Hydrolytic activity of a dinuclear copper(II,II) complex in phosphate diester and DNA cleavage

The hydrolysis of the phosphate diester bis(2,4-dinitrophenyl) phosphate promoted by the dinuclear copper (II,II) complex [Cu2(H2bbppnol)(μ-CH3COO)(H2O)2)]Cl2·2H2O 1 (Inorg. Chim. Acta 281 (1998) 111) in aqueous–methanol solution at 50 °C was examined in detail. A pH dependence on the reaction rate was observed and the pKa value calculated from the pH-rate profile is in good agreement with that determined by potentiometric titration, indicating that deprotonation of one of the two water-coordinated molecules in the complex must occur to form the active catalyst. The rate of phosphate diester hydrolysis was studied as a function of catalyst and substrate concentrations and a mechanism for the hydrolysis reaction based on intramolecular hydroxide attack on the metal-coordinated phosphate is proposed. A rate enhancement factor of 26 was calculated relative to that measured for the uncatalyzed reaction under identical conditions. The complex effectively promoted the cleavage of double-strand plasmid and genomic DNA, at physiological pH and temperature. Studies into the mechanism strongly suggest that the dinuclear copper (II,II) complex mediates a hydrolytic attack on the phosphodiester backbone through cooperativity between the two metal centers, in agreement with the mechanism proposed for the reaction of 1 with the model substrate bis(2,4-dinitrophenyl) phosphate.