A quantitative appraisal of the ambivalent metal ion binding properties of cytidine in aqueous solution and an estimation of the anti–syn energy barrier of cytidine derivatives

The dichlorobis(2-phenylazopyridine)ruthenium(II) complexes, [Ru(azpy)2Cl2], are under renewed investigation due to their potential anticancer activity. The three most common isomers (chi)- ,(beta)- and (gamma)-[RuL2Cl2] with L=o-tolylazopyridine (tazpy) and 4-methyl-2phenylazopyridine (mazpy) ((chi)indicating the coordinating Cl, N(pyridine) and Nazo atoms in mutual cis, trans, cis positions,(beta)indicating the coordinating Cl, N(pyridine) and Nazo atoms in mutual cis, cis, cis positions, and indicating the coordinating Cl, N(pyridine) and Nazo atoms in mutual trans, cis, cis positions) are synthesized and characterized by NMR spectroscopy. The molecular structures of (gamma)-[Ru(tazpy)2Cl2] and (alpha)-[Ru(mazpy)2Cl2] are determined by X-ray diffraction analysis. The IC50 values of the geometrically isomeric [Ru(tazpy)2Cl2] and [Ru(mazpy)2Cl2] complexes compared with those of the parent [Ru(azpy) 2Cl2] complexes are determined in a series of human tumour cell lines (MCF-7, EVSA-T, WIDR, IGROV, M19, A498 and H266). These data unambiguously show for all complexes the following trend: the (alpha) isomer shows a very high cytotoxicity, whereas the (beta) isomer is a factor 10 less cytotoxic. The (gamma) isomers of [Ru(tazpy)2Cl2] and [Ru(mazpy)2Cl2] display a very high cytotoxicity comparable to that of the (gamma) isomer of the parent compound [Ru (azpy)2Cl2] and to that of the (alpha) isomer. These biological data are of the utmost importance for a better understanding of the structure–activity relationships for the isomeric [RuL2Cl2] complexes.