Stereochemistry and antitumour activity of platinum metal complexes of 2-acetylpyridine thiosemicarbazones

Complexes, [M(HL)2], where M = PdII, PtII and HL = neutral 2-acetylpyridine-(2-methylthiosemicarbazone), 2-acetylpyridine-(4-methylthiosemicarbazone) and 2-acetylpyridine-(4-phenylthiosemicarbazone), as well as [M(HL)2]Cl3, where M = RuIII, RhIII and IrIII, have been prepared and characterized by elemental analyses, conductivity measurements, magnetic susceptibility measurements and spectroscopic (i.r., Raman, u.v.-vis. and 1H and 13C-n.m.r) studies. The ligands behave as neutral bidentate components in the PdII and PtII complexes, whereas in RuIII, RhIII and IrIII complexes the ligands exist as neutral tridentates. Various ligand and nephelauxetic parameters have been calculated for the metal complexes. The RuIII, RhIII and IrIII complexes are six-coordinate distorted octahedral, whereas PdII and PtII are four coordinated. The ligands and their platinum group complexes exhibit a potent cytotoxic activity against Ehrlich ascites tumour cells in vitro but appear to be more in vivo.     

Enantioselective allylation of ketones catalyzed by N,N'-dioxide and indium(III) complex

Complexes of (S)-pipecolic acid-, L-proline-, and other amino acid-derived N,N'-dioxides coordinated with different metal ions have been investigated in the enantioselective allylation of ketones. A variety of aromatic ketones were found to be suitable substrates in the presence of the L1-In(III) complex, and afforded the corresponding homoallylic alcohols with good enantioselectivites (up to 83% ee) and moderate to high yields (up to 94%). On the basis of the experimental results, a possible catalytic cycle including a transition state has been proposed to explain the origin of the reactivity and asymmetric inductivity, and a bifunctional catalyst was described with Lewis base N-oxide activating tetraallyltin and Lewis acid indium activating ketone.     

Struktur-Reaktivitäts-Beziehungen bei koordinativ ungesättigten Chelatkomplexen. III. Vergleich des Akzeptorverhaltens der Nickel- und Cobalt(II)-Chelate von dreizähnigen,dianionischen Schiffschen Basen

Structure Reactivity Relations of Coordinatively Unsaturated Chelate Complexes. III. Acceptor Tendency of Nickel and Cobalt Chelates with Tridentate Di-anionic Schiff Base Ligands The reactivity of nickel and cobalt chelate complexes of the type 3 with several donors is compared by isolation of stable adducts. In the case of nickel the reactivity is vigorously influenced by the substituents R¹ and R². The equatorial and the axial unoccupied coordination centers of the nickel chelates exhibit a markedly different behaviour. The cobalt(II) chelates – all of them are high spin complexes – favour O-donors. The complicate composition of the adducts point to a polynuclear structure. With pyridine, high spin diadducts have been isolated probably with coordination number 5 for the metal.     

EPR spin-trapping evidence for the direct,one-electron reduction of tert-butylhydroperoxide to the tert-butoxyl radical by copper(II): paradigm for a previously overlooked reaction in the initiation of lipid peroxidation

Lipid peroxidation is often initiated using Cu(II) ions. It is widely assumed that Cu(II) oxidizes preformed lipid hydroperoxides to peroxyl radicals, which propagate oxidation of the parent fatty acid via hydrogen atom abstraction. However, the oxidation of alkyl hydroperoxides by Cu(II) is thermodynamically unfavorable. An alternative means by which Cu(II) ions could initiate lipid peroxidation is by their one-electron reduction of lipid hydroperoxides to alkoxyl radicals, which would be accompanied by the generation of Cu(III). We have investigated by EPR spectroscopy, in conjunction with the spin trap 5,5-dimethyl-1-pyrroline N-oxide, the reactions of various Cu(II) chelates with tert-butylhydroperoxide. Spectra contained signals from the tert-butoxyl, methyl, and methoxyl radical adducts. In many previous studies, the signal from the methoxyl adduct has been assigned incorrectly to the tert-butylperoxyl adduct, which is now known to be unstable, releasing the tert-butoxyl radical upon decomposition. This either is trapped by 5,5-dimethyl-1-pyrroline N-oxide or undergoes beta-scission to the methyl radical, which either is trapped or reacts with molecular oxygen to give, ultimately, the methoxyl radical adduct. By using metal chelates that are known to be specific in either their oxidation or reduction of tert-butylhydroperoxide (the Cu(II) complex of bathocuproine disulfonic acid and the Fe(II) complex of diethylenetriaminepentaacetic acid, respectively) for comparison, we have been able to deduce, from the relative concentrations of the three radical adducts, that the Cu(II) complexes tested each reduce tert-butylhydroperoxide directly to the tert-butoxyl radical. These findings suggest that a previously overlooked reaction, namely the direct reduction of preformed lipid hydroperoxides to alkoxyl radicals by Cu(II), may be responsible for the initiation of lipid peroxidation by Cu(II) ions.     

Synthesis and structure of two lanthanide complexes with isonicotinic acid N-oxide (HL): [Ln(L)2(H2O)4]n·(NO3)n·n(H2O) (Ln = Sm or Tb)

Two new lanthanide complexes of isonicotinic acid N-oxide (HL), namely [Ln(L)₂(H₂O)₄]_n·(NO₃)_n·n(H₂O) for Ln = Sm or Tb, have been synthesized and characterized by spectroscopic and crystallographic methods. IR spectra suggest that isonicotinic acid N-oxide acts as a O,O′-bidentate ligand, the N-oxide group as well as the nitrate group are not involved in coordination. Single crystal analyses have shown that both complexes are isomorphous, where the Ln(III) centers are eight coordinated by four O atoms of four water ligands and other four O atoms of two isonicotinic acid N-oxide ligands. The carboxylate groups are only involved in the bidentate syn–syn bridging mode into infinite chains. Hydrogen bonds between aqua ligands, lattice molecules, nitrate and N-oxide groups are formed giving a three-dimensional network.     

Complexes of Copper(II) Chloroacetates with Pyridine and Picoline N-Oxides

1:1 Adducts of composition Cu(CH_3-xCl_xCOO)₄L and 1:2 adducts of composition Cu(CH_3-xCl_xCOO)₂L₂ where x=1-3 and L is pyridine N-Oxide (PyNO), 2-picoline N-oxide (2-PicNO) or 3-picoline N-oxide (3-PicNO) have been isolated by the interaction of copper(II) chloroacetates with the appropriate N-oxide ligands. The adducts are soluble in methanol.     

Synthesis, characterisation, reactivity and in vitro antiamoebic activity of hydrazone based oxovanadium(IV), oxovanadium(V) and mu-bis(oxo)bis{oxovanadium(V)} complexes

Binuclear, mu-bis(oxo)bis{oxovanadium(V)} complexes [(VOL)2(mu-O)2](2 and 7)(where HL are the hydrazones Hacpy-nah I or Hacpy-fah II; acpy = 2-acetylpyridine, nah = nicotinic acid hydrazide and fah = 2-furoic acid hydrazide) were prepared by the reaction of [VO(acac)2] and the ligands in methanol followed by aerial oxidation. The paramagnetic intermediate complexes [VO(acac)(acpy-nah)](1) and [VO(acac)(acpy-fah)](6) have also been isolated. Treatment of [VO(acac)(acpy-nah)] and [VO(acac)(acpy-fah)] with aqueous H2O2 yields the oxoperoxovanadium(V) complexes [VO(O2)(acpy-nah)](3) and [VO(O2)(acpy-fah)](8). In the presence of catechol (H2cat) or benzohydroxamic acid (H2bha), 1 and 6 give the mixed chelate complexes [VO(cat)L](HL =I: 4, HL =II: 9) or [VO(bha)L](HL =I: 5, HL =II: 10). Complexes 4, 5, 9 and 10 slowly convert to the corresponding oxo-mu-oxo species 2 and 7 in DMF solution. Ascorbic acid enhances this conversion under aerobic conditions, possibly through reduction of these complexes with concomitant removal of coordinated catecholate or benzohydroxamate. Acidification of 7 with HCl dissolved in methanol afforded a hydroxo(oxo) complex. The crystal and molecular structure of 2.1.5H2O has been determined, and the structure of 7 re-determined, by single crystal X-ray diffraction. Both of these binuclear complexes contain the uncommon asymmetrical {VO(mu-O)}2 diamond core. The in vitro tests of the antiamoebic activity of ligands I and II and their binuclear complexes 2 and 7 against the protozoan parasite Entamoeba histolytica show that the ligands have no amoebicidal activity while their vanadium complexes 2 and 7 display more effective amoebicidal activity than the most commonly used drug metronidazole (IC50 values are 1.68 and 0.45 microM, respectively vs 1.81 microM for metronidazole). Complexes 2 and 7 catalyse the oxidation of styrene and ethyl benzene effectively. Oxidation of styrene, using H2O2 as an oxidant, gives styrene epoxide, 2-phenylacetaldehyde, benzaldehyde, benzoic acid and 1-phenyl-ethane-1,2-diol, while ethyl benzene yields benzyl alcohol, benzaldehyde and 1-phenyl-ethane-1,2-diol.     

Syntheses, Supramolecular Structures and Antibacterial Activities of Five Helical Transition Complexes with 5-Chloro-1-phenyl-1H-pyrazole-3,4-dicarboxylic Acid

Five new transition metal complexes [Cu(HL)₂(H₂O)₂] ( 1 ), [Cu(HL)₂(phen)] ( 2 ), [Cu(HL)₂(H₂O)]₂(4,4′‐bipy) ( 3 ), [Zn(HL)₂(H₂O)₂]·(4,4′‐bipy) ( 4 ), [Ag(HL)(4,4′‐bipy)]_n ( 5 ), (H₂L=5‐chloro‐1‐phenyl‐1H‐pyrazole‐3,4‐dicarboxylic acid, phen=1,10‐phenanthroline; 4,4′‐bipy=4,4′‐bipyridine) have been synthesized and characterized. Complexes 1 , 2 and 4 exhibit monomeric structures, 3 shows a dinuclear structure, 5 displays 1D chain structure, and all extend to 3D supramolecular network via rich hydrogen bonds. Complexes 1 , 2 , 3 , 5 comprise single helical chains, while complex 4 generates quadruple‐stranded helical chains. Furthermore, the antibacterial activities of the titled complexes against bacterial species, three Gram positive bacteria (Staphylococcus aureus, Bacillus subtilis and Candida albicans) and two Gram negative bacteria (Escherichia coli and Pseudomonas aeruginosa) were studied and compared to the activities of free ligands by using the microdilution method.     

一维链状三环己基锡羧酸酯的合成、晶体结构及生物活性

本文以含酯基刚性一元酸L1H(8-乙氧羰基-1-萘甲酸)和含羰基柔性一元酸L2H(4-羰基-4-苯基丁酸)作为多齿配体,分别与三环己基氢氧化锡发生自组装反应,获得了2个新型三环己基锡羧酸酯配合物[(C6H11)3SnL1](1)和[(C6H11)3SnL2](2)(C6H11为环己基)。采用元素分析、1H NMR、FTIR及晶体结构测定等手段对配合物1和2进行了结构表征,在2个新配合物中,锡原子均为六配位,构成以锡原子为中心的扭曲单加帽三角双锥构型,并且通过O→Sn分子间配位键形成了一维超分子链。初步研究了杀菌活性和抗癌活性。     

Synthesis,spectroscopic characterization,and antimicrobial activities of Ni(II) and Fe(II) complexes with N-(2-hydroxyethyl)-5-nitrosalicylaldimine

Metal complexes [Ni(HL1)₂H₂O] (1) and [Fe(HL1)₂] (2), where HL1 is the tridentate Schiff base N-(2-hydroxyethyl)-5-nitrosalicylaldimine, were synthesized and characterized by spectroscopic methods. The crystal structures of 1 and 2 have been determined by single crystal diffraction at 100?K. Complexes 1 and 2 have a distorted octahedral geometry. The ligand and metal complexes were screened for antibacterial and antifungal activities by the disk diffusion, microdilution broth, and single spore culture techniques. Antimicrobial activities of the ligand and its complexes have been tested against 10 bacteria, two yeast, and five filamentous fungi. The ligand and metal complexes were found to be active against all tested micro-organisms.     

Evaluation of dipolar shifts and paramagnetic anisotropy in penta coordinated cobalt(II) complexes

The isotropic proton shifts for the pyridine N-oxide and γ-picoline N-oxide protons have been observed in the penta coordinated adducts of these bases with bis[di(p-tolyl)dithiophosphinato] cobalt(II). The contribution to the observed shifts due to dipolar interaction has been calculated. From the dipolar shifts, it was ascertained that the pyridine N-oxide complexes have a bent structure in solution with a Co-O-N angle of 125°. An estimate of the paramagnetic anisotropy of the cobalt complex yields K_?-K_⊥ = 4244 × 10^?6 cm³/mole.     

Synthesis, crystal structures, and luminescence of organic-lanthanide complexes with nicotinate and isonicotinate ligands

Six lanthanide coordination compounds with two isomeric carboxylic acids, nicotinic acid (HL(1)) and isonicotinic acid (HL(2)), [(L(1))3Ln(H2O)2]2 (Ln = Eu, 1; Gd, 2; Tb, 3) and [( L(2))2Ln(H2O)4][NO3] (Ln = Eu, 4; Gd, 5; Tb, 6), have been synthesized and structurally characterized by single-crystal X-ray diffraction. Complexes 1-3 are dimeric whereas 4-6 are polymeric, all with 8-coordination of Ln(3+). The distinction between these lanthanide complexes is readily accomplished from the 10 K high resolution electronic emission spectra. Spectral interpretation is given for the Eu(3+) complexes 1, 4, whereas the spectra of 3 and 6 are more complex. The relationships between spectroscopic and crystallographic site symmetries are discussed. The calculated second rank crystal field strengths of Eu(3+) in 1 and 4 are intermediate in magnitude.     

Highly trans-1,4 selective (co-)polymerization of butadiene and isoprene with quinolyl anilido rare earth metal bis(alkyl) precursors

The N-R-quinolinyl-8-amino ligands HL(1-3) (R = 2,6-(i)Pr(2)C(6)H(3) (HL(1)), 2,6-Et(2)C(6)H(3) (HL(2)), 2,6-Me(2)C(6)H(3) (HL(3))) have been prepared, which reacted readily with one equiv. of rare earth metal tris(alkyl)s to afford the corresponding bis(alkyl) complexes L(1)Y(CH(2)SiMe(3))(2)(THF) (1) and L(1-3)Lu(CH(2)SiMe(3))(2)(THF) (2-4) via alkane elimination. Contrastingly, treatment of the in situ generated neodymium tri(alkyl)s with HL(1) afforded a mono(alkyl) neodymium complex (5). Complexes 1, 2 and 5 in combination with aluminium alkyls and organoborates established homogenous ternary systems that exhibited versatile catalytic activities and trans-1,4 selectivities for the polymerization of butadiene, depending on the types of aluminium alkyl, organoborate and rare earth metal used. Furthermore, the trans-1,4 selective copolymerization of butadiene and isoprene was achieved by using the ternary system of 1/AlMe(3)/[Ph(3)C][B(C(6)F(5))(4)]. Both the kinetics of copolymerization and the thermal behavior of the copolymers were investigated.     

Topoisomerase Inhibition,Nucleolytic and Electrolytic Contribution on DNA Binding Activity Exerted by Biological Active Analogue of Coordination Compounds

The neutral mononuclear copper complexes with the quinolone antibacterial drug ciprofloxacin and bipyridine derivatives have been synthesized and characterized. Complexes were screened for their antibacterial activity against three Gram⁽⁻⁾ and two Gram⁽⁺⁾ bacteria, and study suggests inhibition of gyrase activity by metal complexes as the possible mechanism. The nucleolytic activity of adducts was carried out on double stranded pUC19 DNA using gel electrophoresis in the presence of radical scavenging agents that suggest hydrolytic cleavage mechanism for plasmid DNA.     

Investigation and characterization of hydrazine and phenylhydrazine complexes of ruthenium(III)1,2-diaminopropanetetraacetate: facile electrochemical and chemical reduction of hydrazines in relevance to nitrogenases

Interaction of hydrazines N₂H₄X⁺ (X=H/Ph) with [Ru(HL)(OH₂)] (1) (L=1,2-diaminopropanetetraacetate, PDTA) has been investigated by potentiometry, spectrophotometry and electrochemistry in aqueous solution at 25°C. The deprotonation and hydrolysis constants of 1 and its hydrazinium adducts formed in 0.1 M Na₂SO₄ solution were determined by potentiometry, while the second order rate constant k₁ and k₂ for the formation of [Ru(HL)(N₂H₄X)]⁺ and [Ru(L)(N₂H₄X)] were determined kinetically by spectrophotometry. At pH 2.8, the complex 1 exhibited a quasi-reversible one-electron reduction step at (E_1/2) −0.251 V vs. SCE and the hydrazinium adducts obtained in situ in the presence of excess (100 equiv) N₂H₄X⁺ showed an additional multi-electron (two-electron per metal at a time) reduction step at (E_1/2) −0.046/−0.158 V (vs. SCE) in the case of X=H/Ph, respectively in sampled-dc. The hydrazines, N₂H₄X⁺ were reduced electrolytically by holding the potential at −0.150 and −0.250 V (Hg-pool) vs. SCE, respectively, and chemically by using H₂ at atmospheric pressure, ascorbic acid, catechol, Zn-dust and NaBH₄ in the presence of these hydrazinium adducts. The turnover numbers, moles of ammonia formed per mole of metal per hour, have been calculated, discussed and compared with those of EDTA (ethylenediaminetetraacetate) analogue. The plausible reaction mechanism for the chemical and the electrochemical reduction of N₂H₄X⁺ to ammonia and/or aniline and the implication of these results on the possible function of nitrogenases have also been proposed. The complex [Ru(HL)(N₂H₅)]HSO₄ and [Ru(HL)(N₂H₄Ph)]Cl were synthesized and characterized.     

Synthese,Kristallstrukturen und Eigenschaften von Lanthanoid(III)-Komplexen mit 7-Oxa-bicyclo[2.2.1]heptan-2,3-dicarbonsäure

Synthesis, Crystal Structures, and Properties of Lanthanoid(III) Complexes with 7-Oxa-bicyclo[2.2.1]heptane-2,3-dicarboxylic Acid The synthesis of coordination compounds [ML(HL)(H₂O)] with M = La³⁺, Ce³⁺, Pr³⁺, Nd³⁺ and H₂L = 7-oxa-bicyclo[2.2.1]heptane-2-exo,3-cis-dicarboxylic acid ( 1 ) has been described. Results of IR spectroscopy and thermal decomposition are given. As a result of X-ray analyses, the four investigated lanthanoid(III) complexes are isotypic. Their stereochemistry approximates to the tri-capped trigonal prism with nine O atoms coordinating the metal atom. The bicyclic ligand acts as a tridentate chelating monoanion HL^? as well as a pentadentate dianion L^2? with both chelating and bridging function. One coordination place at the metal atom is occupied by a water molecule.     

Matrix-assisted laser desorption/ionization Fourier transform mass spectrometry of luteinizing hormone releasing hormone-metal ion complexes

Complexes of luteinizing hormone releasing hormone (LHRH) with divalent metal ions (Ni, Zn, Cu) have been studied by matrix-assisted laser desorption ionization (MALDI) and Fourier transform mass spectrometry. LHRH-metal complexes were detected in high abundance for all three metals from synthesized samples, particularly in negative ion mode. The mixture of the apopeptide with the metal salts yielded in most cases a very minor signal of metal-complex ions. As opposed to Ni and Zn, copper complex ions were mostly observed as Cu(I) adducts. This can be partly attributed to plume reactions of Cu(I) with the apopeptide. the Cu(II) complexes appeared only for the synthetic complex. We show how to distinguish between the contribution to the overall signal from desorbed complexes and from Cu(I) complexes formed in the MALDI plume.     

U(VI) Complexes of oxine and derivatives

Infrared bands due to the hydrogen-bonded (+)N-H cdots, three dots, centered O system in the oxine adduct of U(VI) have been identified and found to occur in the spectra of several newly prepared U(VI) adducts of oxine derivatives. Interligand steric effects in the U(VI) complexes of most 7-substituted oxines prevent the formation of the 1:3 adduct. Complexes of the type ML(2)X, where X is a small co-ordinating species present in solution, are formed instead. With 2-substituted oxines, steric interactions between the 2-substituent and co-ordinated water result in destabilization of the complex and subsequent hydrolysis as the pH of the solution is raised. Experiments involving the use of [(14)C]-oxine were found to distinguish between co-ordinated and lattice-held oxine and are potentially valuable in studies of oxine adducts formed by other metal ions.     

Studies ono-hydroxyacetophenone-2-furoylhydrazone complexes of some 3d-bivalent metal ions

Summary Complexes ofo-hydroxyacetophenone-2-furoylhydrazone, H₂L, of the types M(H₂L)C1₂ · nH₂O [Mn = Co^II, n=0; Ni^II, n=2]; Cu(HL)Cl, M(HL)₂ [M = V^IVO, Co^II, Ni^II or Cu^II] and M(L)(H₂O)_n [M = Co^II or Ni^II, n=2; M = Cu^II, n=0] have been prepared and characterized by elemental analyses, molar conductance, magnetic susceptibility, visible, e.s.r. and i.r. spectral studies. The different modes of ligand chelation and the stereochemistry around the metal ions are discussed.     

N-Hydroxyhomoazaadamantanone and its complexes with dioxo-molybdenum(VI) and copper(II): synthesis and structure

A hydroxamic acid of a new type, N-hydroxyhomoazaadamantanone (HL), has been synthesized, combining several structure peculiarities: cage skeleton, heterocyclicity, and rigidly fixed cis-orientation of the oxygens of the hydroxamate fragment of the molecule. Complexes of HL with dioxo-molybdenum(VI) ((MoO₂LC₂H₅OH)₂O) and copper(II) (CuL₂) have been synthesized. All compounds were characterized by IR and ¹H NMR spectroscopy. X-ray structural analyses of N-hydroxyhomoazaadamantanone hydrochloride and the coordination compounds have been carried out.