Artificial esterase for cooperative catalysis of ester hydrolysis at pH 7

Abstract

Ester is one of the most prevalent functional groups in natural and man-made products. Natural esterases hydrolyze nonactivated alkyl esters readily but artificial esterases generally use highly activated p-nitrophenyl esters as substrates. We report synthetic esterases constructed through molecular imprinting in cross-linked micelles. The water-soluble nanoparticle catalysts contain a thiouronium cation to mimic the oxyanion hole and a nearby base to assist the hydrolysis. Whereas this catalytic motif readily affords large rate acceleration for the hydrolysis of p-nitrophenyl hexanoate, nonactivated cyclopentyl hexanoate demands catalytic groups that can generate a strong nucleophile (hydroxide) in the active site. The hydroxide is stabilized by the protonated base when the external solution is at pH 7, enabling the hydrolysis of activated and nonactivated esters under neutral conditions.