Effect of divalent metal ions on the intramolecular nucleophilic catalysis of phosphate diester hydrolysis

Recent investigations^{1, 2} have demonstrated that remarkable rate enhancements may be obtained in the hydrolysis of phosphate diesters by suitably positioning nucleophilic groups within the reacting molecule. Moreover, these reactions are thought to proceed via metastable pentacovalent intermediates owing to the magnitude of the rate enhancements (10⁴-10⁸), high sensitivity to changes in leaving group pK_a (β = — 1.2), and the marked preference (>90%) for exocyclic ligand loss. We wish to report that the rates for these intramolecular systems are significantly increased by biologically important divalent metal ions and include an important example of Mg²⁺ ion catalysis. The data furthermore suggest that a major fraction of the metal ion catalysis may arise from a unique stabilizing interaction between the metal ion and the intermediate pentacovalent species.