Structure-Reactivity Correlation for the Hydrolysis of Phosphoramidate Monoanions

Eric J. Sampson, Stephen Benkovic

Research output: Contribution to journalArticle

78 Citations (Scopus)

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
StatePublished - Jan 1 1971

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Amines
Hydrolysis
Nucleophiles
Rate constants
Rubiaceae
Phosphates
phosphoramidic acid

All Science Journal Classification (ASJC) codes

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

Cite this

Sampson, Eric J. ; Benkovic, Stephen. / Structure-Reactivity Correlation for the Hydrolysis of Phosphoramidate Monoanions. In: Journal of the American Chemical Society. 1971 ; Vol. 93, No. 16. pp. 4009-4016.
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Structure-Reactivity Correlation for the Hydrolysis of Phosphoramidate Monoanions. / Sampson, Eric J.; Benkovic, Stephen.

In: Journal of the American Chemical Society, Vol. 93, No. 16, 01.01.1971, p. 4009-4016.

Research output: Contribution to journalArticle

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N2 - 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.

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