Kinetics and mechanism of hydrolysis of a model phosphate diester by [Cu(Me3tacn)(OH2)2]2+ (Me3tacn=1,4,7-trimethyl-1,4,7-triazacyclononane)

Abstract

The kinetics of hydrolysis of bis(p-nitrophenyl)phosphate (BNPP) by [Cu(Me3tacn)(OH2)2]2+ has been studied by spectrophotometrical monitoring of the release of the p-nitrophenylate ion from BNPP. The reaction was followed for up to 8000 min at constant BNPP concentration (15 M) and ionic strength (0.15 M) and variable concentration of complex (1.0-7.5 mM) and temperature (42.5-65.0 C). Biphasic kinetic traces were observed, indicating that the complex promotes the cleavage of BNPP to NPP [(p-nitrophenyl)phosphate] and then cleavage of the latter to phosphate, the two processes differing in rate by 50-100-fold. Analysis of the more amenable cleavage of BNPP revealed that the rate of BNPP cleavage is among the highest measured for mononuclear copper(II) complexes and is slightly higher than that reported for the close analogue [Cu(iPr3tacn)(OH2)2]2+. Detailed analysis required the determination of the pKa for [Cu(Me3tacn)(OH2)2]2+ and the constant for the dimerization of the conjugate base to [(Me3tacn)Cu(OH)2Cu(Me3tacn)]2+ (Kdim). Thermodynamic parameters derived from spectrophotometric pH titration and the analysis of the kinetic data were in reasonable agreement. Second-order rate constants for cleavage of BNPP by [Cu(Me3tacn)(OH2)(OH)]+ and associated activation parameters were obtained from initial rate analysis (k = 0.065 M-1 s-1 at 50.0 C, H = 56 ± 6 kJ mol-1, S = -95 ± 18 J K-1 mol-1) and biphasic kinetic analysis (k = 0.14 M-1 s-1 at 50.0 C, H = 55 ± 6 kJ mol-1, S = -92 ± 20 J K-1 mol-1). The negative entropy of activation is consistent with a concerted mechanism with considerable associative character. The complex was found to catalyze the cleavage of BNPP with turnover rates of up to 1 per day. Although these turnover rates can be considered low from an application point of view, the ability of the complexes to catalyze phosphate ester cleavage is clearly demonstrated.