文摘
Many transition metal complexes mediate DNA oxidation in the presence of oxidizing radiation,photosensitizers, or oxidants. The final DNA oxidation products vary depending on the nature of metalcomplexes and the structure of DNA. Here we propose a mechanism of oxidation of a nucleotide,deoxyguanosine 5'-monophosphate (dGMP) by trans-d,l-1,2-diaminocyclohexanetetrachloroplatinum (trans-Pt(d,l)(1,2-(NH2)2C6H10)Cl4, [PtIVCl4(dach)]; dach = diaminocyclohexane) to produce 7,8-dihydro-8-oxo-2'-deoxyguanosine 5'-monophosphate (8-oxo-dGMP) stoichiometrically. The reaction was studied by high-performance liquid chromatography (HPLC), 1H and 31P nuclear magnetic resonance (NMR), andelectrospray ionization mass spectrometry (ESI-MS). The proposed mechanism involves PtIV binding toN7 of dGMP followed by cyclization via nucleophilic attack of a phosphate oxygen at C8 of dGMP. Thenext step is an inner-sphere, two-electron transfer to produce a cyclic phosphodiester intermediate,8-hydroxyguanosine cyclic 5',8-(hydrogen phosphate). This intermediate slowly converts to 8-oxo-dGMPby reacting with solvent H2O.
