Chemistry: analytical and immunological testing – Testing of catalyst
Reexamination Certificate
2000-11-28
2003-11-25
Baker, Maurie Garcia (Department: 1639)
Chemistry: analytical and immunological testing
Testing of catalyst
C435S091500, C435S091500, C435S091500, C436S043000, C436S164000, C436S166000, C436S174000
Reexamination Certificate
active
06653138
ABSTRACT:
BACKGROUND
1. Technical Field
The present invention relates to the field of research for new catalysts or polymers or processes for making polymers. More particularly, this invention is directed toward an apparatus and method of performing homogeneous and supported homogeneous catalysis and related techniques for rapidly creating and testing catalyst libraries prepared by combinatorial techniques. This invention is also directed toward an apparatus and method for making polymers using combinatorial techniques.
2. Discussion
Combinatorial chemistry has revolutionized the process of drug discovery. See, for example, 29
Acc. Chem. Res
. 1-170 (1996); 97
Chem. Rev
. 349-509 (1997); S. Borman,
Chem. Eng. News
43-62 (Feb. 24, 1997); A. M. Thayer,
Chem. Eng. News
57-64 (Feb. 12, 1996); N. Terret, 1
Drug Discovery Today
402 (1996)). Because of its success in eliminating the synthesis bottleneck in drug discovery, many researchers have come to narrowly view combinatorial methods as tools for creating structural diversity. Few researchers have emphasized that, during synthesis, variations in temperature, pressure, ionic strength, and other process conditions can strongly influence the resulting properties of library members. For example, reaction conditions are particularly important in formulation chemistry and polymer chemistry, where one combines a set of components under different reaction conditions or concentrations to determine their influence on product properties.
Recently, combinatorial approaches have been used for discovery programs unrelated to drugs. Combinatorial materials science generally refers to the methods for creating a collection of chemically diverse compounds or materials and to methods for rapidly testing or screening this library of compounds or materials for desirable performance characteristics and properties. For example, some researchers have recognized that combinatorial strategies offer promise for the discovery of inorganic compounds such as high-temperature superconductors, magnetoresistive materials, luminescent materials, and catalytic materials. See, for example, copending U.S. patent application Ser. No. 08/327,513 “The Combinatorial Synthesis of Novel Materials” (published as WO 96/11878) and U.S. Pat. No. 5,776,359, which are both herein incorporated by reference. Compared to traditional discovery methods, combinatorial methods sharply reduce the costs associated with preparing and screening each candidate material.
Some combinatorial research into catalysis and polymer formation has begun. See U.S. patent application no. 08/898,715 “Combinatorial Synthesis and Analysis of Organometallic Compounds and Catalysts” (published as WO 98/03251). The following articles discuss one or more combinatorial techniques in conjunction with catalysis, and each are incorporated herein by reference: Senkan,
Nature
, vol 394, pp. 350-353 (Jul. 23, 1998); Burgess et al.,
Angew. Chem. Int. Ed. Eng
., 1996, 35, No. 2, pp. 220-222; Maier et al.,
Angew. Chem. Int. Ed. Eng
., 1998, 37, No. 19, pp. 2644-2647; Reetz et al.,
Angew. Chem. Int. Ed. Eng
., 1998, 37, No. 19, pp. 2647-2650; Schlögl,
Angew. Chem. Int. Ed. Eng
., 1998, 37, No. 17, pp. 2333-2336; Morken et al.,
Science
, vol. 280, pp. 267-270 (Apr. 10, 1998); and Gilbertson et al.,
Tetrahedron Letters
, vol. 37, no. 36, pp. 6475-6478 (1996).
What is needed is a combinatorial method and apparatus for the research, discovery and development of catalysts and polymers. This invention advances the field by providing an entire system, beginning with a ligand library or a set of reactants and ending with screens for performance, with a variety of reaction and screening options.
SUMMARY OF THE INVENTION
This invention provides methods and apparatus for performing the combinatorial synthesis of libraries and screening of those combinatorial libraries. This invention gives those of skill in the art a variety of synthesis and screening techniques so that a complete combinatorial discovery or optimization research and development program can be successfully implemented for many different reactions, including all types of polymerizations or small molecule catalysis. The broadest concept of the methodology is that a library is created that is screened for a property or compound of interest. The libraries that are created depend on the reaction of interest, but are typically either catalyst libraries or product libraries. This invention provides a number of embodiments for performing such synthesis and screening and the embodiments may be combined together.
One embodiment of the present invention is a method and apparatus for researching for novel catalysts by starting with a ligand library that includes a plurality of member ligands. In the ligand library (also referred to as a parent ligand library) each ligand member may have a common scaffold, but will vary in structural diversity. The ligand library may also include ligand members that have different scaffolds. The important point is that the ligand library includes ligand members that are different from each other by either scaffold or structural diversity or both. Optionally, one or more daughter libraries are created from the parent ligand library by taking one or more aliquots from one or more member ligands in said ligand library. For example, each daughter library may be considered to be a replica of the ligand library, but each daughter ligand member would be smaller than the parent ligand member in terms of either volume or moles or mass. At least one metal precursor is added to at least a portion of the members of the ligand libraries or daughter libraries to create one or more catalyst libraries. The catalyst library is subjected to a reaction of interest. The reaction of interest may be a reaction that creates a product library. For example, if the reaction of interest is a polymerization reaction, a polymer library will be the result. Alternatively, the reaction of interest may be a screen for activity. The reaction of interest can have process conditions that are combinatorialized, such as varying amounts of reactants or different conditions (such as time, temperature, pressure, atmosphere, etc.). The method optionally provides different screening stages, such as a primary screen to eliminate some members from a library from going on to a secondary screen.
In another embodiment, mixtures of starting components (such as ligands, metal precursors, initiators, monomers, solvents, etc.) are combined in different ratios. A reaction of interest is performed under varying conditions to create a product array. This embodiment focuses on combinatorializing the conditions of the reaction of interest. Process conditions that may be combinatorialized include amounts (volume, moles or mass) and ratios of starting components, time for reaction, reaction temperature, reaction pressure, rate of starting component addition to the reaction, residence time (or product removal rate), reaction atmosphere, reaction stir rate and other conditions that those of skill in the art will recognize. The library that is created in this embodiment is a product library that is then screened for a property or compound of interest. Optionally, prior to screening, the product library is daughtered into one or more daughter product libraries.
In addition, the two above embodiments can be combined together. For example, this invention may be practiced in order to discover a polymer of interest by free radical polymerization (e.g., a polymer having predetermined properties, such as molecular weight or particle size). The library of polymers (e.g., a product library) may be created by having diversity in the starting components used or by having diversity the reactions conditions (e.g., time, temperature, mixing speed, etc.). The polymer library is then tested to determine if a polymer of interest has been created using one of many different rapid polymer characterization techniques. Thus, in this example, the screen may be the reaction, the polymer characterization or both.
The embod
Dales G. Cameron
Nielsen Ralph B.
Safir Adam
Turner Howard W.
VanErden Lynn
Baker Maurie Garcia
Senniger Powers Leavitt & Roedel
Symyx Technologies Inc.
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