Structure and reactivity of phosphate diesters. Dependence on the nonleaving group

The hydrolytic reactivity of simple phosphate diesters with very good leaving groups is known to be practically independent of the nonleaving group at 100 degrees C. Calculations on the (too slow to measure) hydrolysis at 25 degrees C of a series of p-nitrophenyl diesters ROPO2--OpNP with a wide range of nonleaving group OR indicate a small but significant effect at the lower temperature, making the R = methyl ester the most reactive. This is in the opposite sense to the much larger effect observed for the reactions of triesters and consistent with a reaction driven primarily by leaving group departure. The calculations use a continuum model with up to four discrete water molecules: two or three waters give the best results.