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

Eric J. Sampson, John Fedor, Patricia A. Benkovic, Stephen J. Benkovic

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

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 Mg2 + 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.

Original languageEnglish (US)
Pages (from-to)1301-1306
Number of pages6
JournalJournal of Organic Chemistry
Volume38
Issue number7
DOIs
StatePublished - Apr 1 1973

All Science Journal Classification (ASJC) codes

  • Organic Chemistry

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