Metal-catalyzed phosphodiester cleavage: secondary 18O isotope effects as an indicator of mechanism

Information about the transition states of metal-catalyzed hydrolysis reactions of model phosphate compounds has been obtained through determination of isotope effects (IEs) on the hydrolysis reactions. Metal complexation has been found to significantly alter the transition state of the reaction from the alkaline hydrolysis reaction, and the transition state is quite dependent on the particular metal ion used. For the diester, ethyl p-nitrophenyl phosphate, the nonbridge 18O effect for the hydrolysis reactions catalyzed by Co(III) 1,5,9-triazacyclononane and Eu(III) were 1.0006 and 1.0016, respectively, indicative of a slightly associative transition state and little net change in bonding to the nonbridge oxygen. The reaction catalyzed by Zn(II) 1,4,7,10-tetraazacyclododecane had an 18O nonbridge IE of 1.0108, showing the reaction differs significantly from the reaction of the noncomplexed diester and resembles the reactions of triesters. Reaction with Co(III) 1,4,7,10-tetraazacyclododecane showed an inverse effect of 0.9948 reflecting the effects of bonding of the diester to the Co(III). Lanthanide-catalyzed hydrolysis has been observed to have unusually large 15N effects. To further investigate this effect, the 15N effect on the reaction catalyzed by Ce(IV) bis-Tris propane solutions at pH 8 was determined to be 1.0012. The 15N effects were also measured for the reaction of the monoester p-nitrophenyl phosphate by Ce(IV) bis-Tris propane (1.0014) and Eu(III) bis-Tris propane (1.0012). These smaller effects at pH 8 indicate that a smaller negative charge develops on the nitrogen during the hydrolysis reaction.