Chemistry: analytical and immunological testing – Testing of catalyst
Reexamination Certificate
1997-10-24
2001-06-05
Venkat, Jyothsna (Department: 1627)
Chemistry: analytical and immunological testing
Testing of catalyst
C436S147000, C436S159000, C436S518000, C436S523000, C436S524000, C436S525000, C436S526000, C436S527000, C436S528000, C436S529000, C436S530000, C436S531000, C436S532000, C435S091500, C435S091500
Reexamination Certificate
active
06242262
ABSTRACT:
FIELD OF THE INVENTION
The present invention concerns the screening of catalyst libraries, and particularly concerns the screening of carrier-bound catalyst libraries that are produced by combinatorial chemistry techniques.
BACKGROUND OF THE INVENTION
While current understanding of chemical reactivity often makes it possible to design or choose an appropriate catalyst for a new molecular transformation, achieving adequate reactivity is often a cumbersome process. Typically, many iterations involving methodical manipulation of catalyst substructure, analysis of the resulting effect and redesign, are required. In an effort to facilitate this recursive catalyst optimization process, various research groups have started to use the techniques of combinatorial chemistry and solid phase synthesis to rapidly produce large numbers of potential catalysts. See, e.g., F. Menger et al.,
J. Org. Chem.
60, 6666 (1995); G. Liu and J. Ellman,
J. Org. Chem.
60, 7712 (1995); K. Burgess et al.,
Angew. Chem. Int. Ed. Engl.
35, 220 (1996); B. Cole et al.,
Angew. Chem. Int. Ed. Engl.
35, 1668 (1996). Unfortunately, despite progress in evaluating the thermodynamics of equilibrium processes on solid support, methods for assessing the kinetics of reactions involving polymer-bound reagents have not been available. This circumstance has prevented the analysis of very large libraries (10
4
-10
6
members) as screening for organic catalysts requires an individual assay for each member of a catalyst library.
According to the observation that most chemical reactions have a non-zero AH, temperature has been used to survey the progress of catalytic reactions. Since all catalysts in a library assay are evaluated under the same reaction conditions, the most active catalyst will exhibit the largest temperature change (&Dgr;T~turnover frequency·&Dgr;H). Moates et al. applied this principle for the parallel evaluation of the ignition temperatures of 16 metal-doped alumina pellets in the presence of H
2
and O
2
at elevated temperatures in gas phase. F. Moates et al.,
Ind. Eng. Chem. Res.
35, 4801-4803 (1996). To date, however, there has not been a way to apply such techniques to the analysis of polymer-bound catalyst libraries for solution-phase chemical reactions.
SUMMARY OF THE INVENTION
A method for isolating an active catalyst from a library of compounds that are potential catalysts is disclosed. The method involves providing a library which comprises a plurality of discrete solid supports, each solid support having a different organic compound bound thereto (the term “organic compound” including organo-metallic compounds herein); and providing a reaction solution in a reaction vessel, the reaction solution containing the reactant or reactants necessary for a chemical reaction to occur in the presence of a catalyst for that reaction. The library and the reaction solution are then combined in the reaction vessel, and then one of the discrete solid supports is detected that is characterized by a temperature change in said solution greater than the temperature change of a plurality of other of said discrete solid supports in said solution. The detected solid support carries an active catalyst for the chemical reaction.
In a preferred embodiment of the invention, the discrete solid supports and the reaction solution are selected so that the solid supports are positioned at (for example, sink or float to) an interface in said reaction vessel. The detecting step is then carried out with an infrared detector directed at that interface. The interface may be either a gas/liquid interface (i.e., the surface of said reaction solution), or a liquid/solid interface (i.e., the bottom of said reaction vessel).
After a solid support that carries an active catalyst is detected, that solid support can be isolated and the organic compound bound thereto identified by analytical chemistry techniques or by decoding a sequential or nonsequential tag carried by that solid support.
The present invention is explained in greater detail in the drawings herein and the specification set forth below.
REFERENCES:
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patent: 5876946 (1999-03-01), Burbaum et al.
patent: 6030917 (2000-02-01), Weinberg et al.
patent: 6063633 (2000-05-01), Wilson, III
Gilbertson et al. The Combinatorial Synthesis of Chiral Phosphine Ligands. Tetrahedron Letters 37(36): 6475-6478, 1996.*
Gallop et al. Applications of Combinatorial Technologies to Drug Discovery. 1. J. Med. Chem. 37(9): 1233-1251, 1994.*
F. M. menger et al. J. Org. Chem, vol. 60, pp 6666-6667, 1995.*
Brenner et al. PNAS USA 89:5381, 1992.*
Ohlmeyer et al.; Complex synthetic chemical libraries indexed with molecular tags,Proc. Natl. Acad. Sci, USA, 90:10922-10926 (1993).
Melamed et al.; An Historical Review of the Development of Flow Cytometers and Sorters,Flow Cytometry and Sorting, Second Edition:1-9 (1990).
Moates et al.; Infrared Thermographic Screening of Combinatorial Libraries of Heterogeneous Catalysts,Ind. Eng. Chem. Res, 35:4801-4803 (1996).
Morken James P.
Taylor Steven J.
Garcia Maurie E.
Myers Bigel & Sibley & Sajovec
The University of North Carolina at Chapel Hill
Venkat Jyothsna
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