Interactions of dinuclear transition metal carboxylates with DNA

Cisplatin, cis-PtCl2(NH3)2, is widely used as a chemotherapeutic agent in the treatment of cancers such as testicular cancer and some cancers of the neck, breast and lung. The covalent binding of two adjacent intrastrand guanine bases through their respective N7 atoms is considered to be the accepted mechanistic pathway of cisplatin's anticancer activity. Compounds of other transition metal compounds have been known to exhibit considerable anticancer activity that is also described as direct metal-DNA interactions. The exact modes of binding as well as the preferred binding sites by which dinuclear transition metal carboxylates of Ru, Rh and Re of the type M2(O2CR)4 and M2(DTolF) 2(O2CCF3)2 (M = Mo, Ru, Rh and Re; R = CH3, CH2CH3, CH2CH 2CH3; DTolF = di-p-tolylformamidinate) interact with DNA is unknown. Recent studies in our laboratories of dinuclear metal carboxylates have elucidated unprecedented bridging modes for the nucleobases 9-ethylguanine and 9-ethyladenine. PCR studies indicate that the replication process is concentration dependent, and is inhibited by the covalent binding of these compounds to the template strand. The synthesis and characterization of the reaction products of these metal compounds with the twelve base pair oligonucleotide, d(5-CCT CTG GTC TCC-3), as well as a deoxyguanylate dinucleotide have also been performed. The PCR results along with 1H NMR spectroscopic, HPLC and X-ray crystallographic results will be presented.

Interactions of dinuclear transition metal carboxylates with DNA Academic Article