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

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review

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Author(s)

  • Ewelina Orlowska
  • Orsolya Dömötör
  • Eva A. Enyedy
  • Peter Rapta
  • Michal Zalibera
  • Lukáš Bučinský
  • Michal Malček
  • Chinju Govind
  • Venugopal Karunakaran
  • Yusuf Chouthury Shaik Farid
  • Tara E. McDonnell
  • Dominique Luneau
  • Dominik Schaniel
  • Wee Han Ang
  • Vladimir B. Arion

Detail(s)

Original languageEnglish
Pages (from-to)10702-10717
Journal / PublicationInorganic Chemistry
Volume57
Issue number17
Online published14 Aug 2018
Publication statusPublished - 4 Sept 2018
Externally publishedYes

Abstract

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)]Cl2·H2O ([3]Cl2·H2O) and trans-[RuOH(Hind)4(NO)]Cl2·H2O ([4]Cl2·H2O), have been prepared from trans-[Ru(NO2)2(Hind)4] ([2]). When the pH-dependent solution behavior of [3]Cl2·H2O and [4]Cl2·H2O 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, 1H NMR) techniques. Compound [2], as well as [3]Cl2·2(CH3)2CO, [4]Cl2·2(CH3)2CO, and [5]·0.8CH2Cl2, 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]Cl2 and [4]Cl2 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]Cl2 and [4]Cl2 showed considerable antiproliferative activity in human cancer cell lines with IC50 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]Cl2 and [4]Cl2 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.

Citation Format(s)

NO Releasing and Anticancer Properties of Octahedral Ruthenium-Nitrosyl Complexes with Equatorial 1 H-Indazole Ligands. / Orlowska, Ewelina; Babak, Maria V.; Dömötör, Orsolya et al.
In: Inorganic Chemistry, Vol. 57, No. 17, 04.09.2018, p. 10702-10717.

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review