title: Array-based split-pool combinatorial screening of potential catalysts.
abstract: A new method for screening split-pool combinatorial libraries for catalytic activity is described. Site-selective detection of catalytic activity for solution-based reactions was made possible without cofunctionalizing beads or adding diffusion-limiting matrixes. This was done by spatially separating resin-bound catalysts on an adhesive array on a microscope slide and introducing the reacting liquid to the top of the slide. Convective mixing and evaporation was controlled using a cover slide and imaging both the formation of products within active beads and the diffusion of products out of the beads. Colored reaction products and pH-sensitive indicators were used to visually detect catalytically active beads in the presence of inactive ones. Quantitative analyses of the images support the assumption that color intensities can be used to assess the quality of hits from a combinatorial screen. The Knoevenagel condensation reaction catalysis as well as esterase screening using methyl red were used to validate the approach. Using the esterase data, it was shown that some information on activity could also be extracted from the colored plume surrounding individual beads although the precision is not as good as that from direct measurement of absorbance through the bead. It was also found that the distribution of products within a single bead can also be gleaned from the absorbance data for different-sized beads.
authors.affiliation: Department of Chemistry and Biochemistry, University of Texas at Austin, Austin, Texas 78712, USA.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Stanton
authors.forename: James A
authors.initials: JA
authors.lastname: Holcombe
mesh_terms: D000818:Animals; D001391:Azo Compounds / Q000737:chemistry; D002384:Catalysis; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D004058:Diffusion; D004950:Esterases / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007202:Indicators and Reagents; D008099:Liver / Q000201:enzymology; D015394:Molecular Structure; D010879:Piperazines / Q000737:chemistry*; D011137:Polystyrenes / Q000737:chemistry*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D001391:Azo Compounds; D007202:Indicators and Reagents; D010879:Piperazines; D011137:Polystyrenes; C520893:piperazinomethyl polystyrene; C008492:methyl red; D004950:Esterases