Metal Complexes with Naphthalene-Based Acetic Acids as Ligands: Structure and Biological Activity.

Naproxen (6-methoxy-α-methyl-2-naphthaleneacetic acid), 1-naphthylacetic acid, 2-naphthylacetic acid and 1-pyreneacetic acid are derivatives of acetic acid bearing a naphthalene-based ring. In the present review, the coordination compounds of naproxen, 1- or 2-naphthylacetato and 1-pyreneacetato ligands are discussed in regard to their structural features (nature and nuclearity of metal ions and coordination mode of ligands), their spectroscopic and physicochemical properties and their biological activities.

In vitro biological activity of copper(II) complexes with NSAIDs and nicotinamide: Characterization, DNA- and BSA-interaction study and anticancer activity.

Through the reaction of copper(II) acetate with nicotinamide (pyridine-3-carboxylic acid amide, niacinamide) and some derivatives of N-phenylanthranilic acid (fenamates), seven new mixed-ligand copper(II) compounds were isolated: [Cu(tolf-O)(tolf-O,O')nia-N)2(EtOH)] (1), [Cu(tolf-O)(tolf-O,O')(nia-N)2(MeOH)] (2), [Cu(meclf-O)(meclf-O,O')(nia-N)2(EtOH)] (3), [Cu(meclf-O)(meclf-O,O')(nia-N)2(MeOH)] (4), [Cu(meclf-O)(meclf-O,O')(nia-N)2(ACN)] (5), [Cu(mef-O)(mef-O,O')(nia-N)2(EtOH)] (6) and [Cu(mef-O)(mef-O,O')(nia-N)2(ACN)] (7) containing a molecule of relevant solvent as ligand in their primary crystal structure (tolf = tolfenamate, meclf = meclofenamate, mef = mefenamate, nia = nicotinamide, EtOH = ethanol, MeOH = methanol, ACN = acetonitrile). The structures of the complexes were determined by single-crystal X-ray analysis. The intermolecular interactions were studied by Hirshfeld surface analysis. The complexes were characterized by IR, UV-vis and EPR spectroscopy and their redox properties were determined by cyclic voltammetry. The interaction of the complexes with bovine serum albumin was studied by fluorescence emission spectroscopy and the albumin-binding constants of the compounds were calculated. The interaction of the complexes with calf-thymus DNA was monitored by diverse techniques (UV-vis spectroscopy, cyclic voltammetry, viscosity measurements) suggesting intercalation as the most possible mode of binding. DNA-competitive studies of the complexes with ethidium bromide were monitored by fluorescence emission spectroscopy. The cytotoxic effects of copper(II) complexes on lung carcinoma cells and healthy cells were determined by the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] colorimetric technique.

Manganese(II) complexes of substituted salicylaldehydes and α-diimines: Synthesis, characterization and biological activity.

The interaction of Mn+2 with substituted salicylaldehydes (X-saloH) led to the formation of five manganese(II) complexes formulated as [Μn(X-salo)2(MeOH)2]. When the reactions took place in the presence of an α-diimine such as 2,2'-bipyridine, 1,10-phenanthroline or 2,2'-bipyridylamine, five manganese(II) complexes of the formula [Mn(X-salo)2(α-diimine)] were isolated. The characterization of the complexes was accomplished by various spectroscopic techniques and single-crystal X-ray crystallography. The antioxidant activity of the compounds was evaluated via the scavenging of 1,1-diphenyl-picrylhydrazyl, 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) and hydroxyl free radicals. The antibacterial activity of the complexes was tested in vitro against Staphylococcus aureus and Xanthomonas campestris bacterial strains and was found moderate. Diverse techniques were employed to examine the interaction of the complexes with calf-thymus DNA which showed intercalation as the most possible interaction mode. The affinity of the complexes for bovine serum albumin was investigated by fluorescence emission spectroscopy and the binding constants were determined.

Synthesis, characterization and (in vitro and in silico) biological activity of a series of dioxouranium(VI) complexes with non-steroidal anti-inflammatory drugs.

The reaction of the dioxouranium(VI) ion with a series of non-steroidal anti-inflammatory drugs (NSAIDs), namely mefenamic acid, indomethacin, diclofenac, diflunisal and tolfenamic acid, as ligands in the absence or presence of diverse N,N'-donors (1,10-phenanthroline,2,2'-bipyridine or 2,2'-bipyridylamine) as co-ligands led to the formation of ten complexes bearing the formulas [UO2(NSAID-O,O')2(O-donor)2] or [UO2(NSAID-O,O')2(N,N'-donor)], respectively. The complexes were characterized with diverse spectroscopic techniques and the crystal structures of three complexes were determined by single-crystal X-ray crystallography. The biological profile of the resultant complexes was assessed in vitro and in silico. The in vitro studies include their antioxidant properties (ability to scavenge free radicals 1,1-diphenyl-picrylhydrazyl and 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) and to reduce H2O2), their interaction with DNA (linear calf-thymus DNA or supercoiled circular pBR322 plasmid DNA) and their affinity for serum albumins (bovine and human serum albumin). In silico molecular docking calculations were performed regarding the behavior of the complexes towards DNA and their binding to both albumins.

Synthesis, structural determination, in vitro and in silico biological evaluation of divalent or trivalent cobalt complexes with indomethacin.

The interaction of cobalt chloride with the non-steroidal anti-inflammatory drug indomethacin (Hindo) led to the formation of the polymeric complex [Co(indo-O)2(H2O)2(µ-Cl)]n·n(MeOH·H2O) bearing one chlorido bridge between the cobalt atoms. The presence of the nitrogen-donor co-ligands 2,2'-bipyridine (bipy), 2,2'-bipyridylamine (bipyam), 1,10-phenanthroline (phen) or 1H-imidazole (Himi) resulted in the isolation of complexes [Co2(µ-indo-O,O')2(indo-O)2(bipy)2(µ-H2O)]·3.3MeOH, [Co(indo-O,O')2(bipyam)]·0.9MeOH·0.2H2O, [Co(indo-O,O')2(phen)] (4) and [Co(indo-O)2(Himi)2] (5), respectively, where the indomethacin ligands were coordinated in diverse manners. The study of the affinity of the complexes for calf-thymus DNA revealed their intercalation between the DNA-bases. The binding of the complexes to albumins was also examined and the corresponding binding constants and binding subdomain were determined. The free radical scavenging activity of the compounds was evaluated towards 1,1-diphenyl-picrylhydrazyl and 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid). Molecular modeling calculations may usually provide a molecular basis for the understanding of both the impairment of DNA by its binding with the studied complexes and the ability of these compounds to transportation through serum albumin proteins. This study can provide information for the elucidation of the mechanism of action of the compounds in a molecular level.

Structure and biological evaluation of pyridine-2-carboxamidine copper(II) complex resulting from N'-(4-nitrophenylsulfonyloxy)2-pyridine-carboxamidoxime.

The interaction of Cu(NO3)2·3H2O with the sulfonyl o-pyridine carboxamidoxime N'-(4-nitrophenylsulfonyloxy)picolinimidamide (L) resulted in the mononuclear complex [Cu(L1)2](L2)2 (1), where L1 = pyridine-2-carboxamidine ligand and (L2)- = 4-nitrobenzenesulfonate anion derived from the homolytic cleavage of the NO bond of L. The complex was characterized by diverse techniques including single-crystal X-ray crystallography. From the antimicrobial tests performed, complex 1 seems to be active against gram-negative bacterial strains. The complex binds tightly and reversibly to serum albumins and tightly to calf-thymus DNA via an intercalative mode and also via electrostatic interactions (as expected due to its cationic nature). Additionally, it interacts with (pBluescriptSK(+)) plasmid DNA in a concentration-dependent manner. The results from the present in silico molecular modeling simulations provide useful complementary insights for the elucidation of the mechanism of action of the studied complex at a molecular level. Molecular modeling calculations provide a molecular basis for the understanding of both the impairment of DNA by its binding with the studied complex and the ability of this compound to act as an antibacterial agent, most probably by its activity against DNA-gyrase, as well as for transportation through serum albumins and possible interaction with other protein targets involved in various diseases.

Cobalt(II) complexes with the non-steroidal anti-inflammatory drug diclofenac and nitrogen-donor ligands.

The interaction of the non-steroidal anti-inflammatory drug sodium diclofenac with CoCl2 in the absence or presence of the nitrogen-donor ligands 2,2'-bipyridine, 1,10-phenanthroline, 2,2'-bipyridylamine, pyridine or imidazole resulted in the formation of six mononuclear Co(II) complexes. The complexes were characterized by diverse physicochemical and spectroscopic techniques and single-crystal X-ray crystallography revealing a monodentate or a bidentate chelating binding mode of the diclofenac ligands. The scavenging activity of the complexes was evaluated in vitro against the free radicals of 1,1-diphenyl-2-picrylhydrazyl, 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and hydroxyl; the complexes present significant scavenging activity of ABTS and hydroxyl radicals. The interaction of the complexes with calf-thymus (CT) DNA and bovine serum albumin (BSA) was also investigated; the complexes can bind tightly to CT DNA via intercalation and can bind to BSA tightly and reversibly.

Copper(II) diclofenac complexes: Synthesis, structural studies and interaction with albumins and calf-thymus DNA.

The reaction of the copper(II) diclofenac complex [Cu(dicl)2(H2O)2] (1) (dicl = deprotonated diclofenac (Hdicl)) with the chelating N-donor ligands ethylenediamine (en), propan-1,3-diamine (pn), unsymmetrical dimethylethylene-diamine (unsym-dmen) and N,N,N',N'-tetramethylethylene-diamine (temed) in methanol-water (4:1 v/v) yielded the novel copper(II) complexes [Cu(en)2(H2O)2](dicl)2·2H2O (2), [Cu(pn)2(H2O)2](dicl)2·2H2O (3), [Cu(unsym-dmen)2(H2O)](dicl)2·H2O (4) and [Cu(temed)(dicl)2] (5), respectively. All the synthesized complexes were characterized by spectroscopic (UV-vis, FT-IR) methods. The structures of complexes 2, 3 and 5 were unambiguously determined by single-crystal X-ray crystallography. X-ray structures of complexes clearly revealed the ionic structure of complexes 2, 3 and the covalent structure of complex 5. The geometry of complex 4 was optimized by Density Functional Theory (DFT) calculations. The ability of the complexes 1-5 to bind to calf-thymus DNA was monitored in vitro by diverse techniques (UV-vis spectroscopy, cyclic voltammetry, viscosity measurements) and via competitive studies with ethidium bromide. The interaction of complexes 1-5 with bovine serum albumin was studied in vitro by fluorescence emission spectroscopy and the corresponding binding constants were calculated. The biological behavior of complexes 1-5 was compared with previously reported Cu(II), Mn(II) and Ni(II) complexes of diclofenac.

Characterization and biological properties of copper(II)-ketoprofen complexes.

From the reaction of Cu(II) with the non-steroidal anti-inflammatory drug ketoprofen (Hketo), complex [Cu2(keto)4(H2O)2] was isolated, while the presence of a N,N'-donor heterocyclic ligand 2,2'-bipyridylamine (bipyam), 1,10-phenanthroline (phen) or 2,2'-bipyridine (bipy) led to the formation of complexes of the formula [Cu(keto)2(N,N'-donor)(H2O)]. The complexes were characterized by physicochemical and spectroscopic techniques and the crystal structure of [Cu(keto)2(bipyam)(H2O)] was determined by X-ray crystallography. The ability of ketoprofen and its complexes to scavenge 1,1-diphenyl-picrylhydrazyl, 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) and hydroxyl radicals was evaluated; the complexes were more active scavengers than free Hketo. The interaction of the complexes with serum albumins was investigated by fluorescence emission spectroscopy and the binding constant of the compounds to the albumins were calculated. Diverse techniques including UV spectroscopy, cyclic voltammetry and viscosity measurements as well as fluorescence emission spectroscopy for the competitive studies of the compounds with ethidium bromide, were employed in our attempt to examine the interaction of the compounds with calf-thymus DNA; as a conclusion, intercalation is the most possible mode of binding.

Nickel-diflunisal complexes: synthesis, characterization, in vitro antioxidant activity and interaction with DNA and albumins.

The reaction of NiCl2 with the non-steroidal anti-inflammatory drug diflunisal (Hdifl) resulted in the formation of complex [Ni(difl-O)2(MeOH)4], 1. The co-existence of a N,N'-donor heterocyclic ligand 2,2'-dipyridylketone oxime (Hpko), 1,10-phenanthroline (phen), 2,2'-bipyridine (bipy) and 2,2'-bipyridylamine (bipyam) led to the formation of complexes [Ni(difl-O)2(Hpko-N,N')2], 2, [Ni(difl)2(phen)(MeOH)2], 3, [Ni(difl)2(bipy)(MeOH)2], 4 and [Ni(difl-O,O')2(bipyam)], 5, respectively. The complexes were characterized by physicochemical and spectroscopic techniques and the crystal structures of complexes 1 and 2 were determined by X-ray crystallography. The ability of the complexes to scavenge in vitro 1,1-diphenyl-picrylhydrazyl, 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) and hydroxyl radicals was investigated; the complexes were more active scavengers than free Hdifl. The interaction of the complexes with serum albumins was investigated by fluorescence emission spectroscopy and the binding constants of the compounds to the albumins were calculated. UV spectroscopy, cyclic voltammetry and viscosity measurements as well as fluorescence emission spectroscopy for the competitive studies of the complexes with ethidium bromide were employed so as to monitor the interaction of the compounds with calf-thymus DNA and revealed intercalation as the most possible mode of binding.

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).