INTERACTION OF BIS(PLATINUM) COMPLEXES WITH THE MONONUCLEOTIDE 5'-GUANOSINE MONOPHOSPHATE - EFFECT OF DIAMINE LINKER AND THE NATURE OF THE BIS(PLATINUM) COMPLEX ON PRODUCT FORMATION

The reactions of bis(platinum) complexes containing bidentate or monodentate coordination spheres with the mononucleotide guanosine 5'-monophosphate (GMP) have been studied in solution by H-1 and Pt-195 NMR spectroscopy. The structures of the complexes are [{cis-PtCl2(NH3)}2(diamine)] (bidentate coordination spheres, 2,2/c,c) and [{trans-PtCl-(NH3)2}2(diamine)]Cl2 (Monodentate coordination spheres, 1,1/t,t) where diamine = 1,4-butanediamine (NH2(CH2)4NH2, BN) or 2,5-dimethyl-2,5-hexanediamine (NH2C(CH3)2(CH2)2C(CH3)2NH2, TMET). The 2,2/c,c complexes were studied as the aqua species [{cis-Pt(H2O)2(NH3)}2(diamine)]4+ by reaction of the iodide with 4 equiv of AgNO3 in water. In the case of the monodentate bis(platinum) complexes, the stepwise substitution of two GMP groups is easily seen, giving [{trans-Pt-(GMP) (NH3)2}2(diamine)]. The rate of reaction at 30-degrees-C as measured by t1/2 from the spectra was faster with TMET (3.5 h) than with BN (4.5 h). For bis(platinum) complexes with bidentate coordination spheres, the final product is [{cis-Pt-(GMP)2 (NH3)}2(diamine)]4- but the mode of formation is dependent on the diamine. Whereas no intermediate species were observed with the linear NH2(CH2)4NH2, the sterically more demanding NH2C(CH3)2(CH2)2C(CH3)2NH2 gave in the initial stages of the reaction the species with only one GMP bound to each Pt [{Pt(GMP)(H2O)(NH3)}2(diamine)). All GMP ligands are N7 bound. The reactions are discussed in relation to the DNA binding and antitumor activity of the complexes.