1H nmr spectroscopic studies of dinuclear transition metal carboxylates with dna oligonucleotides
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abstract
The use of cisplatin, cis-PtCl2(NH3)2, as an accepted anticancer agent in conjunction with chemotherapy has been widely accepted for over twentyfive years. The accepted mechanism of action of cisplatin is considered to be the covalent binding of two adjacent guanine bases through their respective N7 atoms. In recent years similar metal-DNA interactions involving other transition metal compounds have been implicated, but these interactions were reported to be with single-stranded DNA of high adenine content. Furthermore, the adenine binding to the metal centers were proposed as monodentate interactions through the N7 atoms of the purines only. Studies in our laboratories involving model reactions of transition metal carboxylate compounds of the type M2(O2CR)4 and M(DTolF)2(O2CCFa)2 (M = Mo, Ru, Rh and Re; R = CH3, CH2CH3, CH2CH 2CH3; DToIF = di-p-tolylformamidinate) and 9-ethylguanine as well as 9-ethyladenine elucidated an unprecedented bridging mode for the purines involving the N7 and N6/O6 atoms. These results led us into the investigation of what type of interactions would result with oligonucleotides. 1H NMR spectroscopic studies of dinuclear transition metal carboxylates reacted with a twelve base pair oligonucleotide, d(5-CCT CTG GTC TCC-3), which was recently reported in a solid state structure with cisplatin, have been performed. The results of these studies will be presented and compared to results previously reported for cisplatin.
