NO Releasing and Anticancer Properties of Octahedral Ruthenium–Nitrosyl Complexes with Equatorial 1H-Indazole Ligands

International audience; With the aim of enhancing the biological activity of ruthenium−nitrosyl complexes, new compounds with four equatorially bound indazole ligands, namely, trans-[RuCl(Hind) 4 (NO)]Cl 2 •H 2 O ([3]Cl 2 •H 2 O) and trans-[RuOH(Hind) 4 (NO)]Cl 2 •H 2 O ([4]Cl 2 •H 2 O), have been prepared from trans-[Ru(NO 2) 2 (Hind) 4 ] ([2]). When the pH-dependent solution behavior of [3]Cl 2 •H 2 O and [4]Cl 2 • H 2 O was studied, two new complexes with two deprotonated indazole ligands were isolated, namely [RuCl(ind) 2 (Hind) 2 (NO)] ([5]) and [RuOH(ind) 2 (Hind) 2 (NO)] ([6]). All prepared compounds were comprehensively characterized by spectroscopic (IR, UV−vis, 1 H NMR) techniques. Compound [2], as well as [3]Cl 2 •2(CH 3) 2 CO, [4]Cl 2 •2(CH 3) 2 CO, and [5]•0.8CH 2 Cl 2 , the latter three obtained by recrystallization of the first isolated compounds (hydrates or anhydrous species) from acetone and dichloromethane, respectively, were studied by X-ray diffraction methods. The photoinduced release of NO in [3]Cl 2 and [4]Cl 2 was investigated by cyclic voltammetry and resulting paramagnetic NO species were detected by EPR spectroscopy. The quantum yields of NO release were calculated and found to be low (3−6%), which could be explained by NO dissociation and recombination dynamics, assessed by femtosecond pump−probe spectroscopy. The geometry and electronic parameters of Ru species formed upon NO release were identified by DFT calculations. The complexes [3]Cl 2 and [4]Cl 2 showed considerable antiproliferative activity in human cancer cell lines with IC 50 values in low micromolar or submicromolar concentration range and are suitable for further development as potential anticancer drugs. p53-dependence of Ru−NO complexes [3]Cl 2 and [4]Cl 2 was studied and p53-independent mode of action was confirmed. The effects of NO release on the cytotoxicity of the complexes with or without light irradiation were investigated using NO scavenger carboxy-PTIO.