pH luminescence switch, DNA binding and photocleavage, and cytotoxicity of a dinuclear ruthenium complex

Abstract

The ground- and excited-state acid-base properties of [Ru2(bpy)4(H2bipt)]Cl4 1 {bpy = 2,2'-bipyridine, H2bipt = 2,5-bis[1,10]phenanthrolin[4,5-f]-imidazol-2-yl)thiophene} are investigated by emission and UV-visible absorption spectrophotometric pH titrations. The DNA binding properties of 1 are studied by means of DNA viscosity and optical spectroscopic techniques of UV-visible absorption and emission spectral titrations, steady-state emission quenching with ferrocyanide, ethidium bromide competitive binding, and DNA thermal denaturation as well as density functional theoretical calculations. The DNA photocleavage and singlet oxygen generation properties as well as in vitro anticancer activities against five cancer cell lines are studied as well. The results demonstrated that pH-induced luminescence switching, DNA binding, and anticancer properties of 1 are much improved with respect to those of the mononuclear analog [Ru(bpy)2(Htip)]Cl2 {Htip = 2-(thiophen-2-yl)-1H-imidazo[4,5-f][1,10]phenanthroline}.

Off–on–off pH luminescence switching and DNA binding properties of a free terpyridine-appended ruthenium complex

“…[60], and falls into the rather broad ΔT m range of 5.9 to 19.3°C previously reported for analogous Ru(II) complex-based DNA intercalators under identical experimental conditions with [Ru]/DNA = 0.10 [37][38][39][40][41][42][43][44][45]. In addition, this ΔT m value is similar to a ΔT m value of 9.3°C that we have recently reported for a Ru(II) complex DNA binder with a mixed binding mode involving classic intercalation plus partial intercalation [23], and greater than only small T m increases of ≤ 2 and 3°C previously reported for an organic DNA binder of 1,4,7,10-tetraazacyclododecane appended with two anthracenyl moieties that showed mixed binding modes of partial intercalator and groove binding [61], and partially intercalative Ru(II) complex of [Ru(H 2 PDTA)(phen)]Cl (H 4 PDTA = propylene-1,2-diaminetetra-acetic acid) [32], respectively.…”

“…In contrast, a partial or non-classical intercalation mode would bend (or kink) the DNA strands reducing the effective length of the DNA molecule as well as the DNA viscosities. In addition, electrostatic and groove bindings have a little effect on DNA viscosities [23]. It could be anticipated that these two opposite effects would be offset if the mixed binding modes of classic intercalation and partial intercalation coexist, which would result in slightly decreased [23] or increased DNA viscosities.…”

“…Because RuHL 1 strongly binds to the DNA with a K b value on the order of 10 5 -10 6 M − 1 , we tentatively assign the DNA-induced two-stage emission changes to a transition from predominantly classic intercalation to predominantly partial intercalation. The presence of mixed DNA binding modes is common for the purely organic [55] and Ru complex [23,27] DNA binders.…”

“…For example, a large luminescence on-off ratio of 100 has been achieved for a Ru(II) complex (i.e., [(bpy) 2 Ru(ebipc)Ru(bpy) 2 ] 4 + , where bpy = 2,2′-bipyridine and ebipc = N-ethyl-4,7-bis( [1,10]phenanthroline [5,6-f]imidazol-2-yl)carbazole) [21]. However, the development of highly efficient on-off switching in the luminescence of imidazole-containing Ru(II) complexes in the acidic pH region remains challenging [22,23].…”

“…During the last three decades, ruthenium polypyridyl complexes have attracted considerable attention as pH sensors due to their sensitive response to environmental pH variations, high luminescence quantum yields and long excited-state lifetimes that can be discriminated from background fluorescence, affording the possibility of lifetime-based sensing with high sensitivity and precision [9]. The protonatable/deprotonatable groups of carboxylic acid [10][11][12][13], pyridine [14], hydroxyl [15][16][17], phosphonic acid [18], and imidazole [19][20][21][22][23] could efficiently tune the photophysical properties of Ru(II) complexes for on-off switching luminescence and colorimetric sensing of pH. Among these protonatable/deprotonatable groups, protonation/ deprotonation of imidazole groups could significantly alter the absorption, electrochemical and photoelectrochemical properties of Ru(II) complexes.…”