cis-[PtCl2(15NH3)(c-C6H11NH2)]
is an active metabolite of the oral platinum(IV) anticancer drug
cis,trans,cis-[PtCl2(CH3CO2)2(NH2)(c-C6H11NH2)].
Since it is likely that guanine bases on DNA are targets for this drug, we
have analysed the kinetics of reaction of this platinum(II) metabolite with
guanosine 5′-monophosphate (5′-GMP) at 310 K, pH 7, using
[1H, 15N] n.m.r.
methods. Reactions of the trans isomer are reported for
comparison. The 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
trans 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 trans influence of Cl¯, whereas the
rate of the second aquation step (trans to N7 of
5′-GMP) is comparable to that trans to
NH3. These findings have implications for the courses of
reactions with DNA.
