Complexes of zinc with picolinic and aspartic acids inactivate free varicella-zoster virions

Zn(II) picolinate and aspartate, Zn(pic)(2) and Zn(asp)(2), have been shown to inhibit key steps of the replication of HSV-1. In the present study we describe the effect of Zn(pic)(2) and Zn(asp)(2) on the replication of VZV and on the infectivity of free virions. The experiments are done using BHK-21 cells, a clinical isolate of VZV and Zn-complexes in concentration of 10 muM. When Zn-complexes are present during the whole period of infection, the yield of infectious virus progeny decreases up to 98%. The infectivity of VZV is completely restored after the removal of zinc. The virucidal effect is manifested at the 2nd h of contact, when 90% of the virions are inactivated. The results show that both Zn(pic)(2) and Zn(asp)(2) specifically inactivate free VZV virions with no effect on viral replication.     

Effect of Complexes of Cobalt With Aminoacids on the Replication of Herpes Simplex Virus Type 1 (HSV-1)

Cobalt, being essential metal, influences different physiological and enzymatic functions. As cobalt does not accumulate in the body, Co-compounds have relatively low toxicity. The aim of the present study is the effect of complexes of Co(II) with aminoacids - lysine, arginine, histidine and serine on HSV-1 replication. No effect of [O(2)Co(his)(4)].nH(2)O and [O(2)Co(arg)(2)].nH(2)O on HSV-1 infection in vitro was found. Both, [O(2)Co(lys)(2)].nH(2)O and [O(2)Co(ser)(2)].nH(2)O suppress the attachement of HSV-1 particles onto target cells and the viral replication as well. Moreover, the properties of the particular Co-complex (charge, stability, structure) are manifestated by their virucidal effect. Thus, [O(2)Co(ser)(2)].nH(2)O irreversibly inhibits the infectious activity of free HSV-1 virions, while virucidal effect of [O(2)Co(lys)(2)].nH(2)O is completely reversible after the 2h of contact.     

Transition Metal Ion Complexes of Schiff-bases. Synthesis, Characterization and Antibacterial Properties

Some novel transition metal [Co(II), Cu(II), Ni(II) and Zn(II)] complexes of substituted pyridine Schiff-bases have been prepared and characterized by physical, spectral and analytical data. The synthesized Schiff-bases act as deprotonated tridentate for the complexation reaction with Co(II), Ni(II) and Zn(II) ions. The new compounds, possessing the general formula [M(L)(2)] where [M=Co(II), Cu(II), Ni(II) and Zn(II) and HL=HL(1), HL(2), HL(3) and HL(4)] show an octahedral geometry. In order to evaluate the effect of metal ions upon chelation, the Schiff bases and their complexes have been screened for antibacterial activity against the strains such as Escherichia coli,Staphylococcus aureus, and Pseudomonas aeruginosa. The complexed Schiff bases have shown to be more antibacterial against one more bacterial species as compared to uncomplexed Schiff-bases.     

Synthesis and Anti-Candida Activity of Cobalt(II) Complexes of Benzene-1,2-Dioxyacetic Acid (bdoaH(2)). X-Ray Crystal Structures of [Co(bdoa)(H(2)O)(3)] 3.5H(2)O and {[CO(phen)(3)](bdoa)}(2)24H(2)O (phen = 1,10-Phenanthroline)

Co(CH(3)CO(2))(2)4H(2)O reacts with benzene-1,2-dioxyacetic acid (bdoaH(2)) to give the Co(2+) complexes [Co(bdoa)(H(2)O)(3)]H(2)O (1a) and [Co(bdoa)(H(2)O)(3)] 3.5H(2)O (1b). Subsequent reaction of 1a with 1,10- phenanthroline produces [CO(phen)(3)] bdoa10H(2)O (2a) and {[CO(phen)(3)](bdoa)}(2)24H(2)O (2b). Molecular structures of 1b and 2b were determined crystallographically. In 1b the bdoa(2-)- ligates the metal by two carboxylate oxygens and two ethereal oxygens, whereas in 2b the bdoa(2-) is uncoordinated. The Mn(2+) and Cu(2+) complexes [Mn(bdoa)(phen)(2)]H(2)O (3) and [Cu(pdoa)(imid)(2)] (4) were also synthesised, 1a-4 and other metal complexes of bdoa H(2) (metal = Mn(2+), Co(2+) ,Cu(2+), Cu(+) ) were screened for their ability to inhibit the growth ofhe yeast Candida albicans. Complexes incorporating the 1,10-phenanthroline ligand were the most active.     

Synthesis, Characterization and Biological Evaluation of Co(II), Cu(II), Ni(II) and Zn(II) Complexes With Cephradine

Some Co(II), Cu(II), Ni(II) and Zn(II) complexes of antibacterial drug cephradine have been prepared and characterized by their physical, spectral and analytical data. Cephradine acts as bidentate and the complexes have compositions, [M(L)(2)X(2)] where [M = Co(II), Ni(II) and Zn(II), L = cephradine and X = Cl(2)] showing octahedral geometry, and [M(L)(2)] where [M = Cu(II), L = cephradine] showing square planar geometry. In order to evaluate the effect of metal ions upon chelation, eephradine and its complexes have been screened for their antibacterial activity against bacterial strains, Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa.     

Insights into the mode of action of the anti-Candida activity of 1,10-phenanthroline and its metal chelates

Metal complexes of malonie acid (metal = Mn(II), Co(II), Ni(II), Cu(II), Zn(II), Ag(I)) were prepared and only the Ag(I) complex inhibited the growth of Candida albicans. Malonate complexes incorporating the chelating 1,10-phenanthroline (1,10-phen) ligand showed a range of activities: good (Mn(II), Cu(II), Ag(I)); moderate (Zn(II)); poor (Co(II), Ni(II)). Metal-free 1,10-phen and Ag(CH(3)CO(2)) were also highly active. The metal-free non-chelating ligands 1,7- phenanthroline and 4,7-phenanthroline were inactive and the Cu(II), Mn(II) and Zn(II) complexs of 1,7-phen displayed only marginal activity. Whereas the Cu(II) malonate/1,10-phen complex induces significant cellular oxidative stress the Zn(II) analogue does not.     

Zinc(II) Complexes - A New Group of Non-Mutagenic Herpes Simplex Virus Inhibitors

Former studies showed that complexes of Zn(II) with picolinic and with aspartic acids, Zn(pic)(2) and Zn(asp)(2), are able to inhibit HSV infection in cultured cells by affecting key steps of virus replication. As these complexes are candidates for a novel class anti-HSV drugs, further studies on their mutagenicity are of particular interest. In the present paper we present data showing that Zn(pic)(2) and Zn(asp)(2) do not express mutagenic effect in both prokaryotic (Salmonella typhimurium) and eukaryotic (Saccharomices cerevisiae) test systems.     

Influence of the metal centers of 2,6‐bis(imino)pyridyl transition metal complexes on ethylene polymerization/ oligomerization catalytic activities

Much work on bis(imino)pyridyl complexes with Fe(II) and Co(II) as ethylene polymerization catalysts has been reported in terms of designing new analogous ligands, while little work has been dedicated to the study of the effect of the metal center on catalyst performance. A series of bis(imino)pyridyl‐MCl₂ (M = Fe(II), Co(II), Ni(II), Cu(II), Zn(II)) transition metal complexes were synthesized, for which single crystals of the Co(II) and Cu(II) complexes were obtained. The crystal structures indicated that these complexes had similar coordination geometries. Being applied to ethylene polymerization at 25 °C and employing 500 equiv. of methylaluminoxane as co‐catalyst, the complexes with Fe(II), Co(II) and Ni(II) centers showed, respectively, catalytic activities of 1.25 × 10⁶ g (mol Fe)^?1 h^?1 Pa for ethylene polymerization, and 3.98 × 10⁵ g (mol Co)^?1 h^?1 Pa and 5.13 × 10³ g (mol Ni)^?1 h^?1 Pa for ethylene oligomerization. In contrast, the complexes with Cu(II) and Zn(II) centers were inactive. Crystal structure data showed that the coordination interactions provided a comparatively reliable quantification of the selectivity of the bis(imino)pyridyl ligand for the studied metal ions, which was in reasonable agreement with the Irving–Williams list. Moreover, for the Ni(II) and Cu(II) complexes, the strong coordination bonds and small N(imino)? M? N(imino) angles were unfavorable for several steps in the mechanism, such as ethylene coordination to the metal center, ethylene migratory insertion and olefin chain growth. All of these will reduce the speed of the overall reaction, indicating a decrease of catalytic efficiency in a given period. The poor activity of the Zn(II) complex for ethylene polymerization may be related to the reduction process by the alkylating agent. Copyright © 2010 Society of Chemical Industry     

Synthesis, Characterization and Antiviral Properties of Pd(II) Complexes With Penciclovir

With the aim to improve and extend the antiviral activity of the antiherpic drug penciclovir, to a wider spectrum of viruses, we have synthesized and characterized new binary and ternary complexes of Pd(II) of formulae cis-(pen)(2)PdCl(2) and cis,[(nucl)(2)Pd(pen)(2)]Cl(2), where nucl = guanosine, inosine, cytidine or penciclovir. The characterization was mainly based on IR and (1)H NMR spectroscopy, and the results showed that in all prepared complexes, penciclovir coordinates to the metal through N7. The far-i.r. spectrum of the complex cis-(pen)(2)PdCl(2) confirmed the cis- geometry around Pd(II). All the prepared complexes were markedly active against HSV-1 and HSV-2 strains, but not against thymidine kinase-deficient HSV-1 strains.     

Effect of Copper Acyclovir Complexes on Herpes Simplex Virus Type 1 and Type 2 (HSV-1, HSV-2) Infection in Cultured Cells

We have found that when copper, zinc or cobalt is bound to a suitable ligand, the appropriate complex exhibited a significant anti-HSV effect (Varadinova et al., 1993; 1996). Recently published data by Sagripanti et al. (1997) also show that the inhibition of HSV by copper was enhanced by reducing agents and that mechanism of the inactivation is similar as for copper-mediated DNA damage (Aruoma, et al. 1991; Dizdaroglu, et al., 1991; Toyokuni and Sagripanti, 1994). Therefore it was interesting to study the efect of Cu(ll) coordination compounds with acyclovir (ACV) on the replication of HSV in cultured cells. The experiments on cytotoxicity as well as on the activity of three different Cu-ACV complexes [Cu(ACV)(2)Cl(2)(H(2)O)(2)] = (A); [Cu(ACV)(2)(H(2)O)(3)](NO(3))(2).H(2)O = (B) and [Cu(ACV)(2)(H(2)O)(2)](NO(3))(2)] = (C) towards virus replication, with special attention on the growth of ACV-resistant strain R-100 were performed on MDBK cells. ACV was used as a reference compound. The following results were obtained: 1) Increased cell's viability in the presence of 20-40(g/ml ACV and decreased one in the presence of Cu-ACV complexes with relative level (A) > (B) > (C); 2) Cu-ACV complexes are more cytotoxic than the ligand - ACV and the relative level is (C)>(B)>(A); 3) The anti-HSV effect of ACV can be modulated by copper at levels depending on the specificity of the particular virus strain: (i) for the ACV sensitive strain DA (HSV-1) - ACV ((A) > (C) > (B); (ii) for the ACV sensitive strain Bja (HSV-2) (A) > ACV > (C) > (B); (iii) for strain R-100 (ACV(R), TK(a)) - (A) > ACV > (C) > (B). This findings are consistent with previously published data and undoubtedly show that Cu-ACV complexes could be useful in the treatment of HSV infections, especially when the causative agent is a resistant to ACV mutant.     

Synthesis,characterization, and catalytic activity of 4 mol % N,N′‐methylene bisacrylamide crosslinked poly(acrylic acid)–metal complexes

The metal‐ion complexation behavior and catalytic activity of 4 mol % N,N′‐methylene bisacrylamide crosslinked poly(acrylic acid) were investigated. The polymeric ligand was prepared by solution polymerization. The metal‐ion complexation was studied with Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Cu(II), and Zn(II) ions. The metal uptake followed the order: Cu(II) > Cr(III) > Mn(II) > Co(II) > Fe(III) > Zn(II) > Ni(II). The polymeric ligand and the metal complexes were characterized by various spectral methods. The catalytic activity of the metal complexes were investigated toward the hydrolysis of p‐nitrophenyl acetate (NPA). The Co(II) complexes exhibited high catalytic activity. The kinetics of catalysis was first order. The hydrolysis was controlled by pH, time, amount of catalyst, and temperature. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 92: 272–279, 2004     

Synthesis, Characterization and Biological Properties of Tridentate NNO, NNS and NNN Donor Thiazole-Derived Furanyl, Thiophenyl and Pyrrolyl Schiff Bases and Their Co(II), Cu(II), Ni(II) and Zn(II) Metal Chelates

2-Aminothiazole undergoes condensation reactions with furane-, thiophene- and pyrrole-2-carboxylaldehyde to give tridentate NNO, NNS and NNN Schiff bases respectively. These tridentate Schiff bases formed complexes of the type [M (L)(2)]X(2) where [M=Co(II), Cu(II), Ni(II) or Zn(II), L=N-(2-furanylmethylene)-2-aminothiazole (L(1)), N-(2-thiophenylmethylene)-2-aminothiazole (L(2), N-(2-pyrrolylmethylene)-2-aminothiazole (L(3)) and X=Cl. The structures of these Schiff bases and of their complexes have been determined on the basis of their physical, analytical and spectral data. The screening results of these compounds indicated them to possess excellent antibacterial activity against tested pathogenic bacterial organisms e.g., Escherichia coli, Staphylococcus aureous and Pseudomonas aeruginosa. However, in comparison, their metal chelates have been shown to possess more antibacterial activity than the uncomplexed Schiff bases.     

Studies on various divalent metal complexes of poly(2-hydroxy-4-acryloyloxybenzophenone) in aqueous medium

2-Hydroxy-4-acryloyloxybenzophenone (2H4ABP) prepared by reacting acryloyl chloride with 2,4-dihydroxybenzophenone, was polymerized in 2-butanone at 65°C using benzoyl peroxide as initiator. Polychelates were obtained in the alkaline solution of poly(2H4ABP) with aqueous solutions of metal ions such as Ni(II), Mn(II), Co(II), Ca(II), Cd(II) and Zn(II). The polymer and polychelates were characterized by elemental analyses and spectral studies. Elemental analyses of the polychelates suggest that the metal-to-ligand ratio is 1: 2. The IR spectral data of the polychelates indicate that the metals were coordinated through the oxygen of the keto group and oxygen of the phenolic −OH group. The diffuse reflectance spectra, EPR and magnetic moments studies reveal that the polychelates of Cu(II) complex are square planar, and Ni(II), Mn(II) and Co(II) complexes are octahedral, while Ca(II), Cd(II) and Zn(II) complexes are tetrahedral. X-ray diffraction studies revealed that the polychelates are highly crystalline. The thermal and electrical properties of polymer and polymer–metal complexes are discussed. © 1998 SCI.     

New antimicrobial agents: The synthesis of Schiff base polymers containing transition metals and their characterization and applications

A new polymeric Schiff base containing formaldehyde and 2‐thiobarbituric acid moieties was synthesized by the condensation of a monomeric Schiff base derived from 2‐hydroxyacetophenone and hydrazine. Polymer–metal complexes were also synthesized by the reaction of the polymeric Schiff base with Mn(II), Co(II), Ni(II), Cu(II), and Zn(II) acetate. The polymeric Schiff base and its polymer–metal complexes were characterized with magnetic moment measurements, elemental analyses, and spectral techniques (infrared, ¹H‐NMR, and ultraviolet–visible). The thermal behaviors of these coordination polymers were studied by thermogravimetric analysis in a nitrogen atmosphere up to 800°C. The thermal data revealed that all of the polymer–metal complexes showed higher thermal stabilities than the polymeric Schiff base and also ascribed that the Cu(II) polymer–metal complex showed better heat resistant properties than the other polymer–metal complexes. The antimicrobial activity was screened with the agar well diffusion method against various selected microorganisms, and all of the polymer–metal complexes showed good antimicrobial activity. Among all of the complexes, the antimicrobial activity of the Cu(II) polymer–metal complex showed the highest zone of inhibition because of its higher stability constant and may be used in biomedical applications. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Spectral, magnetic and biological studie on some bivalent 3d metal complexes of hydrazine derived schiff-base ligands

Metal(II) complexes of hydrazine derived Schiff-base ligands of the type M(L)(2)Cl(2) where M = Co, Cu, Ni and Zn and L = L(1) and L(2) have been prepared and characterised by molar conductance, magnetic moment, elemental analysis and electronic, IR, H-NMR and (13)C spectral data.The different modes of chelation of the ligands and their comparative biological properties against different bacterial species are reported.     

Metal-5-Fluorouracil-histamine complexes: solution, structural, and antitumour studies

Solution studies were performed pH-metrically to study the interaction of Co(II), Ni(II), Cu(II), Zn(II) and Cd(II) metal ions with 5-fluorouracil (5FU) and histamine (Hm) separately (binary) and in the presence of each other (ternary) at 25+/-0.1( degrees )C temperature and a constant ionic strength of 0.1 M NaNO(3) in aqueous solution. The ternary complexes have been found to be more stable than the corresponding binary complexes as shown by the positive value of DeltalogK. The species distribution curves have been obtained using the computer programme BEST. On the basis of species distribution results, efforts were also made to prepare some mixed complexes of Co(II), Ni(II), Cu(II), Zn(II) and Cd(II) ions by performing the reaction of their metal nitrates, 5FU and Hm in aqueous ethanol medium at suitable pH. The isolated solid complexes were characterized by different physico-chemical method in order to suggest the possible binding site of the ligands and the structure of the resultant complexes. All these complexes were checked for their antitumour activity by injecting in Dalton's lymphoma (DL) and Sarcoma-180 (S-180) bearing C(3)H/He mice. The results indicate that some complexes have good antitumour activity both in vivo and in vitro.     

Novel meso-substituted porphyrins: Synthesis, characterization and photocatalytic activity of their TiO2-based composites

Two series of novel meso-substituted porphyrins, namely 5,10,15,20-tetra[4-(3-phenoxy)-propoxy]phenyl porphyrin, the structural analogue 5,10,15,20-tetra[2-(3-phenoxy)-propoxy]phenyl porphyrin and their Co(II) Cu(II) and Zn(II) complexes were synthesized. The compounds were characterized using various spectroscopic techniques and their molecular structure was proposed based on density functional theory calculations. The diverse properties of the porphyrin derivatives result from the different stereochemistry of the particular substituents at the meso site on the macrocycle and are controlled also by the coordinated metal. The ¹H NMR spectrum of the free-base porphyrin showed a complicated spin-splitting. The photocatalytic activities in degradation of 4-nitrophenol were investigated using polycrystalline TiO₂ impregnated with the porphyrins and metalloporphyrins. The Cu(II) porphyrin was a more effective sensitizer than other metal containing compounds (M = Co, Zn) as well as the free-base. Photocatalytic activity was also influenced by spatial positions of the substitutions on the porphyrin molecules.     

Search for Optimum Conditions of Extraction of Transition Metal Complexes with Alkylimidazoles. I. Extraction of the Co(II), Ni(II), and Zn(II) Complexes of 1-Methylimidazole and of the Co(II) and Zn(II) Complexes of 2-Methylimidazole

Abstract

It has been shown that for the Co(II), Zn(II), and Ni(II) complexes of 1-methylimidazole and for the Co(II) and Zn(II) complexes of 2-methylimidazole, the partition coefficient D between the aqueous and organic phases is proportional to the degree of formation α _n of a definite complex. Tetrahedral species have been found to be extracted with the Co(II) and Zn(II) complexes of 2-methylimidazole and with the Zn(II) complexes of 1-methylimidazole.