Nucleophilic versus general base catalysis in phosphyl (P^v) group transfer: Application to α-chymotrypsin action

The hydrolysis of aryl dimethylphosphinates is shown to be catalysed via a nucleophilic pathway by a series of bases including imidazole which is less efficient than phosphate dianion. The more reactive nucleophilic pathway is allowed because dimethylphosphinate is less sterically hindered than diphenyl phosphinate where general base-catalysis predominates. Acylation of α-chymotrypsin by 4-nitrophenyl diphenylphosphinate, a bona fide general base mechanism, has a low solvent deuterium oxide isotope effect not characteristic of such a mechanism.