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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Transition metal(II) complexes of halogenated derivatives of (E)-4-(2-(pyridin-2-ylmethylene)hydrazinyl)quinazoline: structure, antioxidant activity, DNA-binding DNA photocleavage, interaction with albumin and in silico studies.

Two novel halogenated (Br- and F-) quinazoline derivatives, namely [(E)-4-(2-((6-bromopyridin-2-yl)methylene)hydrazinyl)quinazoline] (L1) and [(E)-4-(2-((3-fluoropyridin-2-yl)methylene)hydrazinyl) quinazoline] (L2), were synthesized and characterized. Their interaction with a series of metal(II) ions (= Mn(II), Ni(II), Cu(II), Zn(II) and Cd(II)) resulted in the formation of six mononuclear complexes characterized by spectroscopic techniques and single-crystal X-ray crystallography. The complexes bear the formulae [Ni(L1)2](NO3)2 (1), [Zn(L2)2](NO3)(PF6) (2), [Cd(L2)(H2O)(CH3OH)(NO3)](NO3) (3), [Cu(L2)Cl2] (4), [Ni(L2)2](NO3)2 (5) and [Mn(L2)(CH3OH)(Cl)2] (6). The biological activity of the compounds was further evaluated in vitro regarding their interaction with calf-thymus DNA, their cleavage ability towards supercoiled circular pBR322 plasmid DNA in the absence or presence of irradiation at various wavelengths (UVA, UVB and visible light), their affinity to bovine serum albumin and their ability to scavenge 1,1-diphenyl-picrylhydrazyl and 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) radicals and to reduce H2O2. In silico molecular docking calculations were employed to study the behavior of the complexes towards calf-thymus DNA and bovine serum albumin.

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.

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.

Silver(I) complexes bearing heterocyclic thioamide ligands with NH2 and CF3 substituents: effect of ligand group substitution on antibacterial and anticancer properties.

In recent years, there has been an increasing interest in the study of Ag(I) coordination compounds as potent antibacterial and anticancer agents. Herein, a series of Ag(I) complexes bearing phosphines and heterocyclic thioamide ligands with highly electronegative NH2- and CF3-group substituents, i.e. [AgCl(atdztH)(xantphos)] (1), [Ag(µ-atdztH)(DPEphos)]2(NO3)2 (2), [Ag(atdzt)(PPh3)3] (3), [Ag(µ-atdzt)(DPEphos)]2 (4), and [Ag(µ-mtft)(DPEphos)]2 (5), where atdztH = 5-amino-1,3,4-thiadiazole-2-thiol, mtftH = 4-methyl-5-(trifluoromethyl)-1,2,4-triazol-3-thiol, xantphos = 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene, and DPEphos = bis(2-diphenylphosphino-phenyl)ether, were synthesized, and their in vitro antibacterial and anticancer properties were evaluated. Complexes 1-4 bearing the NH2-substituted thioamide exhibited moderate-to-high activity against S. aureus, B. subtilis, B. cereus and E. coli bacterial strains. A high antiproliferative activity was also observed for 1-3 against SKOV-3, Hup-T3, DMS114 and PC3 cancer cell lines (IC50 = 4.0-11.7 µM), as well as some degree of selectivity against MRC-5 normal cells. Interestingly, 5 bearing the CF3-substituted thioamide is completely inactive in all bioactivity studies. Binding of 1-3 to drug-carrier proteins BSA and HSA is reasonably strong for their uptake and subsequent release to possible target sites. The three complexes show a significant in vitro antioxidant ability for scavenging free radicals, suggesting likely implication of this property in the mechanism of their bioactivity, but a low potential to destroy the double-strand structure of CT-DNA by intercalation. Complementary insights into possible bioactivity mechanisms were provided by molecular docking calculations, exploring the ability of complexes to bind to bacterial DNA gyrase, and to the overexpressed in the aforementioned cancer cells Fibroblast Growth Factor Receptor 1, affecting their 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.

Hydrophilic bis-MPA hyperbranched dendritic scaffolds as nanocarriers of a fully characterized flavonoid morin-Zn(II) complex for anticancer applications.

In this work the first crystallographically characterized complex of the bioactive flavonoid morin with the Zn(II) ion is presented along with its complete physico-chemical characterization. In view of the antioxidant activity of morin and its toxicity against respiratory tract cancers, the encapsulation of the complex in the hydrophilic bis(methylol)propionic acid hyperbranched dendritic scaffolds (bis-MPA HDSs) was effected. The produced nano-formulations were characterized with physico-chemical and electron microscopy techniques, and biologically evaluated for their antioxidant and anticancer activity against human A549 and H520 lung cancer cells, as well as healthy human MRC-5 lung fibroblasts. The obtained results demonstrate that encapsulation increases the solubility, and thus bioavailability, of the complex in physiological media and enhances anticancer action. They also highlight the importance of the non-toxic bis-MPA HDSs as nanocarriers of bioactive flavonoid metal complexes for anticancer therapeutic applications.

Biocompatible silver(I) complexes with heterocyclic thioamide ligands for selective killing of cancer cells and high antimicrobial activity - A combined in vitro and in silico study.

A series of heteroleptic Ag(I) complexes bearing 4,6-dimethyl-2-pyrimidinethiol (dmp2SH), i.e., [AgCl(dmp2SH)(PPh3)2] (1), [Ag(dmp2SH)(PPh3)2]NO3 (2), [Ag(dmp2SΗ)(xantphos)]NO3 (3), [Ag(µ-dmp2S)(PPh3)]2 (4), [Ag(dmp2S)(xantphos)] (5), [Ag(µ-dmp2S)(DPEphos)]2 (6) (xantphos = 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene and DPEPhos = bis[(2-diphenylphosphino)phenyl]ether) were synthesized. The complexes display systematic variation of particular structural characteristics which were proved to have a significant impact on their in vitro cytotoxicity and antimicrobial properties. A moderate-to-high potential for bacteria growth inhibition was observed for all complexes, with 2, 3 and 5 being particularly effective against Gram-(+) bacteria (IC50 = 1.6-4.5 µM). The three complexes exhibit high in vitro cytotoxicity against HeLa and MCF-7 cancer cells (IC50 = 0.32-3.00 µΜ), suggesting the importance of coordination unsaturation and cationic charge for effective bioactivity. A very low cytotoxicity against HDFa normal cells was observed, revealing a high degree of selectivity (selectivity index ~10) and, hence, biocompatibility. Fluorescence microscopy using 2 showed effective targeting on the membrane of the HeLa cancer cells, subsequently inducing cell death. Binding of the complexes to serum albumin proteins is reasonably strong for potential uptake and subsequent release to target sites. A moderate in vitro antioxidant capacity for free radicals scavenging was observed and a low potential to destroy the double-strand structure of calf-thymus DNA by intercalation, suggesting likely implication of these properties in the bioactivity mechanisms of these complexes. Further insight into possible mechanisms of bioactivity was obtained by molecular modeling calculations, by exploring their ability to act as potential inhibitors of DNA-gyrase, human estrogen receptor alpha, human cyclin-dependent kinase 6, and human papillomavirus E6 oncoprotein.

Structure and in vitro and in silico biological activity of zinc(II) complexes with 3,5-dichloro-salicylaldehyde.

Five Zn(II) complexes with 3,5-dichloro-salicylaldehyde (3,5-diCl-saloH) in the absence or presence of N,N'-donor co-ligands (2,2'-bipyridine, 1,10-phenanthroline, 2,9-dimethyl-1,10-phenanthroline, or 2,2'-bipyridylamine) were synthesized and formulated as [Zn(3,5-diCl-salo)2(CH3OH)2] (1) and [Zn(3,5-diCl-salo)2(N,N'-donor)] (2-5), respectively, and characterized by diverse techniques. The crystal structures of four complexes were determined by single-crystal X-ray crystallography. The ability of the compounds to scavenge 1,1-diphenyl-picrylhydrazyl and 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radicals and to reduce H2O2 was investigated. In addition, their antimicrobial profile against two Gram-positive and two Gram-negative bacterial strains were investigated. The affinity of the complexes for calf-thymus DNA was examined by diverse techniques, and the DNA-binding constants of the complexes were determined. The cleavage ability of the complexes towards supercoiled circular pBR322 plasmid DNA was examined by agarose gel electrophoretic experiments. The binding of the complexes with bovine and human serum albumins was investigated in order to determine the corresponding binding constants and the binding subdomain. In order to explain the described in vitro activity of the compounds and possibly establish a rational approach in the mechanism of action, molecular docking studies were adopted on the crystal structure of E. coli and S. aureus DNA-gyrase, 5-lipoxygenase, and 5-lipoxygenase-activating protein.