MECHANISTIC STUDIES OF HLORO(1,4,7-TRIAZACYCLONONANE)COPPER(II)-CATALYZED PHOSPHATE DIESTER HYDROLYSIS

In order to explore the role of labile metal complexes in promoting ph osphodiester hydrolysis, detailed kinetic and mechanistic studies with Cu[9]aneN(3)Cl(2) (1) were performed. The hydrolysis of bis(4-nitroph enyl) phosphate (2) by 1 is catalytic, as determined by the observatio n of both rate enhancement and turnover. The catalyst is selective for phosphodiesters; the rate of hydrolysis for 4-nitrophenyl phosphate ( 4) is 50 times slower than the hydrolysis rate of 2. A rate enhancemen t of 2000 is observed relative to hydroxide ion mediated hydrolysis, a nd the rates reported herein are comparable to the rates reported for phosphodiester hydrolysis by other labile metal complexes. The reactio n of 1 with 2 showed a half-order dependence on the catalyst, implicat ing a monomer-dimer equilibrium with the monomer as the catalyst. The kinetically determined equilibrium constant is 1220 M(-1), favoring th e dimer. The reaction of 1 with ethyl 4-nitrophenyl phosphate (3) foll ows Michaelis-Menten kinetics (K-M = 62.3 mM and k(cat) = 1.96 x 10(-5 ) s(-1)), providing evidence for the formation of a catalyst-substrate complex. The pH vs rate profile indicates that deprotonation of the m etal-coordinated water (pK(1) = 7.3) occurs to form the active catalys t, and the reaction becomes pH independent above pH 8.5. The activatio n parameters for 3 hydrolysis by 1 (pH 9.0) are Delta H double dagger = 90 kJ mol(-1) and Delta S double dagger = -128 J mol(-1) K-1. A mech anism consistent with the kinetic data is presented.