Carbonic anhydrase mimics with rationally designed active sites for fine-tuned catalytic activity and selectivity in ester hydrolysis

Numerous hydrolytic enzymes utilize zinc as a cofactor for catalysis. We here report water-soluble polymeric nanoparticles with zinc ions in active sites and a nearby base as a mimic of carbonic anhydrase (CA). Their pK(a) of 6.3–6.4 for zinc-bound water is lower than the 6.8–7.3 value for natural enzymes, which allows the catalyst to hydrolyze nonactivated alkyl esters under neutral conditions—a long sought-after goal for artificial esterases. The size and shape of the active site can be rationally tuned through a template used in molecular imprinting. Subtle structural changes in the template, including shifting an ethyl group by one C–N bond and removal of a methylene group, correlate directly with catalytic activity. A catalyst can be made to be highly specific or have broad substrate specificity through modular synthesis of templates.