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Éva A. Enyedy - One of the best experts on this subject based on the ideXlab platform.

  • Solution Equilibrium, structural and cytotoxicity studies on Ru(η6-p-cymene) and copper complexes of pyrazolyl thiosemicarbazones.
    Journal of inorganic biochemistry, 2019
    Co-Authors: Orsolya Dömötör, Nóra V. May, Gabriella Spengler, Márton Kiss, G. Tamás Gál, Márta Nové, Ana Čipak Gašparović, Éva Frank, Éva A. Enyedy
    Abstract:

    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.

  • Structural and Solution Equilibrium studies on half-sandwich organorhodium complexes of (N,N) donor bidentate ligands
    New Journal of Chemistry, 2018
    Co-Authors: János P. Mészáros, Bernhard K. Keppler, Alexander Roller, Orsolya Dömötör, Carmen M. Hackl, Wolfgang Kandioller, Éva A. Enyedy
    Abstract:

    Complex formation Equilibrium processes of [Rh(η5-C5Me5)(H2O)3]2+ with N,N′-dimethylethylenediamine (dmen), N,N,N′,N′-tetramethylethylenediamine (tmeda), 2-picolylamine (pin) and 1,10-phenanthroline (phen) were studied in aqueous Solution by 1H NMR spectroscopy, UV-vis spectrophotometry and pH-potentiometry. Formation and deprotonation of [Rh(η5-C5Me5)(L)(H2O)]2+ complexes and exchange process of the aqua to chlorido ligand were characterized in addition to single-crystal X-ray diffraction analysis of [Rh(η5-C5Me5)(L)(Cl)]+ complexes (L = dmen, tmeda and pin). Formation of complexes with significantly high stability was found except tmeda due to the sterical hindrance between the methyl groups of the chelating ligand and the arenyl ring resulting in an increased methyl group-ring plane torsion angle. [Rh(η5-C5Me5)(L)(H2O)]2+ complexes of dmen, pin, phen predominate at pH 7.4 without decomposition even in the micromolar concentration range. The complexes were characterized by relatively high chloride affinity and a strong correlation was obtained between the log K′ (H2O/Cl−) and pKa of [Rh(η5-C5Me5)(L)(H2O)]2+ constants for a series of (O,O), (O,N) and (N,N)-chelated complexes. For this set of 12 complexes a relationship between log K′ (H2O/Cl−) values and certain crystallographic parameters was found using multiple linear regression approach. DNA binding of these complexes was also monitored and compared by ultrafiltration and fluorimetry.

  • comparative Solution Equilibrium and structural studies of half sandwich ruthenium ii η6 toluene complexes of picolinate derivatives
    Journal of Inorganic Biochemistry, 2018
    Co-Authors: Nóra V. May, Orsolya Dömötör, Jelena Poljarevic, Tamas G Gal, Gabriella Spengler, Aleksandar R Savic, Sanja Grguricsipka, Éva A. Enyedy
    Abstract:

    Abstract Five Ru(II)(η 6 -toluene) complexes formed with 2-picolinic acid and its various derivatives have been synthesized and characterized. X-ray structures of four complexes are also reported. Complex formation processes of [Ru(II)(η 6 -toluene)(H 2 O) 3 ] 2+ organometallic cation with the metal-free ligands were studied in aqueous Solution in the presence of chloride ions by the combined use of 1 H NMR spectroscopy, UV–visible spectrophotometry and pH-potentiometry. Solution stability, chloride ion affinity and lipophilicity of the complexes were characterized together with in vitro cytotoxic and antiproliferative activity in cancer cell lines being sensitive and resistant to classic chemotherapy and in normal cells as well. Formation of mono complexes such as [Ru(η 6 -toluene)(L)(Z)] +/0 (L: completely deprotonated ligand; Z = H 2 O/Cl − ) with high stability and [Ru(η 6 -toluene)(L)(OH)] was found in Solution. The p K a values (8.3–8.7) reflect the formation of low amount of mixed hydroxido species at pH 7.4 at 0.2 M KCl ionic strength. The complexes are fairly hydrophilic and show moderate chloride ion affinity and fast chloride-water exchange processes. The studied complexes exhibit no cytotoxic activity in human cancer cells (IC 50  > 100 μM), only complexes formed with 2-picolinic acid ( 1 ) and its 3-methyl derivative ( 2 ) represented a moderate antiproliferative effect (IC 50  = 84.8 ( 1 ), 79.2 μM ( 2 )) on a multidrug resistant colon adenocarcinoma cell line revealing considerable multidrug resistant selectivity. Complexes 1 and 2 bind to human serum albumin covalently and relatively slowly with moderate strength at multiple binding sites without ligand cleavage.

  • Complexes of pyridoxal thiosemicarbazones formed with vanadium(IV/V) and copper(II): Solution Equilibrium and structure
    Inorganica Chimica Acta, 2018
    Co-Authors: Tamás Jakusch, Nóra V. May, Bernhard K. Keppler, Éva A. Enyedy, Christian R. Kowol, Alexander Roller, Karoly Kozma, Tamás Kiss
    Abstract:

    Abstract The stoichiometry and thermodynamic stability of vanadium(IV/V) and copper(II) complexes of pyridoxal thiosemicarbazone and pyridoxal-N 3 ,N 3 -dimethylthiosemicarbazone have been determined by pH-potentiometry (V IV O), EPR (V IV O/Cu II ), UV–Vis (Cu II , V IV O and V V ) and 51 V NMR spectroscopy (V V ) in 30% (w/w) dimethyl sulfoxide/water solvent mixture. In all cases, mono-ligand complexes are formed in different protonation states. In addition, the proton-dissociation constants of the ligands were also determined by pH-potentiometry, UV–Vis and 1 H NMR spectroscopy. The solid state structures of the monoprotonated forms (V V O 2 (L 1 H)×1.5H 2 O and V V O 2 (L 2 H)×0.8H 2 O) of the V V complexes were characterized by single-crystal X-ray diffraction analysis. The mono-ligand complexes of Cu II and V V are dominant at physiological pH. With all investigated metal ions the pyridoxal moiety of the ligand causes an extra deprotonation step between pH 4 and 7 due to the non-coordinating pyridine-NH + . The pyridoxal-containing ligands form somewhat more stable complexes with both V IV O and Cu II ions than the reference compound salicylaldehyde thiosemicarbazone. Dimethylation of the terminal amino group resulted in the formation of V V and Cu II complexes with even higher stability.

  • Comparative Solution Equilibrium studies on pentamethylcyclopentadienyl rhodium complexes of 2,2'-bipyridine and ethylenediamine and their interaction with human serum albumin.
    Journal of inorganic biochemistry, 2015
    Co-Authors: Éva A. Enyedy, Bernhard K. Keppler, Alexander Roller, János P. Mészáros, Orsolya Dömötör, Carmen M. Hackl, Wolfgang Kandioller
    Abstract:

    Complex formation Equilibrium processes of the (N,N) donor containing 2,2'-bipyridine (bpy) and ethylenediamine (en) with (η(5)-pentamethylcyclopentadienyl)rhodium(III) were investigated in aqueous Solution via pH-potentiometry, (1)H NMR spectroscopy, and UV-vis spectrophotometry in the absence and presence of chloride ions. The structure of [RhCp*(en)Cl]ClO4 (Cp*, pentamethylcyclopentadienyl) was also studied by single-crystal X-ray diffraction. pKa values of 8.56 and 9.58 were determined for [RhCp*(bpy)(H2O)](2+) and [RhCp*(en)(H2O)](2+), respectively resulting in the formation of negligible amount of mixed hydroxido complexes at pH 7.4. Stability and the H2O/Cl(-) co-ligand exchange constants of bpy and en complexes considerably exceed those of the bidentate O-donor deferiprone. The strong affinity of the bpy and en complexes to chloride ions most probably contributes to their low antiproliferative effect. Interactions between human serum albumin (HSA) and [RhCp*(H2O)3](2+), its complexes formed with deferiprone, bpy and en were also monitored by (1)H NMR spectroscopy, ultrafiltration/UV-vis and spectrofluorometry. Numerous binding sites (≥ 8) are available for [RhCp*(H2O)3](2+); and the interaction takes place most probably via covalent bonds through the imidazole nitrogen of His. According to the various fluorescence studies [RhCp*(H2O)3](2+) binds on sites I and II, and coordination of surface side chain donor atoms of the protein is also feasible. The binding of the bpy and en complex is weaker and slower compared to that of [RhCp*(H2O)3](2+), and formation of ternary HSA-RhCp*-ligand adducts was proved. In the case of the deferiprone complex, the RhCp* fragment is cleaved off when HSA is loaded with low equivalents of the compound.

Tamás Kiss - One of the best experts on this subject based on the ideXlab platform.

  • Complexes of pyridoxal thiosemicarbazones formed with vanadium(IV/V) and copper(II): Solution Equilibrium and structure
    Inorganica Chimica Acta, 2018
    Co-Authors: Tamás Jakusch, Nóra V. May, Bernhard K. Keppler, Éva A. Enyedy, Christian R. Kowol, Alexander Roller, Karoly Kozma, Tamás Kiss
    Abstract:

    Abstract The stoichiometry and thermodynamic stability of vanadium(IV/V) and copper(II) complexes of pyridoxal thiosemicarbazone and pyridoxal-N 3 ,N 3 -dimethylthiosemicarbazone have been determined by pH-potentiometry (V IV O), EPR (V IV O/Cu II ), UV–Vis (Cu II , V IV O and V V ) and 51 V NMR spectroscopy (V V ) in 30% (w/w) dimethyl sulfoxide/water solvent mixture. In all cases, mono-ligand complexes are formed in different protonation states. In addition, the proton-dissociation constants of the ligands were also determined by pH-potentiometry, UV–Vis and 1 H NMR spectroscopy. The solid state structures of the monoprotonated forms (V V O 2 (L 1 H)×1.5H 2 O and V V O 2 (L 2 H)×0.8H 2 O) of the V V complexes were characterized by single-crystal X-ray diffraction analysis. The mono-ligand complexes of Cu II and V V are dominant at physiological pH. With all investigated metal ions the pyridoxal moiety of the ligand causes an extra deprotonation step between pH 4 and 7 due to the non-coordinating pyridine-NH + . The pyridoxal-containing ligands form somewhat more stable complexes with both V IV O and Cu II ions than the reference compound salicylaldehyde thiosemicarbazone. Dimethylation of the terminal amino group resulted in the formation of V V and Cu II complexes with even higher stability.

  • Solution Equilibrium studies of anticancer ruthenium(II)-η6-p-cymene complexes of pyridinecarboxylic acids
    Polyhedron, 2014
    Co-Authors: Éva Sija, Tamás Kiss, Christian G. Hartinger, Bernhard K. Keppler, Éva A. Enyedy
    Abstract:

    Stoichiometry and stability of antitumor ruthenium(II)-g 6 -p-cymene complexes of picolinic acid and its

  • Comparative Solution Equilibrium studies of anticancer gallium(III) complexes of 8-hydroxyquinoline and hydroxy(thio)pyrone ligands.
    Journal of inorganic biochemistry, 2012
    Co-Authors: Éva A. Enyedy, Tamás Kiss, Christian G. Hartinger, Orsolya Dömötör, Erika Varga, Robert Trondl, Bernhard K. Keppler
    Abstract:

    Abstract The stoichiometry and stability constants of the Ga(III) complexes of 8-hydroxyquinoline (HQ), 8-hydroxyquinoline-5-sulfonate (HQS), maltol, thiomaltol, allomaltol and thioallomaltol were determined by means of pH-potentiometry, UV–vis spectrophotometry, spectrofluorometry and 1 H NMR spectroscopy in aqueous Solution. Spectrofluorometry was used to determine the stability constants of the Ga(III)–HQ species in water. Formation of [GaL] 2 + , [GaL 2 ] + and [GaL 3 ] complexes was found and the Ga(III) binding ability of the ligands followed the order: thioallomaltol  tris (8-hydroxyquinolinato)gallium(III) (KP46) the dissociation of the complex is negligible at physiological pH even in the biologically relevant low concentration range. Thus KP46 is able to preserve its original entity more considerably than other Ga(III) complexes. Moreover, intrinsic fluorescence of KP46 allows the monitoring of the cellular accumulation and distribution in human cancer cells by fluorescence microscopy.

  • Interaction of Triapine and related thiosemicarbazones with iron(III)/(II) and gallium(III): a comparative Solution Equilibrium study†
    Dalton transactions (Cambridge England : 2003), 2011
    Co-Authors: Éva A. Enyedy, Tamás Kiss, Christian R. Kowol, Michael F. Primik, Vladimir B. Arion, Bernhard K. Keppler
    Abstract:

    Stoichiometry and stability of GaIII, FeIII, FeII complexes of Triapine and five related α-N heterocyclic thiosemicarbazones with potential antitumor activity have been determined by pH-potentiometry, UV-vis spectrophotometry, 1H NMR spectroscopy, and spectrofluorimetry in aqueous Solution (with 30% DMSO), together with the characterization of the proton dissociation processes. Additionally, the redox properties of the iron complexes were studied by cyclic voltammetry at various pH values. Formation of high stability bis-ligand complexes was found in all cases, which are predominant at physiological pH with FeIII/FeII, whilst only at the acidic pH range with GaIII. The results show that among the thiosemicarbazones with various substituents the N-terminal dimethylation does not exert a measurable effect on the redox potential, but has the highest impact on the stability of the complexes as well as the cytotoxicity, especially in the absence of a pyridine-NH2 group in the molecule. In addition the fluorescence properties of the ligands in aqueous Solution and their changes caused by GaIII were studied.

  • Solution Equilibrium characterization of insulin-mimetic Zn(II) complexes.
    Journal of inorganic biochemistry, 2006
    Co-Authors: Tamás Jakusch, K. Gajda-schrantz, Yusuke Adachi, Hiromu Sakurai, Tamás Kiss, László Horváth
    Abstract:

    Abstract Solution speciation (stoichiometry and stability constants) of the insulin mimetic Zn(II) complexes of several bidentate ligands with (O,O), (N,O) or (S,O) coordination modes have been determined by pH-metry at 25 °C and I  = 0.2 M (KCl). All ligands were found to coordinate in a bidentate way forming mono, bis and tris complexes, besides a mixed hydroxo bis complex ZnL 2 (OH) detected in the slightly basic pH range together with the tris complex. Relationships between the stability data, lipophilicity of the complexes and earlier biological data are evaluated. The validity of the linear free energy relationships (LFER) between the proton and Zn(II) complexes and also between the VO(IV) and Zn(II) complexes is tested.

Bernhard K. Keppler - One of the best experts on this subject based on the ideXlab platform.

  • Structural and Solution Equilibrium studies on half-sandwich organorhodium complexes of (N,N) donor bidentate ligands
    New Journal of Chemistry, 2018
    Co-Authors: János P. Mészáros, Bernhard K. Keppler, Alexander Roller, Orsolya Dömötör, Carmen M. Hackl, Wolfgang Kandioller, Éva A. Enyedy
    Abstract:

    Complex formation Equilibrium processes of [Rh(η5-C5Me5)(H2O)3]2+ with N,N′-dimethylethylenediamine (dmen), N,N,N′,N′-tetramethylethylenediamine (tmeda), 2-picolylamine (pin) and 1,10-phenanthroline (phen) were studied in aqueous Solution by 1H NMR spectroscopy, UV-vis spectrophotometry and pH-potentiometry. Formation and deprotonation of [Rh(η5-C5Me5)(L)(H2O)]2+ complexes and exchange process of the aqua to chlorido ligand were characterized in addition to single-crystal X-ray diffraction analysis of [Rh(η5-C5Me5)(L)(Cl)]+ complexes (L = dmen, tmeda and pin). Formation of complexes with significantly high stability was found except tmeda due to the sterical hindrance between the methyl groups of the chelating ligand and the arenyl ring resulting in an increased methyl group-ring plane torsion angle. [Rh(η5-C5Me5)(L)(H2O)]2+ complexes of dmen, pin, phen predominate at pH 7.4 without decomposition even in the micromolar concentration range. The complexes were characterized by relatively high chloride affinity and a strong correlation was obtained between the log K′ (H2O/Cl−) and pKa of [Rh(η5-C5Me5)(L)(H2O)]2+ constants for a series of (O,O), (O,N) and (N,N)-chelated complexes. For this set of 12 complexes a relationship between log K′ (H2O/Cl−) values and certain crystallographic parameters was found using multiple linear regression approach. DNA binding of these complexes was also monitored and compared by ultrafiltration and fluorimetry.

  • Complexes of pyridoxal thiosemicarbazones formed with vanadium(IV/V) and copper(II): Solution Equilibrium and structure
    Inorganica Chimica Acta, 2018
    Co-Authors: Tamás Jakusch, Nóra V. May, Bernhard K. Keppler, Éva A. Enyedy, Christian R. Kowol, Alexander Roller, Karoly Kozma, Tamás Kiss
    Abstract:

    Abstract The stoichiometry and thermodynamic stability of vanadium(IV/V) and copper(II) complexes of pyridoxal thiosemicarbazone and pyridoxal-N 3 ,N 3 -dimethylthiosemicarbazone have been determined by pH-potentiometry (V IV O), EPR (V IV O/Cu II ), UV–Vis (Cu II , V IV O and V V ) and 51 V NMR spectroscopy (V V ) in 30% (w/w) dimethyl sulfoxide/water solvent mixture. In all cases, mono-ligand complexes are formed in different protonation states. In addition, the proton-dissociation constants of the ligands were also determined by pH-potentiometry, UV–Vis and 1 H NMR spectroscopy. The solid state structures of the monoprotonated forms (V V O 2 (L 1 H)×1.5H 2 O and V V O 2 (L 2 H)×0.8H 2 O) of the V V complexes were characterized by single-crystal X-ray diffraction analysis. The mono-ligand complexes of Cu II and V V are dominant at physiological pH. With all investigated metal ions the pyridoxal moiety of the ligand causes an extra deprotonation step between pH 4 and 7 due to the non-coordinating pyridine-NH + . The pyridoxal-containing ligands form somewhat more stable complexes with both V IV O and Cu II ions than the reference compound salicylaldehyde thiosemicarbazone. Dimethylation of the terminal amino group resulted in the formation of V V and Cu II complexes with even higher stability.

  • Comparative Solution Equilibrium studies on pentamethylcyclopentadienyl rhodium complexes of 2,2'-bipyridine and ethylenediamine and their interaction with human serum albumin.
    Journal of inorganic biochemistry, 2015
    Co-Authors: Éva A. Enyedy, Bernhard K. Keppler, Alexander Roller, János P. Mészáros, Orsolya Dömötör, Carmen M. Hackl, Wolfgang Kandioller
    Abstract:

    Complex formation Equilibrium processes of the (N,N) donor containing 2,2'-bipyridine (bpy) and ethylenediamine (en) with (η(5)-pentamethylcyclopentadienyl)rhodium(III) were investigated in aqueous Solution via pH-potentiometry, (1)H NMR spectroscopy, and UV-vis spectrophotometry in the absence and presence of chloride ions. The structure of [RhCp*(en)Cl]ClO4 (Cp*, pentamethylcyclopentadienyl) was also studied by single-crystal X-ray diffraction. pKa values of 8.56 and 9.58 were determined for [RhCp*(bpy)(H2O)](2+) and [RhCp*(en)(H2O)](2+), respectively resulting in the formation of negligible amount of mixed hydroxido complexes at pH 7.4. Stability and the H2O/Cl(-) co-ligand exchange constants of bpy and en complexes considerably exceed those of the bidentate O-donor deferiprone. The strong affinity of the bpy and en complexes to chloride ions most probably contributes to their low antiproliferative effect. Interactions between human serum albumin (HSA) and [RhCp*(H2O)3](2+), its complexes formed with deferiprone, bpy and en were also monitored by (1)H NMR spectroscopy, ultrafiltration/UV-vis and spectrofluorometry. Numerous binding sites (≥ 8) are available for [RhCp*(H2O)3](2+); and the interaction takes place most probably via covalent bonds through the imidazole nitrogen of His. According to the various fluorescence studies [RhCp*(H2O)3](2+) binds on sites I and II, and coordination of surface side chain donor atoms of the protein is also feasible. The binding of the bpy and en complex is weaker and slower compared to that of [RhCp*(H2O)3](2+), and formation of ternary HSA-RhCp*-ligand adducts was proved. In the case of the deferiprone complex, the RhCp* fragment is cleaved off when HSA is loaded with low equivalents of the compound.

  • Vanadium(IV/V) complexes of Triapine and related thiosemicarbazones: Synthesis, Solution Equilibrium and bioactivity.
    Journal of inorganic biochemistry, 2015
    Co-Authors: Christian R. Kowol, Tamás Jakusch, Bernhard K. Keppler, Nóra Veronika Nagy, Alexander Roller, Petra Heffeter, Éva A. Enyedy
    Abstract:

    The stoichiometry and thermodynamic stability of vanadium(IV/V) complexes of Triapine and two related α(N)-heterocyclic thiosemicarbazones (TSCs) with potential antitumor activity have been determined by pH-potentiometry, EPR and (51)V NMR spectroscopy in 30% (w/w) dimethyl sulfoxide/water solvent mixtures. In all cases, mono-ligand complexes in different protonation states were identified. Dimethylation of the terminal amino group resulted in the formation of vanadium(IV/V) complexes with considerably higher stability. Three of the most stable complexes were also synthesized in solid state and comprehensively characterized. The biological evaluation of the synthesized vanadium complexes in comparison to the metal-free ligands in different human cancer cell lines revealed only minimal influence of the metal ion. Thus, in addition the coordination ability of salicylaldehyde thiosemicarbazone (STSC) to vanadium(IV/V) ions was investigated. The exchange of the pyridine nitrogen of the α(N)-heterocyclic TSCs to a phenolate oxygen in STSC significantly increased the stability of the complexes in Solution. Finally, this also resulted in increased cytotoxicity activity of a vanadium(V) complex of STSC compared to the metal-free ligand.

  • Solution Equilibrium studies of anticancer ruthenium(II)-η6-p-cymene complexes of pyridinecarboxylic acids
    Polyhedron, 2014
    Co-Authors: Éva Sija, Tamás Kiss, Christian G. Hartinger, Bernhard K. Keppler, Éva A. Enyedy
    Abstract:

    Stoichiometry and stability of antitumor ruthenium(II)-g 6 -p-cymene complexes of picolinic acid and its

Tamás Jakusch - One of the best experts on this subject based on the ideXlab platform.

  • Complexes of pyridoxal thiosemicarbazones formed with vanadium(IV/V) and copper(II): Solution Equilibrium and structure
    Inorganica Chimica Acta, 2018
    Co-Authors: Tamás Jakusch, Nóra V. May, Bernhard K. Keppler, Éva A. Enyedy, Christian R. Kowol, Alexander Roller, Karoly Kozma, Tamás Kiss
    Abstract:

    Abstract The stoichiometry and thermodynamic stability of vanadium(IV/V) and copper(II) complexes of pyridoxal thiosemicarbazone and pyridoxal-N 3 ,N 3 -dimethylthiosemicarbazone have been determined by pH-potentiometry (V IV O), EPR (V IV O/Cu II ), UV–Vis (Cu II , V IV O and V V ) and 51 V NMR spectroscopy (V V ) in 30% (w/w) dimethyl sulfoxide/water solvent mixture. In all cases, mono-ligand complexes are formed in different protonation states. In addition, the proton-dissociation constants of the ligands were also determined by pH-potentiometry, UV–Vis and 1 H NMR spectroscopy. The solid state structures of the monoprotonated forms (V V O 2 (L 1 H)×1.5H 2 O and V V O 2 (L 2 H)×0.8H 2 O) of the V V complexes were characterized by single-crystal X-ray diffraction analysis. The mono-ligand complexes of Cu II and V V are dominant at physiological pH. With all investigated metal ions the pyridoxal moiety of the ligand causes an extra deprotonation step between pH 4 and 7 due to the non-coordinating pyridine-NH + . The pyridoxal-containing ligands form somewhat more stable complexes with both V IV O and Cu II ions than the reference compound salicylaldehyde thiosemicarbazone. Dimethylation of the terminal amino group resulted in the formation of V V and Cu II complexes with even higher stability.

  • Vanadium(IV/V) complexes of Triapine and related thiosemicarbazones: Synthesis, Solution Equilibrium and bioactivity.
    Journal of inorganic biochemistry, 2015
    Co-Authors: Christian R. Kowol, Tamás Jakusch, Bernhard K. Keppler, Nóra Veronika Nagy, Alexander Roller, Petra Heffeter, Éva A. Enyedy
    Abstract:

    The stoichiometry and thermodynamic stability of vanadium(IV/V) complexes of Triapine and two related α(N)-heterocyclic thiosemicarbazones (TSCs) with potential antitumor activity have been determined by pH-potentiometry, EPR and (51)V NMR spectroscopy in 30% (w/w) dimethyl sulfoxide/water solvent mixtures. In all cases, mono-ligand complexes in different protonation states were identified. Dimethylation of the terminal amino group resulted in the formation of vanadium(IV/V) complexes with considerably higher stability. Three of the most stable complexes were also synthesized in solid state and comprehensively characterized. The biological evaluation of the synthesized vanadium complexes in comparison to the metal-free ligands in different human cancer cell lines revealed only minimal influence of the metal ion. Thus, in addition the coordination ability of salicylaldehyde thiosemicarbazone (STSC) to vanadium(IV/V) ions was investigated. The exchange of the pyridine nitrogen of the α(N)-heterocyclic TSCs to a phenolate oxygen in STSC significantly increased the stability of the complexes in Solution. Finally, this also resulted in increased cytotoxicity activity of a vanadium(V) complex of STSC compared to the metal-free ligand.

  • Solution Equilibrium characterization of insulin-mimetic Zn(II) complexes.
    Journal of inorganic biochemistry, 2006
    Co-Authors: Tamás Jakusch, K. Gajda-schrantz, Yusuke Adachi, Hiromu Sakurai, Tamás Kiss, László Horváth
    Abstract:

    Abstract Solution speciation (stoichiometry and stability constants) of the insulin mimetic Zn(II) complexes of several bidentate ligands with (O,O), (N,O) or (S,O) coordination modes have been determined by pH-metry at 25 °C and I  = 0.2 M (KCl). All ligands were found to coordinate in a bidentate way forming mono, bis and tris complexes, besides a mixed hydroxo bis complex ZnL 2 (OH) detected in the slightly basic pH range together with the tris complex. Relationships between the stability data, lipophilicity of the complexes and earlier biological data are evaluated. The validity of the linear free energy relationships (LFER) between the proton and Zn(II) complexes and also between the VO(IV) and Zn(II) complexes is tested.

Nóra V. May - One of the best experts on this subject based on the ideXlab platform.

  • Solution Equilibrium, structural and cytotoxicity studies on Ru(η6-p-cymene) and copper complexes of pyrazolyl thiosemicarbazones.
    Journal of inorganic biochemistry, 2019
    Co-Authors: Orsolya Dömötör, Nóra V. May, Gabriella Spengler, Márton Kiss, G. Tamás Gál, Márta Nové, Ana Čipak Gašparović, Éva Frank, Éva A. Enyedy
    Abstract:

    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.

  • comparative Solution Equilibrium and structural studies of half sandwich ruthenium ii η6 toluene complexes of picolinate derivatives
    Journal of Inorganic Biochemistry, 2018
    Co-Authors: Nóra V. May, Orsolya Dömötör, Jelena Poljarevic, Tamas G Gal, Gabriella Spengler, Aleksandar R Savic, Sanja Grguricsipka, Éva A. Enyedy
    Abstract:

    Abstract Five Ru(II)(η 6 -toluene) complexes formed with 2-picolinic acid and its various derivatives have been synthesized and characterized. X-ray structures of four complexes are also reported. Complex formation processes of [Ru(II)(η 6 -toluene)(H 2 O) 3 ] 2+ organometallic cation with the metal-free ligands were studied in aqueous Solution in the presence of chloride ions by the combined use of 1 H NMR spectroscopy, UV–visible spectrophotometry and pH-potentiometry. Solution stability, chloride ion affinity and lipophilicity of the complexes were characterized together with in vitro cytotoxic and antiproliferative activity in cancer cell lines being sensitive and resistant to classic chemotherapy and in normal cells as well. Formation of mono complexes such as [Ru(η 6 -toluene)(L)(Z)] +/0 (L: completely deprotonated ligand; Z = H 2 O/Cl − ) with high stability and [Ru(η 6 -toluene)(L)(OH)] was found in Solution. The p K a values (8.3–8.7) reflect the formation of low amount of mixed hydroxido species at pH 7.4 at 0.2 M KCl ionic strength. The complexes are fairly hydrophilic and show moderate chloride ion affinity and fast chloride-water exchange processes. The studied complexes exhibit no cytotoxic activity in human cancer cells (IC 50  > 100 μM), only complexes formed with 2-picolinic acid ( 1 ) and its 3-methyl derivative ( 2 ) represented a moderate antiproliferative effect (IC 50  = 84.8 ( 1 ), 79.2 μM ( 2 )) on a multidrug resistant colon adenocarcinoma cell line revealing considerable multidrug resistant selectivity. Complexes 1 and 2 bind to human serum albumin covalently and relatively slowly with moderate strength at multiple binding sites without ligand cleavage.

  • On the copper(II) binding of asymmetrically functionalized tripodal peptides: Solution Equilibrium, structure, and enzyme mimicking
    New Journal of Chemistry, 2018
    Co-Authors: Ágnes Dancs, Katalin Selmeczi, Nóra V. May, Tamás Gajda
    Abstract:

    Our aim is to combine the preorganized structure of tripodal scaffolds and the advantageous metal-binding ability of histidine subunits. To this end, recently we have studied the copper(II) complexes of the tris(L-histidyl)-functionalized tren derivative, tren3his. Here we report the copper(II)-binding properties of the mono- and bis(L-histidyl)-functionalized tren ligands (tren1his (L1) and tren2his (L2)), and thus explore the impact of increasing histidine ‘density’ on the copper(II) binding of these tripodal peptides. Our Solution Equilibrium study was supplemented by several (UV-vis, CD, ESR, and NMR) spectroscopic and MS methods. The mono-His derivative L1 forms only mononuclear complexes. Above pH 4, the tren-like subunit is the main binding site, which is supplemented by an imidazole coordination. In the case of L2, both mono- and dinuclear copper(II) species are formed. In the acidic–neutral pH range, the highly stable bis-histamine-type binding mode dominates in the equimolar Solution, while at a higher pH amide coordinated complexes are present. The bis-histamine coordination in CuHL2 creates a preorganized structure, which promotes the binding of a second metal at the tren-like binding site with {N−,Ntert,N−} coordination in Cu2H−1L2/Cu2H−2L2. Only the dinuclear Cu2H−2L2 complex was found to efficiently catalyze the oxidation of H2DTBC. The kinetic data resulted in a very high kcat/KM ratio (4360 M−1 s−1), which is due to the exceptionally strong substrate-binding ability of the dinuclear complex. However, the oxidation of the substrate within this adduct, which is a common feature of catalytically active dicopper(II) complexes, does not occur in the absence of dioxygen. This finding implies that the role of dioxygen is the oxidation of the substrate activated by the dinuclear complex. We assume a Cu(II)Cu(II)–catecholate–Cu(II)Cu(I)–semiquinone valence tautomer (VT) Equilibrium. The semiquinone formed in small quantities reacts with dioxygen in a rate-determining step, which eventually results in DTBQ and H2O2 products. The Cu(II)–L2 complexes also exhibit efficient superoxide dismutase-like activity, supporting the versatility of tripodal peptide complexes in redox enzyme mimicking.

  • Complexes of pyridoxal thiosemicarbazones formed with vanadium(IV/V) and copper(II): Solution Equilibrium and structure
    Inorganica Chimica Acta, 2018
    Co-Authors: Tamás Jakusch, Nóra V. May, Bernhard K. Keppler, Éva A. Enyedy, Christian R. Kowol, Alexander Roller, Karoly Kozma, Tamás Kiss
    Abstract:

    Abstract The stoichiometry and thermodynamic stability of vanadium(IV/V) and copper(II) complexes of pyridoxal thiosemicarbazone and pyridoxal-N 3 ,N 3 -dimethylthiosemicarbazone have been determined by pH-potentiometry (V IV O), EPR (V IV O/Cu II ), UV–Vis (Cu II , V IV O and V V ) and 51 V NMR spectroscopy (V V ) in 30% (w/w) dimethyl sulfoxide/water solvent mixture. In all cases, mono-ligand complexes are formed in different protonation states. In addition, the proton-dissociation constants of the ligands were also determined by pH-potentiometry, UV–Vis and 1 H NMR spectroscopy. The solid state structures of the monoprotonated forms (V V O 2 (L 1 H)×1.5H 2 O and V V O 2 (L 2 H)×0.8H 2 O) of the V V complexes were characterized by single-crystal X-ray diffraction analysis. The mono-ligand complexes of Cu II and V V are dominant at physiological pH. With all investigated metal ions the pyridoxal moiety of the ligand causes an extra deprotonation step between pH 4 and 7 due to the non-coordinating pyridine-NH + . The pyridoxal-containing ligands form somewhat more stable complexes with both V IV O and Cu II ions than the reference compound salicylaldehyde thiosemicarbazone. Dimethylation of the terminal amino group resulted in the formation of V V and Cu II complexes with even higher stability.