Platinum(II) complexes with 2-acetyl pyridine thiosemicarbazone. Synthesis, crystal structure, spectral properties, antimicrobial and antitumour activity

An interesting series of new platinum complexes has been synthesized by the reaction of Na(2)PtCl(4) with 2-acetyl pyridine thiosemicarbazone, HAcTsc. The new complexes, [Pt(AcTsc)Cl], [Pt(HAcTsc)(2)]Cl(2) and [Pt(AcTsc)(2)], have been characterized by elemental analyses and spectroscopic studies. The crystal structure of the complex [Pt(AcTsc)Cl] has been solved by single-crystal X-ray diffraction. The anion of HAcTsc coordinates in a planar conformation to the central platinum(II) through the pyridyl N, azomethine N and thiolato S atoms. Double intermolecular hydrogen bonds (NH-Cl), pi-pi and weak Pt-Pt and Pt-pi contacts lead to aggregation and to a two-dimensional supramolecular assembly. The antibacterial and antifungal effect of the novel platinum(II) complexes and the related palladium(II) complexes, [Pd(AcTsc)Cl], [Pd(HAcTsc)(2)]Cl(2) and [Pd(AcTsc)(2)], were studied in vitro. The complexes were found to have a completely lethal effect on Gram+ bacteria, while the same complexes showed no bactericidal effect on Gram- bacteria. Additionally, the complexes [Pt(AcTsc)(2)] and [Pd(AcTsc)(2)] showed effective antifungal activity towards yeast. Among these compounds [33], the most effective in inducing antitumour and cytogenetic effects are the complexes [Pt(AcTsc)(2)] and [Pd(AcTsc)(2)] while the rest, display marginal cytogenetic and antitumour effects.     

Synthesis,structural characterization and antimicrobial activities of 12 zinc(II) complexes with four thiosemicarbazone and two semicarbazone ligands

Twelve zinc(II) complexes with thiosemicarbazone and semicarbazone ligands were prepared and characterized by elemental analysis, thermogravimetric and differential thermal analysis (TG/DTA), FT-IR and 1H and 13C NMR spectroscopy. Seven three-dimensional structures of zinc(II) complexes were determined by single-crystal X-ray analysis. Their antimicrobial activities were evaluated by MIC against four bacteria (B. subtilis, S. aureus, E. coli and P. aeruginosa), two yeasts (C. albicans and S. cerevisiae) and two molds (A. niger and P. citrinum). The 5- and 6-coordinate zinc(II) complexes with a tridentate thiosemicarbazone ligand (Hatsc), ([Zn(atsc)(OAc)](n) 1, [Zn(Hatsc)(2)](NO(3))(2).0.3H(2)O 2, [ZnCl(2)(Hatsc)] 3 and [Zn(SO(4))(Hatsc)(H(2)O)].H(2)O 4 [Hatsc=2-acetylpyridine(thiosemicarbazone)]), showed antimicrobial activities against test organisms, which were different from those of free ligands or the starting zinc(II) compounds. Especially, complex 2 showed effective activities against P. aeruginosa, C. albicans and moderate activities against S. cerevisiae and two molds. These facts are in contrast to the results that the 5- or 6-coordinate zinc(II) complexes with a tridentate 2-acetylpyridine-4N-morpholinethiosemicarbazone, ([Zn(mtsc)(2)].0.2EtOH 5, the previously reported catena-poly [Zn(mtsc)-mu-(OAc-O,O')](n) and [Zn(NO(3))(2)(Hmtsc)] [Hmtsc=2-acetylpyridine (4N-morpholyl thiosemicarbazone)]), showed no activities against the test microorganisms. The 5- and 6-coordinate zinc(II) complexes with a tridentate 2-acetylpyridinesemicarbazone, ([Zn(OAc)(2)(Hasc)] 6 and [Zn(Hasc)(2)](NO(3))(2) 7 [Hasc=2-acetylpyridine(semicarbazone)]), showed no antimicrobial activities against bacteria, yeasts and molds. Complex [ZnCl(2)(Hasc)] 8, which was isostructural to complex 3, showed modest activity against Gram-positive bacterium, B. subtilis. The 1:1 complexes of zinc(II) with pentadentate thiosemicarbazone ligands, ([Zn(dmtsc)](n) 9 and [Zn(datsc)](n) 10 [H(2)dmtsc=2,6-diacetylpyridine bis(4N-morpholyl thiosemicarbazone) and H(2)datsc=2,6-diacetylpyridine bis(thiosemicarbazone)]), did not inhibit the growth of the test organisms. On the contrary, 7-coordinate zinc(II) complexes with one pentadentate semicarbazone ligand and two water molecules, ([Zn(H(2)dasc)(H(2)O)(2)](OAc)(2).5.3H(2)O 11 and [Zn(H(2)dasc)(H(2)O)(2)](NO(3))(2).H(2)O 12 [H(2)dasc=2,6-diacetylpyridine bis(semicarbazone)]), showed modest to moderate activities against bacteria. Based on the X-ray structures, the structure-activity correlation for the antimicrobial activities was elucidated. The zinc(II) complexes with 4N-substituted ligands showed no antimicrobial activities. In contrast to the previously reported nickel(II) complexes, properties of the ligands such as the ability to form hydrogen bonding with a counter anion or hydrated water molecules or the less bulkiness of the 4N moiety would be a more important factor for antimicrobial activities than the coordination number of the metal ion for the zinc(II) complexes.     

Anti-oxidant, in vitro, in vivo anti-inflammatory activity and antiproliferative activity of mefenamic acid and its metal complexes with manganese(II), cobalt(II), nickel(II), copper(II) and zinc(II)

Some new complexes of mefenamic acid with potentially interesting biological activity are described. The complexes of mefenamic acid [Mn(mef)(2)(H(2)O)(2)], 1, [Co(mef)(2)(H(2)O)(2)], 2, [Ni(mef)(2)(H(2)O)(2)], 3, [Cu(mef)(2)(H(2)O)](2), 4 and [Zn(mef)(2)], 5, were prepared by the reaction of mefenamic acid, a potent anti-inflammatory drug with metal salts. Optical and infrared spectral data of these new complexes are reported. Monomeric six-coordinated species were isolated in the solid state for Mn(II), Ni(II) and Co(II), dimeric five-coordinated for Cu(II) and monomeric four-coordinated for Zn(II). In DMF or CHCl(3) solution the coordination number is retained and the coordinated molecules of water are replaced by solvent molecules. The anti-oxidant properties of the complexes were evaluated using the 1,1-diphenyl-2-picrylhydrazyl, DPPH, free radical scavenging assay. The scavenging activities of the complexes were measured and compared with those of the free drug and vitamin C. We have explored their ability to inhibit soybean lipoxygenase, beta-glucuronidase and trypsin- induced proteolysis. The complex [Mn(mef)(2)(H(2)O)(2)] exhibits the highest antioxidant activity and the highest inhibitory effect against the soybean lipogygenase (LOX), properties that are not demonstrated by mefenamic acid. Their inhibitory effects on rat paw edema induced by Carrageenan was studied and compared with those of mefenamic acid. The complex [Zn(mef)(2)] exhibited a strong inhibitory effect at 0.1 mmol/Kg B.W. (81.5 +/- 1.3% inhibition), superior to the inhibition induced by mefenamic acid at the same dose (61.5 +/- 2.3% inhibition). Mefenamic acid and its metal complexes have been evaluated for antiproliferative activity in vitro against the cells of three human cancer cell lines: MCF-7 (human breast cancer cell line), T24 (bladder cancer cell line), A-549 (non-small cell lung carcinoma) and a mouse fibroblast L-929 cell line. The copper(II) complex displays against T24, MCF-7 and L-929 cancer cell lines, IC(50) values in a microM range similar to that of the antitumor drug cis-platin and they are considered for further stages of screening in vitro and/or in vivo as agents with potential antitumor activity.     

Metal(II) complexes of 1-formylisoquinoline thiosemicarbazone: their preparation,characterization and antitumour activity

Complexes of Co(II), Ni(lI), Cu(II), Zn(II) and Pt(II) with 1-formylisoquinoline thiosemicarbazone (1-iqtsc-H) were prepared and characterized by elemental analyses, conductance measurement and spectral studies. On the basis of these studies a distorted octahedral structure for [Co(1-iqtsc)₂]·2H₂O, a distorted trigonal-bipyramidal structure for [Ni- (1-iqtsc-H)Cl₂], [Cu(1-iqtsc-H)Cl₂] and [Zn(1-iqtsc- H)(OAc)₂]·H₂O and a square-planar structure for [Pt(1-iqtsc)Cl] are suggested. All these metal(II) complexes were screened for their antitumour activity in the P388 lymphocytic leukaemia test system in mice. Except for Pt(Il), the complexes were found to possess significant activity; the Ni(II) complex showed a T/C value of 161 at the optimum dosage.     

Zinc(II) complexes of 2-acetyl pyridine 1-(4-fluorophenyl)-piperazinyl thiosemicarbazone: Synthesis, spectroscopic study and crystal structures - Potential anticancer drugs

2-Acetyl pyridine thiosemicarbazone containing an 1-(4-fluorophenyl)-piperazinyl ring incorporated at N(4)-position, HAcPipPheF (1) and the zinc(II) complexes [Zn(AcPipPheF)₂] (2) and [Zn(OAc)(AcPipPheF)]₂ (3) have been prepared and structurally characterized by means of vibrational and NMR (¹H and ¹³C) spectroscopy. The crystal structures of the compounds 1-3 have been determined by X-ray crystallography. The metal coordination geometry of [Zn(AcPipPheF)₂] is described as distorted octahedral configuration in a trans-N-cis-N-cis-S configuration. In [Zn(OAc)(AcPipPheF)]₂ one of the acetato group exhibits monoatomic bridge and the other bridges in a bidentate manner. The zinc(1) metal ion is coordinated in a distorted octahedral configuration while the metal coordination of Zn(2) is described as distorted square pyramidal. Biomedical studies revealed that, compounds 1-3 displayed potent anticancer activity. The antiproliferative activity of 1-3 was found to be considerably stronger than that of cis-platin. The IC₅₀ values range from 26 to 90 nM, against all cell lines tested, while for cis-platin the IC₅₀ values range from 2 to 17 μM and for the zinc salt, ZnCl₂, the IC₅₀ values range from 81 to 93 μM. The complex 3 shows the highest activity against all four cancer cell lines and the highest selectivity against K562 and MDA-MB-453 cancer cell lines. The compounds inhibited tumor cell proliferation by arresting the cell cycle progression at the S phase.     

Synthesis, X-ray crystal structure, DNA binding, antioxidant and cytotoxicity studies of Ni(ii) and Pd(ii) thiosemicarbazone complexes

New complexes, [Ni(HL)(PPh(3))]Cl (1), [Pd(L)(PPh(3))](2), and [Pd(L)(AsPh(3))](3), were synthesized from the reactions of 4-chloro-5-methyl-salicylaldehyde thiosemicarbazone [H(2)L] with [NiCl(2)(PPh(3))(2)], [PdCl(2)(PPh(3))(2)] and [PdCl(2)(AsPh(3))(2)]. They were characterized by IR, electronic, (1)H-NMR spectral data. Further, the structures of the complexes have been determined by single crystal X-ray diffraction. While the thiosemicarbazone coordinated as binegative tridentate (ONS) in complexes 2 and 3, it is coordinated as mono negative tridentate (ONS) in 1. The interactions of the new complexes with calf thymus DNA was examined by absorption and emission spectra, and viscosity measurements. Moreover, the antioxidant properties of the new complexes have also been tested against DPPH radical in which complex 1 exhibited better activity than that of the other two complexes 2 and 3. The in vitro cytotoxicity of complexes 1-3 against A549 and HepG2 cell lines was assayed, and the new complexes exhibited higher cytotoxic activity with lower IC(50) values indicating their efficiency in killing the cancer cells even at very low concentrations.     

Synthesis and characterisation of the first transition metal complex of zoxazolamine (2-amino-5-chlorobenzoxazole): the X-ray crystal structure determination of [ZnCl2(eta 1-Nbenzoxazole-2-amino-5-chlorobenzoxazole)2

The synthesis and characterisation (NMR, X-ray, elemental analysis) of the first transition metal complex of Zoxazolamine (1: 2-amino-5-chlorobenzoxazole), viz. [ZnCl(2)(1)(2)] (2) is described; complex 2 is obtained in 77% yield from the treatment of 1 with ZnCl(2) in acetone solution. The Zn compound is a mononuclear species (X-ray) with a distorted tetrahedral array of ligands around the metal centre with the title ligand bound to Zn via the benzoxazole ring N-atom. The structural properties of 2 are discussed in relation to other mononuclear Zn halide complexes.     

Biological activity of complexes derived from pyridine-2-carbaldehyde thiosemicarbazone. Structure of

Biological studies on [Fe(L)2](NO3).0.5H2O (1), [Fe(L)2][PF6] (2), [Co(L)2](NCS) (3), [Ni(HL)2]Cl2.3H2O (4) and Cu(L)(NO3) (5), where HL=C7H8N4S, pyridine-2-carbaldehyde thiosemicarbazone, have been carried out. The crystal structure of compound 3 has been solved. It consists of discrete monomeric cationic entities containing cobalt(III) ions in a distorted octahedral environment. The metal ion is bonded to one sulfur and two nitrogen atoms of each thiosemicarbazone molecule. The thiocyanate molecules act as counterions. The copper(II) and iron(III) complexes react with reduced glutathione and 2-mercaptoethanol. The reaction of compound 1 with the above thiols causes the reduction of the metal ion and bis(thiosemicarbazonato)iron(II) species are obtained. The redox activity, and in particular the reaction with cell thiols, seems to be related to the cytotoxicity of these complexes against Friend erithroleukemia cells and melanoma B16F10 cells.     

Characterization and crystal structure of cadmium(II) halide complexes with amino acids and their derivatives VI. The comparison of crystal structures of cadmium(II) halide complexes with three kinds of piperidine carboxylic acids

Six cadmium(II) halide complexes with dl-piperidine-2-carboxylic acid (DL-Hpipe-2), dl-piperidine-3-carboxylic acid (DL-Hpipe-3), and piperidine-4-carboxylic acid (Hpipe-4), have been prepared and characterized by means of IR and Raman spectra and thermal analysis. The crystal structures of [CdCl2(DL-Hpipe-2)(H2O)], [CdBr2(DL-Hpipe-3)], and [CdCl2(Hpipe-4)] have been determined by X-ray diffraction. These three complexes have one-dimensional polymer structures bridged by halide atoms. The crystal of [CdCl2(DL-Hpipe-2)(H2O)] is orthorhombic with the space group Pca2(1). The cadmium atom is in an octahedral geometry, ligated by a carboxyl oxygen atom, two bridging chlorine atoms, a terminal chlorine atom, a water molecule and a carboxyl oxygen atom of a neighboring molecule. The carboxyl oxygen atoms of DL-Hpipe-2 are coordinated to two cadmium atoms. The unit cell consists of two types of one-dimensional polymer structures: [CdCl2(D-Hpipe-2)(H2O)] and [CdCl2(L-Hpipe-2)(H2O)]. Therefore, it is better to write [CdCl2(DL-Hpipe-2)(H2O)] as [CdCl2(D-Hpipe-2)(H2O)][CdCl2(L-Hpipe-2)(H2O)]. The crystal structure of [CdBr2(DL-Hpipe-3)] is monoclinic with space group P2(1). The cadmium atom is in a distorted octahedral geometry ligated by two carboxyl oxygen atoms and four bridging bromine atoms. This complex consists of either D-Hpipe-3 or L-Hpipe-3. Therefore [CdBr2(DL-Hpipe-3)] is written as [CdBr2(D or L-Hpipe-3)]. The crystal of [CdCl2(Hpipe-4)] is monoclinic with space group P2(1)/n. The structure is similar to that of [CdBr2(D or L-Hpipe-3)].     

Biological and cytoselective anticancer properties of copper(II)-polypyridyl complexes modulated by auxiliary methylated glycine ligand

A series of ternary copper(II)-1,10-phenanthroline complexes with glycine and methylated glycine derivatives, [Cu(phen)(aa)(H(2)O)]NO(3)·xH(2)O 1-4 (amino acid (aa): glycine (gly), 1; DL: -alanine (DL: -ala), 2; 2,2-dimethylglycine (C-dmg), 3; sarcosine (sar), 4), were synthesized and characterized by FTIR, elemental analysis, electrospray ionization-mass spectra (ESI-MS), UV-visible spectroscopy and molar conductivity measurement. The determined X-ray crystallographic structures of 2 and 3 show each to consist of distorted square pyramidal [Cu(phen)(aa)(H(2)O)](+) cation, a nitrate counter anion, and with or without lattice water, similar to previously reported structure of [Cu(phen)(gly)(H(2)O)]NO(3)·1?H(2)O. It is found that 1-4 exist as 1:1 electrolytes in aqueous solution, and the cationic copper(II) complexes are at least stable up to 24?h. Positive-ion ESI-MS spectra show existence of only undissociated [Cu(phen)(aa)](+) species. Electron paramagnetic resonance, gel electrophoresis, fluorescence quenching, and restriction enzyme inhibition assay were used to study the binding interaction, binding affinity and selectivity of these complexes for various types of B-form DNA duplexes and G-quadruplex. All complexes can bind selectively to DNA by intercalation and electrostatic forces, and inhibit topoisomerase I. The effect of the methyl substituents of the coordinated amino acid in the above complexes on these biological properties are presented and discussed. The IC(50) values (24?h) of 1-4 for nasopharyngeal cancer cell line HK1 are in the range 2.2-5.2?μM while the corresponding values for normal cell line NP69 are greater than 13.0?μM. All complexes, at 5?μM, induced 41-60?% apoptotic cell death in HK1 cells but no significant cell death in NP69 cells.     

Synthesis, crystal structures, and anti-convulsant activities of ternary [Zn(II)(3,5-diisopropylsalicylate)(2)], [Zn(II)(salicylate)(2)] and [Zn(II)(aspirinate)(2)] complexes

Following observations that bis(3,5-diisopropylsalicylato)diaquazinc(II), [Zn(II)(3,5-DIPS)(2)(H(2)O)(2)], had anti-convulsant activity, bis(acetylsalicylate)diaquazinc(II), [Zn(II)(aspirinate)(2)(H(2)O)(2)], and the Zn(II) ternary 1,10-phenanthroline (phen), 2,9-dimethyl-1,10-phenanthroline (neocuproine, NC) or dimethyl sulfoxide (DMSO) complexes of Zn(II)3,5-diisopropylsalicylate, salicylate, and acetylsalicylate were synthesized and spectroscopically characterized. Anti-convulsant and Rotorod toxicity activities of these complexes were determined to examine their anti-convulsant and undesirable central nervous stimulant or depressant activities of these Zn(II) non-steroidal anti-inflammatory agent complexes. Bis(3,5-diisopropylsalicylato)-1,10-phenanthorlinezinc(II), [Zn(II)(3,5-DIPS)(2)(phen)], (1) has one bidentate phen ligand and two mono-deprotonated 3,5-DIPS ligands. One of the carboxylates bonds in an asymmetric chelating mode. The Zn(II) atom exhibits a distorted bicapped rectangular pyramidal environment N(2)O(2)OO (4+1+1 *). In the neocuproine complex, bis(3,5-diisopropylsalicylato)-2,9-dimethyl-1,10-phenanthorlinezinc(II), [Zn(II)(3,5-DIPS)(2)(NC)] (2), the Zn(II) atom has a much more distorted bicapped rectangular pyramidal environment, N(2)O(2)O(2) (4+2 *), compared to 1. The two carboxylate ligands exhibit the same asymmetric coordinating mode with longer metalloelement-oxygen bond distances compared to 1. The space group of [Zn(II)(aspirinate)(2)(H(2)O)(2)] (3), which has been reported as Cc is corrected to C2/c. The zinc atom exhibits a (4+2 *) bicapped square pyramidal environment. While the two ternary phenanthroline-containing complexes, 1 and 2, evidenced weak protection against maximal electroshock (MES)- and subcutaneous Metrazol (scMET) induced seizures, [Zn(II)(3,5-DIPS)(2)(DMSO)(2)], [Zn(II)(aspirinate)(2)(H(2)O)(2)], and bis(salicylato)-1,10-phenanthorlinezinc(II), [Zn(II)(salicylate)(2)(phen)], were found to be particularly useful in protecting against MES and scMET seizures and [Zn(II)(aspirinate)(2)(H(2)O)(2)] and [Zn(II)(salicylate)(2)(phen)] were found to have activity in protecting against Psychomotor seizures, without causing Rotorod toxicity. Activities of these and other Zn(II) complexes of non-steroidal anti-inflammatory agents are consistent with the well-known anti-inflammatory responses of Zn(II)-dependent enzymes. There was also some evidence of Rotorod toxicity consistent with a mechanism of action involving sedative-hypnotic activity of recognized anti-epilepticdrugs.     

Uracilato and 5-halouracilato complexes of Cu(II), Zn(II) and Ni(II). X-ray structures of [Cu(uracilato-N(1))(2)(NH(3))(2)].2(H(2)O), [Cu(5-chlorouracilato-N(1))(2)(NH(3))(2)](H(2)O)(2), [Ni(5-chlorouracilato-N(1))(2)(en)(2)].2H(2)O and [Zn(5-chlorouracilato-N(1))(NH(3))(3)].(5-chlorouracilato-N(1)).(H(2)O)

Four new complexes of uracilato and 5-halouracilato with the divalent metal ions Cu(II), Zn(II) and Ni(II) were obtained and structurally characterized. [Cu(uracilato- N(1))(2)(NH(3))(2)].2(H(2)O) (1) and [Cu(5-chlorouracilato-N(1))(2)(NH(3))(2)](H(2)O)(2) (2) complexes present distorted square planar co-ordination geometry around the metal ion. Although an additional axial water molecule is present [Cu(II)-OH(2)=2.89 A (for 1) and 2.52 A (for 2)] in both cases, only in the complex 2 would be considered in the limit of a bond distance. The Zn(II) in [Zn(5-chlorouracilato-N(1))(NH(3))(3)].(5-chlorouracilato-N(1)).(H(2)O) presents a tetrahedral co-ordination with three ammonia molecules and the N(1) of the corresponding uracilato moiety. A non-coordinated uracilato molecule is present as a counterion and a recognition between co-ordinated and free ligands, by means a tandem of H-bonds, should be mentioned. Finally, the complex [Ni(5-chlorouracilato-N(1))(2)(en)(2)] (H(2)O)(2) (where en is ethylenediamine) presents a typical octahedral trans co-ordination with additional hydrogen bonds between 5-chlorouracilato and the NH(2) groups of ethylenediamine units.     

New palladium(II) complexes of 5-nitrothiophene-2-carboxaldehyde thiosemicarbazones. synthesis,spectral studies and in vitro anti-amoebic activity

Thiosemicarbazones (1-7) and their palladium(II) complexes (1a-7a) of the type [Pd(TSCN)Cl(2)] (where TSCN=thiosemicarbazone) were prepared from 5-nitro thiophene-2-carboxaldehyde and [Pd(DMSO)(2)Cl(2)], respectively. Coordination via the thionic sulphur and the azomethine nitrogen atom of the thiosemicarbazones to the metal ion were confirmed by spectral data. These compounds were screened in vitro against (HK-9) strain of Entamoeba histolytica possess amoebicidal properties. Enhancement of antiamoebic activity resulted due to the introduction of palladium metal in the thiosemicarbazone moiety. The most promising of the group tested are [Pd(5-N-2-TCA-COTSCN)Cl(2)] and [Pd(5-N-2-TCA-AdmTSCN)Cl(2)] comparable to that of metronidazole.     

Zinc(II), cadmium(II) and mercury(II) complexes of the vitamin B1 antagonist oxythiamine

The reaction of oxythiamine chloride hydrochloride (HOxTCl x HCl) with ZnCl2, CdCl2 and HgCl2 in ethanol yielded the complexes [ZnCl3(HOxT)], [CdCl3(HOxT)] and [HgCl3(HOxT)]. In water, the reaction with CdCl2 afforded [CdCl2(OxT)], but reaction with ZnCl2 or HgCl2 yielded unidentified products. The four new complexes were characterized by mass spectrometry and IR spectroscopy in the solid state and by 1H, 13C and 15N nuclear magnetic resonance (NMR) spectroscopy in hexadeuterated dimethylsulfoxide (DMSO-d6), and three were also studied by X-ray diffractometry. In [ZnCl3(HOxT)] and [HgCl3(HOxT)] the oxythiamine ligand is bound to the metal via N(1') and adopts the V conformation exhibited by thiamine in biological contexts. The infrared (IR) spectrum of [CdCl3(HOxT)] suggests a similar coordination mode. In [CdCl2(OxT)] each OxT zwitterion coordinates to one Cd(II) ion via its N(1') atom and to another via its N(3') and O atoms, giving rise to a polymeric chain along the x-axis. The coordination number of the metal is made up to six by Cdc...Cl interactions, two of which link the polymeric chains in pairs. This seems to be the first metal complex containing the oxythiamine ligand as a zwitterion, with the N(3')-H/O(4'alpha)-H group deprotonated. Neither HOxTCl nor its zinc(II) complex showed any significant activity in vitro against HeLa cells.     

Metal(II) chelates of 4-methyl-5-amino-1-formylisoquinoline thiosemicarbazone: Their preparation,characterization and antitumour activity

The metal(II) complexes [M(4-Me-5-NH₂-1-iqtsc- H)Cl₂] (M = Co(II), Ni(II) or Cu(II) and 4-Me-5- NH₂-1-iqtsc-H = 4-methyl-5-amino-1-formylisoquinoline thiosemicarbazone), [Zn(4-Me-5-NH₂-1-iqtsc-H)- (OAc)₂]· H₂O and [Pt(4-Me-5-NH₂-1-iqtsc)Cl)] were isolated and characterized by elemental analysis, conductance measurement, magnetic moments (300- 78 K)and spectral studies. On the basis of these studies distorted trigonal-bipyramidal structures for the Co(II), Ni(II), Cu(II) and Zn(II) complexes and a square-planar structure for the Pt(II) complex are proposed. All these complexes were screened for their antitumour activity in the P388 lymphocytic leukaemia test system in mice. With the exception of the Pt(II) and Zn(II) complexes, the complexes showed no significant activity; the Zn(II) and Pt(II) complexes showed T/C (%) values of 150 and 144 at a much lesser extent [2].     

Zinc complexes of the biomimetic N,N,O ligand family of substituted 3,3-bis(1-alkylimidazol-2-yl)propionates: the formation of oxalate from pyruvate

The coordination chemistry of the 2-His-1-carboxylate facial triad mimics 3,3-bis(1-methylimidazol-2-yl)propionate (MIm(2)Pr) and 3,3-bis(1-ethyl-4-isopropylimidazol-2-yl) propionate (iPrEtIm(2)Pr) towards ZnCl(2) was studied both in solution and in the solid state. Different coordination modes were found depending both on the stoichiometry and on the ligand that was employed. In the 2:1 ligand-to-metal complex [Zn(MIm(2)Pr)(2)], the ligand coordinates in a tridentate, tripodal N,N,O fashion similar to the 2-His-1-carboxylate facial triad. However, the 1:1 ligand-to-metal complexes [Zn(MIm(2)Pr)Cl(H(2)O)] and [Zn(iPrEtIm(2)Pr)Cl] were crystallographically characterized and found to be polymeric in nature. A new, bridging coordination mode of the ligands was observed in both structures comprising N,N-bidentate coordination of the ligand to one zinc atom and O-monodentate coordination to a zinc second atom. A rather unique transformation of pyruvate into oxalate was found with [Zn(MIm(2)Pr)Cl], which resulted in the isolation of the new, oxalato bridged zinc coordination polymer [Zn(2)(MIm(2)Pr)(2)(ox)].6H(2)O, the structure of which was established by X-ray crystal structure determination.     

Syntheses, crystal structures and antimicrobial activities of 6-coordinate antimony(III) complexes with tridentate 2-acetylpyridine thiosemicarbazone, bis(thiosemicarbazone) and semicarbazone ligands

Five novel antimony(III) complexes with the mono- and bis(thiosemicarbazone) ligands of 2N1S or 4N2S donor atoms, N'-[1-(2-pyridyl)ethylidene]morpholine-4-carbothiohydrazide (Hmtsc, L1) and bis[N'-[1-(2-pyridyl)ethylidene]]-1,4-piperazinedicarbothiohydrazide (H(2)ptsc, L7), and the tridentate semicarbazone ligand of 2N1O donor atoms, 2-acetylpyridine semicarbazone (Hasc, L2b), were prepared by reactions of SbCl(3) or SbBr(3), and characterized by elemental analysis, TG/DTA, FT-IR and (1)H NMR spectroscopy. The crystal and molecular structures of five antimony(III) complexes were determined by single-crystal X-ray structure analysis. The neutral, 6-coordinate antimony(III) complexes ([Sb(mtsc)Cl(2)] 1, [Sb(mtsc)Br(2)] 2, [Sb(asc)Cl(2)] 3 and [Sb(asc)Br(2)] 4) are depicted with one electron pair (5s(2)) of the antimony(III) atom, deprotonated forms of multidentate thiosemicarbazone or semicarbazone ligands, and two monodentate halogen ligands, respectively. In the dimer complex 5 ([Sb(2)(ptsc)Cl(4)]) with the ligand in which two tridentate thiosemicarbazone moieties are connected by the piperazine moiety, each antimony(III) was also described as a neutral 6-coordinate structure. These antimony(III) complexes were thermally stable around 200 degrees C. Water-soluble antimony(III) complexes 1 and 2 showed moderate antimicrobial activities against Gram-positive (Bacillus subtilis and Staphylococcus aureus) and -negative bacteria (Escherichia coli and Pseudomonas aeruginosa), yeasts (Candida albicans and Saccharomyces cerevisiae) and molds (Aspergillus niger and Penicillium citrinum). Complex 5 showed moderate antimicrobial activities against four bacteria, and two molds, while the ligand itself showed only modest antimicrobial activities against selected bacteria (B. subtilis, E. coli and S. aureus). The molecular structures and antimicrobial activities of antimony(III) complexes were compared with those of bismuth(III) complexes in the same 15 group in the periodic table.     

Interactions of bismuth complexes with metallothionein(II).

Bismuth complexes are widely used as anti-ulcer drugs and can significantly reduce the side effects of platinum anti-cancer drugs. Bismuth is known to induce the synthesis of metallothionein (MT) in the kidney, but there are few chemical studies on the interactions of bismuth complexes with metallothionein. Here we show that Bi(3+) binds strongly to metallothionein with a stoichiometry bismuth:MT = 7:1 (Bi(7)MT) and can readily displace Zn(2+) and Cd(2+). Bismuth is still bound to the protein even in strongly acidic solutions (pH 1). Reactions of bismuth citrate with MT are faster than those of [Bi(EDTA)](-), and both exhibit biphasic kinetics. (1)H NMR data show that Zn(2+) is displaced faster than Cd(2+), and that both Zn(2+) and Cd(2+) in the beta-domain (three metal cluster) of MT are displaced by Bi(3+) much faster than from the alpha-domain (four metal cluster). The extended x-ray absorption fine structure spectrum of Bi(7)MT is very similar to that for the glutathione and N-acetyl-L-cysteine complexes [Bi(GS)(3)] and [Bi(NAC)(3)] with an inner coordination sphere of three sulfur atoms and average Bi-S distances of 2.55 A. Some sites appear to contain additional short Bi-O bonds of 2.2 A and longer Bi-S bonds of 3.1 A. The Bi(3+) sites in Bi(7)MT are therefore highly distorted in comparison with those of Zn(2+) and Cd(2+).     

Synthesis, structure and biological activity of nickel(II) complexes of 5-methyl 2-furfural thiosemicarbazone

5-Methyl 2-furfuraldehyde thiosemicarbazone (M5HFTSC) with nickel(II) leads to three types of complexes: [Ni(M5HFTSC)(2)X(2)], [Ni(M5FTSC)(2)] and [Ni(M5FTSC)(2)] x 2DMF. In the first type the ligand remains in thione form, while in the two other, the anionic thiolato form is involved. The species [Ni(M5HFTSC)(2)X(2)] has been characterized spectroscopically. The structures of [Ni(M5FTSC)(2)] x 2DMF and [Ni(M5FTSC)(2)] have been solved using X-ray diffraction. Biological studies of [Ni(M5HFTSC)(2)Cl(2)] have been carried out in vitro for antifungal activity on human pathogenic fungi, Aspergillus fumigatus and Candida albicans, and in vivo for toxicity on mice. The results are compared to those of the ligand, the metal salt and a similar copper complex [Cu(M5HFTSC)Cl(2)].     

Unusual dimeric Zn(II)-cytosine complexes: new models of the interaction of Zn(II) with DNA and RNA

Synthesis and crystal structure of two Zn(II) dimer complexes with 1-methylcytosine (1-MeC) are reported. In complex [Zn(2)Cl(4)(mu-1-MeC-O2,N3)(2)] (1), two 1-MeC ligands are bridging two ZnCl(2) moieties. In [Zn(2)(1-MeC-N3)(4)(mu-SO(4))(2)].2H(2)O (2), the sulfates act as bridging ligands and 1-MeC are linked via N3 to Zn(II) as terminal ligands. Both complexes represent the first examples of Zn(II)-pyrimidine dimers. The potential biological significance of 1 and 2 is discussed.