Nitrogen Donor Heterocyclic Ligand Research Articles

Copper(II) complexes containing derivative of aminobenzoic acid and nitrogen-rich ligands: Synthesis, characterization and cytotoxic potential

Four mixed ligand copper(II) complexes bearing mefenamic acid and different heterocyclic nitrogen donor ligands have been synthesized. A direct one-step metal-ligand complexation method was adopted in synthesizing the complexes. These newly formed complexes are [Cu(mef)2(imi)2]; CM-1, [Cu(mef)2(py)2]; CM-2, [Cu2(mef)4(apy)2].2CH3CN; CM-3, and [Cu(mef)2(nic)2(C2H5OH)]; CM-4 (mef = mefenamato, imi = imidazole, py = pyridine, apy = 2-aminopyridine, and nic = nicotinamide). The complexes were characterized by both analytical and spectral methods. FTIR studies confirmed the mefenamato ligand coordinated via a deprotonated carboxylato oxygen atom to the Cu(II) center. The molecular structures of CM-1 and CM-2 showed both are isostructural and exhibit square-planar geometry around Cu(II). CM-3 crystallized in the dimeric form, each Cu(II) is in five-coordinate geometry, with a structural paddle wheel motif. The resulting square pyramidal geometry in CM-4 is due to the ethanol solvent's coordination on the pyramid's axial position. The crystal lattice of the complexes was stabilized by noncovalent interactions such as N-H···O, C-H···O, CH···π, and π···π. The mononuclear complexes were more stable than the dimeric complex CM-3, revealed by thermogravimetric analysis. In addition, the cytotoxic study of the copper (II) complexes on lung carcinoma cells (NCIH-460) and breast cells (MDAMB) were evaluated using MTT dye (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay.

Synthesis, DNA Interaction, DFT Analysis of Cu(II) Complexes with Nitrogen Donor Heterocyclic Ligand and Evaluation of Their Potential Cytotoxic Activity and Antimicrobial Resistance

Synthesis, DNA Interaction, DFT Analysis of Cu(II) Complexes with Nitrogen Donor Heterocyclic Ligand and Evaluation of Their Potential Cytotoxic Activity and Antimicrobial Resistance

Copper(II) and Nickel(II) complexes of the non-steroidal anti-inflammatory drug indomethacin containing aromatic chelating N,N-donor ligand: Synthesis and structural studies

Two complexes [Cu(indo)2(phen)(H2O)];Cu-1 and [Ni(indo)2(phen)(H2O)2].1.5H2O;Ni-1, were synthesized by the reaction of their respective metal(II)acetates with indomethacin (indo) [1-(4-chlorobenzoyl)-5‑methoxy‑2-methyl-1H-indole-3-acetic acid)] and a nitrogen donor heterocyclic ligand 1,10-phenanthroline (phen) in acetonitrile: water mixture (9:1 v/v), by refluxing at 80 °C for 3 h. The complexes were characterized by physicochemical, spectroscopic, and TG analysis. X-ray structural analysis showed that both complexes crystallizes in the triclinic space group P-1.Cu-1 consists of Cu(II) in square pyramidal geometry and coordinated to two monodentate indomethacin ligands, a bidentate 1,10-phenanthroline, and one aqua ligand. Intermolecular O-H···O, C-H···O, C-H···Cl, Cl···Cl, and C-H···π interactions in Cu-1 were responsible for the stability of the complex. Ni-1 is centrosymmetric and consists of Ni(II) in a distorted octahedral geometry, involving two trans monodentate indomethacin ligands, a bidentate 1,10-phenanthroline ligand, and two cis aqua ligands. There were two lattice water molecules outside the coordination sphere of Ni-1, that participated in extensive O-H···O interactions. The complex was further stabilized by C-H···O, C-H···π, and π···π interactions. The monodentate coordination of the carboxylato oxygen of indomethacin ligand in the complexes was confirmed from the FTIR studies. TG analysis provided information on the stability and decomposition pattern of the complexes.

Cytotoxic ruthenium(II) polypyridyl complexes with naproxen as NSAID: Synthesis, biological interactions and antioxidant activity

The non-steroidal anti-inflammatory drug (NSAID) naproxen (nap) bound to ruthenium(II) in the presence of a bidentate nitrogen donor heterocyclic ligands (bpy = 2,2′-bipyridine and phen = 1,10-phenanthroline), namely, [Ru(bpy)2(nap)][PF6] (1) and [Ru(phen)2(nap)][PF6] (2) have been synthesized and characterized using various physicochemical methods. Naproxen was coordinated to the Ru(II) center through carboxylato oxygen atoms (–COO−) in a bidentate fashion. The compounds were evaluated for their photophysical properties, stability in solution, reactivity with 5′-guanosine monophosphate (5′-GMP) and GSH, interactions with CT-DNA and BSA. The complexes showed high binding affinity or reactivity towards these biological targets and bioanalytes. Both the compounds 1 and 2 showed moderate antioxidant activity by scavenging DPPH (1,1-diphenyl-picrylhydrazyl) and ABTS (2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radicals. The complexes 1 and 2 were highly cytotoxic against PC3 and MCF-7 cancer cells giving IC50 values ranging from 17 µM to 27 µM.

Refolding and unfolding of CT-DNA by newly designed Pd(II) complexes. Their synthesis, characterization and antitumor effects

New antitumor Pd(II) compounds derived from oxygen donor ligands salicylate (SA) (1) and sulfosalicylate (SSA) (2) dianions and nitrogen donor heterocyclic ligand 2,2′-bipyridine (bpy) were synthesized and characterized by elemental analysis, UV–Vis, FT-IR, 1H NMR and conductivity measurements. The complexes evaluated for their cytotoxicity effects towards cancer cell line of K562 using MTT assay. They are more cytotoxic than cisplatin. The dependence of their interaction modes with CT-DNA on concentration of the compounds has been discovered in this work. CT-DNA binding studies of these complexes have been investigated by UV–Vis absorption, ethidium bromide (EB) displacement, fluorescence, circular dichroism and gel electrophoresis techniques. The apparent binding constants (Kapp) has been obtained 3.9 and 10.9×104M−1 at lower concentration range and 1.03 and 1.59×104M−1 at higher concentration range for complexes (1) and (2), respectively. These complexes effectively interact with CT-DNA in the order of (2)>(1). Fluorescence studies exhibited that the complexes quench CT-DNA-EB by simultaneous static and dynamic quenching processes. The calculated binding (Kapp, kq, KSV, n) and thermodynamic (ΔG°, ΔH°, ΔS°) parameters revealed that hydrophobic, van der Waals forces and hydrogen binding holds the Pd(II) complexes in the CT-DNA grooves. Gel electrophoresis supports the spectroscopic experiments.

Cobalt(II) complexes of sparfloxacin: Characterization, structure, antimicrobial activity and interaction with DNA and albumins

The cobalt(II) complexes with the quinolone sparfloxacin (Hsf) in the absence or presence of the nitrogen-donor heterocyclic ligands 2,2′-bipyridine (bipy), 1,10-phenanthroline (phen) or 2,2′-bipyridylamine (bipyam) were prepared and characterized physicochemically and spectroscopically. The crystal structures of complexes [Co(sf)2(bipy)]∙3MeOH∙2H2O and [Co(sf)2(phen)]∙4MeOH were determined by X–ray crystallography. The antimicrobial activity of the complexes was tested against four different microorganisms (Escherichia coli, Xanthomonas campestris, Staphylococcus aureus and Bacillus subtilis) and was found similar or higher than that of free Hsf. The binding of the complexes to calf-thymus DNA was monitored by UV-vis spectroscopy and DNA-viscosity measurements and indirectly by competitive studies with ethidium bromide; intercalation is suggested as the most possible interaction mode. Fluorescence emission spectroscopy was used to evaluate the interaction of the complexes with human or bovine serum albumin and the corresponding binding constants were determined.

Preparation, characterization and cytotoxicity studies of some transition metal complexes with ofloxacin and 1,10-phenanthroline mixed ligand

[Zn(Ofl)(Phen)(H2O)2](CH3COO)·2H2O (1), [ZrO(Ofl)(Phen)(H2O)]NO3·2H2O (2) and [UO2(Ofl)(Phen)(H2O)](CH3COO)·H2O (3) complexes of fluoroquinolone antibacterial agent ofloxacin (HOfl), containing a nitrogen donor heterocyclic ligand, 1,10-phenathroline monohydrate (Phen), were prepared and their structures were established with the help of elemental analysis, molar conductance, magnetic properties, thermal studies and different spectroscopic studies like IR, UV-Vis., 1H NMR and Mass. The IR data of HOfl and Phen ligands suggested the existing of a bidentate binding involving carboxylate O and pyridone O for HOfl ligand and two pyridine N atoms for Phen ligand. The coordination geometries and electronic structures are determined from electronic absorption spectra and magnetic moment measurements. From molar conductance studies reveals that metal complexes are electrolytes and of 1:1 type. The calculated bond length and force constant, F(UO), in the uranyl complex are 1.751 Å and 641.04 Nm−1. The thermal properties of the complexes were investigated by thermogravimetry (TGA) technique. The activation thermodynamic parameters are calculated using Coats–Redfern and Horowitz-Metzger methods. Antimicrobial activity of the compounds was evaluated against some bacteria and fungi species. The activity data show that most metal complexes have antibacterial activity than that of the parent HOfl drug. The in vitro cytotoxicities of ligands and their complexes were also evaluated against human breast and colon carcinoma cells.

Nickel(II) complexes of the non-steroidal anti-inflammatory drug tolfenamic acid: Synthesis, structure, antioxidant activity and interaction with albumins and calf-thymus DNA

The reaction of NiCl2·6H2O with the non-steroidal anti-inflammatory drug tolfenamic acid (Htolf) in the absence or presence of a nitrogen-donor heterocyclic ligand such as 2,2′-bipyridine (bipy), 1,10-phenanthroline (phen), 2,2′-bipyridylamine (bipyam), 2,2′-dipyridylketone oxime (Hpko) and pyridine (py) led to the formation of six novel Ni(II) mononuclear complexes. The complexes were characterized by physicochemical and spectroscopic techniques and the crystal structures of complexes [Ni(tolf-O)2(bipy)(MeOH)2], 2 and [Ni(tolf-O)2(Hpko-N,N′)2], 5 were determined by X-ray crystallography. The in vitro investigation of 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 revealed their potential antioxidant activity. The interaction of the complexes to calf-thymus DNA was monitored by diverse techniques (UV spectroscopy, cyclic voltammetry, viscosity measurements) revealing intercalation as the most possible mode of binding. Competitive studies of the complexes with ethidium bromide were monitored by fluorescence emission spectroscopy. The interaction of the complexes with serum albumins was studied by fluorescence emission spectroscopy and the binding constants of the compounds to the albumins were calculated.

Effect of heterocyclic nitrogen donor ligands on coordination behavior of weakly coordinating arylsulfonate: Synthesis, characterization and antimicrobial activities of [Cu(β-pic)4(2-Cl-5-nitrobenzenesulfonate)2](methanol) and [Cu(γ-pic)4(2-Cl-5 nitrobenzenesulfonate)2

Two new copper(II) complexes [Cu(β-pic)4(2-Cl-5-nitrobenzenesulfonate)2](CH3OH) (1) and [Cu(γ-pic)4(2-Cl-5-nitrobenzenesulfonate)2] (2) have been synthesized by reacting appropriate starting materials in methanol:water (v/v 4:1). Both newly synthesized complexes have been characterized on the basis of elemental analyses, spectroscopic techniques (FT-IR, UV–Vis, EPR) and single crystal X-ray structure determination (complex 1). The structural analysis of complex 1 revealed the existence of unusual coordination behavior of arylsulfonate towards copper(II) center in presence of heterocyclic N-donor ligands resulting in elongated octahedral geometry around the metal. The EPR spectroscopy of complexes 1 and 2 unambiguously proved a similar coordination of four picolines in Cu(II) xy plane. Antimicrobial studies of both the complexes 1 and 2 were performed against Gram positive, MRSA (Methicillin-Resistant Staphylococcus aureus) as well as Gram negative (Escherichia coli, Klebsiella pneumoniae) bacteria. The activity was investigated by using both Agar well diffusion as well as MIC assay. Both the complexes show significant bactericidal activity against all the pathogenic strains in comparison to ampicillin, a broad spectrum antibiotic against Gram positive and Gram negative bacteria.

Norfloxacin and N-Donor Mixed-Ligand Copper(II) Complexes: Synthesis, Albumin Interaction, and Anti-Trypanosoma cruzi Activity.

Copper(II) complexes with the first-generation quinolone antibacterial agent norfloxacin containing a nitrogen donor heterocyclic ligand 2,2′-bipyridine (bipy) or 1,10-phenanthroline (phen) were prepared and characterized by IR, EPR spectra, molar conductivity, and elemental analyses. The experimental data suggest that norfloxacin was coordinated to copper(II) through the carboxylato and ketone oxygen atoms. The interaction of the copper(II) complexes with bovine serum albumin (BSA) and human serum albumin (HSA) was investigated using fluorescence quenching of the tryptophan residues and copper(II) EPR spectroscopy. The results of fluorescence titration revealed that copper(II) complexes have a moderate ability to quench the intrinsic fluorescence of the albumins through a static quenching mechanism. EPR experiments showed that BSA and HSA Cu(II) sites compete with NOR for Cu(II)-bipy and Cu(II)-phen to form protein mixed-ligand complexes. Copper(II) complexes, together with the corresponding ligands, were evaluated for their trypanocidal activity in vitro against Trypanosoma cruzi, the causative agent of Chagas disease. The tests performed using bloodstream trypomastigotes showed that the Cu(II)-N-donor precursors and the metal complexes were more active than the free fluoroquinolone.

Copper(II) complexes with new fluoroquinolones: Synthesis, structure, spectroscopic and theoretical study, DNA damage, cytotoxicity and antiviral activity

Copper(II) complexes with fluoroquinolones in the presence of the nitrogen donor heterocyclic ligands 1,10-phenanthroline have been considered in detail. The phenanthroline moiety was introduced into the ligand environment with the aim to determine whether the nuclease activity is feasible. All suitable X-ray structures of the complexes under study reveal a distorted square pyramidal coordination geometry for Cu(II) atom. The conformational and spectroscopic (FT-IR and UV–visible) behavior has been analyzed and has been interpreted with respect to B3LYP/6-311G* calculations including molecular dynamics. The ability of the complexes to cleave DNA was studied by agarose gel electrophoresis with plasmid DNA pBSK+. The results have confirmed that the complexes under study behave as the chemical nucleases. Nuclease like activity in the absence of hydrogen peroxide allows us to deduce an interaction of the complexes with the DNA resulting in the conversion of supercoiled circular DNA to the nicked form. The DNA cleavage activity enhanced by the presence of hydrogen peroxide demonstrates the participation of reactive oxygen species, such as superoxide radical anions and hydroxyl radicals which presence was confirmed independently using the standard radical scavenging agents. It has been suggested that the radical formation through the Fenton/Haber–Weiss reaction is mediated by the redox cycling mechanisms with the participation of cupric/cuprous ions. Cytotoxic activity was evaluated as the 50% cytotoxic concentration (CC50). The potential effects of tested compounds on replication of murine gammaherpesvirus 68 (MHV-68) under in vitro conditions were also evaluated. However, no antiviral activity against MHV-68 was observed.

Copper(II) complexes with the non-steroidal anti-inflammatory drug tolfenamic acid: Structure and biological features

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).

Synthesis, structure and biological activity of nickel(II) complexes with mefenamato and nitrogen-donor ligands

Six novel nickel(II) complexes with the non-steroidal anti-inflammatory drug mefenamic acid (Hmef) with the nitrogen-donor heterocyclic ligands 2,2′-bipyridine (bipy), 2,2′-bipyridylamine (bipyam), 1,10-phenanthroline (phen), 2,2′-dipyridylketone oxime (Hpko) or pyridine (py) and/or the oxygen-donor ligands CH3OH or H2O were synthesized and characterized by physicochemical and spectroscopic techniques. The crystal structures of [Ni(mef-O)2(bipy)(CH3OH)2] (1), [Ni(mef-O)2(phen)(CH3OH)2] (2), [Ni(mef-O,O′)2(bipyam)] (3) and [Ni(mef-O)2(Hpko)2]∙CH3OH (4·CH3OH) 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 was investigated and the in vitro inhibitory activity against soybean lipoxygenase was evaluated; complexes 3 and 4 were the most active compounds. 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 the most possible mode of DNA-binding. The interaction of the complexes with serum albumins was studied by fluorescence emission spectroscopy and the values of the albumin-binding constants were determined.

Synthesis and Structural Studies of Some New Cobalt (II) Complexes with Chloride and Heterocyclic Nitrogen Donor ligands

A new series of cobalt complexes of type [Co(L)6]Cl2 (where L =imidazole, pyridine, piperidine, piperazine, indole, triazole, benzimidazole, benzotriazole, quinoline, iso-quinoline and carbazole) have been synthesized and are well characterized by elemental analysis, IR, UV, Mass spectra and magnetic measurements. The thermal studies of these complexes are also reported. All these complexes are soluble in ethanol and the conductance measurement shows that all the complexes are of 1:2 type electrolyte. The IR spectra show clear indication for coordination between central cobalt atom and nitrogen atom of the ligands. The mass spectra clearly show the molecular ion peak and base peak at appropriate place. On thermo gravimetric analysis, it is found that the metal atom and chlorine are strongly attached to each other. The ligands are loosely attached and are removed first on heating. Finally considering all the spectral analysis, conductance values, thermo gravimetric analysis, octahedral structure are proposed for these complexes

Cobalt(II) complexes with the antimicrobial drug enrofloxacin: Structure, antimicrobial activity, DNA- and albumin-binding

The cobalt(II) complexes with the quinolone antimicrobial agent enrofloxacin (Herx) in the presence of the nitrogen-donor heterocyclic ligands pyridine (py), 2,2′-bipyridylamine (bipyam), 1,10-phenanthroline (phen), 2,2′-bipyridine (bipy) or the oxygen-donor ligand N,N-dimethylformamide (DMF) were synthesized and characterized. The crystal structures of complexes [Co(erx)2(py)2]·MeOH·6H2O and [Co(erx)2(bipyam)]·4.5MeOH·1.25H2O were determined by X-ray crystallography. The deprotonated enrofloxacinato ligands are bidentately bound to cobalt(II) ion through the pyridone oxygen and a carboxylato oxygen. The antimicrobial activity of the complexes was tested against five different microorganisms (Escherichia coli XL1, Xanthomonas campestris ATCC 33013, Staphylococcus aureus ATCC 29213, Bacillus cereus ATCC 11778 and Bacillus subtilis ATCC 6633) and the complexes were more active than free Herx. The binding of the complexes to calf-thymus DNA (CT DNA) was monitored by spectroscopic techniques, viscosity measurements, cyclic voltammetry and by mobility shift experiments in agarose gel electrophoresis with CT DNA and plasmid DNA (pDNA). All complexes exhibited a preference for binding to the supercoiled structure of the pDNA. The ability of the complexes to displace ethidium bromide (EB) from the EB–DNA complex was also investigated. The experiments indicated intercalation as the most possible mode and the DNA-binding strength of the complexes were also calculated. The complexes bind to human or bovine serum albumin protein exhibiting relatively high binding constant values.

Structure and biological perspectives of Cu(II)–indomethacin complexes

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)×106M−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.

Synthesis, Characterization and Antifungal Activity of Adducts of Bis(acetylacetonato)oxovanadium(IV) with Heterocyclic Nitrogen Donor Ligands

Monomeric six coordinated adducts of bis(acetylacetonato)oxovanadium(IV) having general formula, [VO(acac)2(L)], [L= pyrrolidine, morpholine, 2,4,6-trimethylpyridine, 2,4, 2,6, 3,4, 3,5-dimethylpyridines, 2-ethylpyridine, 2-methylpyridine, 3-methylpyridine 2, 3, 4-cyanopyridine, quinoline, isoquinoline] have been synthesized and characterized by elemental analysis, IR, electronic spectroscopy, magnetic and conductivity measurements having 1:1 stoichiometry. The adducts were found to be paramagnetic and their magnetic moments at room temperature lie within the 1.72-1.87 B.M. range and this indicates the presence of one unpaired electron. The values are in accordance with the octahedral geometry. The magnetic moment measurements and electronic spectra depicts a octahedral geometry around the vanadium center. The investigated adducts have also tested against the fungus Fusarium oxysporum.

Manganese(II) Complexes with the Non-steroidal Anti-Inflammatory Drug Tolfenamic Acid: Structure and Biological Perspectives

Manganese(II) complexes with the non-steroidal anti-inflammatory drug tolfenamic acid (Htolf) with the nitrogen-donor heterocyclic ligands 1,10-phenanthroline (phen), pyridine (py), or 2,2'-bipyridylamine (bipyam) and/or the oxygen-donor ligands H2O or N,N-dimethylformamide (DMF) have been synthesized and characterized. The crystal structures of complexes [Mn(tolf-O)(tolf-O,O')(phen)(H2O)], [Mn2(μ2-tolf-O,O')2(tolf-O,O')2(bipyam)2], [Mn2(μ2-H2O)(μ2-tolf-O,O')2(tolf-O)2(py)4]·1.5MeOH·py, and [Mn(μ2-tolf-O,O')2(DMF)2]n have been determined by X-ray crystallography. The interaction of the complexes with serum albumin proteins was investigated, and relative high binding constant values were calculated. The ability of the compounds to scavenge 1,1-diphenyl-picrylhydrazyl, 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid), and hydroxyl radicals was evaluated, and [Mn(tolf)2(phen)(H2O)] was the most active scavenger among the compounds. The compounds have also exhibited noteworthy in vitro inhibitory activity against soybean lipoxygenase. UV titration studies of the interaction of the complexes with calf-thymus (CT) DNA have proved the binding to CT DNA with [Mn(μ2-tolf)2(DMF)2]n exhibiting the highest DNA-binding constant (Kb = 5.21 (±0.35) × 10(5) M(-1)). The complexes bind to CT DNA probably via intercalation as suggested by DNA-viscosity measurements and competitive studies with ethidium bromide (EB), which revealed the ability of the complexes to displace the DNA-bound EB.

Complexes of different nitrogen donor heterocyclic ligands with SbCl3 and PhSbCl2 as potential antileishmanial agents against SbIII-sensitive and -resistant parasites

Novel trivalent antimony complexes with the nitrogen donor heterocyclic ligand 2,2′-bipyridine (bipy), 1,10-phenanthroline (phen) or dipyrido[3,2-d:2′,3′-f]quinoxaline (dpq) have been synthesized by the reaction with SbCl3 or PhSbCl2. The crystal structures of [Sb(phen)Cl3] and [PhSb(phen)Cl2]CH3COOH were determined and shown to adopt a distorted square pyramid geometry with a five-coordinated Sb center. Surprisingly, all the complexes, the ligands and PhSbCl2 showed very high antileishmanial activities, with IC50 in the nanomolar range against SbIII-sensitive and -resistant Leishmania infantum (syn. Leishmania chagasi) and Leishmania amazonensis strains. These compounds were much more active against these Leishmania strains than the old trivalent drug potassium antimonyl tartrate. [PhSb(phen)Cl2]CH3COOH complex was found to be the most active compound and the lack of cross-resistance of PhSbCl2 suggests that the transport pathways of this compound across the cell membrane differ from those responsible for the resistance of Leishmania to Sb(OH)3. In the case of the complexes with PhSbCl2, our data supports the model that both ligand and metal contributed to the overall activity of the complex. Furthermore, among the complexes with SbCl3, only bipy showed an improved activity upon complexation. Cytotoxicity evaluations of these compounds against murine peritoneal macrophages showed high selective indexes in the range of 7–70 for [Sb(phen)Cl3], [Sb(bipy)Cl3] and [Sb(dpq)Cl3] complexes, being much more selective than potassium antimonyl tartrate. In conclusion, this study presents a set of new antileishmanial agents including one of the most active Sb-based compounds ever reported, which can contribute to the development of new chemotherapeutic strategies against leishmaniasis including Sb-resistant cases.

Synthesis, characterization and antibacterial studies of a copper(II) lomefloxacin ternary complex

Solution behavior of lomefloxacin (lmx) complexes with copper(II) in the presence and absence of 1,10-phenanthroline (phen) was studied in aqueous solution, by potentiometry. The results obtained showed that under physiological conditions (micromolar concentration range and pH7.4) only copper(II):lmx:phen ternary complexes are stable. Hence, a novel copper(II) ternary complex of lomefloxacin with the nitrogen donor heterocyclic ligand phen was synthesized and characterized by means of UV–visible and IR spectroscopy, elemental analysis and X-ray crystallography. In the synthesized complex (1), [Cu(lmx)(phen)(NO3)]·5H2O, lmx acts as a bidentate ligand coordinating the metal cation, in its anionic form, through the carbonyl and carboxyl oxygens and phen coordinates through two N-atoms forming the equatorial plane of a distorted square-pyramidal geometry. The fifth ligand of the penta-coordinated Cu(II) center is occupied axially by an oxygen atom from the nitrate ion. Minimum inhibitory concentration (MIC) determinations of the complex and comparison with free lomefloxacin in various E. coli strains indicated that the Cu-complex is an antimicrobial which is as efficient as the free antibiotic but strongly suggest that the cell intake route of both species is different. Moreover, spectrophotometric stability studies suggest that the solution of the complex synthesized is considerably more photostable than the free fluoroquinolone supporting, therefore, the complex's suitability as a candidate for further biological testing in fluoroquinolone-resistant microorganisms with possible reduced side-effects.