JPS584061B2 - Block copolymer metal complex - Google Patents

Description

Detailed Description of the Invention The present invention relates to a block copolymer metal complex, particularly a block formed by covalently bonding the hydrophobic block portion of a hydrophilic-hydrophobic-hydrophilic ternary block copolymer with a tetrapyrrole metal complex. Regarding copolymer metal complex E.

Conventionally, several types of polymer metal complexes in which a tetrapyrrole metal complex faces a polymer are known, but this is especially true when performing reactions such as oxygen adsorption and desorption in an aqueous solution. Molecular metal complexes have poor water solubility and cannot be used.

On the other hand, Angew, Chem, Int, Dd, Dngl
, 16, 117 (1977) and West German Patent Application No. 2645079 (discloses a water-soluble polymeric metal complex in which iron protoporphyrin or its derivative is bonded to glycine-esterified polyethylene glycol at both ends). However, although this substance can bind oxygen,
Since the active center is in easy contact with water, oxidation of the center m(I) immediately occurs as shown in the formula below, and the catalytic ability is lost.

(In the above formula, L is an axial particle such as pyridine or imidazole, and porphyrin is a porphyrin.) This invention was made in view of the above circumstances, and it improves water solubility in the hydrophilic block part of the ternary block copolymer. The block copolymer metal is designed to give a hydrophobic block and the central hydrophobic block {this tetrapyrrole-based metal complex is introduced by covalent bond and placed in a hydrophobic field so that side reactions such as those shown in Formula 1 do not occur}. The purpose is to provide complexes.

According to this invention 1, the general formula (where A is a hydrophilic polymer chain, A-00C- is an ester bond, B is a hydrophobic polymer chain represented by the formula, X, Y are hydrogen,
or hydrocarbon group 21 without mobile hydrogen, AR1 is hydrogen or methyl group AR2 is a C3 or higher alkyl group, X
2 is -CONH{-CH2CH2-}, NH-, n is 1
, 2 or 3, and X and y each unit P is a group VIB of the fourth to sixth period of the periodic table as a central metal,
A metal complex of a macrocyclic tetradentate ligand having a metal ion selected from the metals belonging to Group ■B, Group ■, Group IB and Group nB], and a is 0 or 1). A block copolymer metal complex is provided.

To obtain the block copolymer of the present invention, a primary or secondary amine group-containing styrenic compound represented by the formula (where AX is as described above) and a styrene compound having the formula (where Y is as described above) are combined. ), or a primary amine group-containing vinyl compound represented by the formula (where AR1 and meth)acrylamide-based compound in an oxygen-free atmosphere [Thus, a hydrophobic polymer chain is first produced.

This radical polymerization is carried out under ultraviolet irradiation using a disulfide compound represented by the formula (where a is as described above) as an initiator.

Then, the disulfide compound represented by formula 6 is expressed by the following formula Generate radicals according to the formula or A hydrophobic polymer chain with functionalities at both ends is obtained.

Although the above radical polymerization is carried out without a solvent in most cases, it may be carried out under dilution with an inert organic solvent such as benzene, tetrahydrofuran (THF), or dioxane.

However, if an organic solvent is used or the compound represented by formula (2) A formula (3) A formula (4) or formula (5) is
) The average molecular weight of the obtained product (formula 7 or 8) decreases when the relative proportion of the disulfide compound represented by 20℃ to 30℃,
The amount of ultraviolet rays irradiated is 0.1 to 1 mW/i on the surface of a quartz polymer tube commonly used for polymerization.

The compound represented by the formula 3 used in the above radical polymerization is a general α-olefin having no mobile hydrogen,
Preferred examples include styrene, p-(or m-)alkyloxystyrene (e.g. p-methoxystyrene, p-ethoxystyrene), p(or m-)vinylbenzyl alkyl ether (e.g. p-vinylbenzyl methyl ether, p-vinylbenzyloctyl ether), p-(or m-)acylaminostyrene (
For example, p-acetylaminostyrene, p-butylaminostyrene) p-1: or m-) vinylbenzylacylamine (e.g. p-vinylbenzylacetylamine, p-vinylbenzylpropionylamine), ■-pentene, ■ -hexene, alkyl vinyl ethers (eg, ethyl vinyl ether A butyl vinyl ether), and the like.

Moreover, it is preferable that the compound R2 represented by Formula 5 has up to 8 carbon atoms.

In addition, X in formula 7 or formula 8 is usually 1 molar or more 5
The molar ratio is below 0, preferably around 10 molar.

The end chains of the hydrophobic polymer with both terminal functionalities represented by formula 7 or formula 8 obtained as described above are mixed with a mineral acid by passing hydrogen chloride gas etc. into an inert organic solvent such as benzene, tetrahydrofuran or dioxane. Formula A-OH (where A
(as described above), a triblock copolymer represented by the formula or is obtained by demethanol condensation.

The hydroxy-containing hydrophilic polymer chain used in the above condensation reaction preferably has substantially no mobile hydrogen other than the hydrogen of the 10H group; examples thereof include polyethylene glycol, dextran, and hydroxyl. These include ethyl scooch, dextrin, amylose, pectin, and cyclodextrin.

The above condensation reaction is carried out at a ratio of about 2.2 chains of the hydroxy-containing hydrophilic polymer per chain of the functional polymer at both ends, and at a temperature of 80°C to 120°C under reflux of the boiling point of the solvent for 24 hours to 96 hours. Ask questions.

The solubility of the above block copolymer in water depends on the molecular weight and structure of each block part, but the highest water solubility is when polyethylene 4 ethylene oxide is used as the hydrophilic block part.
Reducing the molecular weight of the hydrophobic block improves water solubility.

However, even if it is a highly hydrophobic unit such as ¥210, if the molecular weight of the hydrophobic block portion is less than 1000, it will not constitute a sufficiently hard polymeric micelle, and the gist of the invention will not be met.

The molecular weight of the hydrophobic block portion is usually 2,000 or more, preferably about 4,000.

If the molecular weight of the hydrophobic block portion is increased so as not to impair water solubility, the molecular weight of the hydrophilic block portion must also be sufficiently increased.

When the hydrophobic block part is 5 parts by weight, the total hydrophilic block part is preferably 95 parts by weight or more.

Due to the manufacturing method, the above-mentioned triblock copolymer may be contaminated with unreacted hydrophobic block portions, hydrophilic block portions, and diblock copolymers in which only one terminal has reacted.

Further, during synthesis, since the hydrophilic block part is charged at a ratio of about 2.2 chains to 1 chain of the hydrophobic block part, an excess of 0.2 chains of the hydrophilic block part is necessarily mixed.

Separate these using ASephadex LH-2
It is sufficient to pass through a gel column such as No. 0, and unreacted hydrophobic block parts and diblock copolymers can be removed by this.

The hydrophilic block cannot be separated if its molecular weight is sufficiently large.

However, even if some hydrophilic block moiety is mixed into the triblock copolymer, this does not impair the gist of the present invention, and therefore the triblock copolymer may be treated as a mixture.

The above ternary block copolymer and a metal complex of a carboxyl group-containing macrocyclic tetradentate facet ligand represented by the formula (V) (where T and X are as described above) are combined. Acid anhydride method peptide bonding method using ethyl chloroformate/triethylamine as an activator in a solvent such as dimethylformamide (DMF)} When reacted in this way, the amine group of the hydrophobic block part of the triblock copolymer and The block copolymer metal complex represented by the formula (I) is obtained by forming a covalent bond with the carboxyl group of the metal complex through a dehydration bond.

Usually, the above reaction is carried out using a metal complex in an amount of about 5 times or more by mole relative to the amine group unit of the triblock copolymer.

Usually, the reaction is carried out at around 0°C in the early stage of the reaction, and at room temperature in the latter stage of the reaction.

If the reaction temperature is high and the hydrophilic block portion has a large number of 10H groups, the metal complex reacts with these sites to form an ester bond.

In such cases, use DMF with an appropriate amount of KOH aqueous solution added.
It can be hydrolyzed by treatment for 1 hour.

Examples of metal complexes of the above-mentioned carboxyl group-containing macrocyclic tetradentate planar ligands include tetrapyrrole metal complexes such as (7) (in each formula, M represents the central metal), phthalocyanine mono- or dicarboxylic acids , metal complexes such as saponified chlorophyll, etc.

The metal complex of formula 9 is commercially available when W is Fe, and when another central metal is required, the desired central metal may be introduced into a commercially available one without M by a known method.

The metal complex of formula 10 is obtained by reacting the metal complex of formula 9 with 1-(3-aminopyr)imidazur and separating the mixture using a silica gel ram.

The metal complex of Formula 11 is obtained by reacting the metal complex of Formula 10 with histidine and separating the mixture using an alumina force ram.

Metal complexes of formulas 12 and 13 are also described in J. Am. Che
m. Soc. , 95, 7868 (1973), can be synthesized by slightly modifying the method described.

From the point of view of oxygen adsorption and desorption, each M is Fe(I), Co(I)
), Ru(I), Mn(I), Cr(I), and Cu
(I) is preferred.

The block copolymer metal complex of the present invention obtained in this way has a macroscopic structure as shown in the formula, where the hydrophilic block portion is represented by 1A and the hydrophobic block portion is represented by 5U, and the tetrapyrrole metal body is represented by 5U. A has a structure and exists in the hydrophobic field of the hard polymer micelle formed by the hydrophobic block part.

The block copolymer metal complex has the above formula (V) and the formula (V
) Which macroscopic structure to adopt depends on the structure of the hydroxy-containing water-soluble polymer chain (A-OH) used.
-OH is the terminal R of polyethylene glycol:,-
When A-0H has OH, it takes the structure of (V), and when A-0H has a side chain -OH, it takes the structure of formula (VD).

As can be seen from the above description, the polymer metal complex of the present invention is of a type in which a metal complex is bonded in a pendant manner to the hydrophobic block portion of a hydrophilic-hydrophobic-hydrophilic ternary block copolymer, and is water-soluble and The metal complex is fixed in the hydrophobic field in the polymer micelle and is protected from water attack, and the interaction of the metal complex allows electron transfer, redox,
Oxygen (advantageous in carrying out catalytic reactions such as acid adsorption and desorption).

In particular, when performing an oxygen adsorption/desorption reaction, it is necessary to protect the central metal from oxidation, ligand exchange reactions, and decomposition of the tetrapyrrole ring due to water attack. The advantage is that these requirements are met by hard polymeric micelles, which exhibit superior properties compared to conventional polymeric metal complexes.

The present invention will be further explained below based on Examples, but first, a synthesis example of a metal complex will be shown.

Synthesis of Metal Complex Synthesis Example 1 10 g of protoporphyrin V ditetrium salt was dissolved in 300 nl of tea-N loloform, and about 5.5 g of phosphorus pentachloride was added thereto, and the mixture was stirred at room temperature for about 1 hour to react.

Add to this 0.8 g of ethanol and 1 m of triethylamine.
100 ml of a chloroform solution in which L3 was dissolved was added dropwise over about 3 hours, and the reaction was further allowed to proceed at room temperature for 2 hours.

After the reaction, the pH was adjusted to 5 liters with triethylamine, 900 ml of chloroform was added, and the mixture was washed 7 times with the same amount of water to separate the layers.

Insoluble components were filtered off, the chloroform layer was separated, 20 g of silica gel powder (80-130 mesh) was added, and the solvent was distilled off under reduced pressure.

Next, a column made with the same silica gel (silica gel 3
609, chloroform/methanol = 20/1) The above silica gel powder was added and developed with a solvent to obtain the second component, protoporphyrin monoethyl ester monocarboxylic acid.

(Yield: 50%, yield: approximately 4.85 g, infrared absorption spectrum ν.

=01740Crrt,1710cn-”).

(B) 3.29% of the monocarboxylic acid obtained in (a) above was dissolved in 150ml of chloroform, cooled to 0°C, and 0.0% of triethylamine was dissolved in 150ml of chloroform. 8 ml and ethyl chloroforme H)
．． 54 ml was added dropwise and stirred for 30 minutes to react.

Add to this 1-(aminopyl)imidazole 0.814
A 10 ml solution of g in chloroform was added thereto, and the mixture was stirred at 0° C. for 1 hour and then at room temperature for 2 hours to react.

This solution was shaken twice with about twice the amount of water, separated, and then 12 g of the same silica gel as above was added to the chloroform layer, and the solvent was distilled off under reduced pressure.

Apply this to a column (silica gel 3.0Q) as described in (a) above.
! , chloroform/methanol-1571), and the reaction product 2.559 (yield 67.5%, infrared absorption spectrum ν) was separated into the second component.

-o1735Crr''1, amide 11650cm-'
, amide No. 1550 crrL-') was obtained.

(C) 1.849 of the reaction product obtained in (B) above was dissolved in THF.
ml and placed under pure nitrogen atmosphere.

Next, about 1 g of FeBr2,2H20 was added and stirred at room temperature, and the temperature was gradually raised to 60° C. and reacted for about 2 hours.

The solvent was distilled off under reduced pressure and a small amount of chloroform/methanol (
2/1) The mixed solvent was dissolved, 6 g of basic alumina powder was added, and the solvent was again distilled under reduced pressure.

Approximately 90 g of basic alumina (diameter 8 mm x 400
The mixture was loaded onto a column of 10 mm, N loloform/methanol (10/1), developed with a solvent, and all eluates were collected and evaporated under reduced pressure.

Dissolve the residue in a small amount of DMF and adjust to pH 61 with hydrochloric acid/THF.
This was adjusted and poured into 3 liters of ether and reprecipitated to give a product of 1.2
g (yield 55%) was obtained (infrared absorption spectrum ν.

=01730cfrL-', amide No. 1160Crr
L, amide No. I1540cr-').

0)) The product 1.29 obtained in (C) above was dissolved in DMF 30m
1.5 ml of 20% KOH water was added thereto, and the mixture was allowed to react at room temperature for a day and night. After adjusting the pH to 4 with hydrochloric acid, it was concentrated under reduced pressure.

This concentrate was dissolved in one mixed solvent of butanol/acetic acid/water/methanol/pyridine (20/2/14/6/3), about 5 times the amount of water was added, and the pH was adjusted to 41 again with hydrochloric acid.
The precipitate was collected by filtration and washed with a large amount of water to isolate the desired product.

Yield 0.9g (yield 87%, infrared absorption spectrum νc-o
1720cr-1, amide No. Il650cr-1, amide No. I1550cr-1') The product corresponds to M=Fe (complex of formula 10 with Cl as counterion on top).

(E) 0.89 of the product obtained in (D) above in 8 ml of DMF
Dissolve the histidine 10-methyl ester i. og
A solution of 5 ml of DMF was added thereto, 0.3 g of Zarako 1-hydroxybenzotriazole was added, and the mixture was cooled to OC.

DM 0.5g of dicyclohexylcarbodiimide to this.
A solution dissolved in 5 ml of F was added, and the mixture was stirred under OC for 2 hours and at room temperature overnight to react.

After the solvent was distilled off under reduced pressure, it was dissolved in DMF and insoluble components were filtered off.

The filtrate was poured into a mixed solvent of ether/ethyl acetate (3/2), reprecipitated, collected by filtration, and thoroughly washed.

This was dissolved in a mixed solvent of chloroform/methanol (5/1), 5.9 g of the same silica gel powder as above was added, and the mixture was distilled off under reduced pressure.

100g of silica gel (diameter 20mm x 600mm,
Butanol/acetic acid/water/methanol-12/3/5/3
) column, the I fraction was collected and the solvent was distilled off under reduced pressure.

This was dissolved in the minimum amount of methanol and developed on a neutral alumina (diameter 10 im x 300 mm, chloroform/methanol = 171) column of about 30 g to obtain the desired product.

Yield 475ru (yield 465%, infrared absorption spectrum ν
c=01740cm-t, amide number I1650cr-'
, amide number I1550cr-1, visible absorption spectrum 4
12,534,565 nm, FD mass spectrometry spectrum parent peak 888).

The obtained complex has M=Fe(I) with (1-
corresponds to the methyl ester of the complex of formula 11 having

The above reaction is shown below in a flow chart.

However, for convenience, protoporphyrin V is used. Abbreviated as (the same applies below).

Complex (Formula i0) (M=Fe(ID) Complex (Formula 11) (M=Fe(Machi, methyl ester) Synthesis Example 2 In (C) of Synthesis Example 1, about 1 g of FeBr2-2H20
CoCl2・6H202. The same procedure as in Synthesis Example 1 was carried out except that Og was used to obtain a compound 510mfl of the following formula (infrared absorption spectrum νC:.

1740m-'Amide No. I1650Cr-1, Amide No. I1550Cr-1, visible absorption spectrum 404 nm,
FD mass spectrometry spectrum parent peak 889).

Complex (formula 11) (M2Co(■), methyl ester) The product obtained corresponds to the methyl ester of the complex of formula 11, where M=Co(I).

Synthesis Example 3 500ml Erlenmeyer flask Hemin (Protoporphyri V)
, -Fe(ID-CI) 5.2 g, 1-(aminopropyl)imidazole LO ml and DMF 200 ml were added, and 0.6 ml of ethyl chloroforme was added at 0°C, and the mixture was heated under OC for 2 hours, then at room temperature for about 20 minutes. The mixture was stirred for an hour and allowed to react.

After removing insoluble components by filtration, the residue was reprecipitated with ether, collected by filtration, and dried.

Add this to Wakogel C-100 (diameter 50mm x 300mm)
, butanol/methanol/acetic acid/water/=2/2/2/
It was developed in the column of 1), the component (1) was collected, and the solvent was distilled off under reduced pressure.

Yield o. B (yield about 12 $). 0.8 g of this product was reacted in the same manner as in (E) of Synthesis Example 1, yielding 490 mg (yield: 48, infrared absorption spectrum νc-o1740cr-
1, Amide No. 11650. m-'Amide No. I 1550
cr-. 'Visible absorption spectrum 412, 534, 565
nm) to obtain the same compound as that obtained in (E) of Synthesis Example 1.

Synthesis Example 4 J-Am-Chem-SoC, 95 7868 (197
3) From the method described here, α, α, α, α one meso [
Tetra(0-aminophenyl)A]porrufin (formula below) was obtained (hereinafter referred to as TNH).

(abbreviated as PP). Add 0.65 g of this TNH2PP to CHCl
3100 ml, and to this solution, a CHC 350 Ll solution containing 0.42 g of pivaloyl chloride and 1 ml of pyridine was added dropwise at 0 G, and the mixture was stirred at 0° C. for about 4 hours to react.

Next, add 310 ml of CHCl solution containing 0.2 g of 2,2-dimethylmalonic acid dichloride and 0.5 ml of pyridine to O
The mixture was added dropwise at ℃ and allowed to react at OC for about 1 hour and then at room temperature for 2 hours.

Add 1 ml of pyridine and 1 ml of dehydrated methanol and reflux at boiling point for 2 hours. After evaporating the solvent under reduced pressure, first CH
Discharge to the second fraction with Cl3, then 10% acetone-C
Distillation with HCl3 gave the desired product in the fourth fraction.

Yield 0.4lo infrared spectral L/OH3000173
0cm-1)7gl1625CrrL-,B visible absorption spectrum 418, 512, 544, 589, 652 nm
ONMR spectrum 8.9 (pyrrole β-H, 8H),
8.7 (amide N-H, 4H), 8.1-7.1 (φ
-H, 16H), 3.9 (ester methyl, 3H), 0
．． 09-0.05 (methyl, 33H), -2.6 (piA
-/NH,2H)ppmo All of the above reaction products were dissolved in 100 ml of THF and poured under pure argon to give FeBr2-2H201. Og and 2.0 ml of pyridine were added, and the mixture was refluxed at boiling point for 5 hours.

After distilling off the solvent and medium under reduced pressure, a basic alumina column (diameter 2.0
The reaction mixture was developed with CHCl3 and all fractions were distilled off under reduced pressure.

The resulting solid was dissolved in HBr acidic CH2Cl2-hebutane and recrystallized to give the product 0.489.

Dissolve all of this in DMF501Ll and IN-KO
After adding 5 ml of HCl and stirring for 1 hour, 6N HCl was gradually added, and the resulting precipitate was collected by filtration, washed with water, and then dried.

Yield 0.32go Elemental analysis C: 63.21, H: 5.8
9, N: 10.0, Fe: 5.3, Br: 7.05 (weight ratio) The product is a complex of formula 12 where M=Fe(1) and Br- is present as a counter ion. be.

Synthesis Example 5 The same procedure as in Synthesis Example 4 was carried out except that 0.2 g of 2,2-dimethylmalonic acid dichloride was replaced with 0.2 g of succinic acid dichloride.

Yield 0.299, elemental analysis C: 61.18, H: 6.0
2, N: 10.8, Fe: 5.6, Br: 7.14 (weight ratio) The product is M2Fe(I) of the complex of formula 13, and Br exists as a counter ion. be.

Example 1 (A) P-aminostyrene 2.59, styrene 10.5
2.1 g was put into a quartz polymer tube with a diameter of 7.5 cm x 20 cr, and after freezing and degassing three times, the tube was sealed.

This was irradiated with 1 mw/ffl of ultraviolet light on the surface of the polymerization tube,
Polymerization was carried out at 30°C for 78 hours.

The reaction solution was poured into a large amount of methanol, and the resulting precipitate was collected and dried under reduced pressure to obtain a product.

Yield 4.8goNMR approximately 2.1ppm -NI2
From the proton and benzene term proton integrated intensity ratio of about 6-8 ppm, the F-aminostyrene unit in the produced polymer was identified to have a molecular weight of 4200 from the molar coefficient A of about 6 and the proton intensity of the ester methyl of about 3.9 ppm. Ta.

(B) All of the product obtained in (5) above and 100.6 g of polyethylene glycol having a molecular weight of 40,000 were dissolved in 2 liters of dioxane, and dried HCl gas was passed through the solution at a boiling point for 3 days.

After distilling off the solvent under reduced pressure, about 2 g of solid was collected and transferred to Sephad.
Using a column of ex LH-20 (diameter 5.OX60 m), the reaction mixture was developed with methanol to obtain the desired triblock copolymer in the first fraction.

Based on the integrated intensity ratio of the peak based on oxyethylene at about 1.8 ppm and the benzene ring proton at about 6 to 8 ppm from NMR, the product was determined to be the above block copolymer as well as 10
It was found that polyethylene glycol had been mixed in at a rate of approximately 30%.

Yield: 1.7g (C) All of the product obtained in (B) above was DM
Dissolve 20 ml of F, and add 0.2 g of separately prepared iron (I) protoporphyrin
．． Add 1 ml of DMF to 30 ml of DMF solution at 0°C.
After stirring at ℃ for 1 hour, the mixture was allowed to react at room temperature for half a day.

After concentration under reduced pressure, it was reprecipitated into a large amount of ether, and the solid was dissolved in CH2C.
72 was dissolved, insoluble matter was removed, and Biobeao. sSX
-1 (A 5×60 diameter CrXD column was used and developed with DMF to obtain the desired triblock copolymer metal complex in the first fraction.

On the other hand, the second fraction distilled out as a quantitative component was collected and the solvent was distilled off under reduced pressure.
Approximately 1.8 ppm in the NMR measurement results conducted inside
Since the absorption of the complex was observed in the integrated intensity ratio of the peak based on this [oxyethylene] and the benzene ring proton at about 6 to 8 ppm and in the visible absorption spectrum, this is a binary copolymer of one hydrophobic block part and one hydrophilic block part. This complex was found to be a bonded product.

Furthermore, elemental analysis of the third fraction after drying under reduced pressure revealed that it was an unreacted complex.

From the above, it was found that the impurities, the diblock copolymer metal complex and the unreacted metal complex, were removed from the first fraction.

The desired triblock copolymer was purified by repeating ether reprecipitation twice and dried under reduced pressure.

Yield: 1.54g.

This product was dissolved in a small amount of CHCl3, adsorbed as a spot on a commercially available silica gel thin layer plate, and then acidified with acetic acid and subjected to a ninhydrin test.

As a result, no blue coloring, which is characteristic when an amine group is present, was observed, and it was found that the product was a product in which -COOH in the complex portion and the amine group in the triblock copolymer were bonded.

The bonding rate of the complex to the amine group unit in the triblock copolymer is determined by the complex part}K-based visible absorption spectrum, 397,
It was determined by absorbance at 500 and 630 nm and was found to be approximately 97 cm.

The water solubility of this polymeric metal complex was approximately 1.2 g/l.

Example 2 A corresponding water-soluble block copolymer metal complex was obtained by carrying out exactly the same operation as in Example 1, except that 0.259% of the iron complex obtained in Synthesis Example 1 (D) was used as the complex.

Yield: 1.56g.

The binding rate of the complex to the amine group unit in the block copolymer is determined by the visible absorption spectrum of the complex at 403 and 506 nm.
It was determined that the absorbance was 99 or higher.

The water solubility of this polymeric metal complex was about 1.1 g/t.

Example 3 The same procedure as in Example 1 was carried out except that 0.28 liters of the iron complex obtained in Synthesis Example 1 (E) was saponified with alkali and used as a -COOH type as a complex, and the corresponding water-soluble block copolymer was prepared. A combined metal complex was obtained.

The binding rate of the complex to the amino group unit in the yield 1.62 go block copolymer is determined by the visible absorption spectrum of the complex part.
Quantitated from absorbance at 10,547,579 nm, 96%
It turns out that this is all.

The water solubility of this polymeric metal complex was approximately 1.4 g/l.

Example 4 The same procedure as in Example 1 was carried out except that 0.28y of the cobalt complex obtained in Synthesis Example 2 was saponified with alkali and used as a -COOH type as a complex, and the corresponding water-soluble block copolymer metal complex was prepared. I got it.

Yield: 1.4890 The binding rate of the complex to the amine group unit in the block copolymer is determined by the visible absorption spectrum of the complex part.
It was determined from the absorbance at 0.04 nm and was found to be 96φ or more.

The water solubility of this polymeric metal complex was approximately 1.1 g/l.

Example 5 Using 0.35 g of the iron complex obtained in Synthesis Example 4 as a complex and using CH2Cl2 as a solvent, the same operation as in Example 1 was performed to obtain a corresponding water-soluble block copolymer metal complex. Ta.

The binding rate of the complex to the amine group unit in the yield 1.659o block copolymer was determined from the absorbance of the visible absorption spectrum of the complex portion at 510 nm when N-ethylimidazole was added, and was found to be 99% or more. did.

The water solubility of this polymeric metal complex was approximately 1.3 g/1.

Example 6 An iron complex corresponding to formula 13 obtained in Synthesis Example 5 was used as a complex.
The same procedure as in Example 5 was carried out except that 32 g was used to obtain a corresponding water-soluble block copolymer metal complex.

The bonding ratio of the complex to the amine 7 group unit in the yield 1.59o-7-unit copolymer is determined from the absorbance of the visible absorption spectrum of the complex portion at 510 nm when N-ethylimidazole is added, and is a coefficient of 99 or higher. It has been found.

The water solubility of this polymeric metal complex was approximately 1.3 g/l.

Example 7 1-amine methylstyrene 2.79, styrene ■ (A)
A corresponding hydrophobic block portion with functionalities at both ends was obtained in the same manner as above.

Yield 5.29oNMR approximately 2.3 ppm monoNH2
From the integrated intensity ratio of protons and benzene ring protons of about 6 to 8 ppm, the P-aminomethylstyrene unit in the produced polymer was identified to have a molar ratio of about 5, and from the proton intensity of ester methyl of about 3.9 ppm, it was identified that the molecular weight was 3800. It was done.

All of the above products and 110 g of dextran having a molecular weight of 40,000 were dissolved in 2 liters of dimethyl sulfoxide (DMSO), heated to 60° C. while passing dry HCl gas, and reacted for 4 days.

The solvent was distilled off under reduced pressure at 30C or lower to solidify, and about 2 g of solid was collected.

This is Biobeads SX- (diameter 5.OX60cr
) was developed with DMSO to obtain the desired triblock copolymer in the first fraction.

The visible absorption maximum due to the benzene ring in the hydrophobic block is approximately 25
Standardization using an aqueous solution using absorbance at 0 nm revealed that the product contained unreacted dextran at a ratio of about 10 in addition to the block copolymer.

Next, all of the above reaction products were dissolved in 050 ml of DMSO, and added at 0°C to a 20 ml DMSO solution containing 0.229% of the iron complex obtained in Synthesis Example 3, 0.1 ml of ethyl chloroformate, and 0.1 ml of triethylamine. After reacting at 0C for 1 hour, the reaction was continued at room temperature for 1 day.

After concentration under reduced pressure, reprecipitation was carried out with ether, the solid was dissolved in DMSO, the insoluble matter was filtered off, and Biobeads SX-1 (diameter 5
．． Using a column of OX60cr), develop with DMSO,
The desired water-soluble block copolymer metal complex was obtained in the first fraction.

After purification by repeating ether reprecipitation twice, the product was dried under reduced pressure.

The binding rate of the complex to the amine group unit in the yield 1.32go block copolymer was determined from the absorbance at 405, 500, and 630 nm in the visible absorption spectrum based on the complex part,
It was shown that there were approximately 98 cases.

The water solubility of this polymeric metal complex was 1.7 g/l.

Example 8 A large excess of ethylene diaminomethacryloyl chloride was added dropwise while cooling with ice, and after distillation under reduced pressure at 30°C or lower, the residue was washed with water, and the resulting solid was dissolved in benzene and recrystallized. H: 9.44, N: 21.86 (weight).

The above product 1.28.9 was polymerized and purified in the same manner as octyl methacrylate.

Yield 3.9goNMR approximately 1.8ppm monoNH2
From the integrated intensity ratio of -CH2 protons of about 2.6 ppm to that of the Ag tower, it was identified that one monomer unit containing an amino group in the produced polymer had a molar ratio of about 7.

Further, the molecular weight was determined to be 4400 based on the proton strength of the ester of about 3.9 ppm.

All of the above polymers and 78 g of hydroxyethyl starch having a molecular weight of 40,000 were dissolved in 1.5 liters of THF, and the mixture was refluxed at the boiling point for 3 days while passing dry HCl gas.

After distilling off the solvent under reduced pressure, about 2 g of solid was collected and developed using methanol using a column of Sephadex LH20 (diameter 5.OX60 cr) to obtain the desired triblock copolymer as the first fraction.

Next, this copolymer part was dissolved in DMF2rrl, and the same operation as in Example 5 was performed to obtain a corresponding water-soluble block copolymer metal complex.

Yield: 1.35 go The binding ratio of the complex to the amine group unit in the block copolymer was determined from the absorbance of the visible absorption spectrum of the complex portion at 510 nm when AN-ethylimidazole was added, and was found to be 97 coefficients or higher. did.

The water solubility of this polymer complex was 0.9 g/l.

Example 9 Example 8 using β-aminoethyl methacrylate 1.279, methacrylic acid octylamide 17.89 and
Perform the same operation as above to obtain a hydrophobic polymer with both terminal functionalities 4,
2g was obtained.

From NMR, about 1.8 ppm of one NH2 proton and about 2
．． The β-amine ethyl methacrylate unit containing an amino group in the produced polymer was identified to have a molar ratio of about 6 from the integrated intensity ratio of -CH3- protons of 6 ppm, and the molecular weight was 4200 from the proton intensity of ester methyl of 3.9 ppm. Ta.

All of the above polymers and 88 g of polyethylene glycol having a molecular weight of 40,000 were treated in the same manner as in Example 1 (B) to obtain the corresponding triblock copolymer, of which 2 g was used in Example 1.
It was purified in the same manner as in (B) to obtain about 1.6 g.

The same treatment as in Example 5 was carried out except that this copolymer and 0.38 g of the iron complex obtained in Synthesis Example 4 were used to obtain a corresponding water-soluble block copolymer metal complex.

Yield 1.32! . The binding rate of the complex to the amine 7-group unit in the block copolymer was determined from the absorbance of the visible absorption spectrum of the complex portion at 510 nm when N-ethylimidazole was added, and was found to be 97% or more.

The water solubility of this polymer complex was 1.3 g/l.

Example 10 2.6 g of P-monomethylamine methylstyrene, Example 1
The same treatment as in (3) was carried out to obtain 4.7 g of the corresponding hydrophobic polymer with functionalities at both ends.

Quantification was performed using the same method as in Example 1(A), and it was shown that the P-monomethylamine methylstyrene unit in the produced polymer had a molecular weight of about 6 and a molecular weight of 3,700.

All of the above polymers were reacted with 112 g of polyethylene glycol according to Example 1(B).

Approximately 2 g of product was purified as in Example 1(B).

Yield: 1.7g.

As a result of identification using the same method as in Example 1 (B), it was found that the product was a triblock copolymer and was also contaminated with about 10 unreacted polyethylene glycols.

Next, the above block copolymer was prepared in exactly the same manner as in Example 1(C), including 0.291 nl of iron(I) protoporphyrin V chloride, 0.1 nl of ethyl chloroformate, and 0.1 m of triethylamine! The reaction resulted in a water-soluble block copolymer metal complex 1.479.

The binding rate of the complex to the amino group unit in the block copolymer is determined by the visible absorption spectrum based on the complex part, 397,50
It was determined by absorbance at 0,630 nm and was found to be approximately 86 cm.

The water solubility of this polymeric metal complex is about L. It was 21/1.

Example 11 A desired triblock copolymer metal complex was obtained by carrying out the same operation as in Example 1 except that iron monocarboxyphthalocyanine chloride was used as the complex in Example 1(C).

The above examples showed that the water-soluble block copolymer metal complex of the present invention can be easily obtained.

In addition, in the final stage reaction, that is, the reaction between the amino group in the block copolymer and the -COOH-containing metal complex, when the amine group is a secondary amine, the reactivity is poorer than when the amine group is a primary amine.

Next, the properties of these water-soluble block copolymer metal complexes will be explained using a few reference examples.

Reference example 1 (3) 1 polyethylene glycol 109 with a molecular weight of 40,000
A solution of 15 g of Boc-glycine in 100 ml of CH2Cl2, which had been dissolved in 0.001 l of CH2Cl2 and prepared separately at 0°C, was added at 0°C.
- indicates a butoxycarbonyl group).

After reacting for 1 hour, the reaction was continued for 1 day at room temperature, concentrated under reduced pressure, and reprecipitated in ether.

50 nl CH2C with 10 ml trifluoroacetic acid
The product was dissolved in 12 ml, concentrated under reduced pressure, and then poured into ether through which ammonia gas was passed.

The product was reprecipitated twice using a CH2Cl2-E-ter system to obtain polyethylene glycol 8.99% glycinated at both ends.

Dissolve this 2,Og in CH2Cl220Ll, o
0.5 g of the iron complex of Synthesis Example 4 prepared in step c, 1.5 ml of ethyl chloroformate, and 0.0 ml of triethylamine.
．． Pour into 8 ml of CH2Cl2 50 ml solution and heat at 0°C.
The reaction was carried out for 1 hour at room temperature for 1 day.

The solution was concentrated under reduced pressure and reprecipitated in ether.

Remove the sediment using Biobeads SX- (diameter 5.OX70
cm) and developed with CH2Cl2 to obtain the desired water-soluble polymer metal complex in the first fraction.

Yield: 1.9go The bonding rate of the complex between the amino group units at both ends of the glycinated polyethylene glycol was 98% or more, as determined from the absorbance at 510 nm, the maximum visible absorption when N-ethylimidazole was added.

(B) 20 mg of the water-soluble polymer metal complex obtained in A above, N
monoethylimidazole 5X10-'mol and Na2s
2o, o. Collect 5 m9 and add 4 m of degassed water with pH 77 under deaeration.
The spectrophotometer cell was sealed with 1.

After stirring thoroughly, we measured the spectrum and found that F
e(I) complex group (a peak at 537 nm was confirmed.

This solution is air or zero. When gas was blown, the absorption maximum immediately shifted to a peak based on Fe(v) at 510 nm, and oxidation of the central metal occurred.

Reference Example 2 40 Da of the block copolymer metal complex obtained in Example 5 and 5 x 10-5 moles of N-ethylimidazole were made into a solution of 4 rl of methylene dichloride, 1 ml of an aqueous solution containing 20420 mg of Na2S was added, and the mixture was charged into the bulb of a Thunberg type cell. is.

After thorough stirring, cool in a dry ice-methanol bath, leaving only the aqueous phase. was solidified and the methylene dichloride phase was transferred to a cell section and dried under reduced pressure.

Under an inert atmosphere, the bulb containing 4 mFg of pH 7 water was replaced with the bulb in which the Na2S204 of light remained, and the water in the bulb was transferred to the cell under degassing to dissolve the polymer metal complex.

In order to ensure complete dissolution, ultrasonic stirring was performed for 10 minutes at less than IOW while degassing.

When the spectrum of this solution was measured, AFe (
I) A peak of <537 nm was confirmed in the complex.

When air or O2 gas was blown into this solution, the absorption maximum immediately shifted to a peak at 542 nm based on the oxygen complex.

When this oxygen complex was sufficiently frozen and degassed at about 10-5 torr, it again showed the original peak of 537 nm.

When left under oxygen, the central iron gradually changes to Fe(I)
However, it took about 4 hours for half of the amount to be oxidized.

Reference example 3 Water-soluble block copolymer metal complex obtained in Example 6 40n
The same operation as in Reference Example 2 was carried out except that 9 was used, and first, a peak at 537 nm based on the Fe(I) complex was confirmed.

As soon as air or O2 gas was blown into this solution, the absorption maximum shifted to 543 nm, indicating the formation of an oxygen complex.

It took about 2.5 hours under Pure 02 to oxidize half of the amount.

As shown in the above reference examples, in a simple water-soluble polymer metal complex that does not form any hydrophobic field, the metal complex part, which is the active center, is immediately deactivated by water attack, whereas the present invention It will be appreciated that the use of water-soluble block copolymer metal complexes of 100 to 100% has a very long life.

Claims (1)

[Claims] 1 General formula (where A is a hydrophilic polymer chain, A-00C is an ester bond, B is a hydrophobic polymer chain represented by the formula, X1 is Y is hydrogen,
or a hydrocarbon group without mobile hydrogen ARl is hydrogen or methyl group AR2 is an alkyl group of 03 or more, X2 is -CONH+CH2CH2neNH-, n is 1, 2 or 3, and X and y are nominal is a large metal having an ion of a metal selected from metals belonging to Group VB, Group ■B, Group ■, Group IB, and Group IB of the fourth to sixth periods of the periodic table as the central metal. A metal complex of a cyclic tetradentate planar ligand, and a block copolymer metal complex in which a is O or 1). 2. The block copolymer metal complex according to claim 1, wherein the metal complex is derived from polyethylene glycol, dextran, hydroxyethyl starch, dextrin, amylose, pegtin, or cyclodextrin. 3. The block copolymer metal complex according to claim 1 or 2, wherein HP is represented by the formula or (in the above formula, each M is a central metal). 4 } The block copolymer metal complex according to claim 1 or 2, wherein P is derived from a metal complex of carboxyl group-containing tactile cyanine or saponified chlorophyll.