Unraveling Multicopper [Cu3] and [Cu6] Clusters with Rare µ3-Sulfato and Linear µ2-Oxido-Bridges as Potent Antibiofilm Agents against Multidrug-Resistant Staphylococcus aureus.

In this research article, two multicopper [Cu3] and [Cu6] clusters, [Cu3(cpdp)(µ3-SO4)(Cl)(H2O)2]·3H2O (1) and [Cu6(cpdp)2(µ2-O)(Cl)2(H2O)4]·2Cl (2) (H3cpdp = N,N'-bis[2-carboxybenzomethyl]-N,N'-bis[2-pyridylmethyl]-1,3-diaminopropan-2-ol), have been explored as potent antibacterial and antibiofilm agents. Their molecular structures have been determined by a single-crystal X-ray diffraction study, and the compositions have been established by thermal and elemental analyses, including electrospray ionization mass spectrometry. Structural analysis shows that the metallic core of 1 is composed of a trinuclear [Cu3] assembly encapsulating a µ3-SO42- group, whereas the structure of 2 represents a hexanuclear [Cu6] assembly in which two trinuclear [Cu3] motifs are exclusively bridged by a linear µ2-O2- group. The most striking feature of the structure of 2 is the occurrence of an unusual linear oxido-bridge, with the Cu3-O6-Cu3' bridging angle being 180.00°. Whereas 1 can be viewed as an example of a copper(II)-based compound displaying a rare µ3:η1:η1:η1 bridging mode of the SO42- group, 2 is the first example of any copper(II)-based compound showing an unsupported linear Cu-O-Cu oxido-bridge. Employing variable-temperature SQUID magnetometry, the magnetic susceptibility data were measured and analyzed exemplarily for 1 in the temperature range of 2-300 K, revealing the occurrence of antiferromagnetic interactions among the paramagnetic copper centers. Both 1 and 2 exhibited potent antibacterial and antibiofilm activities against methicillin-resistant Staphylococcus aureus (MRSA BAA1717) and the clinically isolated culture of methicillin-resistant S. aureus (MRSA CI1). The mechanism of antibacterial and antibiofilm activities of these multicopper clusters was investigated by analyzing and determining the intracellular reactive oxygen species (ROS) generation, lipid peroxidation, microscopic observation of cell membrane disruption, membrane potential, and leakage of cellular components. Additionally, 1 and 2 showed a synergistic effect with commercially available antibiotics such as vancomycin with enhanced antibacterial activity. However, 1 possesses higher antibacterial, antibiofilm, and antivirulence actions, making it a potent therapeutic agent against both MRSA BAA1717 and MRSA CI1 strains.

Morroniside interaction with poly (ADP-ribose) polymerase accentuates metabolic mitigation of alloxan-induced genotoxicity and hyperglycaemia: a molecular docking based in vitro and in vivo experimental therapeutic insight.

The present study tends to evaluate the possible potential of bio-active Morroniside (MOR), against alloxan (ALX)-induced genotoxicity and hyperglycaemia. In silico prediction revealed the interaction of MOR with Poly (ADP-ribose) polymerase (PARP) protein which corroborated well with experimental in vitro L6 cell line and in vivo mice models. Data revealed the efficacy of MOR in the selective activation of PARP protein and modulating other stress proteins NF-κB, and TNF-α to initiate protective potential against ALX-induced genotoxicity and hyperglycaemia. Further, the strong interaction of MOR with CT-DNA (calf thymus DNA) analyzed through CD spectroscopy, UV-Vis study and ITC data revealed the concerted action of bio-factors involved in inhibiting chromosomal aberration and micronucleus formation associated with DNA damage. Finally, MOR does not play any role in microbial growth inhibition which often occurs due to hyperglycemic dysbiosis. Thus, from the overall findings, we may conclude that MOR could be a potential drug candidate for the therapeutic management of induced-hyperglycaemia and genotoxicity.Communicated by Ramaswamy H. Sarma.

Design, Synthesis and Evaluation of a Series of Zinc(II) Complexes of Anthracene-Affixed Multifunctional Organic Assembly as Potential Antibacterial and Antibiofilm Agents against Methicillin-Resistant Staphylococcus aureus.

A novel class of zinc(II)-based metal complexes, i.e., [Zn2(acdp)(µ-Cl)]·2H2O (1), [Zn2(acdp)(µ-NO3)]·2H2O (2), and [Zn2(acdp)(µ-O2CCF3)]·2H2O (3) (Cl- = chloride; NO3- = nitrate; CF3CO2- = trifluoroacetate) of anthracene-affixed multifunctional organic assembly, H3acdp (H3acdp = N,N'-bis[anthracene-2-ylmethyl]-N,N'-bis[carboxymethyl]-1,3-diaminopropan-2-ol), have emerged as promising antibacterial and antibiofilm agents in the domain of medicinal chemistry. Accordingly, complexes 1-3 were synthesized by utilizing H3acdp in combination with ZnCl2, Zn(NO3)2·6H2O, and Zn(CF3CO2)2·H2O respectively, in the presence of NaOH at ambient temperature. The complexation between H3acdp and Zn2+ was delineated by a combined approach of spectrophotometric and spectrofluorometric titration studies. The stoichiometry of acdp3-/Zn2+ in all three complexes is observed to be 1:2, as confirmed by spectrophotometric/spectrofluorometric titration data. Elemental analysis (C, H, N, Zn), molar conductance, FTIR, UV-vis, and thermoanalytical (TGA/DTA) data were effectively used to characterize these complexes. Besides, the structures of 1-3 were established by density functional theory (DFT) calculation using B3LYP/6-311G, specifying a self-assembled compact geometry with average Zn···Zn separation of 3.4629 Å. All three zinc complexes exhibited significantly high antibacterial and antibiofilm activity against methicillin-resistant Staphylococcus aureus (MRSA BAA1717). However, complex 1 showed a more recognizable activity than 2 and 3, with minimum inhibitory concentration (MIC) values of 200, 350, and 450 µg/mL, respectively. The antimicrobial activity was tested by employing the minimum inhibitory concentration (MIC) and time-kill assay. The crystal violet (CV) assay and microscopic study were performed to examine the antibiofilm activity. As observed, complexes 1-3 had an effect on the production of extracellular polymeric substance (EPS), biofilm cell-viability, and other virulence factors such as staphyloxanthin and hemolysin production, autoaggregation ability, and microbial cell-surface hydrophobicity. Reactive oxygen species (ROS) generated due to inhibition of staphyloxanthin production in response to 1-3 were also analyzed. Moreover, complexes 1-3 showed an ability to damage the bacterial cell membrane due to accumulation of ROS resulting in DNA leakage. In addition, complexes 1-3 displayed a synergistic/additive activity with a commercially available antibiotic drug, vancomycin, with enhanced antibacterial activity. On the whole, our investigation disclosed that complex 1 could be a promising drug lead and attract much attention to medicinal chemists compared to 2 and 3 from therapeutic aspects.

Exploring a new family of designer copper(II) complexes of anthracene-appended polyfunctional organic assembly displaying potential anticancer activity via cytochrome c mediated mitochondrial apoptotic pathway.

The present article describes the systematic study on design and synthesis, physicochemical properties and spectroscopic features, and potential anticancer activities of a family of novel copper(II)-based designer metal complexes [Cu2(acdp)(µ-Cl)(H2O)2] (1), [Cu2(acdp)(µ-NO3)(H2O)2] (2) and [Cu2(acdp)(µ-O2CCF3)(H2O)2] (3) of anthracene-appended polyfunctional organic assembly, H3acdp (H3acdp = N,N'-bis[anthracene-2-ylmethyl]-N,N'-bis[carboxymethyl]-1,3-diaminopropan-2-ol). Synthesis of 1-3 was accomplished under facile experimental conditions, preserving their overall integrity in solution. The incorporation of polycyclic anthracene skeleton within the backbone of organic assembly increases lipophilicity of resulting complexes, thereby dictating the degree of cellular uptake with improved biological activity. Complexes 1-3 were characterized by elemental analysis, molar conductance, FTIR, UV-Vis absorption/fluorescence emission titration spectroscopy, PXRD and TGA/DTA studies, including DFT calculations. The cellular cytotoxicity of 1-3 when studied in HepG2 cancer cell line showed substantial cytotoxic effects, whereas no such cytotoxicity was observed when exposed to normal L6 skeletal muscle cell line. Thereafter, the signaling factors involved in the process of cytotoxicity in HepG2 cancer cells were investigated. Alteration of cytochrome c and Bcl-2 protein expression levels along with modulation of mitochondrial membrane potential (MMP) in the presence of 1-3, strongly suggested the possibility of activating mitochondria-mediated apoptotic pathway involved in halting the cancer cell propagation. However, when a comparative assessment on their bio-efficacies was made, 1 showed higher cytotoxicity, nuclear condensation, DNA binding and damage, ROS generation and lower rate of cell proliferation compared to 2 and 3 in HepG2 cell line, indicating that the anticancer activity of 1 is significantly higher than that of 2 and 3.

Ancillary-Ligand-Assisted Variation in Nuclearities Leading to the Formation of Di-, Tri-, and Tetranuclear Copper(II) Complexes with Multifaceted Carboxylate Coordination Chemistry.

The self-assembly of a carboxylate-based dinucleating ligand, N,N'-bis[2-carboxybenzomethyl]-N,N'-bis[2-pyridylmethyl]-1,3-diaminopropan-2-ol (H3cpdp), and copper(II) ions in the presence of various exogenous ancillary ligands results in the formation of the new dinuclear complex [Cu2(cpdp)(µ-Hisophth)]4·2H2isophth·21H2O (1), trinuclear complex [Cu3(Hcpdp)(Cl)4] (2), and tetranuclear complex [Cu4(cpdp)(µ-Hphth)(µ4-phth)(piconol)(Cl)2]·3H2O (3) (H2phth = phthalic acid; H2isophth = isophthalic acid; piconol = 2-pyridinemethanol; Cl- = chloride). In methanol-water, the reaction of H3cpdp with CuCl2·2H2O at room temperature leads to the formation of 2. On the other hand, 1 and 3 have been obtained by carrying out the reaction of H3cpdp with CuCl2·2H2O/m-C6H4(CO2Na)2 and CuCl2·2H2O/o-C6H4(CO2Na)2/piconol, respectively, in methanol-water in the presence of NaOH at ambient temperature. All three complexes have been characterized by elemental analysis, molar electrical conductivity and magnetic moment measurements, FTIR, UV-vis spectroscopy, and PXRD, including single-crystal X-ray structural analyses. The molecular structure of 1 is based on a µ-alkoxide and µ-isophthalate-bridged dimeric [Cu2] core; the structure of 2 represents a trimeric [Cu3] core in which a µ-alcohol-bridged dinuclear [Cu2] unit is exclusively coupled with a [CuCl2] species by two µ:η1:η1-syn-anti carboxylate groups forming a triangular motif; the structure of 3 embodies a tetrameric [Cu4] core, with two copper(II) ions in a distorted-octahedral coordination environment, one copper(II) ion in a distorted-trigonal-bipyramidal coordination environment, and the other copper(II) ion in a square-planar coordination environment. In fact, 2 and 3 represent rare examples of copper(II)-based multinuclear complexes showing outstanding features of rich coordination chemistry: (i) using a symmetrical dinucleating ligand, trinuclear complex 2 is generated with four- and five-coordination environments around copper(II) ions; (ii) the unsymmetrical tetranuclear complex 3 is obtained by using the same ligand with four-, five- and six-coordination environments around copper(II) ions; (iii) tetracopper(II) complex 3 shows four different bridging modes of carboxylate groups simultaneously such as µ:η2, µ:η1:η1, µ3:η2:η1:η1, and µ4:η1:η1:η1:η1, the µ4:η1:η1:η1:η1 mode of phthalate being unprecedented. The formation of these [Cu2], [Cu3], and [Cu4] complexes can be controlled by changing the exogenous ancillary ligands and pH of the reaction solutions, thus allowing an effective tuning of the self-assembly. The magnetic susceptibility measurements suggest that the copper centers in all three complexes are antiferromagnetically coupled. The thermal properties of 1-3 have been investigated by thermogravimetric and differential thermal analytical (TGA and DTA) techniques, indicating that the decomposition of all three complexes proceeds via multistep processes.

Poly lactide-co-glycolide encapsulated nano-curcumin promoting antagonistic interactions between HSP 90 and XRCC1 proteins to prevent cypermethrin-induced toxicity: An in silico predicted in vitro and in vivo approach.

The present study describes the preparation and characterization of poly-lactide-co-glycolide encapsulated nano-curcumin (NCUR) drug, and its potential efficacy against the pesticide, such as cypermethrin-induced DNA damage and genotoxicity. Cypermethrin, the chosen pesticide, contaminates the aquatic environment after being washed off from the agricultural field to nearby water bodies leading to biomagnification-related perturbation of the ecological balance and overall environmental health by elevating adverse effects on non-target organisms producing toxic metabolites through biotransformation. The physico-chemical properties of NCUR were evaluated by employing the AFM, DLS and UV-Vis techniques. Sustainable release of NCUR, their bio-availability and ability to cross the blood-brain-barrier was assessed in the fish model. The in silico molecular docking study to identify the signalling proteins that interact with phyto-core-compound curcumin (CUR) was undertaken to predict the effectiveness of NCUR to combat pesticide-induced toxicity by modulating p53, PARP, HSP 90 and XRCC1 stress proteins, and other associated parameters in in vivo model using tilapia fish and in vitro model using L6 (mammalian skeletal muscle) cell line. Overall results revealed that negatively charged poly-lactide-co-glycolide (PLGA)-encapsulated NCUR (∼46 nm) showed hyperchromic binding with DNA and modulated the signalling cascades involved in stress and DNA repair mechanisms, corroborating well with the in silico prediction that would pave a new pathway in the arena of chemical and biological sciences to serve mankind.

A Family of [Zn6] Complexes from the Carboxylate-Bridge-Supported Assembly of [Zn2] Building Units: Synthetic, Structural, Spectroscopic, and Systematic Biological Studies.

The three discrete [Zn6] complexes [Na3Zn6(cpdp)3(µ-Bz)3(CH3OH)6][ZnCl4][ZnCl3(H2O)]·3CH3OH·1.5H2O (1), [Na3Zn6(cpdp)3(µ-p-OBz)3(CH3OH)6]·2H2O (2), and [Na3Zn6(cpdp)3(µ-p-NO2Bz)3(CH3OH)6]Cl3·2H2O (3), supported by the carboxylate-based multidentate ligand N,N'-bis[2-carboxybenzomethyl]-N,N'-bis[2-pyridylmethyl]-1,3-diaminopropan-2-ol (H3cpdp), have been successfully synthesized and fully characterized (Bz = benzoate; p-OBz = dianion of p-hydroxybenzoic acid; p-NO2Bz = p-nitrobenzoate). The complexes have been characterized by elemental analysis, FTIR, UV-vis, NMR spectroscopy, PXRD, and thermal analysis, including single-crystal X-ray crystallography of 1 and 2. The molecular architectures of 1-3 are built from the self-assembly of their corresponding [Zn2] units, which are interconnected to the central [Na3(CH3OH)6]3+ core by six endogenous benzoate groups, with each linking one Zn(II) and one Na(I) ion in a µ2:η1:η1-syn-anti bidentate fashion. The composition of the (cpdp3-)3/(Zn2+)6 complexes in 1-3 has been observed to be 1:2, on the basis of the UV-vis titration and NMR spectroscopic results, which is further supported by X-ray crystallography. Systematic biological studies performed with a mice model suggested possible antidiabetic efficacy as well as anticancer activities of the complexes. When complexes 1-3 were administered intraperitoneally in mice, 1 showed a lowering in the blood glucose level, overall maintenance of the pancreatic tissue mass, restriction of DNA damage in pancreatic cells, and retention of lipid droplet (LD) frequency, whereas 2 and 3 showed hepatic tissue mass consistency by inhibiting the DNA damage in hepatic cells, prior to the exposure to a potent diabetic inducer, alloxan (ALX). Similar trends of results were observed in inhibiting the generation of reactive oxygen species (ROS) in the pancreatic and hepatic cells, as examined by spectrofluorometric methods. Thus, 1 seems to be a better compound for overall diabetic management and control, whereas 2 and 3 seem to be promising compounds for designing chemopreventive drugs against hepatic carcinoma.

Phosphatase-like Activity of Tetranuclear Iron(III) and Zinc(II) Complexes.

Three new tetranuclear iron(III) and zinc(II) complexes, [Fe4(cpdp)2(phth)2(OH)2]·8H2O (1), [Fe4(cpdp)2(terephth)2(OH)2] (2), and [Zn4(Hcpdp)2(suc)]Br2·12H2O (3), have been synthesized as models for the active site of phosphoester hydrolases by utilizing a polydentate ligand, N, N'-bis[2-carboxybenzomethyl]- N, N'-bis[2-pyridylmethyl]-1,3-diaminopropan-2-ol (H3cpdp) in combination with exogeneous phthalate (phth), terephthalate (terephth), and succinate (suc). Single crystal X-ray analyses reveal that the metallic core of complex 1 consists of four distorted octahedral iron(III) ions with average intraligand Fe---Fe separation of 3.656(2) Å, while the structure 3 represents a tetranuclear metallic core containing four distorted trigonal bipyramidal zinc(II) ions with average intraligand Zn---Zn separation of 3.472(2) Å. The molecular structure of complex 2 has been optimized by the DFT method which shows that its core arrangement is similar to that of 1. Complex 1 has a very interesting centrosymmetric structure that includes two crystallographically equivalent [Fe2(cpdp)]3+ dinuclear units, connected together by a pair of syn-syn bridging phthalates and a pair of bridging hydroxides to generate a "dimer of dimers" structural motif. In complex 3, a succinate group connects two crystallographically equivalent [Zn2(Hcpdp)]2+ dinuclear units in a syn-syn bidentate manner forming a "dimer of dimers" structural design. All three complexes show phosphatase-like activity that has been examined in methanol-water (1:1; v/v) using bis( p-nitrophenyl) phosphate (BNPP) as model substrate by applying the UV-vis spectrophotometric technique. In each case, the kinetic data have been analyzed by the Michaelis-Menten approach. The order of catalytic efficiency for the conversion of substrate to product follows the trend 1 > 2 > 3 with turnover rates ( kcat) of (2.73 ± 0.13) × 10-5 for 1, (1.06 ± 0.07) × 10-5 for 2, and (2.33 ± 0.18) × 10-6 s-1 for 3. These kcat values are comparable to, albeit slightly lower than, the values reported for similar iron(III)- and zinc(II)-based model complexes in the literature. DFT calculations have been carried out to support the proposed mechanism for phosphatase-like activity.

Inorganic Phosphate and Arsenate within New Tetranuclear Copper and Zinc Complexes: Syntheses, Crystal Structures, Magnetic, Electrochemical, and Thermal Studies.

Three, PO4 3-/HPO4 2- and AsO4 3--incorporated, new tetranuclear complexes of copper(II) and zinc(II) ions have been synthesized and fully characterized. In methanol-water, reactions of H3cpdp (H3cpdp = N,N'-Bis[2-carboxybenzomethyl]-N,N'-Bis[2-pyridylmethyl]-1,3-diaminopropan-2-ol) with copper(II) chloride in the presence of either NaOH/Na2HPO4·2H2O or KOH/Na2HAsO4·7H2O lead to the isolation of the tetranuclear complexes Na3[Cu4(cpdp)2(µ4-PO4)](OH)2·14H2O (1) and K2[Cu4(cpdp)2(µ4-AsO4)](OH)·162/3H2O (2), respectively. Similarly, the reaction of H3cpdp with zinc(II) chloride in the presence of NaOH/Na2HPO4·2H2O yields a tetranuclear complex, Na(H3O)2[Zn4(cpdp)2(µ4-HPO4)]Cl3·121/2H2O (3). All complexes are characterized by single-crystal X-ray diffraction and other analytical techniques, such as Fourier transform infrared and UV-vis spectroscopy, thermogravimetric and electrochemical studies. The solid-state molecular framework of each complex contains two monocationic [M2(cpdp)]+ (M = Cu, Zn) units, which are exclusively coordinated to either phosphate/hydrogen phosphate or arsenate groups in a unique mode. All three complexes exhibit a µ4:η1:η1:η1:η1 bridging mode of the PO4 3-/HPO4 2-/AsO4 3- groups, with each bridging among four metal ions. The thermal properties of all three complexes have been investigated by thermogravimetric analysis. Low-temperature magnetic studies of complexes 1 and 2 disclose moderate antiferromagnetic interactions mediated among the copper centers through alkoxide and phosphate/arsenate bridges. Electrochemical studies of complexes 1 and 2 in dimethylformamide using cyclic voltammetry reveal the presence of a fairly assessable one-electron metal-based irreversible reduction and one quasireversible oxidation couple.

Spectroscopic investigation of new water soluble Mn(II)(2) and Mg(II)(2) complexes for the substrate binding models of xylose/glucose isomerases.

In methanol, the reaction of stoichiometric amounts of Mn(OAc)(2)·4H(2)O and the ligand H(3)hpnbpda [H(3)hpnbpda=N,N'-bis(2-pyridylmethyl)-2-hydroxy-1,3-propanediamine-N,N'-diacetic acid] in the presence of NaOH, afforded a new water soluble dinuclear manganese(II) complex, [Mn2(hpnbpda)(µ-OAc)] (1). Similarly, the reaction of Mg(OAc)(2)·4H(2)O and the ligand H3hpnbpda in the presence of NaOH, in methanol, yielded a new water soluble dinuclear magnesium(II) complex, [Mg2(hpnbpda)(µ-OAc)(H2O)2] (2). DFT calculations have been performed for the structural optimization of complexes 1 and 2. The DFT optimized structure of complex 1 shows that two manganese(II) centers are in a distorted square pyramidal geometry, whereas the DFT optimized structure of complex 2 reveals that two magnesium(II) centers adopt a six-coordinate distorted octahedral geometry. To understand the mode of substrate binding and the mechanistic details of the active site metals in xylose/glucose isomerases (XGI), we have investigated the binding interactions of biologically important monosaccharides d-glucose and d-xylose with complexes 1 and 2, in aqueous alkaline solution by a combined approach of FTIR, UV-vis, fluorescence, and (13)C NMR spectroscopic techniques. Fluorescence spectra show the binding-induced gradual decrease in emission of complexes 1 and 2 accompanied by a significant blue shift upon increasing the concentration of sugar substrates. The binding modes of d-glucose and d-xylose with complex 2 are indicated by their characteristic coordination induced shift (CIS) values in (13)C NMR spectra for C1 and C2 carbon atoms.

Synthesis, structure, spectroscopic characterization, and protein binding affinity of new water-soluble hetero- and homometallic tetranuclear [Cu(II)2Zn(II)2] and [Cu(II)4] clusters.

Two new water-soluble hetero- and homometallic tetranuclear clusters, Na4[Cu2Zn2(ccdp)2(µ-OH)2]·CH3OH·6H2O (1) and K3[Cu4(ccdp)2(µ-OH)(µ-OH2)]·14H2O (2), have been synthesized in methanol-water at room temperature by exploiting the flexibility, chelating ability, and bridging potential of a carboxylate-rich dinucleating ligand, N,N'-bis(2-carboxybenzomethyl)-N,N'-bis(carboxymethyl)-1,3 diaminopropan-2-ol (H5ccdp). Complex 1 is obtained through the self-assembly of two monoanionic [CuZn(ccdp)](-)fragments, which are, in turn, exclusively bridged by two µ-OH(-)groups. Similarly, complex 2 is formed through the self-assembly of two monoanionic [Cu2(ccdp)](-) species exclusively bridged by one µ-OH(-) and one µ-OH2 groups. Complexes 1 and 2 are fully characterized in the solid state as well as in solution using various analytical techniques including a single-crystal X-ray diffraction study. The X-ray crystal structure of 1 reveals that two Cu(II) centers are in a distorted square-pyramidal geometry, whereas two Zn(II) centers are in a distorted trigonal-bipyramidal geometry. The solid-state structure of 2 contains two dinuclear [Cu2(ccdp)](-) units having one Cu(II) center in a distorted square-pyramidal geometry and another Cu(II) center in a distorted trigonal-bipyramidal geometry within each dinuclear unit. In the powder state, the high-field EPR spectrum of complex 1 indicates that two Cu(II) ions are not spin-coupled, whereas that of complex 2 exhibits at least one noninteracting Cu(II) center coordinated to a nitrogen atom of the ligand. Both complexes are investigated for their binding affinity with the protein bovine serum albumin (BSA) in an aqueous medium at pH ~7.2 using fluorescence spectroscopy. Synchronous fluorescence spectra clearly reveal that complexes 1 and 2 bind to the active sites in the protein, indicating that the effect is more pronounced toward tyrosine than tryptophan. Density functional theory calculations have been carried to find the Fukui functions at the metal sites in complexes 1 and 2 to predict the possible metal centers involved in the binding process with BSA protein.

New dinuclear cobalt(II) and zinc(II) complexes of a carboxylate-rich dinucleating ligand: synthesis, structure, spectroscopic characterization, and their interactions with sugars.

Sugar-metal ion interactions in aqueous medium are involved in many biochemical processes such as the transport and storage of metals, the function and regulation of sugar-metabolizing metalloenzymes, the mechanism of action of metal-containing pharmaceuticals, and toxic metal metabolism. To understand such interactions we synthesized and fully characterized two new dinuclear cobalt(II) and zinc(II) complexes as carbohydrate binding models for xylose/glucose isomerases (XGI). Synthesis of the dicobalt complex, Na3[Co2(ccdp)(µ-HCO2)]BF4·9H2O·2CH3OH (1), was performed in methanol with stoichiometric amounts of Co(BF4)2·6H2O and the dinucleating ligand, H5ccdp (H5ccdp = N,N'-bis[2-carboxybenzomethyl]-N,N'-bis[carboxymethyl]-1,3-diaminopropan-2-ol), in the presence of NaOH at ambient temperature in an argon glovebox. Similarly, the dizinc complex, [NMe4]2[Zn2(ccdp)(µ-OAc)]·CH3OH (2), was synthesized from Zn(OAc)2·2H2O and H5ccdp in the presence of NMe4OH at ambient temperature in methanol. Binding of the complexes with carbohydrates was investigated under different reaction conditions. In aqueous alkaline media, complexes 1 and 2 showed chelating ability towards the biologically important sugars, d-glucose and d-xylose, and a polyalcohol enzyme inhibitor (xylitol). In solution, each complex forms a 1:1 complex-substrate bound product with specific binding constant values. Synthesis, characterization details, and substrate binding using spectroscopic techniques and single-crystal X-ray diffraction are reported.

New dinuclear copper(II) and zinc(II) complexes for the investigation of sugar-metal ion interactions.

We have studied the binding interactions of biologically important carbohydrates (D-glucose, D-xylose and D-mannose) with the newly synthesized five-coordinate dinuclear copper(II) complex, [Cu(2)(hpnbpda)(µ-OAc)] (1) and zinc(II) complex, [Zn(2)(hpnbpda)(µ-OAc)] (2) [H(3)hpnbpda=N,N'-bis(2-pyridylmethyl)-2-hydroxy-1,3-propanediamine-N,N'-diacetic acid] in aqueous alkaline solution. The complexes 1 and 2 are fully characterized both in solid and solution using different analytical techniques. A geometrical optimization was made of the ligand H(3)hpnbpda and the complexes 1 and 2 by molecular mechanics (MM+) method in order to establish the stable conformations. All carbohydrates bind to the metal complexes in a 1:1 molar ratio. The binding events have been investigated by a combined approach of FTIR, UV-vis and (13)C NMR spectroscopic techniques. UV-vis spectra indicate a significant blue shift of the absorption maximum of complex 1 during carbohydrate coordination highlighting the sugar binding ability of complex 1. The apparent binding constants of the substrate-bound copper(II) complexes have been determined from the UV-vis titration experiments. The binding ability and mode of binding of these sugar substrates with complex 2 are indicated by their characteristic coordination induced shift (CIS) values in (13)C NMR spectra for carbon atoms C1, C2, and C3 of sugar substrates.

Study of potential binding of biologically important sugars with a dinuclear cobalt(II) complex.

The investigation of the sugar-metal ion interactions remains one of the main objectives of carbohydrate coordination chemistry because the interactions between metal ions and carbohydrates are involved in many biochemical processes. The potential binding interaction between a five-coordinate dinuclear cobalt(II) complex, Na(2)[Co(2)(tcdc)(µ-OAc)] (1) [Na(5)tcdc=Sodium-N,N,N',N'-tetrakis(sodium carboxylate methyl)-2,6-diaminocresolate] and biologically important sugar substrates (D-glucose, D-xylose, and D-mannose) has been studied. In alkaline media, the complex 1 shows an excellent chelating ability toward these sugar substrates. A combined approach of FTIR and UV-vis spectroscopic investigations shows that the complex forms a 1:1 complex/substrate-bound product. UV-vis spectra indicate a significant blue-shift of the absorption maximum of metal complex during carbohydrate coordination highlighting the sugar binding ability of complex 1. The apparent binding constants of the substrate-bound cobalt(II) complexes have been determined from the UV-vis titration experiments.

Synthesis and characterization of new mono- and heptazinc complexes with unusual amide coordination modes.

Two novel, a mono- and a heptanuclear, zinc complexes have been prepared and characterized by exploiting the flexibility and chelating and bridging ability of a new carboxylate- and amide-rich dinucleating ligand under different reaction conditions.

Synthesis and characterization of mono- and micro6-sulfato hexanuclear zinc complexes of a new symmetric dinucleating ligand.

Zinc complexes of a new symmetric dinucleating ligand, N,N'-Bis[2-carboxybenzomethyl]-N,N'-Bis[carboxymethyl]-1,3-diaminopropan-2-ol (H5ccdp) with mixed donating groups, have been studied in the solid state as well as in solution. In methanol, the reaction of stoichiometric and substoichiometric amounts of Zn(ClO4)2 x 6H2O and the ligand H5ccdp, in the presence of K2CO3 or Et3N, afforded a mononuclear zinc complex, [Zn(H2O)6][Zn(H2ccdp)(H2O)2]2 x 12H2O (1). The solid state structure of 1 contains two units of the zinc-ligand anion, [Zn(H2ccdp)(H2O)2]-, and one [Zn(H2O)6]2+ counter cation. The Zn(II) center of the anion is in a distorted octahedral geometry. However, in methanol, the reaction of ZnSO4 x 7H2O and the ligand Hsccdp in the presence of NaOH afforded a unique micro6-sulfato hexanuclear zinc complex, Na6[Zn6(ccdp)3(micro6-SO4)](OH) x 10.5H2O (2). The structure of 2 contains a [ZnII6(micro6-SO4)] core unit which is held together by three heptadentate bridging ligands, ccdp5-. Three of the Zn(II) centers are in highly distorted square pyramidal geometry, the other three Zn(II) centers are in a distorted octahedral geometry.

Two new oximate-bridged square-planar dinuclear nickel(II) complexes.

The synthesis and characterization of two new dinuclear nickel(II) complexes, namely bis{mu-3-[2-(dimethylamino)ethylimino]butan-2-one oximato}dinickel(II) bis(perchlorate) acetonitrile solvate, [Ni2(C8H16N3O)2](ClO4)2 x CH3CN, (I), and bis{mu-3-[2-(dimethylamino)ethylimino]-3-phenylpropan-2-one oximato}dinickel(II) bis(perchlorate), [Ni2(C13H18N3O)2](ClO4)2, (II), are reported. Single-crystal X-ray analyses of the complexes reveal that the nickel(II) ions are in square-planar N3O environments and form six-membered (NiNO)2 metallacycles. The cation in (II) possesses crystallographically imposed inversion symmetry.

Structure and properties of a new double-stranded tetranuclear [Cu(II)2]2 helicate.

A novel double-stranded tetranuclear helicate composed of a pair of [Cu(II)(2)] dimers has been prepared and characterized by exploiting the flexibility, chelating ability and bridging potential of a hexadentate bis-oximate ligand.

A novel mu(4)-oxo bridged copper tetrahedron derived by self-assembly: first example of double helical bis(tridentate) coordination of a hexadentate amine phenol ligand.

In methanol, the reaction of Cu(ClO(4))(2).6H(2)O and the hexadentate amine phenol ligand (H(2)bahped) in the presence of triethylamine affords a tetranuclear copper(II) complex having the formula [Cu(4)(mu(4)-O)(bahped)(2)](ClO(4))(2). The X-ray structure of this complex shows a tetrahedral central [Cu(II)(4)(mu(4)-O)]unit coordinated to two hexadentate bridging (via the central ethylenediamine part) ligands. The compound is the first example of a mu(4)-oxo tetranuclear copper(II) complex without any bridging ligand along the six tetrahedral edges. Variable-temperature magnetic data clearly show an S(t) = 0 spin ground state for antiferromagnetic interactions between four (2)B(2) copper(II) ions in a dimer of dimers.