REACTIONS OF UNSYMMETRICALLY SUBSTITUTED DERIVATIVES OF CISPLATIN WITH SHORT OLIGODEOXYNUCLEOTIDES CONTAINING A -GPG- SEQUENCE - H-BONDING INTERACTIONS IN PGPG MOIETIES CROSS-LINKED BY AN ASYMMETRIC PLATINUM COMPLEX ENHANCING THE FORMATION OF ONE GEOMETRICAL ISOMER

The interaction of unsymmetrically substituted cisplatin derivatives [general formula cis-Pt(LL'), L = NH3: L' = CH3NH2 (Pt-mma); L' = CH3CH2NH2 (Pt-mea); L' = NH(CH3)2 (Pt-dma)] with d(GpG), d(pGpG), and d(CpGpG) has been studied by H-1 and P-31 NMR spectroscopy. The formation of two geometrical isomers, which were proven to be GN7,GN7 chelates, is slightly influenced by the presence of a 5'-phosphate group and a C base, enhancing the formation of the geometrical isomer with the NH3 ligand located cis to the 5'G base, thus allowing H bonding toward the 5'-phosphate group. This is only the second clearly performed study demonstrating a correlation between P-31 shifts and H bonding. The complexation rate of cis-PtCl2(NH3)(Am) toward d(GpG) follows the order CH3NH2 > NH3 greater-than-or-equal-to CH3CH2NH2 > (CH3)2NH. In addition cytotoxicity data of various human tumor cell lines for these asymmetric Pt amine complexes are reported and compared with cisplatin and carboplatin.