[1H,15N] N.M.R. Kinetic Studies of Reactions of cis- and trans-[PtCl2(15NH3)(c-C6H1115NH2)] with Guanosine 5'-Monophosphate
Barton, Sarah J., Barnham, Kevin J., Habtemariam, Abraha, Frey, Urban, Sue, Rodney and Sadler, Peter J. (1999) [1H,15N] N.M.R. Kinetic Studies of Reactions of cis- and trans-[PtCl2(15NH3)(c-C6H1115NH2)] with Guanosine 5'-Monophosphate. Australian Journal of Chemistry, 52 (3). pp. 173-177. ISSN 0004-9425 (print), 1445-0038 (electronic)Full text not available from this repository.
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.
|Uncontrolled Keywords:||guanosine 5′-monophosphate|
|Subjects:||Q Science > QD Chemistry|
|School / Department / Research Groups:||School of Computing & Mathematical Sciences|
School of Computing & Mathematical Sciences > Computer & Computational Science Research Group
|Last Modified:||16 Aug 2012 15:21|
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