Solution equilibrium, structural and cytotoxicity studies on Ru(η6-p-cymene) and copper complexes of pyrazolyl thiosemicarbazones

Orsolya Dömötör, Márton A. Kiss, G. Tamás Gál, Nóra V. May, Gabriella Spengler, Márta Nové, Ana Čipak Gašparović, Éva Frank, Éva A. Enyedy

Research output: Contribution to journalArticle

Abstract

Solution chemical properties of two bidentate pyrazolyl thiosemicarbazones 2-((3-methyl-1-phenyl-1H-pyrazol-4-yl)methylene)hydrazinecarbothioamide (Me-pyrTSC), 2-((1,3-diphenyl-1H-pyrazol-4-yl)methylene)hydrazinecarbothioamide (Ph-pyrTSC), stability of their Cu(II) and Ru(η6-p-cymene) complexes were characterized in aqueous solution (with 30% DMSO) by the combined use of UV–visible spectrophotometry, 1H NMR spectroscopy and electrospray ionization mass spectrometry in addition to their solid phase isolation. The solid phase structures of Me-pyrTSC∙H2O, [Ru(η6-p-cymene)(Me-pyrTSC)Cl]Cl and [Cu(Ph-pyrTSCH−1)2] were determined by single crystal X-ray diffraction. High stability mononuclear Ru(η6-p-cymene) complexes with (N,S) coordination mode are formed in the acidic pH range, and increasing the pH the predominating dinuclear [(Ru(η6-p-cymene))2(L)2]2+ complex with μ2-bridging sulphur donor atoms is formed (where L is the deprotonated thiosemicarbazone). [CuL]+ and [CuL2] complexes show much higher stability compared to that of complexes of the reference compound benzaldehyde thiosemicarbazone. [CuL2] complexes predominate at neutral pH. Me-pyrTSC and Ph-pyrTSC exhibited moderate cytotoxicity against human colonic adenocarcinoma cell lines (IC50 = 33–76 μM), while their complexation with Ru(η6-p-cymene) (IC50 = 11–24 μM) and especially Cu(II) (IC50 = 3–6 μM) resulted in higher cytotoxicity. Cu(II) complexes of the tested thiosemicarbazones were also cytotoxic in three breast cancer and in a hepatocellular carcinoma cell line. No reactive oxygen species production was detected and the relatively high catalase activity of SUM159 breast cancer cells was decreased upon addition of the ligands and the complexes. In the latter cell line the tested compounds interfered with the glutathione synthesis as they decreased the concentration of this cellular reductant.

Original languageEnglish
Article number110883
JournalJournal of Inorganic Biochemistry
Volume202
DOIs
Publication statusPublished - Jan 2020

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Thiosemicarbazones
Coordination Complexes
Cytotoxicity
Copper
Cells
Inhibitory Concentration 50
Cell Line
Electrospray ionization
Breast Neoplasms
Reducing Agents
Spectrophotometry
Phase structure
Dimethyl Sulfoxide
Complexation
Sulfur
Electrospray Ionization Mass Spectrometry
Catalase
Chemical properties
Nuclear magnetic resonance spectroscopy
Mass spectrometry

Keywords

  • Cytotoxicity
  • Metal complexes
  • Solution stability
  • Thiosemicarbazones
  • X-ray crystal structures

ASJC Scopus subject areas

  • Biochemistry
  • Inorganic Chemistry

Cite this

Solution equilibrium, structural and cytotoxicity studies on Ru(η6-p-cymene) and copper complexes of pyrazolyl thiosemicarbazones. / Dömötör, Orsolya; Kiss, Márton A.; Gál, G. Tamás; May, Nóra V.; Spengler, Gabriella; Nové, Márta; Gašparović, Ana Čipak; Frank, Éva; Enyedy, Éva A.

In: Journal of Inorganic Biochemistry, Vol. 202, 110883, 01.2020.

Research output: Contribution to journalArticle

Dömötör, Orsolya ; Kiss, Márton A. ; Gál, G. Tamás ; May, Nóra V. ; Spengler, Gabriella ; Nové, Márta ; Gašparović, Ana Čipak ; Frank, Éva ; Enyedy, Éva A. / Solution equilibrium, structural and cytotoxicity studies on Ru(η6-p-cymene) and copper complexes of pyrazolyl thiosemicarbazones. In: Journal of Inorganic Biochemistry. 2020 ; Vol. 202.
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T1 - Solution equilibrium, structural and cytotoxicity studies on Ru(η6-p-cymene) and copper complexes of pyrazolyl thiosemicarbazones

AU - Dömötör, Orsolya

AU - Kiss, Márton A.

AU - Gál, G. Tamás

AU - May, Nóra V.

AU - Spengler, Gabriella

AU - Nové, Márta

AU - Gašparović, Ana Čipak

AU - Frank, Éva

AU - Enyedy, Éva A.

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N2 - Solution chemical properties of two bidentate pyrazolyl thiosemicarbazones 2-((3-methyl-1-phenyl-1H-pyrazol-4-yl)methylene)hydrazinecarbothioamide (Me-pyrTSC), 2-((1,3-diphenyl-1H-pyrazol-4-yl)methylene)hydrazinecarbothioamide (Ph-pyrTSC), stability of their Cu(II) and Ru(η6-p-cymene) complexes were characterized in aqueous solution (with 30% DMSO) by the combined use of UV–visible spectrophotometry, 1H NMR spectroscopy and electrospray ionization mass spectrometry in addition to their solid phase isolation. The solid phase structures of Me-pyrTSC∙H2O, [Ru(η6-p-cymene)(Me-pyrTSC)Cl]Cl and [Cu(Ph-pyrTSCH−1)2] were determined by single crystal X-ray diffraction. High stability mononuclear Ru(η6-p-cymene) complexes with (N,S) coordination mode are formed in the acidic pH range, and increasing the pH the predominating dinuclear [(Ru(η6-p-cymene))2(L)2]2+ complex with μ2-bridging sulphur donor atoms is formed (where L− is the deprotonated thiosemicarbazone). [CuL]+ and [CuL2] complexes show much higher stability compared to that of complexes of the reference compound benzaldehyde thiosemicarbazone. [CuL2] complexes predominate at neutral pH. Me-pyrTSC and Ph-pyrTSC exhibited moderate cytotoxicity against human colonic adenocarcinoma cell lines (IC50 = 33–76 μM), while their complexation with Ru(η6-p-cymene) (IC50 = 11–24 μM) and especially Cu(II) (IC50 = 3–6 μM) resulted in higher cytotoxicity. Cu(II) complexes of the tested thiosemicarbazones were also cytotoxic in three breast cancer and in a hepatocellular carcinoma cell line. No reactive oxygen species production was detected and the relatively high catalase activity of SUM159 breast cancer cells was decreased upon addition of the ligands and the complexes. In the latter cell line the tested compounds interfered with the glutathione synthesis as they decreased the concentration of this cellular reductant.

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KW - Metal complexes

KW - Solution stability

KW - Thiosemicarbazones

KW - X-ray crystal structures

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