[H-1,(15) N] NMR kinetic studies of reactions of cis- and trans-[PtCl2((NH3)-N-15)(c-(C6H11NH2)-N-15)] with guanosine 5 '-monophosphate

cis-[PtCl2((NH3)-N-15)(c-C6H11NH2)] is an active metabolite of the oral pla tinum(IV) anticancer drug cis,trans,cis-[PtCl2(CH3CO2)(2)(NH3)(c-C6H11NH2)] . Since it is likely that guanine bases on DNA are targets for this drug, w e have analysed the kinetics of reaction of this platinum(II) metabolite wi th guanosine 5'-monophosphate (5'-GMP) at 310 K, pH 7, using [H-1, N-15] n. m.r. methods. Reactions of the trans isomer are reported for comparison. Th e reactions proceed via aquated intermediates, and, for the cis isomer, the rates of aquation and substitution of H2O by 5'-GMP are 2-5 times faster t rans to the amine ligand (c-C6H11NH2) compared to trans to NH3 for both the first and second steps. For the trans complex, the first aquation step is c. 3 times faster than for the cis complex, as expected from the higher tra ns influence of Cl-?, whereas the rate of the second aquation step (trans t o N7 of 5'-GMP) is comparable to that trans to NH3. These findings have imp lications for the courses of reactions with DNA.