Benzothiazole bipyridine complexes of ruthenium(II) with cytotoxic activity

Spillane, Caitriona B. and Fletcher, Nicholas C. and Rountree, Sandra M. and Van Den Berg, Hendrik and Chanduloy, Severine and Morgan, Joy L. and Keene, F. Richard (2007) Benzothiazole bipyridine complexes of ruthenium(II) with cytotoxic activity. Journal of Biological Inorganic Chemistry, 12 (6). pp. 797-807. ISSN 0949-8257

Abstract

A series of benzothiazole-substituted trisbipyridine ruthenium(II) analogues {[Ru(bpy)2(4,5′-bbtb)]2+, [Ru(bpy) 2(5,5′-bbtb)]2+ and [Ru(bpy)2(5-mbtb)] 2+ [bpy is 2,2′-bipyridine, bbtb is bis(benzothiazol-2-yl)-2, 2′-bipyridine, 5-mbtb is 5-(benzothiazol-2-yl),5′-methyl-2,2′- bipyridine]} have been prepared and compared with the complex [Ru(bpy) 2(4,4′-bbtb)]2+ reported previously. From the UV-vis spectral studies, substitution at the 5-position of the bpy causes the ligand-centred transitions to occur at considerably lower energy than for those with the functionality at the 4-position, while at the same time causing the emission to be effectively quenched. However, substitution at the 4-position causes the metal-to-ligand charge transfer to occur at lower energies. Fluorescent intercalator displacement studies indicate that the doubly substituted complexes displace ethidium bromide from a range of oligonucleotides, with the greater preference shown for bulge and hairpin sequences by the Λ enantiomer. Since the complexes only show small variation in the UV-vis spectra on the introduction of calf thymus DNA and a small increase in fluorescence they do not appear to be intercalators, but appear to associate within one of the grooves. All of the reported bisbenzothiazole complexes show reasonable cytotoxicity against a range of human cancer cell lines.