Structure-Reactivity Correlation for the Hydrolysis of Phosphoramidate Monoanions

Eric J. Sampson, Stephen J. Benkovic

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Abstract

The structure-reactivity relationship which correlates the rate constants for the hydrolysis of phosphoramidate monoanions with the pKaof the leaving amine is nonlinear. The inflection point in the data which occuss at pKa≈ 8 is attributed to changes in the nonsteady-state zwitterion concentration which are directly proportional to the pKaof the parent amine. The equilibrium favors the zwitterionic species in aqueous solution for those phosphoramidates whose second dissociation constant is greater than 7.2. On the basis of these data, a semiquantitative description of the transition state for nucleophilic attack on phosphoramidates is developed which features bond cleavage to the departing group as greatly exceeding bond formation to the incoming nucleophile. This finding in conjunction with data for O- and S-phosphate mon- and diesters suggests that penta-covalent intermediates probably do not occur on the reaction pathways for acyclic mon- and diester hydrolysis.

Original languageEnglish (US)
Pages (from-to)4009-4016
Number of pages8
JournalJournal of the American Chemical Society
Volume93
Issue number16
DOIs
Publication statusPublished - Jan 1 1971

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All Science Journal Classification (ASJC) codes

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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