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

Ewelina Orlowska, Maria V. Babak, Orsolya Dömötör, E. 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

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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.

Original languageEnglish
Pages (from-to)10702-10717
Number of pages16
JournalInorganic Chemistry
Volume57
Issue number17
DOIs
Publication statusPublished - Sep 4 2018

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Indazoles
Ruthenium
releasing
ruthenium
Spectroscopy
Ligands
ligands
Methylene Chloride
Quantum yield
Cytotoxicity
Acetone
activity (biology)
Bioactivity
Hydrates
cultured cells
Discrete Fourier transforms
hydrates
spectroscopy
acetone
Cyclic voltammetry

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Inorganic Chemistry

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NO Releasing and Anticancer Properties of Octahedral Ruthenium-Nitrosyl Complexes with Equatorial 1 H-Indazole Ligands. / Orlowska, Ewelina; Babak, Maria V.; Dömötör, Orsolya; Enyedy, E.; Rapta, Peter; Zalibera, Michal; Bučinský, Lukáš; Malček, Michal; Govind, Chinju; Karunakaran, Venugopal; Farid, Yusuf Chouthury Shaik; McDonnell, Tara E.; Luneau, Dominique; Schaniel, Dominik; Ang, Wee Han; Arion, Vladimir B.

In: Inorganic Chemistry, Vol. 57, No. 17, 04.09.2018, p. 10702-10717.

Research output: Contribution to journalArticle

Orlowska, E, Babak, MV, Dömötör, O, Enyedy, E, Rapta, P, Zalibera, M, Bučinský, L, Malček, M, Govind, C, Karunakaran, V, Farid, YCS, McDonnell, TE, Luneau, D, Schaniel, D, Ang, WH & Arion, VB 2018, 'NO Releasing and Anticancer Properties of Octahedral Ruthenium-Nitrosyl Complexes with Equatorial 1 H-Indazole Ligands', Inorganic Chemistry, vol. 57, no. 17, pp. 10702-10717. https://doi.org/10.1021/acs.inorgchem.8b01341
Orlowska, Ewelina ; Babak, Maria V. ; Dömötör, Orsolya ; Enyedy, E. ; Rapta, Peter ; Zalibera, Michal ; Bučinský, Lukáš ; Malček, Michal ; Govind, Chinju ; Karunakaran, Venugopal ; Farid, Yusuf Chouthury Shaik ; McDonnell, Tara E. ; Luneau, Dominique ; Schaniel, Dominik ; Ang, Wee Han ; Arion, Vladimir B. / NO Releasing and Anticancer Properties of Octahedral Ruthenium-Nitrosyl Complexes with Equatorial 1 H-Indazole Ligands. In: Inorganic Chemistry. 2018 ; Vol. 57, No. 17. pp. 10702-10717.
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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.",
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T1 - NO Releasing and Anticancer Properties of Octahedral Ruthenium-Nitrosyl Complexes with Equatorial 1 H-Indazole Ligands

AU - Orlowska, Ewelina

AU - Babak, Maria V.

AU - Dömötör, Orsolya

AU - Enyedy, E.

AU - Rapta, Peter

AU - Zalibera, Michal

AU - Bučinský, Lukáš

AU - Malček, Michal

AU - Govind, Chinju

AU - Karunakaran, Venugopal

AU - Farid, Yusuf Chouthury Shaik

AU - McDonnell, Tara E.

AU - Luneau, Dominique

AU - Schaniel, Dominik

AU - Ang, Wee Han

AU - Arion, Vladimir B.

PY - 2018/9/4

Y1 - 2018/9/4

N2 - 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.

AB - 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.

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