Synthesis, characterization and interactions with the oligonucleotide d(5′-CGCGAATTCGCG-3′)2, of bis(terpyridine)ruthenium(II)–peptide conjugates

The homoleptic [Ru(trpyCO-TrpCONH2)2](PF6)2 (1), [Ru(trpyCO-Gly-TrpCONH2)2](PF6)2 (2) and the heteroleptic complexes [Ru(trpy)(trpyCO-TrpCONH2)](PF6)2 (3), [Ru(trpy)(trpyCO-Gly-TrpCONH2)](PF6)2 (4), where trpyCO-TrpCONH2 and trpyCO-Gly-TrpCONH2 are 2,2′:6′,2″-terpyridine-4-carboxylic acid-tryptophanamide and 2,2′:6′,2″-terpyridine-4-carboxylic acid-glycyl-tryptophanamide respectively, were synthesized and characterized by various spectroscopic and analytical techniques. The interactions of complexes (1) and (4) with the oligonucleotide d(5′-CGCGAATTCGCG-3′)2 were studied by means of NMR spectroscopy. Both complexes bound very weakly to the oligonucleotide, perturbing slightly the helix from B-form, probably through electrostatic interactions between the positive charge of the complexes and the DNA phosphates. In the case of complex (1), the conjugated tryptophane did not approach the oligonucleotide helix, as in the case of complex (4), the unsubstituted trpy of which was clearly orientated towards the oligonucleotide helix. These observations indicate that the bulky substitute on the ligand trpy reduces the binding affinity of the complexes to DNA, allowing only electrostatic interactions. However, complex (4) shows high cytotoxicity against LMS, MCF-7, U2OS and K562 cancer cell lines, with IC50 values ranging 0.464–0.925 μM, which can be attributed to a non classical mechanism for metal based anticancer agents.