Catalytic combinatorial libraries

To date, the most frequently used ligand for combinatorial approaches to catalyst development have been imine-type ligands. From a synthetic point of view this is logical, since imines are readily accessible from the reaction of aldehydes with primary or secondary amines. Since there are large numbers of aldehydes and amines that are commercially available the synthesis of a variety of imine ligands with different electronic and steric properties is easily achieved. Additionally, catalysts based on imine ligands are useful in a number of different catalytic processes. Libraries of imine ligands have been used in catalysts of the Strecker reaction, the aza-Diels-Alder reaction, diethylzinc addition, epoxidation, carbene insertions, and alkene polymerizations. 

Sharpless et al. coined the word ligand-accelerated catalysis (LAC), which means the construction of an active chiral catalyst from an achiral precatalyst via ligand exchange with a chiral ligand. By contrast, a combinatorial library approach in which an achiral pre-catalyst combined with several chiral ligand components (L, L, —) may selectively assemble in the presence of several chiral activators (A, A, —) into the most catalytically active and enantioselective activated catalyst (ML A" ) (Scheme 8.16). ... 

Catalytic antibodies, like enzymes, must be isolated and purified to homogeneity before they can be studied. Initially this was done by using the hybridoma technique for isolation of monoclonal antibodies (Box 31-A). After induction of antibody formation by injecting a selected hapten into a mouse, large numbers of monoclonal antibodies had to be tested for catalytic activity. Even if several thousand different monoclonal antibodies were tested, only a few with catalytic properties could be found.1 Newer methods have incorporated recombinant DNA techniques (Box 31-A) and use of combinatorial libraries and phage display.) Incorporation of acidic or basic groups into the haptens used to induce antibody formation may yield antibodies capable of mimicking the acid-base catalysis employed by natural enzymes. 0... 

Relative Quantification of Catalytic Activity in Combinatorial Libraries by Emissivity-Corrected Infrared Thermography... 

Holzwarth, A., W. F. Maier, Catalytic phenomena in combinatorial libraries of heterogeneous catalysts. Platinum Metals Rev., 44(1) (2000) 16. 

Aires-de-Sousa, J. and Gasteiger, J. (2005) Prediction of enantiomeric excess in a combinatorial library of catalytic enantioselective reactions. /. Comb. Chem., 7, 298. 

This strategy has been applied to select catalytic antibodies from phage-displayed libraries. Two catalytic single-chain antibodies catalyzing the hydrolysis of ampicillin with rate accelerations kcit/kunc lt of 5200 and 320 (kcat = 0.29 and 0.018min-1) were isolated from combinatorial libraries prepared from mice immunized with penam sulfone conjugates and selected with a biotinylated penam sulfone [61]. 

Holzwarth, A. Schmidt, H.-W. Maier, W., Detection of catalytic activity in combinatorial libraries of heterogeneous catalysts by IR thermography, Angew. Chem. Int. Ed. 1998,37, 2644—2647... 

Figure 4.5. DEBS combinatorial library. Colors indicate the location of the engineered carbon(s) resulting from catalytic domain substitutions inmodule2 (red),module5 (green),module6 (blue),or modules 1,3, or 4 (yellow). See color insert.

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