Microenvironmental engineering of active sites for selective catalytic hydrolysis of acetals

Rational design of synthetic catalysts that mimic enzymes in catalysis and substrate selectivity is a long-standing goal of chemists. We report bottom-up synthesis of artificial acetal hydrolase that hydrolyzes its substrate with high selectivity under otherwise impossible neutral and basic conditions. Our synthetic method allows facile modification of the active site, including introduction of a local water pool near the acetal group of the bound substrate to alter the catalytic mechanism or installment of a secondary catalytic group to enhance the catalytic activity.