Nikolaos Kourkoumelis

Palladium(II) and platinum(II) complexes of pyridine-2-carbaldehyde thiosemicarbazone with potential biological activity. Synthesis, structure and spectral properties. Extended network via hydrogen bond linkages of [Pd(PyTsc)Cl]

Abstract The reactions of Li2PdCl4 and Na2PtCl4 with pyridine-2-carbaldehyde thiosemicarbazone, HPyTsc, afforded the complexes [Pd(PyTsc)Cl], [Pd(PyTsc)2] and [Pt(PyTsc)Cl], [Pt(PyTsc)2]. The new complexes have been characterized by elemental analyses and spectroscopic studies. A crystal structure of [Pd(PyTsc)Cl] shows that the anion of PyTsc coordinates in a planar conformation to the central palladium(II) through the pyridyl N, azomethine N and thiolato S atoms. The planar molecules are linked into polymeric chains by N–H··N and N–H··S hydrogen bonding. The protonation constants of the ligand, Ka1 and Ka2, were determined by spectrophotometry and the logarithms of their values were found to be equal to 11.58±0.05 and 3.94±0.02 respectively. Correlation of the antitumor activity of these complexes to the structure and to reduction potential is reported. The compounds [Pt(PyTsc)2] and [Pd(PyTsc)2] were found to exhibit the higher in vivo antitumor activity and the lower cytotoxicity.

Synthesis, structural characterization and biological studies of the triphenyltin(IV) complex with 2-thiobarbituric acid

The reaction between 2-thiobarbituric acid (H(2)TBA), which was treated with an equimolar amount of potassium hydroxide, in a water with triphenytin chloride in methanol, results in the formation of the {[Ph(3)Sn(O-HTBA)]}(n) (1) complex. Crystals of the hydrated 1 with formula {[Ph(3)Sn(O-HTBA)]·0.7(H(2)O)}(n) were growth from methanol/acetonitrile solution, of the white precipitation, filtered off, from the reaction. The crystal structure of complex 1 has been determined by X-ray diffraction at 120 K. Complex 1 is polymeric. The geometry around the tin(IV) ions is trigonal bi-pyramidal with coordination to three C atoms from phenyl groups and one O atom from a de-protonated HTBA ligand. Complex 1 and the already known [(n-Bu)(3)Sn(O-HTBA)·H(2)O] (2) were evaluated for their in vitro cytotoxic activity (cell viability) against human cancer cell lines: HeLa (cervical), OAW-42 (ovarian), MCF-7 (breast, ER positive), MDA-MB-231 (breast, ER negative), A549 (lung), Caki-1 (renal) and additionally, the normal human lung cell line MRC-5 (normal human fetal lung fibroblast cells) and normal immortalized human mammary gland epithelial cell line MTSV17 with a Trypan Blue assay. Moreover complex 1 was evaluated for its in vitro cell growth proliferation activity against leiomyosarcoma cells (LMS), MCF-7 and MRC-5 cells with a Thiazolyl Blue Tetrazolium Bromide (MTT) assay. The type of cell death caused by complexes 1 and 2 was also evaluated by use of flow cytometry assay. The results showed that these compounds mediate a strong cytotoxic response to normal and cancer cell lines tested through apoptosis and induce cell cycle arrest in S phase of the cell cycle, suggesting DNA intercalation (direct or indirect) with the complexes. Finally, the influence of these complexes 1 and 2 upon the catalytic peroxidation of linoleic acid to hydroperoxylinoleic acid by the enzyme lipoxygenase (LOX) was kinetically and theoretically studied.

Synthesis, structural characterization and in vitro cytotoxicity of new Au(III) and Au(I) complexes with thioamides

The reactions of tetrachloroauric(III) acid (HAuCl4) with the thioamides; 2-mercapto-benzothiazole (mbztH) and 5-ethoxy-2-mercapto-benzimidazole (EtmbzimH) lead to the desulfuration of the ligands and the formation of the ionic complexes {[AuCl4]- [bztH2]+} (1), and {[AuCl4]- [EtbzimH2]+ (H2O)} (2) (where bztH2+ and EtbzimH2+ are the desulfurated cations of the starting ligands). The reaction of HAuCl4 with 2-mercapto-nicotinic acid (mnaH2), however results in the formation of 2-sulfonate-nicotininc acid (C6H5NO5S) (3) with the simultaneous oxidation of the sulfur atom. On the other hand, the reactions of the gold(I) complex [Au(tpp)Cl] (4) (tpp = triphenylphosphine (Ph3P)) with the thioamides; 2-mercapto-thiazolidine (mtzdH), 2-mercapto-benzothiazole (mbztH) and 5-chloro-2-mercapto-benzothiazole (ClmbztH) in the presence of potassium hydroxide resulted in the formation of the gold(I) complexes of formulae [Au(tpp)(mtzd)] (5), [Au(tpp)(mbzt)] (6) and [Au(tpp)(Clmbzt)] (7) without ligand desulfuration. All complexes have been characterized by elemental analysis, FT-IR, far-FT-IR,1H-NMR, spectroscopic techniques and X-Ray crystallography. The electrochemical behavior of 1, 2 and 4-7 complexes and the ligands EtmbzimH, mbztH and mnaH2 was also studied in acetonitrile and DMF using cyclic voltammetry. The results are in support of a mechanism of desulfuration of the ligands by Au(III), involving a first oxidation of S to -SO3-, followed by a C-S bond cleavage. This is also supported by PM6 calculations of bond dissociation energies of the various compounds involved. Complexes 1, 2 and 4-7 were tested for in vitro cytotoxicity against leiomyosarcoma cells and the results are discussed in relation with the geometry of the complexes and compared with those of cisplatin and other metals. Complexes 1 and 5 showed higher activity than that of cisplatin, while HAuCl4 was inactive against sarcoma cells.

Synthesis and spectroscopic studies of diorganotin derivatives with tolfenamic acid. Crystal and molecular structure of the first complex of tolfenamic acid, 1,2:3,4-di-μ2-2-[(3-chloro-2-methylphenyl)amino]-benzoato-O,O-1,3-bis-2-[(3-chloro-2-methylphenyl)amino]benzoato-O-1,2,4:2,3,4-di-μ3-oxo-tetrakis[di-n-butyltin(IV)]

Abstract The complexes [Me2LSnOSnLMe2]2 (1) [Bu2LSnOSnLBu2]2 (2) and Bu2SnL2.H2O (3), where HL is 2-[bis(3-chloro-2-methylphenyl)amino]benzoic acid (tolfenamic acid), have been prepared and characterized structurally by means of 19Sn Mossbauer, vibrational and 1H- and 13C-NMR spectroscopies. The crystal structure of complex 2 has been determined by X-ray crystallography. Three distannoxane rings are present to the dimeric tetraorganodistannoxanes of planar ladder arrangement with distorted trigonal-bipyramidal geometry about the five-coordinated tin centers. The structure, which has twofold symmetry, features a central Sn2O2 unit with two additional tin atoms linked at O. Pairs of tin atoms are bridged by bidentate carboxylate ligands and the external tin atoms have their coordination geometry completed by a monodentate carboxylate ligand. The tin atom geometries are similar and are based on a trigonal bipyramidal arrangement. Significant π→π stacking, C–H–π interactions and intrarmolecular hydrogen bonds stabilize this structure. The polar imino hydrogen atom on N(1) and N(2) participate in a bifurcate intramolecular hydrogen bond. In this case complex 2 is self-assembled via C–H–π and π→π stacking interactions. Tin-119 Mossbauer, vibrational and NMR data are discussed in terms of the crystal structure and the proposed structures for 1 and 3. From the variable-temperature Mossbauer effect, the Debye temperatures for 1–3 were determined.

Structural Motifs and Biological Studies of New Antimony(III) Iodide Complexes with Thiones

Eight new antimony(III) iodide complexes of the heterocyclic thioamides, 2-mercapto-1-methylimidazole (MMI), 2-mercaptobenzimidazole (MBZIM), 5-ethoxy-2-mercaptobenzimidazole (EtMBZIM), 2-mercaptothiazolidine (MTZD), 3-methyl-2-mercaptobenzothiazole (NMeMBZT), 2-mercapto-3,4,5,6-tetrahydropyrimidine (tHPMT), 2-mercaptopyridine (PYT), and 2-mercaptopyrimidine (PMT) of formulas {[SbI(3)(MMI)(2)].MeOH} (1), [SbI(3)(MBZIM)(2)] (2), {[SbI(2)(mu(2)-I)(EtMBZIM)(2)](2).H(2)O} (3), [SbI(3)(MTZD)] (4), [(NMeMBZT)SbI(2)(mu(2)-I)(2)(mu(2)-S-NMeMBZT)SbI(2) (NMeMBZT)] (5), {[SbI(3)(tHPMT)(3)].MeOH} (6), [SbI(3)(PYT)] (7), and [SbI(3)(PMT)(2)] (8), have been synthesized and characterized by elemental analysis, FT-IR spectroscopy, FT-Raman spectroscopy, and TG-DTA analysis. The crystal structures of 3, 4, 5, 6, and 7 were also determined by X-ray diffraction. The complexes show interesting structural motifs. Complex 6 is a monomer, with octahedral (Oh) geometry around the metal ion formed by three sulfur and three iodide atoms. Complexes 3 and 5 are dimers, with a square pyramidal (SP) geometry in each monomeric unit, while complexes 4 and 7 are polymers with pseudotrigonal bipyramidal (psi-TBP). Two or three sulfur atoms from thioamide ligands and three iodide atoms are bound to Sb atoms forming building blocks for the dimers and polymers. Strong intramolecular interactions between mu(2)-I and/or mu(2)-S and Sb atoms stabilize both structures. In dimer complex 5, two terminal iodide and one terminal sulfur atom are bonded to the Sb ion, while two mu(2)-I and one mu(2)-S bridging atoms bridge the metal ions forming psi-Oh geometry. Computational studies using multivariant linear regression (MLR) and artificial neural networks (ANN) and considering biological results (50% inhibitory concentration, IC(50)) as dependent variables derived a theoretical equation for IC(50) values of the complexes studied. The calculated IC(50) values are compared satisfactorily with the experimental inhibitory activity of the complexes measured. Complexes 3-7 were used to study their influence upon the catalytic peroxidation of linoleic acid by the enzyme Lipoxygenase (LOX). Compounds 1-8 were also tested for in vitro cytotoxicity, and they showed mostly a moderate cytostatic activity against a variety of tumor cell lines but comparable with those found for the antimony(III) chloride and bromide complexes, reported earlier [Ozturk et al. Inorg. Chem. 2007, 46, 2861-2866; Ozturk et al. Inorg. Chem. 2009, 48, 2233-2245].

New Antimony(III) Bromide Complexes with Thioamides : Synthesis, Characterization, and Cytostatic Properties

New antimony(III) bromide complexes with the heterocyclic thioamides, thiourea (TU), 2-mercapto-1-methylimidazole (MMI), 2-mercapto-benzimidazole (MBZIM), 2-mercapto-5-methyl-benzimidazole (MMBZIM), 5-ethoxy-2-mercapto-benzimidazole (EtMBZIM), 2-mercapto-3,4,5,6-tetrahydro-pyrimidine (tHPMT), 2-mercaptopyridine (PYT), 2-mercapto-thiazolidine (MTZD), 3-methyl-2-mercaptobenzothiazole (MMBZT), and 2-mercaptopyrimidine (PMTH) of formulas [SbBr(3)(TU)(2)] (1), [SbBr(3)(MMI)(2)] (2), {[SbBr(2)(MBZIM)(4)](+) [Br](-) H(2)O} (3), {[SbBr(2)(mu(2)-Br)(MMBZIM)(2)](2)} (4), {[SbBr(2)(mu(2)-Br)(EtMBZIM)(2)](2) MeOH} (5), {[SbBr(3)(mu(2)-S-tHPMT)(tHPMT)](n)} (6), {[SbBr(2)(mu(2)-Br)(PYT)(2))(n)} (7), {[SbBr(2)(mu(2)-Br)(MTZD)(2)](n)} (8), [SbBr(3)(MMBZT)(2)] (9), and {[SbBr(5)](2-)[(PMTH(2)(+))(2)]} (10) have been synthesized and characterized by elemental analysis, conductivity measurements, FTIR spectroscopy, FT-Raman spectroscopy, TG-DTA analysis, and X-ray powder diffraction. The crystal structures of 3, 4, 5, 6, 7, 8, and 10 were also determined by X-ray diffraction. In 3, four sulfur atoms from thione ligands and two bromide ions form an octahedral (O(h)) cationic [SbS(4)Br(2)](+) species in which the two bromide anions lie at axial positions. A third bromide counteranion neutralizes the whole complex. 4 and 5 are dimers, whereas 6, 7 and 8 are polymers, built up by monomeric units of square pyramidal (SP) geometry around the metal center, which were formed by two sulfur atoms of thioamide ligands and three bromide ions. Finally, 10 is ionic salt containing 1D polymeric network of {[SbBr(5)](2-)}(n) anions and (-)[(PMTH(2)(+))2] counter cations in the lattice. The complexes showed mostly a moderate cytostatic activity against a variety of tumor cell lines.

Synthesis, characterization and biological studies of new antimony(III) halide complexes with ω-thiocaprolactam.

Three new antimony(III) halide complexes (SbX(3), X=Cl, Br and I) with the heterocyclic thione ω-thiocaprolactam (1-azacycloheptane-2-thione, (Hthcl)) of formulae {[SbCl(2)(μ(2)-Cl)(Hthcl)(2)](n)} (1), {[(SbBr(2)(μ(2)-Br)(Hthcl)(2))(2)]} (2) and {[(SbI(2)(μ(2)-I)(Hthcl)(2))(2)]} (3) were synthesized from the reaction of antimony(III) halides with ω-thiocaprolactam in 1:2 stoichiometry. The complexes were characterized by elemental analysis, FT-IR spectroscopy, (1)H, (13)C NMR spectroscopy and Thermal Gravimetry-Differential Thermal Analysis (TG-DTA). Crystal structures of the ligand ω-thiocaprolactam and its complexes 1-3 were determined with single crystal X-ray diffraction analysis. Complexes 1-3 and ω-thiocaprolactam were evaluated for their in vitro cytotoxic activity against leiomyosarcoma (LMS) and human breast adenocarcinoma (MCF-7) tumor cell lines. Antimony complexes 1-3 exhibit strong antiproliferative activity against both cell lines tested. The higher such activity was found for 3 with IC(50) values of 0.12±0.04 μM (LMS) and 0.76±0.16 μM (MCF-7) which are 60 and 10 times respectively, stronger than that of cisplatin. The influence of these complexes 1-3 and ω-thiocaprolactam upon the catalytic peroxidation of linoleic acid to hyperoxolinoleic acid by the enzyme lipoxygenase (LOX) was kinetically and theoretically studied. The results were shown negligible inhibitory activity of 1-3 against LOX.

Trinuclear Palladium(II) Complexes with 2-Hydroxy-4-methoxyacetophenone N4-Dimethylthiosemicarbazone: Synthesis, Spectral Studies and Crystal Structure of a Tripalladium Complex

The synthesis and spectral characterization of a new triangular, trinuclear palladium(II) complex with the dianion of 2-hydroxy-4-methoxyacetophenone N4-dimethylthiosemicarbazone, 4MeOAp4Me is reported. The X-ray crystal structure determination of [Pd(4MeOAp4Me2)]3·DMSO shows it to contain a chair-type hexagon of alternating Pd and S atoms which form a molecular bowl. The crystal structure of H24MeOAp4Me2 shows that it is the E isomer with respect to the imine bond of the thiosemicarbazone moiety.

Synthesis, structural characterization and in vitro inhibitory studies against human breast cancer of the bis-(2,6-di-tert-butylphenol)tin(IV) dichloride and its complexes

Four new organotin(IV) complexes of bis-(2,6-di-tert-butylphenol)tin(IV) dichloride [(tert-Bu-)(2)(HO-Ph)](2)SnCl(2) (1) with the heterocyclic thioamides 2-mercapto-pyrimidine (PMTH), 2-mercapto-4-methyl-pyrimidine (MPMTH), 2-mercapto-pyridine (PYTH) and 2-mercapto-benzothiazole (MBZTH), of formulae {[(tert-Bu-)(2)(HO-Ph)](2)Sn(PMT)(2)} (2), {[(tert-Bu-)(2)(HO-Ph)](2)Sn(MPMT)(2)} (3), {[(tert-Bu-)(2)(HO-Ph)](2)SnCl(PYT)} (4) and {[(tert-Bu-)(2)(HO-Ph)](2)SnCl(MBZT)} (5), have been synthesized and characterized by elemental analysis, (1)H-, (13)C-, (119)Sn-NMR, EPR, FT-IR, Raman and Mössbauer spectroscopic techniques. The crystal and molecular structures of compounds 1–5 have been determined by X-ray diffraction. The geometries around the metal center adopted in complexes 1–5 varied between tetrahedral in 1, trigonal bipyramidal in 3, 4, 5 and distorted octahedral in 2. Two carbon atoms from aryl groups and two chlorine atoms form a distorted tetrahedron in the case of 1. Two carbon, two sulfur and two nitrogen atoms from thione ligands form a distorted octahedral geometry around tin(IV) with trans-C(2), cis-N(2), cis-S(2)-configurations in 2. However, in the case of 4 and 5 complexes two carbon, one sulfur, one nitrogen and one chloride atom form a distorted trigonal bipyramidal arrangement. Finally, in the case of 3 the trigonal bipyramidal geometry is achieved by two carbon, two sulfur and one nitrogen atom in a unique coordination mode of thioamides toward the tin(IV) cation. Compounds 1–5 were tested for their in vitro cytotoxicity against the human breast adenocarcinoma (MCF-7) cell line. Compound 3 exhibits strong cytotoxic activity against MCF-7 cells (IC(50) = 0.58 ± 0.1 μM).

Spectroscopic Assessment of Normal Cortical Bone: Differences in Relation to Bone Site and Sex

Bone is a highly complex, composite tissue and its properties normally vary with age, type, and disorders. Fourier transform infrared spectroscopy and energy-dispersive X-ray spectroscopy techniques were used to study the effect of bone sites and sex to mineral and matrix content and composition. The results show that in rats, all inorganic phases consist of poorly crystalline B-type carbonated apatite, while overall mineralization and carbonate content is virtually unaffected among samples. Statistically significant differences were detected for the nonapatitic environments of acid phosphate and carbonate content. The mean values for the Ca/P ratio point to an increasing trend from tibia to forearm, and to femoral sections.