasal form via use of suitable intranasal vehicles, or via transdermal routes, using those forms of transdermal skin patches well known to those of ordinary skill in that art.
  • the dosage administration will generally be continuous rather than intermittent throughout the dosage regimen.
  • Parenteral and intravenous forms may also include minerals and other materials such as solutol and/or ethanol to make them compatible with the type of injection or delivery system chosen.
  • the compounds and compositions of the present invention can be administered in oral dosage forms as tablets, capsules, pills, powders, granules, elixirs, tinctures, suspensions, syrups, and emulsions.
  • the compounds may also be administered in intravenous (bolus or infusion), intraperitoneal, subcutaneous, or intramuscular form, or introduced directly, e.g. by topical administration, injection or other methods, to the afflicted area, such as a wound, including ulcers of the skin, all using dosage forms well known to those of ordinary skill in the pharmaceutical arts.
  • Specific examples of pharmaceutically acceptable carriers and excipients that may be used to formulate oral dosage forms of the present invention are described in U.S. Pat. No.
  • the active ingredient can be administered orally in solid dosage forms, such as capsules, tablets, powders, and chewing gum; or in liquid dosage forms, such as elixirs, syrups, and suspensions, including, but not limited to, mouthwash and toothpaste. It can also be administered parentally, in sterile liquid dosage forms.
  • Solid dosage forms, such as capsules and tablets, may be enteric-coated to prevent release of the active ingredient compounds before they reach the small intestine.
  • Materials that may be used as enteric coatings include, but are not limited to, sugars, fatty acids, proteinaceous substances such as gelatin, waxes, shellac, cellulose acetate phthalate (CAP), methyl acrylate-methacrylic acid copolymers, cellulose acetate succinate, hydroxy propyl methyl cellulose phthalate, hydroxy propyl methyl cellulose acetate succinate (hypromellose acetate succinate), polyvinyl acetate phthalate (PVAP), and methyl methacrylate- methacrylic acid copolymers.
  • CAP cellulose acetate phthalate
  • PVAP polyvinyl acetate phthalate
  • the compounds and compositions of the invention can be coated onto stents for temporary or permanent implantation into the cardiovascular system of a subject.
  • the in vivo profile of the ligands in pre-targeting strategy were evaluated with using a CB7-modified carcinoembryonic antigen (CEA) targeting humanized full-length antibody (CB7-M5A) as the secondary pre-targeting agent.
  • CEA carcinoembryonic antigen
  • CB7-M5A humanized full-length antibody
  • the pre- targeting studies were performed in CEA+ and CEA- human pancreatic cancer mouse xenografts.
  • the biodistribution of the pre-targeted Adma-radioligand was compared to that of a zirconium-89-labeled directly radiolabeled antibody.
  • the dosimetry of the two antibody-based imaging approaches were compared.
  • t-BOC-N-Amido-PEG3-Amine and t-Boc-N-amido-PEG7-amine were acquired from BroadPharm.
  • the cucurbit[7]uril-azide (CB7-N 3 ) was synthesized by the Chemical Synthesis Core of Vanderbilt University, Tennessee USA.
  • the M5A (hT84.66-M5A) antibody was received from Dr. Yazaki at City of Hope, California USA.
  • the [ 89 Zr]Zr(C 2 O 4 ) 2 and [ 64 Cu]CuCl 2 were purchased from Washington University School of Medicine MIR Cyclotron Facility. All cell culturing media solutions were purchased from VWR International unless mentioned otherwise.
  • reagents for the SDS PAGE and Western Blotting were purchased from ThermoFisher Scientific.
  • PBS7.4 solution was prepared from phosphate buffered saline powder pH 7.4.
  • INSTRUMENTS [1263] 4-9 were purified with a reverse phase (RP) HPLC set up including an Agilent HPLC 1260 Infinity II LC System comprised of a 1260 Quat Pump VL, 1260 DAD WR and LabLogic Flow-RAM radio-HPLC Detector equipped with a LabLogic Systems Limited NaI Detector with a Luna 5 ⁇ m C18(2) 100 ⁇ LC column 250 ⁇ 10 mm (Phenomenex) column.
  • RP reverse phase
  • the chemical purity of 5, 7, 9 and the radiochemical purity of 1-3 were measured with the same HPLC instrument using a Kinetex 5 ⁇ m EVO C18100 ⁇ column, 150 ⁇ 4.6 mm (Phenomenex) analytical column.
  • the radiochemical purity of [ 89 Zr]Zr-DFO-M5A was analyzed with BioScan AR-2000 radio-TLC scanner.
  • the quality control of CB7-M5A and DFO-M5A was performed with BioRad NGC-Chormatography System including SystemPump10 and Multi UV/Vis- Conductivity detector using a Superdex 200 Increase 10/300GL Cytiva size exclusion column (SEC).
  • the radioactivity of log D, blood half-life, cell internalization and in vivo biodistribution samples were measured with Hidex Automatic Gamma Counter.
  • the radioactivity of the radiotracer doses was measured with a CRC-55tR Capintec Inc dose calibrator.4-9 were characterized with a 500 MHz Bruker Avance III proton nuclear magnetic resonance spectroscopy and Q-Exactive HF (Thermo-Fisher) Orbi-trap mass spectrometer high-resolution mass spectrometry instrument.
  • the % solvent B remained at 5 the first minute of the run followed by gradient from 5 to 95 over 17 minutes using a 1 mL/min flow rate.
  • the final RP HPLC method was used to analyze the in vitro plasma stability samples of 1-3.
  • the solvent A and B were H 2 O and acetonitrile.
  • the % of solvent B remained at 0 for the first 5 minutes of the run.
  • the solvent B% was increased to 95 over a 15-minute gradient.
  • the FPLC – size exclusion method used to analyze the purity of the CB7-M5A and DFO-M5A involved the use of PBS7.4 as the only solvent over a 70-minute period with a flow rate of 0.7 mL/min.
  • the water phase was extracted with diethyl ether (3 ⁇ 40 mL) followed by combining and evaporating the diethyl ether phases to yield oily material.
  • Iodomethane (30 mL) and sodium hydroxide (119 mg; 2.98 mmol; 1.6 eq.) were added to the reaction vial.
  • the methylation reaction was stirred for 2 hours, which was followed by evaporating the iodomethane and adding fresh iodomethane which was repeated once more.
  • the solvent was evaporated and replaced with dichloromethane. Undissolved sodium hydroxide was filtered out and the dichloromethane evaporated.
  • the crude product NBOC-Adma material was dissolved in acetonitrile (7 mL).
  • MIAPaCa-2 human pancreatic carcinoma cells were grown in DMEM/High glucose medium containing 4mM L-glutamine, 4.5 g/L glucose, and sodium pyruvate, 1% (vol/vol) Penicillin-Streptomycin,10% (vol/vol) fetal bovine serum and 2.5% (vol/vol) Horse Serum (donor herd) (Sigma-Aldrich). Both cells were kept in a 37 °C environment containing 5% CO 2 and extracted using 0.25% Trypsin-EDTA. [1295] ANIMALS [1296] All animals were female nude mice (NU/NU Charles River). The mice were housed in static microisolator caging with corn cob bedding (The Anderson Bed-o’Cobs 1/8”).
  • mice were housed in 12-hour light/dark cycles. The mice were maintained in maximum isolation rooms, which are health monitored quarterly for pathogens and ecto/endo parasites quarterly.
  • xenografts the mice were injected subcutaneously with BxPC3 or MIAPaCa-2 cells (5-6 ⁇ 10 6 cells in respective media and matrigel, 1:1 %V/V; 150 ⁇ L). The mice were used once the tumor volume reached ⁇ 100 mm 3 which occurred 5-6 weeks after implantation of the xenografts. All experiments involving laboratory animals were performed in accordance with Institutional Animal Care and Use Committee at Stony Brook Medicine.
  • each radioligand’s percental fast (t 1/2fast ) and slow phase (t 1/2slow ) values were used to calculate the radioligand’s weighted blood half-life with equation one.
  • ⁇ ⁇ ⁇ / ⁇ ⁇ / ⁇ ⁇ % ⁇ ( ⁇ / ⁇ ⁇ % ⁇ ) ⁇ ⁇ (1)
  • the tubes were weighed and counted on a gamma counter to determine the %ID/g value of each sample.
  • Table 3 The %ID/g of collected urine samples in healthy nude female mice. 20 min post injection of 2 60 min post injection of 2 %ID/g (urine) 1047 ⁇ 454 [1304] WESTERN BLOTTING FOR CARCINOEMBRYONIC ANTIGEN [1305] The cell lysates for BxPC3 and MIAPaCa-2 were obtained by incubating the cells with the Cell Lysis Buffer II containing PMSF protease inhibitor and HaltTM Protease inhibitor cocktail. Protein quantification was performed with Pierce TM BCA Protein Assay Kit.
  • the protein lysates were prepared in NuPAGE LDS Sample buffer. Each protein sample (20 ⁇ g) was separated by SDS-PAGE using a NuPAGETM 4 to 12%, Bis-Tris, 1.0–1.5 mm, Mini Protein Gels at 100V for 15 minutes followed by an increase to 150V for an additional 60 minutes. Proteins were transferred electrophoretically onto Invitrolon TM PVDF/Filter Paper Sandwiches at 100 V for 60 minutes. Membranes were blocked in 5% Non- Fat Dry Milk prepared in TBS Tween TM 20 Buffer for 1 hour and incubated with the primary antibodies overnight at 4°C.
  • the primary antibodies used were CEA Monoclonal Antibody (H.426.3) (ThermoFisher Scientific), beta Tubulin Loading Control Monoclonal Antibody (BT7R) (ThermoFisher Scinetific) and the hT84.66-M5A.
  • the membranes were washed with TBS Tween TM 20 Buffer followed by incubation with the respective secondary antibodies (Goat anti-Mouse IgG (H+L), Superclonal Recombinant Secondary Antibody, HRP and Goat anti-human IgG FC Antibody, Horseradish Peroxidase HRP conjugate, cross absorbed) at room temperature for 1 hour.
  • the imaging was performed on a small animal Siemens Inveon PET/CT. Data from all possible lines of response (LOR) were saved in the list mode raw data format. The raw data was then binned into 3D sinograms with a span of 3 and ring difference of 79. The images were reconstructed into transaxial slices (128 x 128 x 159) with voxel sizes of 0.800000 x 0.800000 x 0.7999150 mm 3 , using the MAP algorithm with 16 subsets and 18 iterations at a beta value of 0.00427838.
  • the labeling reaction yield was checked with radio thin layer chromatography (radio-TLC) scanner using iTLC-SG- Glass microfiber chromatography paper and 50 mM ethylenediaminetetraacetic acid as the mobile phase.
  • the synthesized [ 89 Zr]Zr-DFO-M5A was purified with a PD10 desalting column using PBS as the elution buffer.
  • the radiochemical purity of the purified product was determined using the previously described radio-TLC method.
  • the mixture was stirred on a thermomixer for 10 minutes (900 rpm) at room temperature followed by centrifuging the sample for 5 minutes (1000 rcf).200 ⁇ L of each phase was transferred, and the samples were weighed and counted on a gamma counter to determine the relative amount of radioactivity in each phase.
  • the cohorts were euthanized for in vivo biodistribution 4, 8 or 24 h post radioligand injection and the 24h cohort was also imaged with a small animal PET/computer tomography (PET/CT) scanner (Siemens Inveon) at 4, 8 and 24 h post radioligand injection prior to euthanasia.
  • PET/CT PET/computer tomography
  • An additional cohort/timepoint for pretargeted 2 was assigned, which was euthanized 2 h post radioligand injection for dosimetry calculations.
  • a cohort of BxPC3 and MIAPaCa-2 tumor bearing female nude mice (n 4/cohort) were injected intravenously with [ 89 Zr]Zr-DFO-M5A (0.7 nmol; 100 ⁇ g; 2.3-3.4 MBq in 200 ⁇ L in PBS). The mice were imaged with a small animal PET/CT scanner 72 h post injection followed by in vivo biodistribution.
  • mice Pretargeting with 2 in MIAPaCa-2 xenografts
  • the mice were imaged with a small animal PET/CT scanner 24 h post radioligand injection, followed by in vivo biodistribution.
  • the dosimetry of pretargeted 2 [1340] The estimated dosimetry of the pretargeted 2 in an adult human male (70 kg) was calculated based on the in vivo biodistribution of the pretargeted 2 in BxPC3 tumor bearing mice. The biodistribution data was fitted using a linear interpolation between time points. The linear function of each organ was used to interpolate the concentration at intervals of 1 h to give a better estimate of the kinetics. The integration time was extended 48 h with the assumption that the %ID/organ was constant after the first 24 h and the only change in concentration between 24 and 48 h was due to radioactive decay. A trapezoidal approximation was then used to obtain the integral over the time intervals.
  • M5A demonstrated high specificity towards the CEA, which was validated with in vivo experiment with directly labeled M5A ([ 89 Zr]Zr-DFO-M5A) and pretargeted 2 in CEA-positive (BxPC3) and CEA-negative (MIAPaCa-2) tumor bearing mice.
  • Figure 5 Both imaging experiments in the two tumor models showed that the high specificity and excellent tumor-to-background signal which antibody- based imaging provides is not lost when the antibody imaging is done with the CB7-Adma pretargeting strategy.
  • the present invention describes the development and characterization of three Adma- radioligands for CB7-Adma host-guest pretargeted PET.
  • the use of copper-64-labeled Adma radioligand along with a CB7-modified anti-CEA full-length antibody as the pretargeting agent pair for pretargeted PET in BxPC3 tumor bearing nude mice resulted in high, long remaining target uptake of the radioligand.
  • the total body radiation dose of the pretargeting strategy was only 3.3% of that of the directly zirconium- 89-labeled hT84.66-M5A.
  • the cucurbit[7]uril-adamantane strategy is highly suitable for pretargeted positron emission tomography.
  • the exceptional stability of the pretargeting agents and the specific and high tumor uptake of the pretargeted adamantane radioligands provides great potential for the platform.
  • Cyclodextrins promising scaffolds for MRI contrast agents.
  • Strebl MG Yang J, Isaacs L, Hooker JM.
  • Adamantane/Cucurbituril A Potential Pretargeted Imaging Strategy in Immuno-PET. Mol Imaging.2018;17:1536012118799838. 10.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Optics & Photonics (AREA)
  • Physics & Mathematics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Immunology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Molecular Biology (AREA)
  • Biophysics (AREA)
  • Dispersion Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)

Abstract

La présente invention concerne un composé ayant la structure : ou un sel ou un ester de ce dernier.
PCT/US2023/073725 2022-09-09 2023-09-08 Composition radionucléidique et procédé d'utilisation associée pour la détection de cellules tumorales Ceased WO2024054972A2 (fr)

Priority Applications (7)

Application Number Priority Date Filing Date Title
CN202380075881.0A CN120129539A (zh) 2022-09-09 2023-09-08 放射性核素组合物及其用于检测肿瘤细胞的方法
EP23864036.1A EP4583928A2 (fr) 2022-09-09 2023-09-08 Composition radionucléidique et procédé d'utilisation associée pour la détection de cellules tumorales
CA3266257A CA3266257A1 (fr) 2022-09-09 2023-09-08 Composition radionucléidique et procédé d'utilisation associée pour la détection de cellules tumorales
AU2023338487A AU2023338487A1 (en) 2022-09-09 2023-09-08 Radionuclide composition and method of using same for detection of tumor cells
JP2025514746A JP2025530298A (ja) 2022-09-09 2023-09-08 腫瘍細胞の検出のための放射性核種組成物及びその使用方法
KR1020257010933A KR20250065366A (ko) 2022-09-09 2023-09-08 방사성핵종 조성물 및 이를 이용한 종양세포 검출 방법
IL319424A IL319424A (en) 2022-09-09 2023-09-08 Compounds containing radionucleotides and their use for detecting cancer cells

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US202263375159P 2022-09-09 2022-09-09
US63/375,159 2022-09-09
US202363481517P 2023-01-25 2023-01-25
US63/481,517 2023-01-25

Publications (2)

Publication Number Publication Date
WO2024054972A2 true WO2024054972A2 (fr) 2024-03-14
WO2024054972A3 WO2024054972A3 (fr) 2024-04-18

Family

ID=90191967

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2023/073725 Ceased WO2024054972A2 (fr) 2022-09-09 2023-09-08 Composition radionucléidique et procédé d'utilisation associée pour la détection de cellules tumorales

Country Status (8)

Country Link
EP (1) EP4583928A2 (fr)
JP (1) JP2025530298A (fr)
KR (1) KR20250065366A (fr)
CN (1) CN120129539A (fr)
AU (1) AU2023338487A1 (fr)
CA (1) CA3266257A1 (fr)
IL (1) IL319424A (fr)
WO (1) WO2024054972A2 (fr)

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20160331852A1 (en) * 2015-05-11 2016-11-17 Memorial Sloan Kettering Cancer Center Radioligands for pretargeted pet imaging and methods of their therapeutic use
WO2019195890A1 (fr) * 2018-04-11 2019-10-17 Clarity Pharmaceuticals Pty Ltd Formulations et kits pour radiothérapie et imagerie diagnostique

Also Published As

Publication number Publication date
WO2024054972A3 (fr) 2024-04-18
JP2025530298A (ja) 2025-09-11
IL319424A (en) 2025-05-01
CN120129539A (zh) 2025-06-10
CA3266257A1 (fr) 2024-03-14
AU2023338487A1 (en) 2025-03-20
EP4583928A2 (fr) 2025-07-16
KR20250065366A (ko) 2025-05-12

Similar Documents

Publication Publication Date Title
JP7304588B2 (ja) Ｐｓｍａを標的としたイメージング及び放射線治療のための金属／放射性金属標識ｐｓｍａ阻害剤
CN111991570B (zh) 一种FAP-α特异性肿瘤诊断SPECT显像剂
CN111511408A (zh) 靶向成纤维细胞活化蛋白-α(FAP-α)的成像剂及放射治疗剂
ES2844586T3 (es) Inhibidores del antígeno prostático específico de membrana (PSMA) etiquetados con 18F y su uso como agentes de obtención de imágenes para el cáncer de próstata
KR20230165818A (ko) 섬유아세포 활성화 단백질 알파 및/또는 전립선-특이적 막 항원을 표적화하는 이종이가 및 동형이가 제제
CN118146170A (zh) 用于前列腺癌的腔内放射疗法的前列腺特异性膜抗原靶向的高亲和力剂
BR112019023246B1 (pt) Compostos compreendendo uma fração quelante, métodos para produção dos mesmos e usos dos mesmos
CN109476655B (zh) 靶向碳酸酐酶ix的核成像剂和放射治疗剂及其用途
US20250025582A1 (en) Ligands and their use
Zhou et al. Synthesis and preclinical evaluation of novel 18F-labeled fibroblast activation protein tracers for positron emission tomography imaging of cancer-associated fibroblasts
CN115745903B (zh) 一种肽脲素衍生物、含其的药物组合物及其应用
Chaudhary et al. Design, development and bio-evaluation of a novel radio-ligand 99mTc-THQ-DTPA as a sigma 2 receptor specific breast tumor imaging agent
CN110172084A (zh) 68Ga标记NODAGA修饰c-Met分子探针及制备与应用
Liu et al. Synthesis of novel DOTA-/AAZTA-based bifunctional chelators: Solution thermodynamics, peptidomimetic conjugation, and radiopharmaceutical evaluation
WO2024054972A2 (fr) Composition radionucléidique et procédé d'utilisation associée pour la détection de cellules tumorales
Feng et al. Development of a novel 99mTc-labeled folate derivative containing phenyl isonitrile to target folate receptor with reduced renal uptake
US20250339568A1 (en) Precursor and radiotracer for neuroendocrine theranostics
CN117430537A (zh) 用于诊断或治疗表达前列腺特异性膜抗原肿瘤的新型核素标记巯基衍生物及其应用
WO2020045638A1 (fr) Composé dérivé d'imidazothiadiazole radioactif
HK40099290A (zh) 配体及其用途
WO2026055371A2 (fr) Composition à teneur en radionucléides et son procédé d'utilisation pour la détection de cellules tumorales
HK40094491A (zh) 靶向成纤维细胞活化蛋白α的化合物、药物组合物及用途
JP2026513316A (ja) 環状ポリペプチド系化合物、及びその使用

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 23864036

Country of ref document: EP

Kind code of ref document: A2

WWE Wipo information: entry into national phase

Ref document number: AU2023338487

Country of ref document: AU

WWE Wipo information: entry into national phase

Ref document number: 319424

Country of ref document: IL

ENP Entry into the national phase

Ref document number: 2025514746

Country of ref document: JP

Kind code of ref document: A

WWE Wipo information: entry into national phase

Ref document number: 2025514746

Country of ref document: JP

ENP Entry into the national phase

Ref document number: 2023338487

Country of ref document: AU

Date of ref document: 20230908

Kind code of ref document: A

WWE Wipo information: entry into national phase

Ref document number: 11202501334W

Country of ref document: SG

WWP Wipo information: published in national office

Ref document number: 11202501334W

Country of ref document: SG

ENP Entry into the national phase

Ref document number: 20257010933

Country of ref document: KR

Kind code of ref document: A

WWE Wipo information: entry into national phase

Ref document number: 1020257010933

Country of ref document: KR

WWE Wipo information: entry into national phase

Ref document number: 2023864036

Country of ref document: EP

NENP Non-entry into the national phase

Ref country code: DE

ENP Entry into the national phase

Ref document number: 2023864036

Country of ref document: EP

Effective date: 20250409

WWE Wipo information: entry into national phase

Ref document number: 202380075881.0

Country of ref document: CN

121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 23864036

Country of ref document: EP

Kind code of ref document: A2

WWP Wipo information: published in national office

Ref document number: 202380075881.0

Country of ref document: CN

WWP Wipo information: published in national office

Ref document number: 2023864036

Country of ref document: EP