Influence of cis-[PtCl2(Me2SO)2] on the thermal denaturation of albumin

The interaction of cis-[PtCl2(Me2SO)2] with human serum albumin (HSA) and the sensitivity of the complex towards the thermal denaturation depending on the duration of incubation have been studied by absorption and fluorescence spectroscopy methods. Optimum conditions for cis-[PtCl2(Me2SO)2] binding to HSA have been determined. The results have been compared with the data obtained for HAS-cisplatin complex. It has been found that binding of HSA to cis-[PtCl2(Me2SO)2] does not result in significant structural changes of the protein.     

Viscosity behavior of some alpha-amino acids and their groups in water-sodium acetate mixtures

Viscosities of glycine, DL-alpha-alanine, DL-alpha-amino-n-butyric acid, DL-valine and DL-leucine have been determined in water-sodium acetate mixtures at 298.15 and 308.15 K. The viscosity B-coefficients have been calculated. The corresponding activation free energies (Deltamu(2)(0 not equal )) for viscous flow have been evaluated with the help of the Feakins equation. The contributions of the charged end group (NH(3)(+),COO(-)) and CH(2) groups of the amino acids to B-coefficient and Deltamu(2)(0 not equal) have been also determined using the linear correlation between B-coefficient or Deltamu(2)(0 not equal) and the number of carbon atoms in alkyl chains of the amino acids. The results have been interpreted in the light of the solute-solvent interactions in aqueous media.     

A study on the structures of the substituted (aminomethyl)lithium and (thiomethyl)lithium compounds

The structures of substituted (aminomethyl)lithium and (thiomethyl)lithium compounds have been examined. Geometric parameters, charge densities, bond orders, dipole moments and heats of formation for all the members of the two series of monomers and dimers of the units LiCN(R)2 and LiCSR where R=H, CH3(Me), C6H5(Ph) have been calculated. The structures of the three complex compounds containing the same units; [[Li(CH2SMe)(THF)]X], [Li2(CH2SPh)2(THF)4] and [Li2(CH2NPh2)2(THF)3] have also been modeled. Geometry optimizations have been performed with the semiempirical PM3 method. The molecular orbital calculations have been carried out by a self-consistent field method using the restricted Hartree-Fock formalism. Comparisons have been made with the corresponding properties of methyl lithium monomer and dimer. The results show that in all of the nitrogen-containing monomers, the C-Li bonds weaken and the Li-C-H(N) angles decrease due to the coordination of lithium with nitrogen. Substitution of hydrogen atoms by methyl or phenyl groups decreases the Li-N coordination. In the sulfur-containing compounds, sulfur behaves similarly to nitrogen but the changes are smaller because the 3p lone-pair orbital of sulfur is higher in energy than the 2p lone-pair of nitrogen. All the dimers of nitrogen/sulfur-containing methyl lithium derivatives form six-membered rings in which the Li-N(S) coordination is greater than the one in the corresponding monomers. Dimerization reactions have been found to be exothermic and the formation of all the dimers is favored. The results obtained for the three complex structures are comparable to the experimental results reported in the literature.Keywords:     

Zinc complexes with cyclic derivatives of alpha-ketoglutaric acid thiosemicarbazone: Synthesis, X-ray structures and DNA interactions

Six new cyclic ligands derived from alpha-ketoglutaric acid thiosemicarbazone (H(3)ct) and their zinc complexes have been synthesized and characterized by analytical and spectroscopic (IR and NMR) studies. The X-ray structures of ligands Me-H(2)ct(C) (1), Allyl-H(2)ct(c) (3) and of complex [Zn(Me-Hct(C))(2)(OH(2))(2)].2H(2)O (7) have been determined. In complex (7) the zinc atom lies on a twofold axis and is surrounded in a tetrahedral coordination by two water molecules and two carboxylic oxygen donor atoms from the ligand. DNA titration in the UV-visible region and thermal denaturation have been employed to determine the details of DNA binding for the studied compounds. Studies of nuclease activity have also been performed with all our compounds through a gel electrophoresis experiment using plasmid pBR322 showing that no DNA breakings take place. Tests in vitro on human leukemia cell line U937 have been carried out on cell growth inhibition where solubility of the compounds allowed the experiments.     

Thermal and pH stability of 2 -isopentenyl pyrophosphate

The isoprenoid precursors Delta(3)-isopentenyl pyrophosphate and gamma,gamma-dimethylallyl pyrophosphate (Delta(2)-isopentenyl pyrophosphate) have been separated by thin-layer chromatography. The products from Delta(2)-isopentenyl pyrophosphate incubated under various conditions of pH and temperature have been separated, and the survival of Delta(2)-isopentenyl pyrophosphate under these conditions has been calculated. The acid-labile Delta(2)-isopentenyl pyrophosphate can be stored indefinitely at pH 11.5 and -100 degrees C.     

Platinum(II) and palladium(II) complexes with dithiocarbamates and amines: synthesis, characterization and cell assay

The [M(ESDT)Cl]n (M = Pd or Pt; ESDT = EtO2CCH2(CH3)NCS2, methylamino-acetic acid ethyl ester-dithiocarboxylate) species have been reacted with various amines (py, pyridine; PrNH2, n-propylamine; c-BuNH2, cyclobutylamine; en, ethylenediamine) in dichloromethane or chloroform with the aim to obtain mixed ligand complexes. The neutral complexes [M(ESDT)(L)Cl] (L = py, PrNH2 or c-BuNH2) and the ionic species ([M(ESDT)(L)2]Cl and [M(ESDT)(En)]Cl) have been isolated, and characterized by IR and proton NMR spectroscopies. The crystal structure of [Pd(ESDT)(PrNH2)Cl] has been determined by X-ray crystallography. The behaviour of the complexes in various solvents was described on the basis of the proton NMR spectra. The complexes and the dithiocarbamato intermediates have been tested for in vitro cytostatic activity against human leukemic HL-60 and HeLa cells.     

alpha(1)-Adrenoceptor agonists: the identification of novel alpha(1A )subtype selective 2'-heteroaryl-2-(phenoxymethyl)imidazolines

Novel 2'-heteroaryl-2-(phenoxymethyl)imidazolines have been identified as potent agonists of the cloned human alpha(1)-adrenoceptors in vitro. The nature of the 2'-heteroaryl group can have significant effects on the potency, efficacy, and subtype selectivity in this series. alpha(1A) Subtype selective agonists have been identified.     

Homoleptic ruthenium (II) complexes containing asymmetric tridentate 2-(benzimidazole-2-yl)-1,10-phenanthroline likes ligands: syntheses, characterization and DNA binding

Two novel homoleptic ruthenium (II) complexes containing asymmetric tridentate ligands, 2-(benzimidazole-2-yl)-1,10-phenanthroline (PHBI) and 2-(naphtho[2,3-d]imidazole-2-yl)-1,10-phenanthroline (PHNI) have been synthesized and characterized by elemental analysis, mass spectra, (1)H NMR, and electronic spectroscopy. The DNA-binding properties of the complexes have been investigated by spectroscopic methods and viscosity measurements. The results indicate that the two complexes interact with DNA via electrostatic interaction, and the mechanisms of DNA binding with the complexes have also been discussed.     

The quantum chemical study of the electronic states of S2Cl and its monovalent ions

High-level quantum chemical techniques have been utilized to accurately describe the geometrical parameters, vibrational frequencies and dissociation pathways of the X (2)A″, 1 (2)A', 2 (2)A', 2 (2)A″ states of S(2)Cl; X (1)A', 1 (3)A″, 1 (1)A″, 1 (3)A' states of S(2)Cl(+); X (1)A', 1 (3)A', (1)A″ states of S(2)Cl(-), and the corresponding excitation energies have been obtained from the energies extrapolated to their complete basis set limits. It has been established that the 2 (2)A' and 2 (2)A″ terms of S(2)Cl exhibit a strong multi-reference character, while all the remaining excited states are dominated by the single replacements from the reference determinants. The enthalpies of the decomposition reactions have been obtained to aid in the investigations into the photolysis of S(2)Cl(2) and related systems. The value of the ionization potential of S(2)Cl has been found within the error bars of the experiment, and a reliable estimate of its electron affinity, EA (0)?=?-2.352?eV, has been proposed.     

Synthesis, characterization, antibacterial and cytotoxic study of platinum (IV) complexes

Platinum (IV) complexes [Pt (L)2Cl2] [where, L= benzyl-N-thiohydrazide (L1), (benzyl-N-thio)-1,3-propanediamine (L2), benzaldehyde-benzyl-N-thiohydrazone (L3) and salicylaldehyde-benzyl-N-thiohydrazone (L4)] have been synthesized. The thiohydrazide, thiodiamine and thiohydrazones can exist as thione-thiol tautomer and coordinate as a bidentate N-S ligand. The ligands were found to act in monobasic bidentate fashion. Analytical data reveal that metal to ligand stoichiometry is 1:2. The complexes have been characterized by elemental analysis, IR, mass, electronic and 1H NMR spectroscopic studies. In vitro antibacterial and cytotoxic studies have been carried out for some complexes. Various kinetic and thermodynamic parameters like order of reaction (n), activation energy (Ea), apparent activation entropy (S#) and heat of reaction (DeltaH) have also been carried out for some complexes.     

QT/QS2 index in patients with arterial hypertension, mitral valve prolapse and hyperthyroidism]

QT/QS2 ratio has been assessed in 26 patients with both borderline and mild hypertension and mitral valve prolapse syndrome (19 patients), and hyperthyroidism (16 patients) in comparison with method control groups. The following polycardiographic parameters have been analyzed: QT, QTp, QS2, QT/QS2, and QTp/QS2. Higher values of QT/QS2 ratio have been noted in patients with mitral valve prolapse syndrome and hyperthyroidism than that in the control group. There has been no difference in patients with mild hypertension while the values of the analyzed parameter have been significantly lower in patients with borderline hypertension. QT has been longer than QS2 (QT)QS2 1/in 9 (56%) patients with hyperthyroidism. A positive correlation between QT/QS2 ratio and ++thyroxine levels have been noted in these patients. QT values have been higher than QS2 values only in 1 patient with mild hypertension. It seems that QT/QS2 value has limited value as an indirect index of the adrenergic activity in the dysfunction of the autonomic nervous system.     

Strong protective action of Copper(II) N-substituted sulfonamide complexes against reactive oxygen species

Copper(II) complexes of N-benzothiazolsulfonamides, [Cu(N-2-(5,6-dimethylbenzothiazole)toluenesulfonamidate)(2)(dmso)(2)] (1), [Cu(N-2-(6-chlorobenzothiazole)benzenesulfonamidate)(2)(dmso)(2)] (2) and [Cu(N-2-(6-chlorobenzothiazole)toluenesulfonamidate)(2)(dmso)(2)] (3) with interesting protective properties against superoxide radicals have been prepared. The compounds have been characterized by X-ray diffraction and their chemical properties have been studied by spectroscopic methods. The crystal structure of 1 shows that the copper(II) is surrounded by two benzothiazole N atoms from the sulfonamide ligands and two O atoms from the dimethylsulfoxide molecules in a square planar arrangement. The coordination polyhedron around copper(II) in 2 and 3 is distorted square pyramidal being the metal ion linked to benzothiazole N and sulfonamidate O atoms of the ligand and to two dimethylsulfoxide O atoms. The three complexes have a strong protective action over Delta sod1 mutant of Saccharomyces cerevisiae against reactive oxygen radicals derived from respiration and against those generated by hydrogen peroxide and menadione.     

2-Arylbenzothiazole, benzoxazole and benzimidazole derivatives as fluorogenic substrates for the detection of nitroreductase and aminopeptidase activity in clinically important bacteria

A series of 2-(2-nitrophenyl)benzothiazole 7, 2-(2-nitrophenyl)benzoxazole 10 and 2-(2-nitrophenyl)benzimidazole 13 derivatives have been synthesised and assessed as indicators of nitroreductase activity across a range of clinically important Gram negative and Gram positive bacteria. The majority of Gram negative bacteria produced strongly fluorescent colonies with substrates 7 and 10 whereas fluorescence production in Gram positive bacteria was less widespread. The l-alanine 16 and 19 and β-alanine 21 and 23 derivatives have been prepared from 2-(2-aminophenyl)benzothiazole 14 and 2-(2-aminophenyl)benzoxazole 17. These four compounds have been evaluated as indicators of aminopeptidase activity. The growth of Gram positive bacteria was generally inhibited by these substrates but fluorescent colonies were produced with the majority of Gram negative bacteria tested.     

Synthesis, characterization, EXAFS investigation and antibacterial activities of new ruthenium(III) complexes containing tetradentate Schiff base

A series of new hexa-coordinated ruthenium(III) complexes of the type [Ru(X)(2-atmp-ba)(EPh3)] (where H2-2-atmp-ba=N,N'-bis(2-aminothiophenol)benzoylacetone; X=Cl or Br; E=P or As) have been prepared by reacting [RuX3(EPh3)3] (where X=Cl or Br; E=P or As) with tetradentate Schiff base ligand (H2-2-atmp-ba) in 1:1 molar ratio. The complexes have been characterized by elemental analyses, Infra red, electronic, electron paramagnetic resonance spectroscopy and cyclic voltammetry. In order to confirm the coordination and structure of the complexes extended X-ray absorption fine structure spectroscopy (EXAFS) studies have been carried out. Based on the above data, an octahedral structure has been confirmed for the complexes. The new complexes were also screened for their antibacterial properties.     

Synthesis, spectroscopic, cytotoxic, and DNA binding studies of binuclear 2,2'-bipyridine-platinum(II) and -palladium(II) complexes of meso-alpha,alpha'-diaminoadipic and meso-alpha,alpha'-diaminosuberic acids.

Four new binuclear complexes of formula [M2(bipy)2(BAA)]Cl2 (where M is Pt(II) or Pd(II), bipy is 2,2'-bipyridine, and BAA is a dianion of meso-alpha-alpha'-diaminoadipic acid (DAA) or meso-alpha,alpha'-diaminosuberic acid (DSA) have been synthesized. These complexes have been characterized by chemical analysis and ultraviolet-visible, infrared, and 1H NMR spectroscopy. The mode of binding of ligands in these complexes has been ascertained by infrared and detailed 1H NMR spectroscopy. These complexes are 1:2 electrolyte in conductivity water. They have also been tested against P388 lymphocytic leukemia cells and their target is DNA molecules. [Pt2(bipy)2(DSA)]Cl2, [Pd2(bipy)2(DSA)Cl2, and [Pd2(bipy)2(DAA)]Cl2 show I.D.50 values comparable or lower than cis-diamminedichloroplatinum(II) and [Pt(bipy)(Ala)]Cl. In addition, binding studies of [Pt2(bipy)2(DSA)]Cl2 and [Pd2(bipy)2(DAA)]Cl2 to calf thymus DNA have been carried out and the mode of binding seems to be hydrogen bonding, as suggested earlier for analogous mononuclear amino acid-DNA complexes.     

Phospholipase A2

Phospholipase A2 (PLA2) catalyzes the hydrolysis of the sn-2 position of membrane glycerophospholipids to liberate arachidonic acid (AA), a precursor of eicosanoids including prostaglandins (PGs) and leukotrienes (LTs). The same reaction also produces lysophosholipids, which represent another class of lipid mediators. So far, at least 19 enzymes that possess PLA2 activity have been identified in mammals. The secretory PLA2 (sPLA2) family, in which 10 isozymes have been identified, consists of low-molecular-weight, Ca2+-requiring, secretory enzymes that have been implicated in a number of biological processes, such as modification of eicosanoid generation, inflammation, host defense, and atherosclerosis. The cytosolic PLA2 (cPLA2) family consists of 3 enzymes, among which cPLA2alpha plays an essential role in the initiation of AA metabolism. Intracellular activation of cPLA2alpha is tightly regulated by Ca2+ and phosphorylation. The Ca2+-independent PLA2 (iPLA2) family contains 2 enzymes and may play a major role in membrane phospholipid remodeling. The platelet-activating factor (PAF) acetylhydrolase (PAF-AH) family represents a unique group of PLA2 that contains 4 enzymes exhibiting unusual substrate specificity toward PAF and/or oxidized phospholipids. In this review, we will overview current understanding of the properties and functions of each enzyme belonging to the sPLA2, cPLA2, and iPLA2 families, which have been implicated in signal transduction.     

Synthetic, spectral, thermal and antimicrobial studies on some mixed 1,3-dithia-2-stannacyclopentane derivatives with dialkyldithiocarbamates

1,3-dithia-2-stannacyclopentane derivatives with dialkyldithiocarbamates of the types SCH(2)CH(2)SSn[S(2)CNR(2)]Cl (I) and SCH(2)CH(2)SSn[S(2)CNR(2)](2) (II) (where R = CH(3), C(2)H(5) and -CH(2)-CH(2)-) have been synthesized by the reaction of 2,2-dichloro-1,3-dithia-2-stannacyclopentane and sodium/ammonium salts of dialkyldithiocarbamates in 1:1 and 1:2 molar ratios, respectively, in anhydrous benzene. These newly synthesized derivatives have been characterized by elemental analyses (C, H, N, S and Sn), thermal [thermogravimetry (TG) and differential thermal analyses (DTA)] as well as spectral [UV, IR and multinuclear NMR ((1)H, (13)C and (119)Sn)] studies. The monodentate behaviour of the dialkyldithiocarbamate ligands was confirmed by IR and (119)Sn NMR spectral data and distorted tetrahedral structures have been suggested for both type (I) and (II) compounds. The free ligands and their tin complexes have also been screened for their antibacterial and antifungal activities. These results made it desirable to delineate a comparison between free ligands and their tin complexes. These exhibit higher antibacterial effect than some of the previously investigated antibiotics.     

Synthesis, structural characterization, antiradical and antidiabetic activities of copper(II) and zinc(II) Schiff base complexes derived from salicylaldehyde and beta-alanine

A series of copper(II) and zinc(II) complexes involving a tridentate O,N,O'-donor Schiff base derived from salicylaldehyde and beta-alanine {i.e. N-salicylidene-beta-alanine(2-), (L)}, having the composition [Cu(2)(L)(2)(H(2)O)].H(2)O (1), [Cu(L)(H(2)O)](n) (2), and [Zn(L)(H(2)O)](n) (3), have been prepared and characterized by elemental analyses, UV-visible (UV-VIS), FT-IR and ESI-MS spectra, and thermal analyses. Complexes 1 and 2 have been investigated by single crystal X-ray analysis and also by temperature dependent magnetic susceptibility measurements (294-80K). All prepared complexes have been evaluated by the antiperoxynitrite activity assay and alloxan-induced diabetes model. The significant antioxidant and antidiabetic activities have been found in the case of both copper(II) complexes 1 and 2. In spite of first two complexes, the zinc(II) complex 3, as well as the potassium salt of the ligand (KHL) showed only insignificant protective effect against the tyrosine nitration in vitro.     

Can the 1,5-disubstituted tetrazole ring modify the co-ordinating ability and biological activity of opiate-like peptides?

The copper(II) complexing ability and the biological activity of beta-casomorphin-7 tetrazole analogues have been investigated. Potentiometric and spectroscopic (UV-Vis, CD and EPR) studies have been used to establish the thermodynamic stability, speciation and structure of Cu(II) complexes with YP-psi(CN4)-FPGPI-NH2 (1), YPF-psi(CN4)-AGPI-NH2 (2) and YPFP-psi(CN4)-GPI-NH2 (3). Comparison of the binding ability of the tetrazole analogues reveals that the most effective ligand for copper(II) is YPF-psi(CN4)-AGPI-NH2. The effectiveness of this ligand comes from its particular conformation suited for the Cu(II) 2N co-ordination mode in the physiological pH region. The ability of casomorphin tetrazole analogues to activate rat mast cells to histamine release in vitro in the presence of copper(II) has been studied.     

A Bifunctional Enzyme in Pseudomonas aeruginosa: a New Pattern in the Organization of Enzymes Concerned with Phenylalanine and Tyrosine Biosynthesis

Two isozymes of chorismate mutase (CA mutase(1) and CA mutase(2)) and two isozymes of prephenate dehydratase (PPA dehydratase(1) and PPA dehydratase(2)) have been found in Pseudomonas aeruginosa. The activities CA mutase(2)-PPA dehydratase(2) catalyzing phenylalanine biosynthesis have been purified almost 40-fold and were found to be associated as a bifunctional enzyme or an enzyme complex. The enzymes specific for tyrosine biosynthesis did not appear to manifest such physical association. Thus, the organization of enzymes concerned with phenylalanine and tyrosine biosynthesis in P. aeruginosa is unique and is unlike most other organisms. Single site mutants have been isolated which have lost both CA mutase(2)-PPA dehydratase(2) activities resulting in a requirement for phenylalanine for growth. Single site revertants of these mutants regained both these activities simultaneously and were able to grow on minimal medium. A mutant, r(6), was also isolated which had normal CA mutase(2) but lacked PPA dehydratase(2) activity.