Royal Society of Chemistry, Dalton Transactions, 31(44), p. 13914-13925
DOI: 10.1039/c5dt01105a
Full text: Unavailable
The interaction of the anticancer Ru(III) complex AziRu - in comparison with its analogue NAMI-A, currently in advanced clinical trials as an antimetastatic agent - with DNA model systems, both single strand and duplex oligonucleotides, was investigated using a combined approach, including absorption UV-vis spectroscopy, circular dichroism (CD) and electrospray mass spectrometry (ESI-MS) techniques. Absorption spectra of the Ru complexes were registered at different times in a pseudo-physiological solution, to monitor the ligand exchange processes in the absence and in the presence of the examined oligonucleotides. CD experiments provided information on the overall conformational changes of the DNA model systems induced by these metal complexes. UV- and CD-monitored thermal denaturation studies were performed to analyse the effects of NAMI-A and AziRu on the stability of the duplex structures. ESI-MS experiments, carried out on the oligonucleotide/metal complex mixtures under investigation, allowed to detect the formation of stable adducts between the guanine-containing oligomers and the ruthenium complexes. These data unambiguously demonstrate that both AziRu and NAMI-A can interact with DNA model systems. The two metal compounds, although very similar in structure, manifest a markedly different reactivity with the analysed sequences, with respectively either a naked Ru3+ ion or a Ru(Im)3+ (Im=imidazole) fragment being incorporated into the oligonucleotide structure via stable linkages.