Iron(III) Complexes with Non-Steroidal Anti-Inflammatory Drugs: Structure, Antioxidant and Anticholinergic Activity, and Interaction with Biomolecules.

One the main research goals of bioinorganic chemists is the synthesis of novel coordination compounds possessing biological potency. Within this context, three novel iron(III) complexes with the non-steroidal anti-inflammatory drugs diflunisal and diclofenac in the presence or absence of the nitrogen donors 1,10-phenanthroline or pyridine were isolated and characterized by diverse techniques. The complexes were evaluated for their ability to scavenge in vitro free radicals such as hydroxyl, 1,1-diphenyl-2-picrylhydrazyl and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radicals, revealing their selective potency towards hydroxyl radicals. The in vitro inhibitory activity of the complexes towards the enzymes acetylcholinesterase and butyrylcholinesterase was evaluated, and their potential to achieve neuroprotection appeared promising. The interaction of the complexes with calf-thymus DNA was examined in vitro, revealing their ability to intercalate in-between DNA nucleobases. The affinity of the complexes for serum albumins was evaluated in vitro and revealed their tight and reversible binding.

Inhibition of Cancer Cell Proliferation and Bacterial Growth by Silver(I) Complexes Bearing a CH3-Substituted Thiadiazole-Based Thioamide.

Ag(I) coordination compounds have recently attracted much attention as antiproliferative and antibacterial agents against a wide range of cancer cell lines and pathogens. The bioactivity potential of these complexes depends on their structural characteristics and the nature of their ligands. Herein, we present a series of four Ag(I) coordination compounds bearing as ligands the CH3-substituted thiadiazole-based thioamide 5-methyl-1,3,4-thiadiazole-2-thiol (mtdztH) and phosphines, i.e., [AgCl(mtdztH)(PPh3)2] (1), [Ag(mtdzt)(PPh3)3] (2), [AgCl(mtdztH)(xantphos)] (3), and [AgmtdztH)(dppe)(NO3)]n (4), where xantphos = 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene and dppe = 1,2-bis(diphenylphosphino)ethane, and the assessment of their in vitro antibacterial and anti-cancer efficiency. Among them, diphosphine-containing compounds 3 and 4 were found to exhibit broad-spectrum antibacterial activity characteristics against both Gram-(+) and Gram-(-) bacterial strains, showing high in vitro bioactivity with IC50 values as low as 4.6 µΜ. In vitro cytotoxicity studies against human ovarian, pancreatic, lung, and prostate cancer cell lines revealed the strong cytotoxic potential of 2 and 4, with IC50 values in the range of 3.1-24.0 µΜ, while 3 and 4 maintained the normal fibroblast cells' viability at relatively higher levels. Assessment of these results, in combination with those obtained for analogous Ag(I) complexes bearing similar heterocyclic thioamides, suggest the pivotal role of the substituent groups of the thioamide heterocyclic ring in the antibacterial and anti-cancer efficacy of the respective Ag(I) complexes. Compounds 1-4 exhibited moderate in vitro antioxidant capacity for free radicals scavenging, as well as reasonably strong ability to interact with calf-thymus DNA, suggesting the likely implication of these properties in their bioactivity mechanisms. Complementary insights into the possible mechanism of their anti-cancer activity were provided by molecular docking calculations, exploring their ability to bind to the overexpressed fibroblast growth factor receptor 1 (FGFR1), affecting cancer cells' functionalities.

Detection and Sorption of Heavy Metal Ions in Aqueous Media by a Fluorescent Zr(IV) Metal-Organic Framework Functionalized with 2-Picolylamine Receptor Groups.

Increasing global environmental pollution due to heavy metal ions raises the importance of research on new multifunctional materials for simultaneous detection and removal of these contaminants from water resources. In this study, we report a microporous 8-connected Zr4+ metal-organic framework (MOF) based on a terephthalate ligand decorated with a chelating 2-picolylamine side group (dMOR-2), which shows highly efficient fluorescence sensing and sorption of heavy metal cations. We demonstrate by detailed fluorescence studies the ability of a water-dispersible composite of dMOR-2 with polyvinylpyrrolidone for real-time detection of Cu2+, Pb2+, and Hg2+ in aqueous media. The limits of detection were found to be below 2 ppb for these species, while the system's performance is not affected by the presence of other potentially competitive ions. In addition, sorption studies showed that a composite of dMOR-2 with calcium alginate (dMOR-2@CaA) is an excellent sorbent for Pb2+ and Cu2+ ions with capacities of 376 ± 15 and 117 ± 4 mg per gram of dMOR-2@CaA, respectively, while displaying the capability for simultaneous removal of various heavy metal ions in low initial concentrations and in the presence of large excesses of other cationic species. Structural and spectroscopic studies with model ligands analogous to our material's receptor unit showed chelation to the 2-picolylamine moiety to be the main binding mode of metal ions to dMOR-2. Overall, dMOR-2 is shown to represent a rare example of a MOF, which combines sensitive fluorescence detection and high sorption capacity for heavy metal ions.

Copper(II) Complexes of 5-Fluoro-Salicylaldehyde: Synthesis, Characterization, Antioxidant Properties, Interaction with DNA and Serum Albumins.

The synthesis, characterization and biological profile (antioxidant capacity, interaction with calf-thymus DNA and serum albumins) of five neutral copper(II) complexes of 5-fluoro-salicylaldehyde in the absence or presence of the N,N'-donor co-ligands 2,2'-bipyridylamine, 2,9-dimethyl-1,10-phenanthroline, 1,10-phenanthroline and 2,2'-bipyridine are presented herein. The compounds were characterized by physicochemical and spectroscopic techniques. The crystal structures of four complexes were determined by single-crystal X-ray crystallography. The ability of the complexes to scavenge 1,1-diphenyl-picrylhydrazyl and 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radicals and to reduce H2O2 was investigated in order to evaluate their antioxidant activity. The interaction of the compounds with calf-thymus DNA possibly takes place via intercalation as suggested by UV-vis spectroscopy and DNA-viscosity titration studies and via competitive studies with ethidium bromide. The affinity of the complexes with bovine and human serum albumins was examined by fluorescence emission spectroscopy revealing the tight and reversible binding of the complexes with the albumins.

Selective Reduction of Nitroarenes to Arylamines by the Cooperative Action of Methylhydrazine and a Tris(N-heterocyclic thioamidate) Cobalt(III) Complex.

We report an efficient catalytic protocol that chemoselectively reduces nitroarenes to arylamines, by using methylhydrazine as a reducing agent in combination with the easily synthesized and robust catalyst tris(N-heterocyclic thioamidate) Co(III) complex [Co(κS,N-tfmp2S)3], tfmp2S = 4-(trifluoromethyl)-pyrimidine-2-thiolate. A series of arylamines and heterocyclic amines were formed in excellent yields and chemoselectivity. High conversion yields of nitroarenes into the corresponding amines were observed by using polar protic solvents, such as MeOH and iPrOH. Among several hydrogen donors that were examined, methylhydrazine demonstrated the best performance. Preliminary mechanistic investigations, supported by UV-vis and NMR spectroscopy, cyclic voltammetry, and high-resolution mass spectrometry, suggest a cooperative action of methylhydrazine and [Co(κS,N-tfmp2S)3] via a coordination activation pathway that leads to the formation of a reduced cobalt species, responsible for the catalytic transformation. In general, the corresponding N-arylhydroxylamines were identified as the sole intermediates. Nevertheless, the corresponding nitrosoarenes can also be formed as intermediates, which, however, are rapidly transformed into the desired arylamines in the presence of methylhydrazine through a noncatalytic path. On the basis of the observed high chemoselectivity and yields, and the fast and clean reaction processes, the present catalytic system [Co(κS,N-tfmp2S)3]/MeNHNH2 shows promise for the efficient synthesis of aromatic amines that could find various industrial applications.

Toward Multifunctional Materials Incorporating Stepladder Manganese(III) Inverse-[9-MC-3]-Metallacrowns and Anti-Inflammatory Drugs.

The interaction of Mn(ClO4)2·6H2O with salicylaldoxime (H2sao) 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 [Mn6(O)2(dicl)2(sao)6(CH3OH)6] (1) and [Mn6(O)2(indo)2(sao)6(H2O)4] (2) both characterized as stepladder inverse-9-metallacrown-3 accommodating dicl- or indo- ligands, respectively. When the interaction of MnCl2·4H2O with Nadicl or Hindo is in the absence of H2sao, the mononuclear Mn(II) complexes [Mn(dicl)2(CH3OH)4] (3) and [Mn(indo)2(CH3OH)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.

Alkaline Earth Metal Ion/Dihydroxy-Terephthalate MOFs: Structural Diversity and Unusual Luminescent Properties.

Alkaline earth (group 2) metal ion organic frameworks (AEMOFs) represent an important subcategory of MOFs with interesting structures and physical properties. Five MOFs, namely, [Mg2(H2dhtp)2(µ-H2O)(NMP)4] (AEMOF-2), [Mg2(H2dhtp)1.5(DMAc)4]Cl·DMAc (AEMOF-3), [Ca(H2dhtp)(DMAc)2] (AEMOF-4), [Sr3(H2dhtp)3(DMAc)6]·H2O (AEMOF-5), and [Ba(H2dhtp)(DMAc)] (AEMOF-6) (H4dhtp = 2,5-dihydroxy-terepthalic acid; DMAc = N,N-dimethylacetamide; NMP = N-methylpyrrolidone), are presented herein. The reported MOFs display structural variety with diverse topologies and new structural features. Interestingly, AEMOF-6 is the first example of a Ba(2+)-H2dhtp(2-) MOF, and AEMOF-5 is only the second known Sr(2+)-H2dhtp(2-) MOF. Detailed photoluminescence studies revealed alkaline earth metal ion-dependent fluorescence properties of the materials, with the heavier alkaline earth metal ions exhibiting red-shifted emission with respect to the lighter ions at room temperature. A bathochromic shift of the emission was observed for the MOFs (mostly for AEMOF-3 and AEMOF-4) at 77 K as a result of excited state proton transfer (ESIPT), which involves an intramolecular proton transfer from a hydroxyl to an adjacent carboxylic group of the H2dhtp(2-) ligand. Remarkably, AEMOF-6 displays rare yellow fluorescence at room temperature, which is attractive for solid state lighting applications. To probe whether the alkaline earth metal ions are responsible for the unusual luminescence properties of the reported MOFs, the potential energy surfaces (PESs) of the ground, S0, and lowest energy excited singlet, S1, states of model complexes along the intramolecular proton transfer coordinate were calculated by DFT and TD-DFT methods.

Coordination compounds of cobalt(II) with carboxylate non-steroidal anti-inflammatory drugs: structure and biological profile.

Fourteen cobalt(II) complexes with the non-steroidal anti-inflammatory drugs sodium meclofenamate, tolfenamic acid, mefenamic acid, naproxen, sodium diclofenac, and diflunisal were prepared in the presence or absence of a series of nitrogen-donors (namely imidazole, pyridine, 3-aminopyridine, neocuproine, 2,2'-bipyridine, 1,10-phenanthroline and 2,2'-bipyridylamine) as co-ligands and were characterised by spectroscopic and physicochemical techniques. Single-crystal X-ray crystallography was employed to determine the crystal structure of eight complexes. The biological profile of the complexes was investigated regarding their interaction with serum albumins and DNA, and their antioxidant potency. The interaction of the compounds with calf-thymus DNA takes place via intercalation. The ability of the complexes to cleave pBR322 plasmid DNA at the concentration of 500 µM is rather low. The complexes demonstrated tight and reversible binding to human and bovine serum albumins and the binding site of bovine serum albumin was also examined. In order to assess the antioxidant activity of the compounds, the in vitro scavenging activity towards free radicals, namely 1,1-diphenyl-picrylhydrazyl and 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid), and their ability to reduce H2O2 were studied.

Amine-substituted heterocyclic thioamide Cu(I) and Ag(I) complexes as effective anticancer and antibacterial agents targeting the periplasm of E. coli bacteria.

Metal complexes showing dual activity against cancer and bacterial infections are currently the focus of significant interest for their potential in treating life-threatening diseases. Aiming to investigate the impact of ligand substituents on these bioactivity properties of Group 11 d10 metal complexes, we herein present a series of mononuclear Cu(I) and Ag(I) complexes featuring the bis-NH2-substituted heterocyclic thioamide dap2SH (=4,6-diaminopyrimidine-2-thione), namely [AgCl(dap2SH)(PPh3)2] (1), [CuBr(dap2SH)(PPh3)2] (2), [CuBr(dap2SH)(xantphos)] (3), [Ag(dap2S)(xantphos)] (4), and [Cu(dap2S)(xantphos)] (5) (xantphos = 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene). Complexes were characterized by means of different physicochemical methods (i.e., single crystal X-ray diffraction as well as FTIR, NMR, UV-Vis and fluorescence spectroscopy), and studied in-vitro for their antibacterial and anticancer activity against a variety of bacterial strains and cancer cell lines. Complexes 1-3 effectively inhibited both Gram (+) and Gram (-) bacterial growth, while cellular uptake studies for the most potent complex 1 against E. coli bacteria revealed the accumulation of Ag(I) ions in the periplasm of the bacteria. A high anti-proliferative effect was observed for 1 and 5 against A549, MCF7 and PC3 cancer cell lines, with 1 being capable of inducing apoptosis in A549 cells, as suggested by flow cytometry analysis. DNA interaction studies revealed the capacity of 1 to intercalate between base-pairs of CT DNA. All complexes had a moderate-to-high capacity to scavenge free radicals preventing oxidative stress. Molecular docking calculations, in combination with the experimentally obtained data, provided insights for potential mechanisms of the bioactivity of the complexes.

N-heterocyclic-carbene vs diphosphine auxiliary ligands in thioamidato Cu(I) and Ag(I) complexes towards the development of potent and dual-activity antibacterial and apoptosis-inducing anticancer agents.

Group 11 metal complexes exhibit promising antibacterial and anticancer properties which can be further enhanced by appropriate ligands. Herein, a series of mononuclear thioamidato Cu(I) and Ag(I) complexes bearing either a diphosphine (P^P) or a N-heterocyclic carbene (NHC) auxiliary ligand (L) was synthesized, and the impact of the co-ligand L on the in vitro antibacterial and anticancer properties of their complexes was assessed. All complexes effectively inhibited the growth of various bacterial strains, with the NHC-Cu(I) complex found to be particularly effective against the Gram (+) bacteria (IC50 = 1-4 µg mL-1). Cytotoxicity studies against various human cancer cells revealed their high anticancer potency and the superior activity of the NHC-Ag(I) complex (IC50 = 0.95-4.5 µΜ). Flow cytometric analysis on lung and breast cancer cells treated with the NHC-Ag(I) complex suggested an apoptotic cell-death pathway; molecular docking calculations provided mechanistic insights, proving the capacity of the complex to bind on apoptosis-regulating proteins and affect their functionalities.

Synergy of redox-activity and hemilability in thioamidato cobalt(III) complexes for the chemoselective reduction of nitroarenes to anilines: catalytic and mechanistic investigation.

Reduction of nitro-compounds to amines is one of the most often employed and challenging catalytic processes in the fine and bulk chemical industry. Herein, we present two series of mononuclear homoleptic and heteroleptic Co(III) complexes, i.e., [Co(LNS)3] and [Co(LNS)2L1L2]x+, respectively (x = 0 or 1, LNS = pyrimidine- or pyridine-thioamidato, L1/L2 = thioamidato, phosphine or pyridine), which successfully catalyze the transformation of nitroarenes to anilines by methylhydrazine. The catalytic reaction can be accomplished for a range of electronically and sterically diverse nitroarenes, using mild experimental conditions and low catalyst loadings, resulting in the corresponding anilines in high yields, with high chemoselectivity, and no side-products. Electronic and steric properties of the ligands play pivotal role in the catalytic efficacy of the respective complexes. In particular, complexes bearing ligands of high hemilability/lability and being capable of stabilizing lower metal oxidation-states exhibit the highest catalytic activity. Mechanistic investigations suggest the participation of the Co(III) complexes in two parallel reaction pathways: (a) coordination-induced activation of methylhydrazine and (b) reduction of nitroarenes to anilines by methylhydrazine, through the formation of Co(I) and Co-hydride intermediates.

Erbium(III) coordination compounds with substituted salicylaldehydes: Characterization and biological profile.

Five erbium(III) complexes with salicylaldehyde (saloH for 1), and mono- (5-X-saloH; X = NO2 and Me for 2 and 3, respectively) or di-substituted salicylaldehydes (3,5-diX-saloH; X = Cl and Br for 4 and 5, respectively) were synthesized and characterized by physicochemical and spectroscopic techniques and single-crystal X-ray crystallography. All five complexes have the general formula [Er(deprotonated salicylaldehyde)3(MeOH)(H2O)]. The structure of complexes [Er(3,5-diCl-salo)3(MeOH)(H2O)]·1.5MeOH (complex 4) and [Er(3,5-diBr-salo)3(MeOH)(H2O)]·1.75MeOH (complex 5) were verified by single-crystal X-ray crystallography. The evaluation of antioxidant activity of the complexes was focused on their ability to scavenge 1,1-diphenyl-picrylhydrazyl and 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) free radicals and to reduce H2O2. The interaction of the complexes with calf-thymus DNA was investigated by UV-vis spectroscopy, viscosity measurements and via competitive studies with ethidium bromide in order to evaluate the possible DNA-binding mode and to determine the corresponding DNA-binding constants. The affinity of the complexes for bovine and human serum albumins was explored by fluorescence emission spectroscopy and the corresponding binding constants were determined.

Copper(II) complexes with 3,5-dihalogeno-salicylaldehydes: Synthesis, structure and interaction with DNA and albumins.

Eight copper(II) complexes of 3,5-dichloro-salicyladehyde or 3,5-dibromo-salicyladehyde (3,5-diX-saloH, X = Br or Cl) were synthesized in the absence or presence of a N,N'-donor co-ligand such as 2,2'-bipyridylamine, 1,10-phenanthroline, or 2,2'-bipyridine. The resultant compounds were formulated as [Cu(3,5-diX-salo)2(MeOH)2] (1-2) and [Cu(3,5-diX-salo)(N,N'-donor)Cl] (3-8) and were characterized by diverse techniques. The crystal structures of three complexes were determined by single-crystal X-ray crystallography. Diverse techniques were employed in order to investigate the interaction of the complexes with calf-thymus DNA which showed intercalation as the most possible mode of their interaction. The affinity of the complexes for bovine serum albumin and human serum albumin was evaluated by fluorescence emission spectroscopy in order to calculate the binding constants which suggested a tight and reversible binding. SYNOPSIS: A series of copper(II) complexes with 3,5-dihalogen-substituted salicylaldehydes as ligands were isolated and characterized. In vitro biological studies showed the intercalation of the compounds with calf-thymus DNA and their tight and reversible binding with serum albumins.

Neutral and cationic nickel(II) complexes with substituted salicylaldehydes: Characterization, antibacterial activity, and interaction with biomacromolecules.

Four neutral and six cationic nickel(II) complexes of the substituted salicylaldehydes (X-diCl-saloH), namely 3,5-dichloro-salicylaldehyde (3,5-diCl-saloH) and 5-fluoro-salicylaldehyde (5-F-saloH), were synthesized in the absence or presence of the N,N'-donors 1,10-phenanthroline (phen), 2,9-dimethyl-1,10-phenanthroline (neoc), or 2,2'-bipyridylamine (bipyam) as co-ligands and were characterized by various techniques. The obtained complexes bear the general formulas [Ni(X-salo)2(H2O)2], [Ni(3,5-diCl-salo)2(neoc/phen)] and [Ni(X-salo)(N,N'-donor)2](PF6). The crystal structures of three complexes were determined by single-crystal X-ray crystallography revealing a bidentate coordination of the salicylaldehydes. The interaction of the compounds with calf-thymus DNA was studied by diverse techniques which revealed an intercalative interaction for the neutral complexes [Ni(X-salo)2(H2O)2] and [Ni(3,5-diCl-salo)2(neoc/phen)]and the co-existence of electrostatic interactions for the cationic complexes [Ni(X-salo)(N,N'-donor)2](PF6). The compounds bind tightly and reversibly to serum albumins. The antibacterial activity of the compounds was investigated against Staphylococcus aureus ATCC 6538, Bacillus subtilis ATCC 6633, Escherichia coli NCTC 29,212 and Xanthomonas campestris ATCC 1395 and the complexes bearing neoc as co-ligand proved the most potent.

Possible implementation of salicylate anions in lead detoxification.

The water-soluble coordination polymer of formula {[Pb(Sal)2(H2O)]n} (SaLead), was obtained from the reaction between Pb(NO3)2 and the potassium salt of salicylic acid (SalH), an anti-inflammatory drug, which is also use as food preservation, in cosmetics etc. The compound was characterized by melting point, Attenuated Total Reflectance-Fourier Transform Infra-Red (ATR-FTIR) spectroscopy and X-ray diffraction crystallography (XRD) in solid state and in solution by Ultra Violet (UV) and 1H NMR spectroscopies. The binding affinity of SalK to Pb(II) ions towards SaLead was determined in order to examine its possible implementation in lead detoxification. The in vitro non-toxic behaviour of SalK and its complex SaLead was evaluated against normal human fetal lung fibroblast cells (MRC-5). The corresponding IC50 values are 260 ± 13 and > 1600 µM respectively. The non-genotoxic in vitro activity of SaLead was confirmed with the micronucleus (MN) assay, while its in vivo non-toxicity behaviour was evaluated with Allium cepa and Artemia salina assays.

Transition metal(II) complexes with the non-steroidal anti-inflammatory drug oxaprozin: Characterization and biological profile.

A series of copper(II), nickel(II) and cobalt(II) complexes with the non-steroidal anti-inflammatory drug oxaprozin (Hoxa) have been synthesized and characterized by diverse techniques. The crystal structures of two copper(II) complexes, namely the dinuclear complex [Cu2(oxa)4(DMF)2] (1) and the polymeric complex {[Cu2(oxa)4]·2MeOH·0.5MeOH}2 (12) were determined by single-crystal X-ray diffraction studies. In order to evaluate in vitro the antioxidant activity of the resultant complexes, their scavenging ability towards 1,1-diphenyl-picrylhydrazyl (DPPH), hydroxyl and 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radicals was investigated revealing their high effectiveness against these radicals. The binding of the complexes to bovine serum albumin and human serum albumin was examined and the corresponding determined albumin-binding constants showed a tight and reversible interaction. The interaction of the complexes with calf-thymus DNA was monitored by diverse techniques including UV-vis spectroscopy, cyclic voltammetry, DNA-viscosity measurements and competitive studies with ethidium bromide. Intercalation may be proposed as the most possible DNA-interaction mode of the complexes.

New Apoptosis Inducers Containing Anti-inflammatory Drugs and Pnictogen Derivatives: A New Strategy in the Development of Mitochondrial Targeting Chemotherapeutics.

{[Ag8(Mef)8(µ2-S,O-DMSO)2(µ2-O-DMSO)2(O-DMSO)8]·2(H2O)} (1), [Ag(Mef)(tpP)2] (2), [Ag(Mef)(tpAs)3] (3), and {2 [Ag(Mef)(tpSb)3] (DMSO)} (4) were obtained by the conjugation of mefenamic acid (MefH), a nonsteroidal anti-inflammatory drug (NSAID), with a mitochondriotropic derivative of pnictogen tpE (tp = triphenyl group; E = P, As, and Sb) through silver(I). Their hydrophilicity was adjusted by their dispersion into sodium lauryl sulfate (SLS), forming SLS@1-4. 1-4 and SLS@1-4 were characterized by their spectral data and X-ray crystallography. They inhibit the proliferation of human breast adenocarcinoma cells MCF-7 (hormone-dependent (HD)) and MDA-MB-231 (hormone-independent (HI)). X-ray fluorescence reveals the Ag cellular uptake. The in vitro and in vivo nongenotoxicity was confirmed with micronucleus (MN), Artemia salina, and Allium cepa assays. Their mechanism of action was studied by cell morphology, DNA fragmentation, acridine orange/ethidium bromide (AO/EB) staining, cell cycle arrest, mitochondrial membrane permeabilization tests, DNA binding affinity, and LOX inhibitory activity and was rationalized by regression analysis.

Manganese(II) complexes with 5-nitro-2-hydroxy-benzaldehyde or substituted 2-hydroxy-phenones: Structure and interaction with bovine serum albumin and calf-thymus DNA.

A series of Mn(II) complexes of 5-nitro-salicyladehyde or substituted 2-hydroxy-phenones (HL) were synthesized in the absence or presence of a N,N'-donor co-ligand such as 2,2'-bipyridine, 1,10-phenanthroline, or 2,2'-bipyridylamine. The resultant coordination compounds were formulated as [Mn(L)2(CH3OH)2] (1-3) and [Mn(L)2(N,N'-donor)] (4-14), respectively, and characterized by diverse techniques. The crystal structures of three complexes were determined by single-crystal X-ray crystallography. Diverse techniques were employed to study the interaction of the complexes with calf-thymus DNA and showed intercalation as the most possible mode of their tight interaction. The affinity of the complexes for bovine serum albumin was investigated by fluorescence emission spectroscopy in order to calculate the binding constants which suggested a tight and reversible binding.

Zinc(II) complexes of 3-bromo-5-chloro-salicylaldehyde: characterization and biological activity.

Five neutral zinc(II) complexes of 3-bromo-5-chloro-salicylaldehyde (3-Br-5-Cl-saloH) were synthesized in the absence or presence of the nitrogen-donor co-ligands 2,2'-bipyridine (bipy), 1,10-phenanthroline (phen), 2,9-dimethyl-1,10-phenanthroline (neoc), or 2,2'-bipyridylamine (bipyam) and were characterized by various techniques. The obtained complexes were [Zn(3-Br-5-Cl-salo)2(H2O)2] (1), [Zn(3-Br-5-Cl-salo)2(bipy)] (2), [Zn(3-Br-5-Cl-salo)2(phen)] (3), [Zn(3-Br-5-Cl-salo)2(neoc)] (4) and [Zn(3-Br-5-Cl-salo)2(bipyam)] (5). The crystal structures of complexes 1 and 3 were determined by single-crystal X-ray crystallography. The interaction of the compounds with calf-thymus DNA takes place via intercalation. The compounds may moderately cleave pBR322 plasmid DNA at a concentration of 500 µM. The compounds may bind tightly and reversibly to serum albumins. The antioxidant activity of the compounds was examined towards 1,1-diphenyl-picrylhydrazyl and 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radicals and H2O2. The antimicrobial potency of the compounds was investigated against Staphylococcus aureus ATCC 6538, Bacillus subtilis ATCC 6633, Escherichia coli NCTC 29212 and Xanthomonas campestris ATCC 1395.

Palladium(II) Complexes of Substituted Salicylaldehydes: Synthesis, Characterization and Investigation of Their Biological Profile.

Five palladium(II) complexes of substituted salicylaldehydes (X-saloH, X = 4-Et2N (for 1), 3,5-diBr (for 2), 3,5-diCl (for 3), 5-F (for 4) or 4-OMe (for 5)) bearing the general formula [Pd(X-salo)2] were synthesized and structurally characterized. The crystal structure of complex [Pd(4-Et2N-salo)2] was determined by single-crystal X-ray crystallography. The complexes can scavenge 1,1-diphenyl-picrylhydrazyl and 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radicals and reduce H2O2. They are active against two Gram-positive (Staphylococcus aureus and Bacillus subtilis) and two Gram-negative (Escherichia coli and Xanthomonas campestris) bacterial strains. The complexes interact strongly with calf-thymus DNA via intercalation, as deduced by diverse techniques and via the determination of their binding constants. Complexes interact reversibly with bovine and human serum albumin. Complementary insights into their possible mechanisms of bioactivity at the molecular level were provided by molecular docking calculations, exploring in silico their ability to bind to calf-thymus DNA, Escherichia coli and Staphylococcus aureus DNA-gyrase, 5-lipoxygenase, and membrane transport lipid protein 5-lipoxygenase-activating protein, contributing to the understanding of the role complexes 1-5 can play both as antioxidant and antibacterial agents. Furthermore, in silico predictive tools have been employed to study the chemical reactivity, molecular properties and drug-likeness of the complexes, and also the drug-induced changes of gene expression profile (as protein- and mRNA-based prediction results), the sites of metabolism, the substrate/metabolite specificity, the cytotoxicity for cancer and non-cancer cell lines, the acute rat toxicity, the rodent organ-specific carcinogenicity, the anti-target interaction profiles, the environmental ecotoxicity, and finally the activity spectra profile of the compounds.