Norah Barba-Behrens

Coordination chemistry of some biologically active ligands

Abstract We have been interested in the coordination behaviour of biologically active ligands containing N and O donor atoms towards metal ions and boron. Structural and spectroscopic studies have been carried out. Also, the stability, chemical structure and behaviour of some of the coordination compounds in solution have been studied and their effect on photosynthetic activities investigated.

Synthesis, structure and biological activities of cobalt(II) and zinc(II) coordination compounds with 2-benzimidazole derivatives

In this work we present the synthesis, structural and spectroscopic characterisation of a series of cobalt(II) and zinc(II) coordination compounds with benzimidazole (bz) and its 2-benzimidazole derivatives: 2-aminobenzimidazole (2ab), albendazole (abz) and tris(2-benzimidazolylmethyl)amine (ntb). The compounds were evaluated for their in vitro antimicrobial activity against Staphylococcus aureus, Micrococcus luteus, Salmonella typhi, Pseudomonas aeruginosa, Escherichia coli and Proteus vulgaris. Their cytotoxic activity was also evaluated using human cancer lines, HeLa, HCT-15 and SKLU-1. The halide tetrahedral compounds [Co(bz)2Br2] 3, [Zn(2ab)2Cl2].0.5H2O 11, [Co(abz)Cl2(H2O)].3H2O 14, [Co(abz)Br2(H2O)] 15, [Zn(abz)Cl2(H2O)].3H2O 17 and [Zn(abz)Br2(H2O)].H2O 18 displayed similar minimal inhibition concentration (MIC) values against Micrococcus luteus and Escherichia coli, comparable to those of amoxicillin and chloramphenicol. Additionally, 11 showed a wide range of activity towards Gram(+) and Gram(-) microorganisms. The tetradentate ntb and its trigonal bipyramidal cobalt(II) and zinc(II) compounds were active, regardless of the anion present in the complex. Compound [Co(abz)Cl2(H2O)].3H2O 14 showed promising activity in HeLa cells, while [Co(ntb)Br]Br.H2O 21 inhibited Hela and HCT-15 cell lines.

Coordination compounds of thiabendazole with main group and transition metal ions

Abstract We report LiI, NaI, KI, PbII, CoII, NiII, CuII, ZnII, CdII and HgII coordination compounds derived from thiabendazole [2-(4′-thiazolyl)benzimidazole (tbz)]. The compounds were characterised by analytical and spectroscopic techniques. NMR studies of diamagnetic compounds were performed in solution. X-ray diffraction analysis of NaI, PbII, CoII, NiII, CuII and CdII complexes showed that tbz stabilises bis- and tris-chelated coordination compounds. In solution and in solid state the ligand coordinates to the metal ions through the imidazolic and thiazole nitrogen atoms regardless of the nature of the metal ion.

Synthesis, X-ray and spectroscopic characterisation of chromium(III) coordination compounds with benzimidazolic ligands

Abstract The syntheses and characterisation of chromium(III) complexes with tris(2-benzimidazolylmethyl)amine (ntb), 2-guanidinobenzimidazole (2gb), 2,6-bis(2-benzimidazolyl)pyridine (bbimpy) and 2-(2-pyridyl)benzimidazole (2pb), of composition [Cr(ntb)Cl2]Cl·4.5H2O (1), [Cr(2gb)3]Cl[ZnCl4]·CH3OH (2), [Cr(2gb)3]Cl3·4H2O (3), [Cr2(2gb)4(μ-OH)2](ClO4)4·5H2O (4), [Cr(bbimpy)Cl3] (5) and [Cr(2pb)2Cl2]Cl·C2H5OH·0.5H2O (6) are presented. The compounds are obtained from Cr(III) in alcoholic solution, or a Cr(II) aqueous acidic solution. The latter were carried out under air-free conditions. The reaction of 2gb with Cr(II) in aqueous solution yielded a dinuclear compound. The X-ray crystal structures of 1 and 4 are discussed.

Cytotoxic copper(II), cobalt(II), zinc(II), and nickel(II) coordination compounds of clotrimazole.

Sixteen novel mononuclear Cu(II), Co(II), Zn(II), and Ni(II) complexes of the biologically active ligand clotrimazole (clotri) of the forms [M(clotri)(2)Cl(2)]·nH(2)O (1-4), [M(clotri)(2)Br(2)]·nH(2)O (5-7), [M(clotri)(3)Br(2)] (8), [M(clotri)(3)NO(3)]NO(3)·nH(2)O (9, 11), [M(clotri)(3)(NO(3))(2)]·nH(2)O (10), and [M(clotri)(3)(OH(2))(2)NO(3)]NO(3)·nH(2)O (12) were synthesized and fully characterized. Dinuclear [Cu(2)(clotri)(4)μ(2)-Cl(4)]·2H(2)O (1a) and [Cu(2)(clotri)(4)μ(2)-Br(2)]·2H(2)O (5b) as well as tetranuclear [Cu(4)(clotri)(4)μ(4)-Br(6)μ(4)-O] (5a) complexes were also isolated. Complexes 1-7, 9, and 11 present a tetrahedral geometry; complex 8 exhibits a pentacoordinated structure; complexes 1a, 10 and 12 an octahedral geometry. X-ray crystal structures of [Cu(clotri)(2)Cl(2)](1), [Cu(clotri)(2)(EtOH)Cl(2)](1·EtOH), [Zn(clotri)(2)Cl(2)] (3), [Zn(clotri)(2)Br(2)] (7), and [Cu(4)(clotri)(4)μ(4)-Br(6)μ(4)-O] (5a) were obtained. Complexes 1-12 were tested for cytotoxic activity against the human carcinoma cell lines HeLa (cervix-uterine), PC3 (prostate), and HCT-15 (colon) displaying IC(50) values <30 μM. Confocal microscopy and nuclear dying (DAPI) for complex 1 showed condensation of cromatin and nuclear membrane fragmentation. Immunocytochemical detection/expression of biomarkers suggests that complexes 1 and 9 induce cell death via apoptosis. TUNEL assay detected DNA fragmentation in HeLa cells, resulting from apoptotic signaling cascades induced by Cu(II) complexes 1 and 9. (1)H NMR studies of the Zn(II) complexes showed that they can bind to nucleotides.

Cytotoxic activity, X-ray crystal structures and spectroscopic characterization of cobalt(II), copper(II) and zinc(II) coordination compounds with 2-substituted benzimidazoles

Herein we present the synthesis, structural and spectroscopic characterization of coordination compounds of cobalt(II), copper(II) and zinc(II) with 2-methylbenzimidazole (2mbz), 2-phenylbenzimidazole (2phbz), 2-chlorobenzimidazole (2cbz), 2-benzimidazolecarbamate (2cmbz) and 2-guanidinobenzimidazole (2gbz). Their cytotoxic activity was evaluated using human cancer cell lines, PC3 (prostate), MCF-7 (breast), HCT-15 (colon), HeLa (cervic-uterine), SKLU-1 (lung) and U373 (glioblastoma), showing that the zinc(II) and copper(II) compounds [Zn(2mbz)(2)Cl(2)].0.5H(2)O, [Zn(2cmbz)(2)Cl(2)].EtOH, [Cu(2cmbz)Br(2)].0.7H(2)O and [Cu(2gbz)Br(2)] had significant cytotoxic activity. The isostructural cobalt(II) complexes showed not significant activity. The cytotoxic activity is related to the presence of halides in the coordination sphere of the metal ion. Recuperation experiments with HeLa cells, showed that the cells recuperated after removing the copper(II) compounds and, on the contrary, the cells treated with the zinc(II) compounds did not. These results indicate that the mode of action of the coordination compounds is different.

Supramolecular structures of metronidazole and its copper(II), cobalt(II) and zinc(II) coordination compounds

In this work we present the synthesis and structural and spectroscopic characterization of Cu(II), Co(II) and Zn(II) coordination compounds with the antibiotic metronidazole ([double bond]emni). Coordination to metal ions is through its imidazolic nitrogen, while the hydroxyethyl and nitro groups act as supramolecular synthons. [Co(emni)(2)Br(2)], and [Zn(emni)(2)X(2)] (X(-)=Cl, Br) stabilize zig-zag chains, and a 2D supramolecular structure is formed by inter-chain contacts through inter-molecular hydrogen-bonding. Pleated sheet or layers are formed by [Co(emni)(2)Cl(2)] and [Cu(emni)(2)Cl(H(2)O)](2)Cl(2), respectively. The dinuclear Cu(II) compound [Cu(emni)mu(O(2)CMe)(2)](2) gives a one-dimensional zig-zag arrangement. The contribution of metal ions in metronidazole coordination compounds is shown in the stabilization of the different aggregate structures.

Preparation and characterization of new transition metal complexes of nitroimidazoles. X-Ray crystal structures of two copper complexes: bis-[(μ-chloro)chloro-bis-(1-(2-hydroxyethyl)-2-methyl-5-nitroimidazole)copper(II)] and dichloro-bis-(2-methyl-s-nitroimidazole)copper(II). First observation of nitro group coordination to the metal ion in these heterocycles

Abstract 2-Methyl-5-nitroimidazole [MNIH, (1)] forms the complexes Cu(MNIH)2X2 [X = Cl (1a), Br (1b), NO3 (1C), OH (1d)] and Co(MNIH)2X2 [X = Cl (1e), OAc (1f)]. X-ray crystal structure of 1a shows a distorted octahedral geometry for the copper(II) ion bonded to two chlorine atoms and two nitroimidazole molecules through N(1) and with a trans diaxial coordination to one of the oxygen atoms of the nitro groups. This is the first example of nitroimidazole derivatives in which the nitro group occupies a coordination site. Spectroscopic evidence suggests that for compounds 1b–1f the preferred coordination site for the metal ion is N(1), with interaction of the nitro group adjacent to it, giving extra stability to the complexes. The copper complexes, 1b and 1c, contain six coordinated metal atoms, while 1e is tetrahedral and 1f is a carboxylate-bridged dimer. The other ligand, 1-(2-hydroxyethyl)-2-methyl-5-nitroimidazole [metronidazole, HEMNI (2)] forms the complexes Cu(HEMNI)2X2[X = Cl (2a, 2b), Br (2c), OAc (2d)] and Co(HEMNI)2Cl2 (2e). An X-ray crystal structure determination on Cu(HEMNI)2Cl2 (2a shows a centrosymmetric chlorobridged dimer. The coordination geometry around each copper atom is trigonal bipyramidal with three equatorial chlorine atoms and two axial imidazole molecules. The rest of the metronidazole complexes obtained were shown to be a dimeric compound with bridging acetates, 2d, two monomeric octahedral (X = Cl, Br) copper compounds, 2b and 2c, and a tetrahedral cobalt compound, 2e.

Coordination behaviour of 2-guanidinobenzimidazole towards cobalt(II), nickel(II), copper(II) and zinc(II). An experimental and theoretical study

SummaryThe following coordination compounds derived from 2-guanidinobenzimidazole (2GB) (1); [Ni(2GB)2]Cl2· H2O, (2); [Ni(2GB)2]Br2·3H2O, (3); [Ni(2GB)2-(NO3)2, (4); [Ni(2GB)2](OAc)2, (5); [Cu(2GB)Cl2], (6); [Cu(2GB)Br2], (7); [Cu(2GB)2]Br2·2H2O, (8); [Cu(2GB)2](NO3)2·H2O, (9); [Cu(2GB)2](OAc)2· H2O, (10); [Zn(2GB)Cl2]·H2O, (11); [Zn(2GB)Br2]·H2O, (12); [Co(2GB)Cl2(H2O)2]·5H2O, (13); [Co-(2GB)2Cl2]·3H2O, (14); [Co(2GB)2(H2O)2](NO3)2· 4H2O, (15); and [Co(2GB)2(H2O)2](OAc)2, (16) have been synthesized and characterized by i.r. and electronic spectroscopy. In addition (6)–(10) were analysed by e.p.r. The X-ray diffraction structure of compound (4) was obtained. It crystallizes in the monoclinic system, C2/c (a = 22.511(7), b = 6.735(6) and c= 15.345(5)Å, β =115.31(3)°, Z = 4, final R = 0.0360 and Rw = 0.0388 for 1167 observed independent reflections). The nickel(II) atom coordinates two ligands in a square-planar geometry through the imidazolic N(3) and the guanidino N(12).The probable ligand isomers involved in the coordination were determined by theoretical calculations, and the possible structures of the coordination compounds were investigated in order to verify that the experimentally proposed structures were stable. Two different types of coordination compounds were found. One, where the ligand is chelating through the imidazolic N(3) and the guanidino N(12), which is the case for most of the complexes [(2)–(13)]. With only one ligand in the coordination sphere, the structure was either tetrahedral (copper and zinc chloride and bromide complexes) or octahedral (cobalt). With two chelating 2GB units a square-planar geometry was stabilized [(2)–(5) and (8)–(10)]. The second type of coordination behaviour was observed in the cobalt compounds [(14)–(16)]. Here the ligand coordinates monodentate through the imidazolic N(3); the structure is tetrahedral.

Synthesis, X-ray and NMR characterisation of cobalt(III) coordination compounds with 2-guanidinobenzimidazole

Abstract The synthesis and characterisation of cobalt(III) coordination compounds with 2-guanidinobenzimidazole (2gb), namely [Co(2gb)3]Cl2(NO3)·H2O, [Co(2gb)3]Cl(NO3)2·H2O, [Co(2gb)3]Cl3·3H2O and [Co(2gb)3](Cl3CCOO)3·H2O, are presented. The compounds with the 2-guanidinobenzimidazole ligand were synthesised from [Co(NH3)4CO3]NO3 or Na3[Co(CO3)3]·3H2O or from cobalt(II) chloride. 1H, 13C and 2D NMR spectra together with the X-ray diffraction data for the distorted octahedral [Co(2gb)3]3+ cation showed that only the mer isomer was formed.