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The in vitro and in silico biological properties of two manganese complexes with the non-steroidal anti-inflammatory drug mefenamic acid (Hmef) in the presence or absence of salicylaldoxime (Η 2 sao), i.e. [Μn 6 (O) 2 (mef) 2 (sao) 6 (CH 3 OH) 4 ] 1, and [Μn(mef) 2 (CH 3 OH) 4 ] 2, respectively, are presented in the present contribution. More specifically, the in vitro biological activity of the complexes was investigated by studying their affinity to calf-thymus DNA (by diverse spectroscopic and physicochemical techniques) and their binding towards bovine (BSA) or human serum albumin (HSA) (by fluorescence emission spectroscopy). Molecular docking simulations on the crystal structures of HSA and DNA, exploring in silico the ability of the complexes to bind to these macromolecules, were also employed in order to explain the described in vitro activity of the compounds. Furthermore, in silico predictive tools have been employed to study the properties of the most active complex 2 to act as anticancer agent, in continuation of the previously reported cytotoxic activity. It is adopted in silico studies on a multitude of proteins involved in cancer growth, as well as prediction of drug-induced changes of gene expression profile, protein- and mRNA-based prediction results, prediction of sites of metabolism, quantitative prediction of antitarget interaction profiles etc., (Copyright © 2018 Elsevier Inc. All rights reserved.)

In the present contribution, the biological properties of four manganese complexes with the non-steroidal anti-inflammatory drugs sodium diclofenac (Nadicl) or indomethacin (Hindo) in the presence or absence of salicylaldoxime (Η 2 sao), i.e. [Μn 6 (O) 2 (dicl) 2 (sao) 6 (CH 3 OH) 6 ] 1, [Μn 6 (O) 2 (indo) 2 (sao) 6 (H 2 O) 4 ], 2, [Μn(dicl) 2 (CH 3 OH) 4 ], 3, and [Μn(indo) 2 (CH 3 OH) 4 ], 4 are presented. More specifically, the in vitro cytotoxic effects of the complexes were evaluated against three cancer cell lines (HeLa, MCF-7 and A549 cells) as well as their combinatory activity with the well-known chemotherapeutic drugs irinotecan, cisplatin, paclitaxel and 5-fluorouracil. The biological activity of the complexes was investigated in vitro by studying their affinity to calf-thymus DNA and their binding towards bovine or human serum albumin (HSA). Molecular docking simulations on the crystal structure of HSA and human estrogen receptor alpha (hERa) were employed in order to study in silico the ability of the studied complexes to bind to these proteins., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The reaction of ZnCl 2 with the non-steroidal anti-inflammatory drug niflumic acid (Hnif) resulted in the formation of complex [Zn(nif-O) 2 (MeOH) 4 ], 1. When this reaction was performed in the presence of a N,N'-donor heterocyclic ligand such as 2,2'-bipyridine (bipy), 2,2'-bipyridylamine (bipyam), 1,10-phenanthroline (phen) and 2,2'-dipyridylketone oxime (Hpko), the complexes [Zn(nif-O,O')(bipy)Cl], 2, [Zn(nif-O)(nif-O,O') 2 (bipyam)], 3, [Zn(nif-O,O') 2 (phen)], 4 and [Zn(nif-O) 2 (Hpko-N,N') 2 ], 5 were formed, respectively. The complexes were characterized by physicochemical and spectroscopic techniques and X-ray crystallography (for complexes 1-3). The complexes can scavenge 1,1-diphenyl-picrylhydrazyl, 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) and hydroxyl radicals, may inhibit soybean lipoxygenase and are more active compounds than free Hnif. The interaction of the complexes with serum albumins was monitored by fluorescence emission spectroscopy and the corresponding binding constants were calculated. The affinity of the complexes with calf-thymus DNA was investigated by UV-vis spectroscopy, viscosity measurements and fluorescence emission spectroscopy for the competitive studies of the complexes with ethidium bromide revealing their interaction probably via intercalation., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The interaction of Mn(ClO 4 ) 2 ·6H 2 O with salicylaldoxime (H 2 sao) in the presence of nonsteroidal anti-inflammatory drug (NSAID) sodium diclofenac (Nadicl) or indomethacin (Hindo) leads to the formation of the hexanuclear Mn(III) clusters [Mn 6 (O) 2 (dicl) 2 (sao) 6 (CH 3 OH) 6 ] (1) and [Mn 6 (O) 2 (indo) 2 (sao) 6 (H 2 O) 4 ] (2) both characterized as stepladder inverse-9-metallacrown-3 accommodating dicl - or indo - ligands, respectively. When the interaction of MnCl 2 ·4H 2 O with Nadicl or Hindo is in the absence of H 2 sao, the mononuclear Mn(II) complexes [Mn(dicl) 2 (CH 3 OH) 4 ] (3) and [Mn(indo) 2 (CH 3 OH) 4 ] (4) were isolated. The complexes were characterized by physicochemical and spectroscopic techniques, and the structure of complexes 1 and 2 was characterized by X-ray crystallography. Magnetic measurements (dc and ac) were carried out in order to investigate the nature of magnetic interactions between the magnetic ions and the overall magnetic behavior of the complexes.

From the reaction of ZnCl 2 with the non-steroidal anti-inflammatory drug diflunisal (Hdifl), complex [Zn(difl-O) 2 (MeOH) 4 ], 1 was formed, while in the presence of a N,N'-donor heterocyclic ligand 2,2'-bipyridylamine (bipyam), 2,2'-bipyridine (bipy), 1,10-phenanthroline (phen) and 2,2'-dipyridylketone oxime (Hpko), the complexes [Zn(difl-O,O') 2 (bipyam)], 2, [Zn(difl-O,O') 2 (bipy)], 3, [Zn(difl-O,O') 2 (phen)], 4 and [Zn(difl-O) 2 (Hpko) 2 ], 5 were isolated, respectively. The complexes were characterized by physicochemical and spectroscopic techniques and the crystal structures of complexes 2, 3 and 5 were determined by X-ray crystallography. The ability of the complexes to scavenge 1,1-diphenyl-picrylhydrazyl, 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) and hydroxyl radicals and to inhibit soybean lipoxygenase was studied and the complexes were more active than free Hdifl. The interaction of the complexes with serum albumins was monitored by fluorescence emission spectroscopy and the corresponding binding constants were calculated. UV-vis spectroscopy, viscosity measurements and fluorescence emission spectroscopy for the competitive studies of the complexes with ethidium bromide were employed to investigate the interaction of the complexes with calf-thymus DNA and revealed intercalation as the most possible DNA-binding mode. Computational techniques were used to identify possible binding sites of albumins and DNA, and determine the druggability of human and bovine serum albumins with the five novel complexes. The majority of the complexes are stronger binders than the free Hdifl. This is the first study incorporating experimental and computational results to explore the binding activity of metal-NSAID complexes with DNA and serum albumins, suggesting their application as potential metallodrugs., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The reaction of ZnCl 2 with the non-steroidal anti-inflammatory drug flufenamic acid (Hfluf) led to the formation of complex [Zn(fluf-O) 2 (MeOH) 4 ], 1. When the reaction takes places in the presence of a N,N'-donor heterocyclic ligand such as 2.2'-bipyridylamine (bipyam), 2.2'-bipyridine (bipy), 1.10-phenanthroline (phen) and 2.2'-dipyridylketone oxime (Hpko), the complexes [Zn(fluf) 2 (bipyam)], 2, [Zn(fluf) 2 (bipy)], 3, [Zn(fluf)(phen) 2 (H 2 O)](fluf)·0.2MeOH, 4·0.2MeOH and [Zn(fluf) 2 (Hpko) 2 ], 5 were isolated, respectively. The complexes were characterized by physicochemical and spectroscopic techniques and the crystal structures of complexes 2 and 4 were determined by X-ray crystallography. The ability of the complexes to scavenge 1.1-diphenyl-picrylhydrazyl, 2.2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) and hydroxyl radicals and to inhibit soybean lipoxygenase was evaluated; the complexes were more active than free Hfluf. The interaction of the complexes with serum albumins was investigated by fluorescence emission spectroscopy and the corresponding binding constants were calculated. UV-vis spectroscopy, viscosity measurements and fluorescence emission spectroscopy for the competitive studies of the complexes with ethidium bromide were the techniques employed to monitor the interaction of the complexes with calf-thymus DNA and revealed intercalation as the most possible mode of binding., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Cobalt(II) complexes with a series of non-steroidal anti-inflammatory drugs (diflunisal, flufenamic acid, mefenamic acid and niflumic acid) in the presence of nitrogen-(2,2'-bipyridylamine, 2,2'-bipyridine, 1,10-phenanthroline) and/or oxygen-donor ligands (methanol) have been synthesized and characterized with physicochemical and spectroscopic techniques. The deprotonated NSAID ligands are coordinated to Co(II) ion through their carboxylato groups in diverse binding modes. The crystal structures of complexes [Co(diflunisal-O)2(methanol)4], [Co(niflumato-O)2(methanol)4], [Co(flufenamato-O,O')2(2,2'-bipyridylamine)], [Co(mefenamato-O,O')2(2,2'-bipyridylamine)] and [Co3(flufenamato-O,O')4(flufenamato-O,O,O')2(2,2'-bipyridine)2] have been determined by X-ray crystallography. The interaction of the complexes with serum albumins was studied by fluorescence emission spectroscopy and the albumin-binding constants were determined. The ability of the complexes to scavenge 1,1-diphenyl-picrylhydrazyl, 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) and hydroxyl radicals was investigated and the complexes were more active than the corresponding free drugs. Spectroscopic (UV and fluorescence), electrochemical (cyclic voltammetry) and physicochemical (viscosity measurements) techniques were employed in order to study the binding mode of the complexes to calf-thymus (CT) DNA and to calculate the corresponding binding constants; for all complexes, intercalation was suggested as the most possible DNA-binding mode., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Copper(II) complexes with the non-steroidal anti-inflammatory drug tolfenamic acid (Htolf) with the oxygen-donor ligands methanol (MeOH) or N,N-dimethylformamide (DMF) and/or the nitrogen-donor heterocyclic ligands 2,2'-bipyridine (bipy), 2,2'-bipyridylamine (bipyam), 1,10-phenanthroline (phen) or pyridine (py) were synthesized and characterized. The crystal structures of five novel complexes were determined by X-ray crystallography where tolfenamic acid is deprotonated being in different binding modes. Equimolar quantities of CuCl2, tolf(-1) and bipy led to the formation of [Cu(tolf-O,O')(bipy)Cl] (1), while with a 1:2 Cu(II):tolf ratio, complexes [Cu(tolf-O,O')2(bipy)] (2), [Cu(tolf-O,O')2(bipyam)] · 0.5MeOH (3 0.5MeOH), [Cu(tolf-O,O')(tolf-O)(phen)(MeOH)] (4) and [Cu(tolf-O)2(py)2(MeOH)2] (5) were isolated. The interaction of the complexes with serum albumin proteins was studied by fluorescence spectroscopy with the determined binding constant bearing relative high values. The scavenging ability of the complexes towards 1,1-diphenyl-picrylhydrazyl, 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) and hydroxyl radicals was investigated and the in vitro inhibitory activity against soybean lipoxygenase was evaluated and complexes 4 and 5 were the more active compounds among those tested. Spectroscopic (UV), electrochemical (cyclic voltammetry) and physicochemical (viscosity measurements) techniques were employed in order to study the binding mode and strength of the complexes to calf-thymus (CT) DNA suggesting intercalation as the most possible mode of binding. Competitive studies with ethidium bromide (EB) revealed the ability of the complexes to displace the DNA-bound EB. The biological properties of complexes 1-5 were evaluated in regard to previously reported complex [Cu2(tolf-O,O')4(DMF)2] (6)., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The copper(II) complexes with the non-steroidal anti-inflammatory drug indomethacin (Hindo) in the presence of the nitrogen-donor heterocyclic ligands 2,2'-bipyridine (bipy), 1,10-phenanthroline (phen) or 2,2'-bipyridylamine (bipyam) have been synthesized and characterized. The crystal structures of [Cu(indo)2(bipy)]∙1.5MeOH∙0.5H2O and [Cu(indo)2(phen)] ∙1.85MeOH∙0.15H2O have been determined by X-ray crystallography. All compounds have been tested for their antioxidant and free radical scavenging activity as well as for their in vitro inhibitory activity against soybean lipoxygenase showing significant activity with the previously reported complex [Cu2(indo)4(H2O)2] being the most active. The complexes exhibit good binding affinity to human or bovine serum albumin protein with high binding constant values. UV study of the interaction of the complexes with calf-thymus (CT) DNA has shown that the complexes can bind to CT DNA with [Cu(indo)2(bipyam)] showing the highest binding constant to CT DNA (Kb=1.56(±0.19)×10(6)M(-1)). The complexes can bind to CT DNA via intercalation as concluded by cyclic voltammetry, DNA viscosity measurements and competitive studies with ethidium bromide (EB) which revealed the ability of the complexes to displace the DNA-bound EB., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The zinc(II) complex of the non-steroidal anti-inflammatory drug tolfenamic acid (=Htolf) in the presence of 2,2'-dipyridylketone oxime (=Hpko) as a N,N'-donor heterocyclic ligand, [Zn(tolf-O)₂(Hpko-N,N')₂]·MeOH (=1·MeOH), has been synthesized and characterized by physicochemical techniques including X-ray crystallography. The complex exhibits good binding affinity to human or bovine serum albumin with high binding constant values. Complex 1 and previously reported Zn-tolfenamato complexes were tested for their free radical scavenging activity and in vitro inhibitory activity against soybean lipoxygenase and exhibited significant activity with [Zn(tolf)₂(1,10-phenantroline)] being the most active compound. The complexes interact with calf-thymus (CT) DNA via intercalation, and can displace the DNA-bound ethidium bromide with 1 exhibiting the highest binding constant to CT DNA., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Zinc(II) complexes of a non-steroidal anti-inflammatory drug, mefenamic acid(=Hmef) in the absence or presence of the nitrogen donor heterocyclic ligands 2,2'-bipyridine(=bipy), 2,2'-bipyridylamine(=bipyam), 2,2'-dipyridylketone oxime(=Hpko) or 1,10-phenanthroline(=phen) have been synthesized and characterized. The crystal structures of [Zn(mef-O,O')2(bipy)], 2, [Zn(mef-O)2(Hpko-N,N')2]·EtOH, 4 and [Zn(mef-O)(mef-O,O')(phen)(H2O)], 5, have been determined by X-ray crystallography showing distinct binding modes of mefenamato carboxylato group, bidentate in 2, monodentate in 4 or both in 5. Interaction studies of the complexes with calf-thymus DNA (CT DNA) have shown that complexes can bind to CT DNA with [Zn(mef-O)2(Hpko)2] exhibiting the highest binding constant to CT DNA (Kb = 1.93(±0.04) × 10(7) M(-1)). The complexes can bind to CT DNA via intercalation as concluded by DNA solution viscosity measurements. Competitive studies with ethidium bromide (EB) have shown that the complexes can displace the DNA-bound EB. The complexes exhibit good binding affinity to serum albumin proteins with [Zn(mef-O)2(H2O)4], 1 exhibiting the highest quenching ability (kq = 1.46 × 10(15) M(-1) s(-1) for human and 5.55 × 10(15) M(-1) s(-1) for bovine serum albumin). All compounds have been tested for their antioxidant and free radical scavenging activity as well as for their in vitro inhibitory activity against soybean lipoxygenase. The scavenging activity is low to moderate against 1,1-diphenyl-picrylhydrazyl (DPPH) radicals and high against hydroxyl and 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS(+·)) radicals, with [Zn(mef-O)2(H2O)4], 1 (ABTS%, 0.1 mM: 94.75(±1.06)%; (·)OH%, 0.1mM: 96.69(±0.27)%; LOX: IC50 = 27.34(±0.90) μM) exhibiting the highest scavenging activity of the ABTS radical cation among the complexes. Additionally, the complexes exhibit higher scavenging and LOX inhibitory activity than free mefenamic acid (ABTS%, 0.1 mM: 66.32(±0.38)%; (·)OH%, 0.1 mM: 92.51(±0.44)%; LOX: IC50 = 48.52(±0.88) μM)., (© 2013.)

The structural features of copper(II), nickel(II), cobalt(II) and zinc(II) complexes with the antimicrobial drugs quinolones and non-steroidal anti-inflammatory drugs (NSAIDs) as ligands are discussed. The binding properties of these complexes to biomolecules (calf-thymus DNA, bovine or human serum albumin) are presented and evaluated. The biological activity (antimicrobial, antioxidant and antiproliferative) of selected complexes is investigated. Further perspectives concerning the synthesis and the biological activity of novel complexes with quinolones or NSAIDs attractive to synthetic chemists, biochemists and/or biologists are presented.

Interaction of equimolar quantities of ZnCl2 with the quinolone antibacterial drugs flumequine (Hflmq), oxolinic acid (Hoxo) or enrofloxacin (Herx) and the N,N'-donor heterocyclic ligands 1,10-phenanthroline (phen) or 2,2'-bipyridine (bipy) results in the formation of 1:1 drug to metal complexes with the general formula [Zn(quinolone)(N,N'-donor)Cl], while excess of the quinolone leads to 1:2 metal to drug [Zn(quinolone)2(N,N'-donor)] complexes. In all complexes, the deprotonated bidentate quinolonato ligands are coordinated to zinc ion through the pyridone oxygen and a carboxylato oxygen. The crystal structures of [Zn(oxo)(phen)Cl], [Zn(flmq)(phen)Cl] and [Zn(flmq)2(phen)] have been determined by X-ray crystallography. All complexes exhibit good binding propensity to human or bovine serum albumin protein showing relatively high binding constant values. Interaction of the complexes with calf-thymus (CT) DNA, studied by UV spectroscopy, has shown that they bind to CT DNA, while [Zn(flmq)(phen)Cl] and [Zn(flmq)2(phen)] complexes exhibit the highest binding constants to CT DNA. Competitive study with ethidium bromide (EB) has shown that all complexes can displace the DNA-bound EB indicating that they bind to DNA in strong competition with EB. Intercalative binding mode is proposed for the interaction of the complexes with CT DNA and has also been verified by DNA solution viscosity measurements. DNA electrophoretic mobility experiments suggest that all complexes bind to linearized pDNA and supercoiled pDNA by intercalative manner resulting in catenanes formation as well as in double-stranded cleavage reflecting (or ending) in the formation of linear DNA. The complexes exhibit significant antimicrobial activity tested on five different microorganisms., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The copper(II) complexes with the first-generation quinolone antibacterial agent flumequine(Hflmq) in the presence or absence of the nitrogen donor heterocyclic ligands 2,2'-bipyridylamine(bipyam), 2,2'-bipyridine(bipy), 1,10-phenanthroline(phen) or pyridine(py) have been synthesized and characterized. Flumequine acts as bidentate ligand coordinated to Cu(II) atom through the pyridone oxygen and a carboxylato oxygen. The crystal structures of the complexes [Cu(flmq)(bipyam)Cl], [Cu(flmq)(bipy)Cl] and [Cu(flmq)(phen)Cl] have been determined by X-ray crystallography revealing a distorted square pyramidal geometry for Cu(II) atom. The interaction of the complexes with bovine or human serum albumin proteins has been studied by fluorescence spectroscopy revealing their good binding propensity to the proteins with relatively high binding constant values. UV study of the interaction of the complexes with calf-thymus DNA (CT DNA) has shown that they bind to CT DNA and [Cu(flmq)(2)(py)(2)] exhibits the highest binding constant to CT DNA. The cyclic voltammograms of the complexes have shown that in the presence of CT DNA the complexes can bind to CT DNA by the intercalative binding mode which has also been verified by DNA solution viscosity measurements. Competitive study with ethidium bromide(EB) has shown that the complexes can displace the DNA-bound EB indicating that they bind to DNA in strong competition with EB., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The interaction of ZnCl(2) with 2-dipyridylketonoxime (=Hpko) and flufenamic acid (=Hfluf) in a basic methanolic solution leads to the formation of a hexanuclear 24-membered metallacoronate, [Zn(6)(OH)(2)(pko)(4)(fluf)(6)] (1), with a [Zn-O-C-O] repeat unit and a nonsteroidal antiinflammatory drug as the constructing ligand. Compound 1 retains its structure in a dimethyl sulfoxide solution, as shown by (1)H NMR spectroscopy and molar conductance.

The interaction of Zn(II) with the non-steroidal anti-inflammatory drug tolfenamic acid leads to the formation of the structurally characterized trinuclear [Zn(3)(tolfenamato)(6)(CH(3)OH)(2)] complex. In the presence of the N,N'-donor heterocyclic ligands 1,10-phenanthroline and 2,2'-bipyridine at a range of ratios, the mononuclear Zn complexes of the general formulae [Zn(tolfenamato)(N,N'-donor)Cl] and [Zn(tolfenamato)(2)(N,N'-donor)] have been isolated and structurally characterized by X-ray crystallography. The deprotonated tolfenamato ligands are coordinated to the Zn(II) ion through carboxylato oxygen atoms. Tolfenamic acid and its complexes exhibit good binding propensity to human or bovine serum albumin protein having relatively high binding constant values.

Cobalt(II) complexes with the non-steroidal anti-inflammatory drug naproxen in the presence or absence of nitrogen-donor heterocyclic ligands (pyridine, 2,2'-bipyridine or 1,10-phenanthroline) have been synthesized and characterized with physicochemical and spectroscopic techniques. The deprotonated naproxen acts as monodentate ligand coordinated to Co(II) ion through a carboxylato oxygen. The crystal structure of [bis(aqua)bis(naproxenato)bis(pyridine)cobalt(II)], 2 has been determined by X-ray crystallography. The EPR spectrum of complex 2 in frozen solution reveals that it retains its structure. UV study of the interaction of the complexes with calf-thymus DNA (CT DNA) has shown that the complexes can bind to CT DNA and [(2,2'-bipyridine)bis(methanol)bis(naproxenato)cobalt(II)] exhibits the highest binding constant to CT DNA. The cyclic voltammograms of the complexes recorded in DMSO solution and in the presence of CT DNA in 1/2 DMSO/buffer (containing 150 mM NaCl and 15 mM trisodium citrate at pH 7.0) solution have shown that they can bind to CT DNA by the intercalative binding mode which has also been verified by DNA solution viscosity measurements. Competitive study with ethidium bromide (EB) has shown that the complexes can displace the DNA-bound EB indicating that they bind to DNA in strong competition with EB. Naproxen and its cobalt(II) complexes exhibit good binding propensity to human or bovine serum albumin proteins having relatively high binding constant values. The antioxidant activity of the compounds has been evaluated indicating their high scavenging activity against hydroxyl free radicals and superoxide radicals., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Cobalt(II) complexes with the non-steroidal anti-inflammatory drug tolfenamic acid in the presence or absence of nitrogen-donor heterocyclic ligands (2,2'-bipyridine, 1,10-phenanthroline, 2,2'-bipyridylamine or pyridine) have been synthesized and characterized with physicochemical and spectroscopic techniques. The deprotonated tolfenamato ligands are coordinated to Co(II) ion through carboxylato oxygen atoms. The crystal structures of complexes [bis(2,2'-bipyridine) bis(methanol)bis(tolfenamato)cobalt(II)] 2 and [bis(2,2'-bipyridylamine)bis(tolfenamato)cobalt(II)] 4 have been determined by X-ray crystallography. UV studies of the interaction of the complexes with calf-thymus DNA (CT DNA) have shown that the complexes can bind to CT DNA and [bis(methanol)(1,10-phenanthroline)bis(tolfenamato)cobalt(II)] exhibits the highest binding constant to CT DNA. The cyclic voltammograms of the complexes recorded in DMSO solution and in the presence of CT DNA in 1/2 DMSO/buffer (containing 150 mM NaCl and 15 mM trisodium citrate at pH 7.0) solution have shown that they can bind to CT DNA by the intercalative binding mode which has also been verified by DNA solution viscosity measurements. Competitive study with ethidium bromide (EB) has shown that the complexes can displace the DNA-bound EB indicating that they bind to DNA in strong competition with EB. Tolfenamic acid and its cobalt(II) complexes exhibit good binding propensity to human or bovine serum albumin protein having relatively high binding constant values., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Copper(II) complexes with the non-steroidal anti-inflammatory drug diflunisal in the presence of N,N-dimethylformamide or nitrogen donor heterocyclic ligands (pyridine, 1,10-phenanthroline, 2,2'-bipyridine or 2,2'-bipyridylamine) have been synthesized and characterized. The deprotonated diflunisal ligands are coordinated to Cu(II) ion through carboxylato oxygen atoms. The crystal structures of [tetrakis(diflunisal)bis(N,N-dimethylformamide)dicopper(II)] 1 and [bis(diflunisal)bis(pyridine)copper(II)], 2 have been determined by X-ray crystallography and are the first reported crystal structures of diflunisal complexes. UV study of the interaction of the complexes with calf-thymus DNA (CT DNA) suggests binding of the complexes to CT DNA with the dinuclear [tetrakis(diflunisal)bis(N,N-dimethylformamide)dicopper(II)] compound exhibiting the highest binding constant, K(b). Intercalative binding mode may also be concluded using cyclic voltammetry and solution viscosity measurements of the complexes in the presence of CT DNA. Competitive studies with ethidium bromide (EB) indicate that the complexes can displace the DNA-bound EB suggesting competition with EB. Diflunisal and its complexes exhibit good binding propensity to human or bovine serum albumin protein showing relatively high binding constant values., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Zinc complexes with the third-generation quinolone antibacterial drugs levofloxacin and sparfloxacin have been synthesized and characterized. The deprotonated quinolones act as bidentate ligands coordinated to zinc ion through the pyridone and a carboxylato oxygen atom. The crystal structures of [bis(aqua)bis(levofloxacinato)zinc(II)], 1, and [bis(sparfloxacinato)(1,10-phenanthroline)zinc(II)], 3, have been determined by X-ray crystallography. The biological activity of the complexes has been evaluated by examining their ability to bind to calf-thymus DNA (CT DNA) by UV spectroscopy and viscosity measurements. UV studies of the interaction of the complexes with DNA have revealed that they can bind to CT DNA probably by the intercalative binding mode which has also been verified by DNA solution viscosity measurements. The DNA binding constants have been also calculated. A competitive study with ethidium bromide (EB) showed that the complexes exhibit the ability to displace the DNA-bound EB indicating that they bind to DNA in strong competition with EB for the intercalative binding site. The interaction of the complexes with human and bovine serum albumin proteins has been studied by fluorescence spectroscopy showing that the complexes exhibit good binding propensity to these proteins having relatively high binding constant values. The biological properties of the complexes have been evaluated in comparison to the previously reported Zn(II) complexes with the first- and second-generation quinolones oxolinic acid and enrofloxacin.

The nickel(II) complexes with the quinolone antibacterial agents oxolinic acid, flumequine, enrofloxacin and sparfloxacin in the presence of the N,N'-donor heterocyclic ligand 2,2'-bipyridylamine have been synthesized and characterized. The quinolones act as bidentate ligands coordinated to Ni(II) ion through the pyridone oxygen and a carboxylato oxygen. The crystal structure of [(2,2'-bipyridylamine)bis(sparfloxacinato)nickel(II)] has been determined by X-ray crystallography. UV study of the interaction of the complexes with calf-thymus DNA (CT DNA) has shown that they bind to CT DNA with [(2,2'-bipyridylamine)bis(flumequinato)nickel(II)] exhibiting the highest binding constant to CT DNA. The cyclic voltammograms of the complexes have shown that in the presence of CT DNA the complexes can bind to CT DNA by the intercalative binding mode which has also been verified by DNA solution viscosity measurements. Competitive study with ethidium bromide (EB) has shown that the complexes can displace the DNA-bound EB indicating that they bind to DNA in strong competition with EB. The complexes exhibit good binding propensity to human or bovine serum albumin protein having relatively high binding constant values. The biological properties of the [Ni(quinolonato)(2)(2,2'-bipyridylamine)] complexes have been evaluated in comparison to the previously reported Ni(II) quinolone complexes [Ni(quinolonato)(2)(H(2)O)(2)], [Ni(quinolonato)(2)(2,2'-bipyridine)] and [Ni(quinolonato)(2)(1,10-phenanthroline)]. The quinolones and their Ni(II) complexes have been tested for their antioxidant and free radical scavenging activity. They have been also tested in vitro for their inhibitory activity against soybean lipoxygenase., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Copper(II) complexes with the non-steroidal antiinflammatory drug mefenamic acid in the presence of aqua or nitrogen donor heterocyclic ligands (2,2'-bipyridine, 1,10-phenanthroline, 2,2'-bipyridylamine or pyridine) have been synthesized and characterized. The crystal structures of [(2,2'-bipyridine)bis(mefenamato)copper(II)], 2, [(2,2'-bipyridylamine)bis(mefenamato)copper(II)], 4, and [bis(pyridine)bis(methanol)bis(mefenamato)copper(II)], 5, have been determined by X-ray crystallography. UV study of the interaction of the complexes with calf-thymus DNA (CT DNA) has shown that the complexes can bind to CT DNA and [bis(aqua)tetrakis(mefenamato)dicopper(II)] exhibits the highest binding constant to CT DNA. The cyclic voltammograms of the complexes in the presence of CT DNA solution have shown that the complexes can bind to CT DNA by the intercalative binding mode verified also by DNA solution viscosity measurements. Competitive studies with ethidium bromide (EB) indicate that the complexes can displace the DNA-bound EB suggesting strong competition with EB. Mefenamic acid and its complexes exhibit good binding propensity to human or bovine serum albumin protein having relatively high binding constant values. All the compounds have been tested for their antioxidant and free radical scavenging activity as well as for their in vitro inhibitory activity against soybean lipoxygenase showing significant activity., (This journal is © The Royal Society of Chemistry 2011)

Copper(II) complexes with the non-steroidal anti-inflammatory drugs (NSAIDs) naproxen and diclofenac have been synthesized and characterized in the presence of nitrogen donor heterocyclic ligands (2,2'-bipyridine, 1,10-phenanthroline or pyridine). Naproxen and diclofenac act as deprotonated ligands coordinated to Cu(II) ion through carboxylato oxygens. The crystal structures of (2,2'-bipyridine)bis(naproxenato)copper(II), 1, (1,10-phenanthroline)bis(naproxenato)copper(II), 2 and bis(pyridine)bis(diclofenac)copper(II), 4 have been determined by X-ray crystallography. The UV study of the interaction of the complexes with calf-thymus DNA (CT DNA) has shown that the complexes can bind to CT DNA with (2,2'-bipyridine)bis(naproxenato)copper(II) exhibiting the highest binding constant to CT DNA. Competitive study with ethidium bromide (EB) indicates that the complexes can displace the DNA-bound EB suggesting strong competition with EB. The cyclic voltammograms of the complexes recorded in the presence of CT DNA have shown that the complexes can bind to CT DNA by the intercalative binding mode which has also been verified by DNA solution viscosity measurements. The NSAID ligands and their complexes exhibit good binding propensity to human or bovine serum albumin protein having relatively high binding constant values. The biological properties of the previously reported complexes [Cu(2)(naproxenato)(4)(H(2)O)(2)], [Cu(2)(diclofenac)(4)(H(2)O)(2)] and [Cu(naproxenato)(2)(pyridine)(2)(H(2)O)] have been also evaluated. The dinuclear complexes exhibit similar affinity for CT DNA as the 2,2'-bipyridine or 1,10-phenanthroline containing complexes. The pyridine containing complexes exhibit the lowest affinity for CT DNA and the lowest ability to displace EB from its EB-DNA complex., (Copyright © 2010 Elsevier Inc. All rights reserved.)

The nickel(II) complexes with the second-generation quinolone antibacterial agent enrofloxacin in the presence or absence of the nitrogen-donor heterocyclic ligands 1,10-phenanthroline, 2,2'-bipyridine or pyridine have been synthesized and characterized. Enrofloxacin acts as bidentate ligand coordinated to Ni(II) ion through the ketone oxygen and a carboxylato oxygen. The crystal structure of (1,10-phenanthroline)bis(enrofloxacinato)nickel(II) has been determined by X-ray crystallography. UV study of the interaction of the complexes with calf-thymus DNA (CT DNA) has shown that they bind to CT DNA and bis(pyridine)bis(enrofloxacinato)nickel(II) exhibits the highest binding constant to CT DNA. The cyclic voltammograms of the complexes have shown that in the presence of CT DNA the complexes can bind to CT DNA by the intercalative binding mode which has also been verified by DNA solution viscosity measurements. Competitive study with ethidium bromide (EB) has shown that the complexes can displace the DNA-bound EB indicating that they bind to DNA in strong competition with EB. The complexes exhibit good binding propensity to human or bovine serum albumin protein having relatively high binding constant values. The biological properties of the complexes have been evaluated in comparison to the corresponding Zn(II) enrofloxacinato complexes as well as Ni(II) complexes with the first-generation quinolone oxolinic acid., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Nickel(II) complexes with the first-generation quinolone antibacterial agent flumequine in the presence or absence of nitrogen donor heterocyclic ligands (4-benzylpyridine, pyridine, 2,2'-bipyridine or 1,10-phenanthroline) have been structurally characterized by physicochemical and spectroscopic techniques. The experimental data suggest that flumequine acts as deprotonated bidentate ligand coordinated to Ni(II) through the carboxylato and ketone oxygen atoms. The crystal structures of bis(4-benzylpyridine)bis(flumequinato)nickel(II) 2, (2,2'-bipyridine)bis(flumequinato)nickel(II) 4 and (1,10-phenanthroline)bis(flumequinato)nickel(II) 5 have been determined by X-ray crystallography and are the first crystal structures of flumequinato complexes reported. UV study of the interaction of the complexes with calf-thymus DNA (CT DNA) has shown that the complexes bind to CT DNA and bis(aqua)bis(flumequinato)nickel(II) exhibits the highest binding constant to CT DNA. Competitive study with ethidium bromide (EB) has shown that the complexes can displace the DNA-bound EB indicating that they bind to DNA in strong competition with EB. The cyclic voltammograms of the complexes recorded in DMSO solution and in 1/2 DMSO/buffer (containing 150 mM NaCl and 15 mM trisodium citrate at pH 7.0) solution have shown that in the presence of CT DNA they bind to CT DNA by the intercalative binding mode. The complexes exhibit good binding propensity to human or bovine serum albumin protein having relatively high binding constant values., (2010 Elsevier Inc. All rights reserved.)

Cobalt(II) complexes with the non-steroidal anti-inflammatory drug mefenamic acid in the presence or absence of nitrogen donor heterocyclic ligands (2,2'-bipyridine, 1,10-phenanthroline or pyridine) have been synthesized and characterized with physicochemical and spectroscopic techniques. The experimental data suggest that mefenamic acid acts as deprotonated monodentate ligand coordinated to Co(II) ion through a carboxylato oxygen. The crystal structures of tetrakis(methanol)bis-(mefenamato)cobalt(II), 1 and (2,2'-bipyridine)bis(methanol)bis(mefenamato)cobalt(II), 2 have been determined by X-ray crystallography. The EPR spectra of complexes 1 and 2 in frozen solution reveal that they retain their structures. UV study of the interaction of the complexes with calf-thymus DNA (CT DNA) has shown that the complexes can bind to CT DNA and bis(methanol)bis(pyridine)bis-(mefenamato)cobalt(II) exhibits the highest binding constant. Competitive study with ethidium bromide (EB) has shown that the complexes can displace the DNA-bound EB indicating that they bind to DNA in strong competition with EB. The cyclic voltammograms of the complexes recorded in dmso solution and in the presence of CT DNA in 1 : 2 dmso : buffer (containing 150 mM NaCl and 15 mM trisodium citrate at pH 7.0) solution have shown that they can bind to CT DNA by the intercalative binding mode. Mefenamic acid and its cobalt(II) complexes exhibit good binding propensity to human or bovine serum albumin protein having relatively high binding constant values. The antioxidant activity of the compounds has been evaluated indicating their high scavenging activity against hydroxyl free radicals and superoxide radicals.

Zinc mononuclear complexes with the second-generation quinolone antibacterial drug enrofloxacin in the absence or presence of a nitrogen donor heterocyclic ligand 1,10-phenanthroline or 2,2'-bipyridine have been synthesized and characterized. Enrofloxacin is on deprotonated mode acting as a bidentate ligand coordinated to zinc ion through the ketone and a carboxylato oxygen atoms. The crystal structure of bis(enrofloxacinato)(1,10-phenanthroline)zinc(II), 2, has been determined by X-ray crystallography. The biological activity of the complexes has been evaluated by examining their ability to bind to calf-thymus DNA (CT DNA) with UV and fluorescence spectroscopies. UV studies of the interaction of the complexes with DNA have shown that they can bind to CT DNA and the DNA binding constants have been calculated. Competitive studies with ethidium bromide (EB) have shown that the complexes exhibit the ability to displace the DNA-bound EB indicating that they bind to DNA in strong competition with EB for the intercalative binding site. The complexes exhibit good binding propensity to human and bovine serum albumin proteins having relatively high binding constant values., (Copyright 2010 Elsevier Ltd. All rights reserved.)

The mononuclear nickel(II) complexes with the first-generation quinolone antibacterial agent oxolinic acid in the presence or absence of nitrogen-donor heterocyclic ligands (2,2'-bipyridine, 1,10-phenanthroline or pyridine) have been synthesized and characterized. The experimental data suggest that oxolinic acid acts as deprotonated bidentate ligand coordinated to Ni(II) ion through the ketone and carboxylato oxygens. The crystal structure of (2,2'-bipyridine)bis(oxolinato) nickel(II), 2 has been determined by X-ray crystallography. The cyclic voltammograms of the complexes recorded in dmso solution and in 1/2 dmso/buffer (containing 150mM NaCl and 15mM trisodium citrate at pH 7.0) solution have shown that in the presence of calf-thymus DNA (CT DNA) they can bind to CT DNA by the intercalative binding mode. UV study of the interaction of the complexes with CT DNA has shown that the complexes bind to CT DNA and bis(aqua)bis(oxolinato) nickel(II) exhibits the highest binding constant to CT DNA. Competitive study with ethidium bromide (EB) has shown that the complexes can displace the DNA-bound EB indicating that they bind to DNA in strong competition with EB. The complexes exhibit good binding propensity to human or bovine serum albumin protein having relatively high binding constant values.

Interaction of phenyl 2-pyridyl ketoxime (PhPyCNO)/X(-)"blends" (X(-) = OH(-), Cl(-), ClO(4)(-), 2,4-D) (2,4-DH = 2,4-dichlorophenoxyacetic acid) with copper perchlorate has yielded trinuclear clusters that have been characterized as inverse-9-metallacrown-3, accommodating one or two anions. The structure of the complex [Cu(3)(PhPyCNO)(3)(mu(3)-OH)(2,4-D)(2)] x 1.25CH(3)OH.0.25CH(3)CN (1) has been determined by single-crystal X-ray crystallography. Spectroscopic studies of the interaction of copper inverse {(OH)[9-MC(CuN(PhPyCNO))-3]} metallacrowns with DNA showed that these compounds bind to dsDNA by intercalative mode with an additional covalent {(OH)[9-MC(Cu(PhPyCNO))-3]}-DNA interaction leading to hydrolytic cleavage of DNA that may be assigned to the presence of the hydroxyl group in the inverse metallacrown ring. The binding strength of [Cu(3)(PhPyCNO)(3)(mu(3)-OH)(2,4-D)(2)] (1) complex for CT-DNA was determined to be 0.56 x 10(5) M(-1). All the complexes exhibited the ability to displace the DNA-bound EthBr. DNA electrophoretic mobility experiments showed that all complexes, at low cluster concentration, are capable of binding to pDNA and linear DNA. At higher cluster concentration and in the absence of any reducing agent they showed marked chemical nuclease activity.

The mononuclear nickel(II) complexes with the third-generation quinolone antibacterial agent sparfloxacin in the absence or presence of nitrogen donor heterocyclic ligands (1,10-phenanthroline or 2,2'-bipyridine) have been synthesized and characterized. The experimental data suggest that sparfloxacin acts as deprotonated bidentate ligand coordinated to Ni(II) ion through the ketone and carboxylato oxygens. The crystal structure of (1,10-phenanthroline)bis(sparfloxacinato) nickel(II), 2 has been determined by X-ray crystallography. The cyclic voltammograms of the complexes recorded in dmso solution and in 1/2 dmso/buffer (containing 150 mM NaCl and 15 mM trisodium citrate at pH 7.0) solution have shown that in the presence of CT DNA they can bind to CT DNA by the intercalative binding mode. UV study of the interaction of the complexes with calf-thymus DNA (CT DNA) has shown that the complexes can bind to CT DNA and 2 exhibits the highest binding constant to CT DNA. Competitive study with ethidium bromide (EB) has shown that the complexes can displace the DNA-bound EB indicating that they bind to DNA in strong competition with EB for the intercalative binding site. The antimicrobial activity of the complexes has been tested on three different microorganisms and has revealed that the inhibition provided by the complexes is slightly decreased in comparison to free sparfloxacin. The complexes exhibit good binding propensity to human and bovine serum albumin proteins having relatively high binding constant values.

The neutral mononuclear zinc complexes with the quinolone antibacterial drug oxolinic acid in the absence or presence of a nitrogen donor heterocyclic ligand 2,2'-bipyridine or 1,10-phenanthroline have been synthesized and characterized. The experimental data suggest that oxolinic acid is on deprotonated mode acting as a bidentate ligand coordinated to the metal ion through the ketone and one carboxylato oxygen atoms. The crystal structures of (chloro)(oxolinato)(2,2'-bipyridine)zinc(II), 2, and bis(oxolinato)(1,10-phenanthroline)zinc(II), 3, have been determined with X-ray crystallography. The biological activity of the complexes has been evaluated by examining their ability to bind to calf-thymus DNA (CT DNA) with UV and fluorescence spectroscopies. UV studies of the interaction of the complexes with DNA have shown that they can bind to CT DNA and the DNA-binding constants have been calculated. Competitive studies with ethidium bromide (EB) have shown that complex 3 exhibits the ability to displace the DNA-bound EB indicating that it binds to DNA in strong competition with EB.

Use of PhPyCNO (-)/X (-) "blends" (PhPyCNOH = phenyl 2-pyridyl ketoxime; X (-) = OH (-), alkanoato, ClO 4 (-)) in copper chemistry yielded trinuclear clusters that have been characterized as inverse-9-metallacrown-3 compounds and accommodate one or two guest ligands. The magnetic behavior showed a large antiferromagnetic interaction and a discrepancy between the low-temperature magnetic behavior observed experimentally and that predicted from a magnetic model. The discrepancy between the Brillouin curve and the experimental result provides clear evidence of the influence of the antisymmetric interaction. Introducing the antisymmetric terms derived from the fit of the susceptibility data into the magnetization formula caused the simulated curve to become nearly superimposable on the experimental one. The EPR data indicated that the compound [Cu 3(PhPyCNO) 3(mu 3-OH)(2,4,5-T) 2] ( 1), where 2,4,5-T is 2,4,5-trichlorophenoxyacetate, has isosceles or lower magnetic symmetry (delta not equal 0), that antisymmetric exchange is important ( G not equal 0), and that Delta E > hnu. The structures of the complexes 1 and [Cu 3(PhPyCNO) 3(mu 3-OH)(H 2O)(ClO 4) 2] ( 2) were determined using single-crystal X-ray crystallography. Theoretical calculations based on density functional theory were performed using the full crystal structures of 1, 2, [Cu 3(PhPyCNO) 3(OH)(CH 3OH) 2(ClO 4) 2] ( 3), and [Cu 3(PhPyCNO) 3(mu 3-OMe)(Cl)(ClO 4)] ( 4). The geometries of the model compounds [Cu 3(kappa (3) N, N, O-HNCHCHNO) 3(mu 3-OH)(mu 2-HCOO)(HCOO)] ( 5), [Cu 3(kappa (3) N, N, O-HNCHCHNO) 3(mu 2-HCOO)(HCOO)] (+) ( 6), [Cu 3(kappa (3) N, N, O-HNCHCHNO) 3(mu 3-O)] (+) ( 7), and [Cu 3(kappa (3) N, N, O-HNCHCHNO) 3] (3+) ( 8) were optimized at the same level of theory for both the doublet and quartet states, and vibrational analysis indicated that the resulting equilibrium geometries corresponded to minima on the potential energy surfaces. Both e g and t 2g magnetic orbitals seem to contribute to the magnetic exchange coupling. The latter contribution, although less important, might be due to overlap of the t 2g orbitals with the p-type orbitals of the central triply bridging oxide ligand, thereby affecting its displacement from the Cu 3 plane and contributing to the antiferromagnetic coupling. The crucial role of the triply bridging oxide (mu 3-O) ligand on the antiferromagnetic exchange coupling between the three Cu(II) magnetic centers is further evidenced by the excellent linear correlation of the coupling constant J with the distance of the mu 3-O ligand from the centroid of the Cu 3 triangle.

The reaction between Mn(ClO 4) 2 and di-(2-pyridyl)-ketone in the presence of the sodium salt of propanediol as a base in MeOH leads to the formation of a hexanuclear manganese cluster. This cluster has been characterized by the formula [Mn(II) 3Mn(III) 3O(OH)(CH 3pdol) 3(Hpdol) 3(pdol)](ClO 4) 4 ( 1). Molecular conductance measurements of a 10 (-3) M solution of compound 1 in CH 3CN, DMSO, or DMF give Lambda m = 529, 135, or 245 muS/cm, respectively, which suggests a 1:4 cation/anion electrolyte. The crystal structure of hexanuclear manganese cluster 1 consists of two distinct trinuclear units with a pseudocubane-like arrangement. The trinuclear units show two different valence distributions, Mn(II)/Mn(III)/Mn(II) and Mn(III)/Mn(II)/Mn(III). Additional features of interest for the compound include the fact that (a) two of the Mn(III) ions show a Jahn-Teller elongation, whereas the third ion shows a Jahn-Teller compression; (b) one bridge between Mn(III) atoms is an oxo (O (2-)) ion, whereas the bridge between Mn(II) and Mn(III) is a hydroxyl (OH (-)) group; and (c) the di-(2-pyridyl)-ketone ligand that is methanolyzed to methyl-Hpdol and R 2pdol (R = CH 3, H) acts in three different modes: methyl-pdol(-1), Hpdol(-1), and pdol(-2). For magnetic behavior, the general Hamiltonian formalism considers that (a) all of the interactions inside the two "cubanes" between Mn(II) and Mn(III) ions are equal to the J 1 constant, those between Mn(II) ions are equal to the J 2 constant, and those between the Mn(III) ions are equal to the J 3 constant and (b) the interaction between the two cubanes is equal to the J 4 constant. The fitting results are J 1 = J 2 = 0.7 cm (-1), J 3 approximately 0.0, J 4 = -6.2 cm (-1), and g = 2.0 (fixed). According to these results, the ground state is S = 1/2, and the next excited states are S = 3/2 and 5/2 at 0.7 and 1.8 cm (-1), respectively. The EPR spectra prove that the spin ground state at a low temperature is not purely S = 1/2 but is populated with the S = 3/2 state, which is in accordance with the susceptibility and magnetization measurements.

Two tetranuclear Mn complexes with an average Mn oxidation state of +2.5 have been prepared. These valence isomers have been characterized by a combination of X-ray crystallography, X-ray absorption spectroscopy, and magnetic susceptibility. The Mn(II)3Mn(IV) tetramer has the Mn ions arranged in a distorted tetrahedron, with an S = 6 ground spin state, dominated by ferromagnetic exchange among the manganese ions. The Mn(II)2Mn(III)2 tetramer also has a distorted tetrahedral arrangement of Mn ions but shows magnetic behavior, suggesting that it is a single-molecule magnet. The X-ray absorption near-edge structure (XANES) spectra for the two complexes are similar, suggesting that, while Mn XANES has sufficient sensitivity to distinguish between trinuclear valence isomers (Alexiou et al. Inorg. Chem. 2003, 42, 2185), similar distinctions are difficult for tetranuclear complexes such as that found in the photosynthetic oxygen-evolving complex.

Reaction of Mn(II) with phenoxyalkanoic acids and di-2-pyridyl ketone oxime (Hpko) leads to neutral tetranuclear complexes of the general formula Mn(4)(O)(pko)(4)(phenoxyalkanoato)(4) (phenoxyalkanoic acids: H-mcpa=2-methyl-4-chloro-phenoxy-acetic acid, H-2,4,5-T=2,4,5-trichloro-phenoxy-acetic acid or H3,4-D=3,4-dichloro-phenoxy-acetic acid). The compounds were synthesized by adding di-2-pyridyl ketone oxime to MnCl(2) in the presence of the sodium salts of the alkanoic acids in methanol. The crystal structure of Mn(4)(II/II/II/IV)(O)(pko)(4)(2,4,5-T)(4).2.5CH(3)OH.0.25H(2)O 1 shows that the complex consists of a [Mn(4)(mu(4)-O)](8+) core with a Mn(IV) and 3 Mn(II) ions in octahedral environment and a mu(4)-O atom bridging the four manganese ions. Spectroscopic studies of the interaction of these tetranuclear clusters with DNA showed that these compounds bind to dsDNA. The binding strength of the Mn(4)(II/II/II/IV)(O)(pko)(4)(2,4,5-T)(4) complex for calf thymus DNA is equal to 1.1x10(4)M(-1). Among the deoxyribonucleotides they bind preferentially to deoxyguanylic acid (dGMP). Competitive studies with ethidium bromide (EthBr) showed that the Mn(4)(II/II/II/IV)(O)(pko)(4)(2,4,5-T)(4) complex exhibited the ability to displace the DNA-bound EthBr indicating that the complex binds to DNA via intercalation in strong competition with EthBr for the intercalative binding site. Additionally, DNA electrophoretic mobility experiments showed that all three complexes, at low cluster concentration, are obviously capable of binding to pDNA causing its cleavage (relaxation) at physiological pH and temperature. At higher cluster concentration, catenated dimer forms of pDNA was formed.

The use of phenyl 2-pyridyl ketoxime (PhPyCNO)/X(-)"blends" (X(-) = OH(-), Cl(-), ClO(4)(-)) in copper chemistry has yielded trinuclear clusters that have been characterized as inverse-9-metallacrown-3 accommodating one or two anions. The magnetic behaviour has shown a large antiferromagnetic interaction. The discrepancy between the Brillouin curve and the experiment has been assigned to the influence of the antisymmetric interaction. By introducing in the magnetization formula the antisymmetric terms derived from the fitting of the susceptibility data the simulated curve become almost superimposable to the experimental one. From the EPR findings it has been shown that the compound [Cu(3)(PhPyCNO)(3)(OCH(3))(Cl)(ClO(4))] () having isosceles magnetic symmetry or lower (delta not equal 0), the antisymmetric exchange is important (G not equal 0) and DeltaE > hv. The structures of the two complexes have been determined by single-crystal X-ray crystallography.

The use of di-2-pyridyl ketone oxime (Hpko)/X- "blends" (X- = OH-, Cl-, ClO4-) in copper chemistry has yielded neutral binuclear and cationic trinuclear, pentanuclear or hexanuclear complexes. Various synthetic procedures have led to the synthesis of compounds [Cu5(pko)7].[ClO4]3.2CH3OH.2H2O (1), [Cu3(pko)3(OH)(Cl)]2[Ph4B]2.4DMF.2H2O (2), [Cu2(pko)4] (3), {[Cu6(pko)6ClO4(CH3CN)6][Cu6(pko)6(ClO4)3(CH3CN)4]}.8ClO4.14CH3CN.H2O (4). The structures of the complexes have been determined by single-crystal X-ray crystallography.

The structural characterization of complexes [Mn(II)4Mn(III)22(pdol)12(OCH3)12(O)16(N3)6] (1) and [Mn(II)4Mn(III)22(pdol)12(OCH3)12(O)16(OH)2(H3O)(OCH3)3].ClO4.5CH3OH (2), where pdol(2-) is di-2-pyridyl methanediol, reveals that each has a metallacryptand shell that encapsulates a manganese oxide core. Variable-temperature direct current magnetic susceptibility measurements on 2 indicate a paramagnetic ground state that results from an overall antiferromagnetic interaction in the cluster, with chiT values decreasing from 300 K (51.2 cm3 K mol(-1)) to 2 K (19.8 cm3 K mol(-1)). Variable-temperature alternating current magnetic susceptibility measurements imply that both 1 and 2 behave as single-molecule magnets. Fitting the frequency-dependent out-of-phase magnetic susceptibility to the Arrhenius equation yields an effective energy barrier, Ueff, to magnetization relaxation of 16.5 +/- 0.7 K (11.5 +/- 0.5 cm(-1)) for 1 and 36.2 +/- 2.0 K (25.1 +/- 1.4 cm(-1)) for 2. The larger value for 2 is in agreement with the lower molecular symmetry, larger magnetoanisotropy, and higher ground spin state of 2 compared to those of 1. This observation suggests a new strategy for increasing the blocking temperatures in high-nuclearity manganese clusters.

Interaction of manganese with salicylhydroxamic ligands (shi) in methanol, in the presence of pyridine, leads to the formation of a series of 15-membered metallacrown (MC) Mn(II)(L)2[15-MCMn(III)N(shi)-5](py)6 or 7, (L=formato, benzoate or alkanoato ligand, py=pyridine). In the absence of pyridine, the Mn(II)(L)2[12-MCMn(III)N(shi)-4](MeOH)6 metallacrown was isolated and structurally characterized. The crystal structure of {[Mn(II)(HCOO)2][(15-MCMn(III)N(shi)-5)(py)7]}.py.1.9CH3OH.H2O (1) contains a neutral 15-membered metallacrown ring consisting of five Mn(III) and five shi(-3) ligands. The 15-membered metallacrown ring is formed by the succession of five structural moieties of the type [Mn(III)-N-O]. The diverse in the configuration (planar or propeller) for the ring Mn(III) ions gives the metallacrown core a bending structure. The crystal structure of {[Mn(II)(C6H5COO)2][(12-MCMn(III)N(shi)-4)(CH3OH)6]}.2CH3OH (2) contains a neutral 12-membered metallacrown ring consisting of four Mn(III) and four shi(-3) ligands. The 12-membered metallacrown ring is formed by the same way of succession of four structural moieties of the type [Mn(III)-N-O], while the presence of a planar only configuration of shi ligands around ring Mn(III) ions gives to the metallacrown core a planar structure. The encapsulated Mn(II) is six and seven-coordinate for (1) and (2), respectively, and is bound to the hydroximate oxygen of the metallacrown core and two oxygen atoms from the carboxylate ligands. Antibacterial screening data showed that, among all the compounds tested, manganese metallacrowns are more active compared to the simple manganese herbicide or carboxylate complexes, with increased efficiency for [15-MCMn(III)N(shi)-5] compared to the analogous [12-MCMn(III)N(shi)-4].

Reaction of Mn(ClO4)2 with di-pyridyl ketone oxime, (2-py)2C=NOH, gives the novel cluster [Mn(II)4Mn(III)6Mn(IV)2(mu4-O)2(mu3-O)4(mu3-OH)4(mu3-OCH3)2(pko)12](OH)(ClO4)3 1. It is the only example of a 24-MC-8, and the first metallacrown with ring metal ions in three different oxidation states. Magnetic measurements show antiferromagnetic behavior.

The trinuclear complex Mn(3)(pko)(4)(CH(3)O)(2)(SCN)(2).CH(3)OH, 1, where Hpko is 2,2'-dipyridylketonoxime, is a rare example of a complex simultaneously containing Mn(II) and Mn(IV). X-ray crystallography and XANES spectroscopy clearly distinguish the Mn(II)(2)Mn(IV) valence isomer from the more commonly observed Mn(III)(2)Mn(II) formulation. Fits to variable-temperature magnetic susceptibility data indicate that the Mn(II) and Mn(IV) are ferromagnetically coupled (J = +6.13 cm(-1)) and that 1 has an S = (13)/(2) ground state.

The effect on DNA and the antibacterial activity of a series of high nuclearity nickel compounds with three, four and five metal atoms were examined. The compounds have a mixed ligand composition with salicylhydroxamic acid and di-2-pyridyl-ketonoxime as chelate agents. In the trinuclear compound Ni(3)(shi)(2)(Hpko)(2)(py)(2)(1), two metal ions show a square planar geometry while the third one is in an octahedral environment. The compounds with four and five nickel atoms construct metallacrown cores with two distinct connectivities. The tetranuclear vacant metallacrown [12-MC(Ni(II)N(Hshi)2(pko)2)-4](2+) shows the connectivity pattern [-O-Ni-O-N-Ni-N-](2), while the pentanuclear ([Ni(II)][12-MC(Ni(II)N(shi)2(pko)2)-4])(2+) follows the pattern [-Ni-O-N-](4). Two distinct arrangements of the chelates around the ring metal ions were observed; a 6-5-6-5-6-5-6-5 arrangement for the [12-MC(Ni(II)N(Hshi)2(pko)2)-4] core and a 6-6-5-5-6-6-5-5 arrangement for the [12-MC(Ni(II)N(shi)2(pko)2)-4] core. Magnetic variable temperature susceptibility study of the trinuclear compound revealed the presence of one paramagnetic nickel(II) ion with strong crystal field dependence, with D=5.0(4) cm(-1), g(xy)=2.7(3) and g(z)=2.3(3). The effect of the synthesized Ni(II) complexes on the integrity and electrophoretic mobility of nucleic acids was examined. Only compounds 2, 3 and 4 altered the mobility of pDNA, forming high molecular weight concatamers at low concentrations or precipitates at higher concentrations. Antibacterial activity screening of the above compounds suggests that nickel compounds 2, 3 and 4 were the most active and can act as potent antibacterial agents.

The synthesis, characterization and the biological study of a series of Ni(ll)(2)(carboxylato)(2) [12- MC(Ni(II)N(shi)2(pko)2)-4][12-MC(Ni(ii)N(sh03(pko))-4] (CH(3)OH)(3)(H(3)O) fused 12-membered metallacrowns with 10 metal ions and commercial available herbicides or anti-inflammatory drugs as carboxylato ligands are reported. All the compounds have a mixed ligand composition with salicylhydroxamic acid and di-2-pyridylketonoxime as chelate agents. The compounds construct metallacrown cores {[12-MC(Ni(n)N(sj02(pko)2)-4][12-MC(Ni(ll)N(shO3(pko))-4]}(2+) following the pattern [-Ni-O-N-](4). The neutral decanuclear [Ni(II)(A)](2)[12-MC(Ni(II)N(shi)2(pko)2)-4][12-MC(Ni(II)N(pko)3(pko))-4] fused metallacrown, consists of two [12-MC(M(ox)N(ligand))-4] units the {Ni(ll)(A)[12-MC(Ni(II)N(shi)2(pko)2)-4]} and {Ni(II)(A)[12-MC(Ni(II)N(shi)3(pko))-4]} with 1(+) and 1(-) charge, respectively. Each metallacrown unit has four ring Ni(II) ions and one additional encapsulated Ni(II) ion in planar arrangement. The anionic unit is bonded with cationic one creating binuclear moieties. The herbicide or antiiflammatory carboxylato ligands are bridging the central octahedral nickel atom with a ring metal ion in a bindetate fashion. The effect on DNA and their antibacterial activity was examined. The changes in the mobility can be attributed to the altered structures of the pDNA treated with Ni(II) complexes. Evaluating the data of the antibacterial activity of the compounds tested, we can conclude that nickel complexes present strong antibacterial activity.

In this paper we report the synthesis and characterization of Ca(II), Gd(III) and Ce(III) complexes with chlorophenoxyalkanoic acids, which are commonly used as herbicides. The Gd(III) and Ca(II) complexes were characterized by the typical formulas [Gd(III)(L)(3)(H(2)O)(2).2dmf](n) and [Ca(L)(2)(MeOH)(2)](n) [L=[2,4-D=2,4-dichlorophenoxyacetic acid, 2,4,5-T=2,4,5-trichlorophenoxyacetic acid, MCPA=2-methyl-4-chlorophenoxy acetic acid and 2,4-DP=2-(2,4-dichlorophenoxy)propanoic acid]]. The crystal structure of the Gd(III) complex with 2,4-D shows that the compound is a one-dimensional polymer with a [Gd(III)(2)(2,4-D)(6)(H(2)O)(4)] dimeric repeat unit and the gadolinium atoms are in a nine-coordination environment, while the crystal structure of the Ca analog shows that it also has a polymeric structure with a [Ca(2)(2,4-D)(4)(CH(3)OH)(4)] dimeric repeat unit and the calcium atoms are in an eight-coordination environment. The gadolinium compound displays three different coordination modes for the carboxylato moiety, bidentate chelate, bidentate double bound and bidentate triple bound, while the calcium compound displays only one, bidentate triple bound. Coordination spheres are completed with oxygens of H(2)O or MeOH molecules, respectively. The complexes were tested against a few common bacteria by minimum inhibitory concentration (MIC) experiments and did not exhibit any antimicrobial action at concentrations up to 1600 microg/ml.

Interaction of ZnCl(2) with Hpko (Hpko, di-2-pyridyl-ketonoxime) results in the formation of a uninuclear Zn(Hpko)Cl(2) (1) compound or in a 12-membered tetranuclear metallacrown (OH)(2)[inv12-MC(Zn(II)N(pko))-4]Cl(2) (2) depending on the pH of the mother solution. The addition of H(3)shi (H(3)shi, salicylhydroxamic acid) leads to the formation of the octanuclear 12-membered tetranuclear metallacrown [Zn(2)]([Zn(2)(pko)(4)][12-MC(Zn(II)N(shi))-4](CH(3)OH)(2)) (3). The metallacrown core of 2 is characterized as "inverse" because the zinc atoms, rather than oxygen atoms, are oriented toward the central cavity. Two triply bridging hydroxides are accommodated in the center of the metallacrown ring. The pko(-) ligands form a propeller configuration that imposes absolute stereoisomerism with Lambda and Delta chirality. Each hydroxo oxygen bridges two octahedral zinc atoms and a tetrahedral one. The octanuclear cluster Zn(8)(shi)(4)(pko)(4)(CH(3)OH)(2) contains a 12-membered tetranuclear metallacrown core constructed by four Zn metal atoms and four shi(3-) ligands. So, a part of the cluster can be described as having the formally anionic [12-MC(Zn(II)N(shi))-4](4-) core. Two of the zinc atoms are in octahedral coordination environment while for the other two the geometry is best described as distorted trigonal bipyramidal. The metallacrown core accommodates a binuclear compound with the formula [Zn(2)(pko)(4)]. Two of the ring metal ions create binuclear units with two zinc ions, respectively, with two oxamato oxygens, and two phenolato oxygens, of the four interlinked shi(3-) ligands acting as bridging atoms.

Interaction of manganese with salicylhydroxamic ligands leads to the formation of a series of 15-membered metallacrown Mn(II)(L)(2)[15-MC(Mn(III)N(shi))-5](py)(6) (L=alkanoato ligand). The crystal structure contains a neutral 15-membered metallacrown ring of the type [15-MC(Mn(III)N(shi))-5]. The metallacrown core consists of five Mn(III) and five shi(-3) ligands. The 15-membered metallacrown ring is formed by the succession of five structural moieties of the type [Mn(III)-N-O]. The diversity in the configuration (planar or propeller) for the ring Mn(III) ions gives to the metallacrown core flexibility and simultaneously allows the encapsulation of the sixth Mn(II). The encapsulated Mn(II) is seven-coordinate and is bound to the five hydroximate oxygen donors provided by the metallacrown core, and two oxygen atoms from the carboxylate herbicide ligands. Antibacterial screening data showed that among all the compounds tested, manganese metallacrowns are more active than the simple manganese herbicide or carboxylate complexes while an increase in the efficiency of [15-MC(Mn(III)N(shi))-5] towards the analogous [12-MC(Mn(III)N(shi))-4] can be observed.

Assembly reactions that can prepare reliably regioselective metallamacrocyclic complexes have been a target in the development of metallacrowns. To this end, a series of mixed ligand and mixed ligand/mixed metal metallacrowns have been synthesized in high yield and structurally characterized. Two distinct connectivities have been observed in these types of metallacrowns. The monomeric, vacant metallacrown with mixed ligand composition [12-MC(Ni(II)N(Hshi)2(pko)2-4)] (1a) shows the connectivity pattern [-O-Ni-O-N-Ni-N-]2 while the other Ni metallacrowns, [12-MC(Ni(II)N(shi)2(pko)2-4)] (2a) and the coupled [12-MC(Ni(II)N(shi))2(pko)2-4)][12-MC(Ni(II)N(shi))3(pko)-4)] (3a) fused metallacrowns as well as the mixed metal Mn-Ni metallacrown [12-MC(Ni(II)Mn(III)N(shi)2(pko)2-4)] (4a), follow the pattern [-Ni-O-N-]4. Also, three distinct arrangements of the chelate rings around the metal ions have been observed. The syntheses are completely general, allowing for the substitution of different ligands into the metallacrown core. Compounds 1 and 4 show the 6-5-6-5-6-5-6-5 arrangement, compounds 2 and 3(1) the 6-6-5-5-6-6-5-5, and the 3(2) component the 6-6-5-5-6-5-6-5. The obtained structures can be rationalized by balancing the charge at each metal site in the metallacrown. Variable temperature magnetic susceptibility measurements show that exchange interactions for all the compounds are weak and dominantly antiferromagnetic (e.g., 2a gives an exchange coupling of J = -1.2 cm(-1) with g = 2.2). In solution, the metallacrowns are shown to be stable both to decomposition and ligand exchange.

The copper complexes with the phenoxyalkanoic acids MCPA, 2,4-D, 2,4,5-T and 2,4-DP in the presence of a nitrogen donor heterocyclic ligand, phen or bipyam, were prepared and characterized. Interaction of Cu(II) with phenoxyalkanoic acids and bipyam leads to dinuclear or uninuclear neutral complexes while in the presence of phen uninuclear neutral or cationic forms have been isolated. The crystal structure of bis(1,10-phenanthroline)(2-methyl-4-chloro-phenoxyacetato)copper(ll) chloride-methanol(1/1)-water(1/0.6), 1 has been determined and refined by least-squares methods using three-dimensional MoK, data. 1 crystallizes in space group P1, in a cell of dimensions a = 14.577(6)A, b = 1 1.665(5) A, c = 12.249(6) A, alpha = 98.38( 1)degrees, beta = 112.18( 1) degrees, gamma = 104.56(1 ) degrees, V= 1,798( 1) A3 and Z= 2. The cyclic voltammograms of uninuclear cationic complexes in dmf exhibit an extra cathodic wave due to the chloride ion. The available evidence supports an increasing antimicrobial effeciency for the cationic complexes.