Array-based split-pool combinatorial screening of potential catalysts
Stanton, Matthew Lee, 1980-
MetadataShow full item record
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 co-functionalizing beads or adding diffusion limiting matrixes. This was done by spatially separating resin-bound catalysts on an adhesive array, controlling convection with 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 from two catalytic Knoevenagel condensations and a colored pH sensitive indicator added to a proton forming esterase reaction were used to visually distinguish catalyst containing beads in the presence of unmodified 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. In addition, these analyses showed that product diffusion through the bead was slow for the reactions studied since products concentrated near the beads’ surface at times less than 20 minutes. This method was then applied to the development of a metalcomplexed peptide catalyst for the catalytic hydrolysis of para-nitrophenyl esters. While the array-based screening method seemed compatible with this reaction, the detection of site-selective catalytic activity was unattainable using this method in its present state due to slow rates of the catalytic reaction.