Intramolecular and Divalent Metal Ion Catalysis. The Hydrolytic Mechanism of O-Phenyl N-(Glycyl)phosphoramidate

The pH-rate profile for the hydrolysis of O-phenyl N-(glycyl)phosphoramidate (II) reveals intramolecular catalysis by the neighboring carboxylate function which serves to accelerate greatly the rate of P-0 bond cleavage. In fact, P-0 bond fission in the reference compound, O-(phenyl)phosphoramidate (I), is not detected. The catalysis of II is further enhanced (>10²) by the addition of Zn²⁺ or Mg^{2 +} ions, which do not affect the rate of hydrolysis of I. A mechanism is postulated featuring formation of a five-membered cyclic acyl phosphate (product studies in hydroxylamine buffer) which decomposes via water attack on phosphorus rather than carbon (¹⁸O tracer experiments). These findings suggest that two types of biologically important catalysis may be incorporated into a model system in order to confer dramatic reactivity on a normally unreactive phosphate diester. These results contrast with the Cu(II)-catalyzed hydrolysis of salicyl phosphate, which apparently is of the general- acid type with carboxylate merely serving as a coordinating ligand.