The platinum-based chemotherapy drug, cisplatin, has proven effective in the treatment of testicular cancer. Despite its success, severe side effects often result from treatment with cisplatin due to its lack of specificity for cancer cells. Additionally, certain cell lines have been shown to acquire resistance to platinum drugs that crosslink DNA in a manner similar to cisplatin. These issues with cisplatin have led to a search for new compounds that are more specific to tumor regions and are active in cisplatin-resistant cell lines. Several dirhodium (II,II) complexes have been shown to be inert toward cells until activated with visible light, thus providing spatial control over the treatment area for regions containing the complex that are irradiated. The two complexes cis-H,H-[Rh2(HNOCCH3)2(L)(CH3CN)4]2+ where L represents bpy (1, 2,2´-bipyridine) and dppz (2, dipyrido[3,2-a:2′,3′-c]phenazine) both contain acetonitrile ligands that exchange with solvent H2O molecules following irradiation with visible light. Both 1 and 2 were shown to be unreactive toward DNA in the dark. However, ESI-MS experiments show that the photoproducts of 1 and 2 covalently bind to DNA following irradiation with visible light. The present work investigates the photoinduced reaction of 1 and 2 with the 6-mer oligonucleotide d(GTCGAC)2 using 2-D 1H—H1 NOESY NMR. The change in chemical shifts of the DNA protons suggests that both 1 and 2 undergo photoinduced covalent binding to the terminal guanine base of the duplex. Furthermore, the dppz ligand of 2 was shown to shield the terminal cytosine protons, which indicates that the complex is end-capping the duplex rather than intercalating between adjacent base pairs. The photoinduced interactions of 1 and 2 with DNA as well as their non-crosslinking binding mode make them promising potential light-activated chemotherapy agents.

Photoinduced dual-binding by dirhodium (II,II) complexes with DNA

249th National Meeting (2015)

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