WO2004010347A2 - Procede et installation pour resoudre des problemes de chimie adaptative - Google Patents

Procede et installation pour resoudre des problemes de chimie adaptative Download PDF

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Publication number
WO2004010347A2
WO2004010347A2 PCT/EP2003/007895 EP0307895W WO2004010347A2 WO 2004010347 A2 WO2004010347 A2 WO 2004010347A2 EP 0307895 W EP0307895 W EP 0307895W WO 2004010347 A2 WO2004010347 A2 WO 2004010347A2
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WO
WIPO (PCT)
Prior art keywords
mixtures
compounds
substance
substances
produced
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Ceased
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PCT/EP2003/007895
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German (de)
English (en)
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WO2004010347A3 (fr
Inventor
Peter Zinn
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Individual
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Individual
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Priority to AU2003257481A priority Critical patent/AU2003257481A1/en
Publication of WO2004010347A2 publication Critical patent/WO2004010347A2/fr
Publication of WO2004010347A3 publication Critical patent/WO2004010347A3/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C40—COMBINATORIAL TECHNOLOGY
    • C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
    • C40B99/00—Subject matter not provided for in other groups of this subclass
    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16C—COMPUTATIONAL CHEMISTRY; CHEMOINFORMATICS; COMPUTATIONAL MATERIALS SCIENCE
    • G16C20/00—Chemoinformatics, i.e. ICT specially adapted for the handling of physicochemical or structural data of chemical particles, elements, compounds or mixtures
    • G16C20/10—Analysis or design of chemical reactions, syntheses or processes
    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16C—COMPUTATIONAL CHEMISTRY; CHEMOINFORMATICS; COMPUTATIONAL MATERIALS SCIENCE
    • G16C20/00—Chemoinformatics, i.e. ICT specially adapted for the handling of physicochemical or structural data of chemical particles, elements, compounds or mixtures
    • G16C20/70—Machine learning, data mining or chemometrics

Definitions

  • the present invention relates to a method and a plant for the analysis and production of mixtures and compounds.
  • An iterative process is used to optimize the analysis and the manufacturing process.
  • the aim of the invention is therefore to present a new method which overcomes both the limitations of classic chemistry and the problems of combinatorics. At the same time, an installation for carrying out the method is to be presented.
  • the object is achieved according to the invention by a method of adaptive chemistry, which combines combinatorial chemistry with principles of goal orientation and self-organization, and by the corresponding system.
  • the invention is applicable to both chemical analysis and synthesis problems.
  • the invention is first described for chemical analysis.
  • a starting population of random substances is first mixed from at least two components of the entirety in different mixing ratios.
  • at least one measured variable is determined for each of the substance mixtures produced and compared with the corresponding measured variable of the substance mixture to be analyzed.
  • this is a spectroscopic method; however, other methods are also conceivable.
  • a fitness value is derived for each member of the population as a measure of the agreement. As a rule, the mixtures of the starter generation are little adapted to the sample.
  • next generation blends can be determined using genetic algorithms. Now a new generation of substance mixtures is generated, with which the procedure is as before. This procedure is continued over so many generations until the fitness value for at least one member of the population demonstrates a sufficiently large correspondence with the substance mixture to be analyzed.
  • the search space of the mixtures can be limited by boundary conditions, if these are known, during the production of the start generation.
  • a wide field of applications opens up for the described adaptive analysis, particularly in finding product formulations.
  • the analysis of a perfume by adaptive adjustment is one Library of fragrances possible using odor sensors or the like.
  • adaptive chemistry can also be used for synthesis purposes.
  • the main difference to the analysis method described above is that the synthesis cannot be adapted to a size of the test substance, since such a quantity is not available. Accordingly, the goal orientation must be done in a different way.
  • a starting population of compounds or mixtures of substances is first generated before certain measured variables are determined for each member of the population.
  • a fitness value is now determined by comparison with a target as a measure of the agreement with the target.
  • the mixing ratios for producing the next generation of compounds or mixtures of substances can be derived.
  • the procedure is the same as before. This process is repeated over so many generations until a sufficiently large correspondence with the target value via the fitness value is determined for at least one compound or substance mixture.
  • the search space for the compounds or mixtures of substances can also be limited here by known boundary conditions.
  • An example of adaptive synthesis is the development of dyes in which certain color coordinates serve as the target. Starting from a basic framework, e.g. B. different side chains can be coupled. The properties of the synthesized dyes are better adapted to the given color coordinates from generation to generation. In the field of drug research, antibody-antigen interactions are possible as targets, which can be detected via immunoassays. The use of genetic algorithms makes it possible to "breed" new active substances.
  • the properties of given substance mixtures or compounds can be imitated without automatically having to be identical with regard to the starting materials used.
  • the mixtures or compounds newly produced by means of imitation can therefore u. U. be advantageous compared to the educts for the original mixture or the original compound, for example with regard to the educt costs or environmental friendliness.
  • An example of such an imitation of the target is the adaptive adaptation of a library of fragrances to a given perfume.
  • the process according to the invention makes it possible to find a mixture of substances which largely resembles the specified product in terms of smell, but which contains less expensive or more skin-compatible components.
  • a color mixture can also be produced in a similar way, although in with regard to the color itself is practically identical to the target, but uses different starting materials.
  • genetic algorithms are used to solve the problems.
  • conventional algorithms which are designed to solve a given problem exactly
  • the genetic algorithms imitate nature in order to find the "best” solution. They work according to the principles of selection known from natural evolution , Crossing and mutation: In this way, better and better solutions are generated over time, ie from generation to generation.
  • Intersection new individuals are made up of two individuals each.
  • Mutation Mutations are caused by selective changes in individuals.
  • the selection runs in two steps.
  • the quality of adaptation of each individual is represented by a numerical value, the fitness. The larger this number, the better the corresponding individual is adapted to the requirements.
  • the actual selection takes place in the second step. Each individual survives with a certain probability, the higher the fitness, the higher.
  • a sample robot is particularly advantageously used to produce the substance mixtures or compounds. This sample robot leads the
  • Such a sample robot used in the context of adaptive chemistry should have devices for performing standard chemical operations. These typical chemical standard operations include steps such as the metering of starting materials, reagents or catalysts and the effective mixing of the substance or reaction mixtures. In the case of adaptive synthesis, further features are useful.
  • the sample robot should also have a temperature control option to keep a reaction mixture at a certain temperature. Since, as a rule, further processing steps are required after a synthesis has been successfully carried out, automation is also desirable here. So z. B. advantageously simple processing steps such as extraction can be implemented in the sample robot.
  • the system for carrying out the method expediently also includes the use of an analyzer system with which the measured variables can be determined, on the basis of which the fitness values are determined as a measure for the agreement of the measured variables with a target.
  • Such an analyzer system can e.g. B. include a spectrometer of various types, a chromatograph or an electro- or biochemical detector or sensor.
  • the method according to the invention can include the use of a UV, NMR, fluorescence or mass spectrometer.
  • the exact choice of the device depends on the exact task and the composition of the substance mixtures or compounds.
  • several analysis methods can also be coupled.
  • An example of this is the LC-MS coupling.
  • the sample robot used is also able to transport samples and comparison samples to the analyzer system. While conventional analyzer systems often use specially adapted samplers for routine analyzes, the integration of a freely movable sample robot in a modular overall system achieves maximum flexibility to enable the most varied of adaptive chemistry tasks to be processed.
  • sequence control is intended to synchronize the various processes running and to control the entire process autonomously.
  • the sample robots and analyzer systems used are expediently used as modules within a feedback system.
  • the devices should be macro-capable.
  • Mechanisms of program interaction send macro commands directly from the higher-level process control to the device-side control software.
  • the process control receives data from the devices used via macro interfaces.
  • Part of this higher-level process control is the software core, which works with genetic algorithms and thus determines the composition of the members of the population.
  • the process control should receive information and data from the sample robot or analyzer system via interfaces, so that it is able to make autonomous decisions and to forward control commands to the other system components.
  • the necessary analyzer and robot control programs are commercially available.
  • the sequence control should expediently be designed in such a way that, in the case of adaptive analysis, it evaluates the fitness values serving as a measure for the correspondence of the measured quantities of the substance mixtures produced with those of the substance mixture to be analyzed with the aid of genetic algorithms and then the compositions of the substance mixtures of the next generation sets.
  • the sequential control system should use genetic algorithms to evaluate the fitness values for the substance mixtures or compounds produced, which form a measure of the agreement with the target, in order to determine the conditions for the production of the compounds of the next generation. In this way, the system according to the invention enables the autonomous implementation of adaptive analyzes or syntheses without the user having to intervene in the meantime.
  • the sequence control can take into account further parameters that are characteristic of the components or starting materials used, such as costs, MAK values, ecological data, usability or availability.
  • Figure 1 is a feedback loop showing the general approach to adaptive chemistry.
  • the method of adaptive analysis or synthesis on which the invention is based is illustrated once again in FIG.
  • a measure of the agreement with this fitness value is determined.
  • genetic algorithms are used to determine the conditions for the production of the next generation population. This cycle can be repeated until after X generations at least one member of the population has a sufficiently good fitness level.
  • the spectrophotometric multi-component analysis is described as an example of the adaptive analysis. This is a common method for the analysis of mixtures, in which the additivity of the extinctions of the components is exploited without being separated into individual components.
  • the spectra of newly produced mixtures are now gradually adapted to the sample spectrum.
  • a start generation of mixtures is randomly produced.
  • a spectrum is measured for each mixture of substances and compared with the spectrum of the sample of unknown composition.
  • fitness values are derived from the comparison, which provide information about the agreement with the sample spectrum. In the starting population, these fitness values will generally not show good agreement with the sample to be analyzed.
  • the measured fitness will be better than for others. Because of these differences, the mixtures of the next generation are then determined using genetic algorithms. This process is repeated over so many generations until the adaptation to the sample spectrum is achieved with a desired fitness.
  • Various parameters can be adapted when using genetic algorithms. In the context of the crossing in particular, this is the so-called crossover rate, which makes a statement about the probability with which two arbitrarily removed individuals are "paired" or put back unchanged back into the population.
  • This mutation rate provides information about the probability of a change occurring at any point within the individual.

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  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Computing Systems (AREA)
  • Biochemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Bioinformatics & Computational Biology (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Theoretical Computer Science (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Molecular Biology (AREA)
  • Analytical Chemistry (AREA)
  • Investigating Or Analysing Materials By Optical Means (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)

Abstract

La présente invention concerne un procédé et une installation d'analyse ou de synthèse adaptative de composés ou de mélanges de substances dans le domaine de la chimie. L'invention comprend tout d'abord la production de populations de départ aléatoires qui sont analysées au moyen d'appareils de mesure. Les résultats ainsi obtenus sont comparés à une directive cible, une valeur d'adaptation étant déterminée en tant que grandeur représentative de la concordance avec la directive cible. Des algorithmes génétiques sont utilisés sur la base de ces valeurs d'adaptation afin d'établir la composition de la population de la génération suivante. Ce procédé est mis en oeuvre sur de nombreuses générations jusqu'à ce que les valeurs d'adaptation déterminées coïncident suffisamment avec la directive cible au moins pour un individu de la population. La chimie adaptative de l'invention peut être utilisée dans le cadre de la recherche de formulations de produits ou pour trouver de nouveaux composés ayant des propriétés souhaitées.
PCT/EP2003/007895 2002-07-20 2003-07-18 Procede et installation pour resoudre des problemes de chimie adaptative Ceased WO2004010347A2 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2003257481A AU2003257481A1 (en) 2002-07-20 2003-07-18 Method and installation for solving problems of adaptive chemistry

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE10233022A DE10233022B4 (de) 2002-07-20 2002-07-20 Verfahren zur Lösung von Aufgaben der adaptiven Chemie
DE10233022.0 2002-07-20

Publications (2)

Publication Number Publication Date
WO2004010347A2 true WO2004010347A2 (fr) 2004-01-29
WO2004010347A3 WO2004010347A3 (fr) 2004-10-28

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PCT/EP2003/007895 Ceased WO2004010347A2 (fr) 2002-07-20 2003-07-18 Procede et installation pour resoudre des problemes de chimie adaptative

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AU (1) AU2003257481A1 (fr)
DE (1) DE10233022B4 (fr)
WO (1) WO2004010347A2 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006030218A1 (fr) * 2004-09-15 2006-03-23 Bp Oil International Limited Procede d'evaluation d'une charge d'alimentation de raffinerie
CN103547509A (zh) * 2010-11-05 2014-01-29 可口可乐公司 生产的方法、装置和系统
US9757706B2 (en) 2012-05-25 2017-09-12 The University Court Of The University Of Glasgow Methods of evolutionary synthesis including embodied chemical syntheses

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE4232141A1 (de) * 1992-09-25 1994-03-31 Forschungszentrum Juelich Gmbh Verfahren zur experimentellen Ermittlung der Parameter für optimale Ergebnisse
US5434796A (en) * 1993-06-30 1995-07-18 Daylight Chemical Information Systems, Inc. Method and apparatus for designing molecules with desired properties by evolving successive populations
JPH10513290A (ja) * 1995-01-31 1998-12-15 松下電器産業株式会社 比率予測システムと混合物生成方法
US6081796A (en) * 1995-01-31 2000-06-27 Matsushita Electric Industrial Co., Ltd. Proportion predicting system and method of making mixture
US5864633A (en) * 1996-05-17 1999-01-26 Therma-Wave, Inc. Method and apparatus for optical data analysis
JP2002530727A (ja) * 1998-10-28 2002-09-17 グラクソ グループ リミテッド 定量的構造活性相関におけるファーマコフォア・フィンガープリント並びにプライマリ・ライブラリの構築
ES2341217T3 (es) * 1999-01-19 2010-06-17 Maxygen, Inc. Recombinacion de acidos nucleicos mediada por oligonucleotidos.
DE10051806A1 (de) * 2000-10-18 2002-04-25 Bayer Ag Verfahren zur Charakterisierung, Identifizierung und Kennzeichnung von mikrobiellen Mischungen

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006030218A1 (fr) * 2004-09-15 2006-03-23 Bp Oil International Limited Procede d'evaluation d'une charge d'alimentation de raffinerie
JP2008513562A (ja) * 2004-09-15 2008-05-01 ビーピー オイル インターナショナル リミテッド 精油所供給原料を評価する方法
US8546146B2 (en) 2004-09-15 2013-10-01 Bp Oil International Limited Process for evaluating a refinery feedstock
EA019100B1 (ru) * 2004-09-15 2014-01-30 Бп Ойл Интернешнл Лимитед Способ оценки нефтезаводского сырья
CN103547509A (zh) * 2010-11-05 2014-01-29 可口可乐公司 生产的方法、装置和系统
US9757706B2 (en) 2012-05-25 2017-09-12 The University Court Of The University Of Glasgow Methods of evolutionary synthesis including embodied chemical syntheses
US9962677B2 (en) 2012-05-25 2018-05-08 The University Court Of The University Of Glasgow Methods of evolutionary synthesis including embodied chemical syntheses

Also Published As

Publication number Publication date
AU2003257481A8 (en) 2004-02-09
WO2004010347A3 (fr) 2004-10-28
DE10233022A1 (de) 2004-04-15
DE10233022B4 (de) 2004-09-16
AU2003257481A1 (en) 2004-02-09

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