Hydrogels containing water soluble conjugates of silver(I) ions with amino acids, metabolites or natural products for non infectious contact lenses.

The poor handling and hygiene practices of contact lenses are the key reasons for their frequent contamination, and are responsible for developing ocular complications, such as microbial keratitis (MK). Thus there is a strong demand for the development of biomaterials of which contact lenses are made, combined with antimicrobial agents. For this purpose, the known water soluble silver(I) covalent polymers of glycine (GlyH), urea (U) and the salicylic acid (SalH2) of formulae [Ag3(Gly)2NO3]n (AGGLY), [Ag(U)NO3]n (AGU), and dimeric [Ag(salH)]2 (AGSAL) were used. Water solutions of AGGLY, AGU and AGSAL were dispersed in polymeric hydrogels using hydroxyethyl-methacrylate (HEMA) to form the biomaterials pHEMA@AGGLY-2, pHEMA@AGU-2, and pHEMA@AGSAL-2. The biomaterials were characterized by X-ray fluorescence (XRF) spectroscopy, thermogravimetric differential thermal analysis (TG-DTA), differential scanning calorimetry (DTG/DSC), attenuated total reflection spectroscopy (FT-IR-ATR) and single crystal diffraction analysis. The antibacterial activity of AGGLY, AGU, AGSAL, pHEMA@AGGLY-2, pHEMA@AGU-2 and pHEMA@AGSAL-2 was evaluated against the Gram negative species Pseudomonas aeruginosa (P. aeruginosa) and Gram positive ones Staphylococcus epidermidis (S. epidermidis) and Staphylococcus aureus (S. aureus), which mainly colonize in contact lenses. The in vitro toxicity of the biomaterials and their ingredients was evaluated against normal human corneal epithelial cells (HCECs) whereas the in vitro genotoxicity was evaluated by the micronucleus (MN) assay in HCECs. The Artemia salina and Allium cepa models were applied for the evaluation of in vivo toxicity and genotoxicity of the materials. Following our studies, the new biomaterials pHEMA@AGGLY-2, pHEMA@AGU-2, and pHEMA@AGSAL-2 are suggested as efficient candidates for the development of antimicrobial contact lenses.

An Efficient Disinfectant, Composite Material {SLS@[Zn3(CitH)2]} as Ingredient for Development of Sterilized and Non Infectious Contact Lens.

The [Zn3(CitH)2] (1) (CitH4= citric acid), was dispersed in sodium lauryl sulphate (SLS) to form the micelle of SLS@[Zn3(CitH)2] (2). This material 2 was incorporated in hydrogel made by hydroxyethyl-methacrylate (HEMA), an ingredient of contact lenses, toward the formation of pHEMA@(SLS@[Zn3(CitH)2]) (3). Samples of 1 and 2 were characterized by UV-Vis, 1H-NMR, FT-IR, FT-Raman, single crystal X-ray crystallography, X-ray fluorescence analysis, atomic absorption and TG/DTA/DSC. The antibacterial activity of 1-3 as well as of SLS against Gram-positive (Staphylococcus epidermidis (St. epidermidis) and Staphylococcus aureus (St. aureus)) and Gram-negative (Pseudomonas aeruginosa (PAO1), and Escherichia coli (E. coli)) bacteria was evaluated by the means of minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and inhibitory zone (IZ). 2 showed 10 to 20-fold higher activity than 1 against the bacteria tested. Moreover the 3 decreases the abundance of Gram-positive microbes up to 30% (St. aureus) and up to 20% (PAO1) the Gram-negative ones. The noteworthy antimicrobial activity of the obtained composite 3 suggests an effective antimicrobial additive for infection-free contact lenses.

Synthesis and encapsulation of V(IV,V) compounds in silica nanoparticles targeting development of antioxidant and antiradical nanomaterials.

The quest for effective treatments of oxidative stress has concentrated over the years on new nanomaterials with improved antioxidant and antiradical activity, thereby attracting broad research interest. In that regard, research efforts in our lab were launched to pursue such hybrid materials involving a) synthesis of silica gel matrices, b) evaluation of the suitability of atoxic matrices as potential carriers for the controlled release of V(IV)(VOSO4), V(V)(NaVO3) compounds and a newly synthesized heterometallic lithium-vanadium(IV,V) tetranuclear compound containing vanadium-bound hydroxycarboxylic 1,3-diamine-2-propanol-N,N,N',N'-tetraacetic acid (DPOT), and c) investigation of structural and textural properties of silica nanoparticles (NPs) by different and complementary characterization techniques, inquiring into the nature of the encapsulated vanadium species and their interaction with the siloxane matrix, collectively targeting novel antioxidant and antiradical nanomaterials biotechnology. The physicochemical characterization of the vanadium-loaded SiO2 NPs led to the formulation of optimized material configuration linked to the delivery of the encapsulated antioxidant-antiradical load. Entrapment and drug release studies showed a) the competence of hybrid nanoparticles with respect to encapsulation efficiency of the vanadium compound (concentration dependence), b) congruence with the physicochemical features determined, and c) a well-defined release profile of NP load. Antioxidant properties and the free radical scavenging capacity of the new hybrid materials (containing VOSO4, NaVO3, and V-DPOT) were demonstrated through a) 2-diphenyl-1-picrylhydrazyl (DPPH) free radical, and b) intracellular-extracellular reactive oxygen species (ROS) assays, through UV-Visible spectroscopy techniques, collectively showing that the hybrid silica NPs (empty-loaded) could serve as an efficient platform for nanodrug formulations counteracting oxidative stress.

Mononuclear copper(II) complexes with 2-thiophene carboxylate and N-N donors; DNA interaction, antioxidant/anti-inflammatory and antitumor activity.

Redox-active compounds such as copper-phenanthroline are known as artificial/chemical nucleases with a great impact and potential for their applications as metallotherapeutics. In that vein, the mononuclear copper(II) complexes [Cu(L)2(bipy)] (1), [Cu(L)2(bipy)(H2O)] (2) and [Cu(L)2(phen)(H2O)] (3), where L = 2-thiophene carboxylate, bipy = 2,2΄-bipyridine and phen = 1,10-phenanthroline, have been prepared and pharmacochemically studied, while the crystal structure of 1 is also reported. All the tested complexes preferably bind to CT-DNA via minor groove as resulted from UV spectroscopy studies, luminescent titration, EB competition assays and viscosity measurements. Complexes 2 and 3 in aqua behave like a "light switch" for DNA. The intensity enhancement, with the increase of DNA concentration, reached about 3-fold for 2 and 10-fold for 3. In vitro antioxidant activity of compounds 1-3, was evaluated using two different antioxidant assays: a) interaction with 1,1-diphenyl-2-picryl-hydrazyl (DPPH) stable free radical and b) inhibition of lipid peroxidation. Moreover, their inhibitory activity on soybean lipoxygenase (LOX) was evaluated for their anti-inflammatory potency. The tested complexes showed good activity on both lipid peroxidation and soybean LOX inhibition while complex 2 exhibited the best antioxidant/anti-inflammatory activity. A computational analysis over the LOX protein structure 1JNQ was performed, in an effort to support their possible mode of action. The cytotoxicity of the complexes was determined and their efficacy against several human cancer cell lines (ovarian, OAW-42; lung, A549; colon, HT29; breast, MDA-MB-231; kidney, Caki-2; and cervical, Hela) and human non-tumor cell lines (lung, MRC-5; and breast, MTSV1-7) were evaluated. The best cytotoxic activity was appeared for complex 3. In silico, computational methods support antiestrogen activity of the administered complexes on normal breast cells.

A water-soluble silver(I) formulation as an effective disinfectant of contact lenses cases.

The antibacterial effect of the already known water-soluble compound {[Ag6(µ3-Hmna)4(µ3-mna)2]2-·[(Et3NH)+]2·(DMSO)2·(H2O)} (AGMNA) (H2mna = 2­mercapto­nicotinic acid) was evaluated by the mean of the Minimum Inhibitory Concentration (MIC), the Minimum Bactericidal Concentration (MBC) and the Inhibitory Zone (IZ), against the bacterial strains Pseudomonas aeruginosa (PAO1) and Staphylococcus aureus (St. aureus) which settle in the cornea, in bacterial keratitis. The MICs' of AGMNA against PAO1 and St. aureus were 25.7 ±â€¯2.4 µM and 42.0 ±â€¯0.3 µM respectively. Τhe Biofilm Elimination Concentration (ΒΕC) was used to evaluate the influence of AGMNA on the formation of biofilm of PAO1. AGMNA exhibits stronger antimicrobial activity than that of H2mna or AgNO3. The toxicity of AGMNA was examined against normal human corneal epithelial cells (HCET cells) and by micronucleus (MN) assay in HCET cells. Thus, the IC50 value of AGMNA, towards HCET cells is higher than 120 µΜ, while its effect on MN frequency, of HCET cells, is meaningless, when they are treated with it at 120 µΜ, suggesting no in vitro genotoxicity. The Mitotic Index (MI), Chromosomal Aberrations (CA) and Nuclear Abnormalities (NA) analyses of Allium cepa reveal insignificant variations between treated and untreated ones indicating no in vivo genotoxicity.

Silver ciprofloxacin (CIPAG): a successful combination of chemically modified antibiotic in inorganic-organic hybrid.

The new silver(I) ionic, water soluble, compound {[Ag(CIPH)2]NO3∙0.75MeOH∙1.2H2O} (CIPAG) was obtained by reacting silver(I) nitrate with the antibiotic ciprofloxacin (CIPH). The complex was characterized by m.p., mid-FT-IR, 1H-NMR, UV-Vis spectroscopic techniques. The crystal structures of both CIPAG and the hexahydrated neutral free drug {[CIPH]∙6(H2O)} (2) were characterized by X-ray crystallography. Two neutral ligands are datively bonded to the metal ion through the piperidinic nitrogen atoms forming a cationic {[Ag(CIPH)2]+} counter part which is neutralized by a nitrate group. The antibacterial effect of CIPAG and the commercially available hydrochloric salt of the antibiotic ({[CIPH 2+ ]∙Cl - } (3)) were tested against the bacterial species Pseudomonas aeruginosa (PAO1), Staphylococcus epidermidis (St. epidermidis) and Staphylococcus aureus (St. aureus) by the mean of minimum inhibitory concentration, minimum bactericidal concentration and their inhibitory zone (IZ). The influence of CIPAG and 3 against the formation of biofilm of PAO1 or St. aureus was also evaluated by mean of biofilm elimination concentration. The IZ caused by CIPAG which has been loaded in poly-hydroxyethylmethacrylate, is determined. The genotoxicity of CIPAG and 3 is tested in vitro against normal human corneal epithelial cells (HCET cells), by the presence of micronucleus in HCET cells and in vivo by mean of Allium cepa test.

Synthetic investigation of binary-ternary Cr(III)-hydroxycarboxylic acid-aromatic chelator systems. Structure-specific influence on adipogenic biomarkers linked to insulin mimesis.

In an attempt to understand the aqueous interactions of Cr(III) with low-molecular mass physiological ligands and examine its role as an adipogenic metallodrug agent in Diabetes mellitus II, the pH-specific synthesis in the binary-ternary Cr(III)-(HA = hydroxycarboxylic acid)-(N,N)-aromatic chelator (AC) (HA = 2-hydroxyethyl iminodiacetic acid/heidaH2, quinic acid; AC = 1,10-phenanthroline/phen) systems was pursued, leading to four new crystalline compounds. All materials were characterized by elemental analysis, UV-Visible, FT-IR, and ESI-MS spectroscopy, cyclic voltammetry, and X-Ray crystallography. Concurrently, the aqueous speciation of the binary Cr(III)-(2-hydroxyethyl iminodiacetic acid) system, complemented by ESI-MS, provided key-details of the species in solution correlating with the solid-state species. The structurally distinct Cr(III) soluble species were subsequently used in an in vitro investigation of their cytotoxic activity in 3T3-L1 fibroblast cultures. Compound 1 exhibited solubility, bioavailability, and atoxicity over a wide concentration range (0.1-100 µΜ) in contrast to 3, which was toxic. The adipogenic potential of 1 was subsequently investigated toward transformation of pre-adipocytes into mature adipocytes. Confirmation of that capacity relied on molecular biological techniques a) involving genes (glucose transporter type 4, peroxisome proliferator-activated receptor gamma, glucokinase, and adiponectin) serving as sensors of the transformation process, b) comparing the Cr(III)-adipogenicity potential to that of insulin, and c) exemplifying the ultimate maturity of adipocytes poised to catabolize glucose. The collective effort points out salient structural features in the coordination sphere of Cr(III) inducing adipogenic transformation relevant to combating hyperglycemia. The multiply targeted mechanistic insight into such a process exemplifies the role of well-defined Cr(III) complex forms as potential insulin-mimetic adipogenic agents in Diabetes mellitus II.

"Switching on" the single-molecule magnet properties within a series of dinuclear cobalt(iii)-dysprosium(iii) 2-pyridyloximate complexes.

The use of 2-pyridinealdoxime (paoH), methyl 2-pyridyl ketone oxime (mepaoH), phenyl 2-pyridyl ketone oxime (phpaoH) and pyridine-2-amidoxime (NH2paoH) for the synthesis of dinuclear CoIII/DyIII complexes is described in the absence or presence of an external base. Complexes [CoDy(pao)3(NO3)3] (1), [CoDy(mepao)3(NO3)3] (2), [CoDy(phpao)3(NO3)3] (3) and [CoDy(NH2pao)3(NO3)3]·3MeOH (4·3MeOH) have been isolated and their structures have been determined by single-crystal X-ray crystallography. The complexes crystallize in non-centrosymmetric (2, 3) or centrosymmetric (1, 4·3MeOH) trigonal space groups and form a family of triply-oximate bridged dinuclear Co(iii)-Dy(iii) complexes. The crystals of 1, 3 and 4·3MeOH contain mixtures of Δ and Λ enantiomers, whereas complex 2 is enantiomerically pure (Λ). A 3-fold crystallographic axis (C3) passes through two metal ions in all complexes. The low-spin CoIII and DyIII ions are bridged by three oximate groups belonging to the η1:η1:η1:µ 2-pyridyloximate ligands. The CoIII centre is octahedrally coordinated by the six nitrogen atoms of the deprotonated organic ligands in a facial arrangement. The DyIII centre is bound to an O9 set of donor atoms, its coordination sphere being completed by three bidentate chelating nitrato groups. The coordination polyhedron around DyIII in 1 is best described as the Johnson tricapped trigonal prism, while the coordination geometries of the DyIII centres in 2, 3 and 4·3MeOH are best described as consisting of spherical tricapped trigonal prismatic coordination polyhedra. The spectroscopic data of the complexes are also reported and discussed in the infra-red region in terms of the coordination modes of the ligands involved. The magnetic properties of these complexes were studied between 300 and 1.8 K revealing mainly the depopulation of the DyIIImj sublevels of the ground 6H15/2 state. The intrinsic magnetic anisotropy of the DyIII centers is clearly observed by the non-superimposed magnetization (M) versus H/T data, but single-molecule magnet (SMM) properties were detected only for the mepao--containing complex 2. The origin of these properties in 2 is critically discussed and supported by computational studies.

Synthesis, structure elucidation and biological evaluation of triple bridged dinuclear copper(II) complexes as anticancer and antioxidant/anti-inflammatory agents.

Seeking for copper based metallo-therapeutics, three triple bridged dinuclear copper(II) complexes [Cu2(µ2-L2)(bipy)2(µ2-OH)(µ2-H2O)](NO3)2·H2O (1·H2O), [Cu2(µ2-L2)(bipy)2(µ2-OH)(µ2-NO3)](NO3)·0.6MeOH·0.4H2O (2·0.6MeOH·0.4H2O) and [Cu2(µ2-L1)(bipy)2(µ2-OH)(µ2-NO3)(H2O)](NO3)·2H2O (3·2H2O) where L2=2-thiophene acetato, L1=2-thiophene carboxylato and bipy=2,2'-bipyridine were synthesized and structurally characterized. The complexes were subjected in vitro to a pharmacochemical evaluation for their antioxidant/anti-inflammatory activity, cytotoxicity and efficacy against human ovarian, lung, colon, breast, kidney and cervical cancer cell lines along with non tumor human lung and breast cell lines. The biological results support the structure related cytotoxic activity of the compounds. Complex 3 presented a combination of best anticancer and anti-inflammatory activities. A computational analysis over the LOX-3 protein structure 1JNQ was performed to support the possible mode of action.

Sol-gel encapsulation of binary Zn(II) compounds in silica nanoparticles. Structure-activity correlations in hybrid materials targeting Zn(II) antibacterial use.

In the emerging issue of enhanced multi-resistant properties in infectious pathogens, new nanomaterials with optimally efficient antibacterial activity and lower toxicity than other species attract considerable research interest. In an effort to develop such efficient antibacterials, we a) synthesized acid-catalyzed silica-gel matrices, b) evaluated the suitability of these matrices as potential carrier materials for controlled release of ZnSO4 and a new Zn(II) binary complex with a suitably designed well-defined Schiff base, and c) investigated structural and textural properties of the nanomaterials. Physicochemical characterization of the (empty-loaded) silica-nanoparticles led to an optimized material configuration linked to the delivery of the encapsulated antibacterial zinc load. Entrapment and drug release studies showed the competence of hybrid nanoparticles with respect to the a) zinc loading capacity, b) congruence with zinc physicochemical attributes, and c) release profile of their zinc load. The material antimicrobial properties were demonstrated against Gram-positive (Staphylococcus aureus, Bacillus subtilis, Bacillus cereus) and negative (Escherichia coli, Pseudomonas aeruginosa, Xanthomonas campestris) bacteria using modified agar diffusion methods. ZnSO4 showed less extensive antimicrobial behavior compared to Zn(II)-Schiff, implying that the Zn(II)-bound ligand enhances zinc antimicrobial properties. All zinc-loaded nanoparticles were less antimicrobially active than zinc compounds alone, as encapsulation controls their release, thereby attenuating their antimicrobial activity. To this end, as the amount of loaded zinc increases, the antimicrobial behavior of the nano-agent improves. Collectively, for the first time, sol-gel zinc-loaded silica-nanoparticles were shown to exhibit well-defined antimicrobial activity, justifying due attention to further development of antibacterial nanotechnology.

Heptanuclear antiferromagnetic Fe(III)-D-(-)-quinato assemblies with an S = 3/2 ground state-pH-specific synthetic chemistry, spectroscopic, structural, and magnetic susceptibility studies.

Iron is an essential metal ion with numerous roles in biological systems and advanced abiotic materials. D-(-)-quinic acid is a cellular metal ion chelator, capable of promoting reactions with metal M(II,III) ions under pH-specific conditions. In an effort to comprehend the chemical reactivity of well-defined forms of Fe(III)/Fe(II) toward α-hydroxycarboxylic acids, pH-specific reactions of: (a) [Fe3O(CH3COO)6(H2O)3]·(NO3)·4H2O with D-(-)-quinic acid in a molar ratio 1:3 at pH 2.5 and (b) Mohr's salt with D-(-)-quinic acid in a molar ratio 1:3 at pH 7.5, respectively, led to the isolation of the first two heptanuclear Fe(III)-quinato complexes, [Fe7O3(OH)3(C7H10O6)6]·20.5H2O (1) and (NH4)[Fe7(OH)6(C7H10O6)6]·(SO4)2·18H2O (2). Compounds 1 and 2 were characterized by analytical, spectroscopic (UV-vis, FT-IR, EPR, and Mössbauer) techniques, CV, TGA-DTG, and magnetic susceptibility measurements. The X-ray structures of 1 and 2 reveal heptanuclear assemblies of six Fe(III) ions bound by six doubly deprotonated quinates and one Fe(III) ion bound by oxido- and hydroxido-bridges (1), and hydroxido-bridges (2), all in an octahedral fashion. Mössbauer spectroscopy on 1 and 2 suggests the presence of Fe(III) ions in an all-oxygen environment. EPR measurements indicate that 1 and 2 retain their structure in solution, while magnetic measurements reveal an overall antiferromagnetic behavior with a ground state S = 3/2. The collective physicochemical properties of 1 and 2 suggest that the (a) nature of the ligand, (b) precursor form of iron, (c) pH, and (d) molecular stoichiometry are key factors influencing the chemical reactivity of the binary Fe(II,III)-hydroxycarboxylato systems, their aqueous speciation, and ultimately through variably emerging hydrogen bonding interactions, the assembly of multinuclear Fe(III)-hydroxycarboxylato clusters with distinct lattice architectures of specific dimensionality (2D-3D) and magnetic signature.

Aromatic chelator-specific lattice architecture and dimensionality in binary and ternary Cu(II)-organophosphonate materials.

Synthetic efforts linked to the design of defined lattice dimensionality and architecture materials in the binary/ternary systems of Cu(II) with butylene diamine tetra(methylene phosphonic acid) (H8BDTMP) and heterocyclic organic chelators (pyridine and 1,10-phenanthroline) led to the isolation of new copper organophosphonate compounds, namely, Na6[Cu2(BDTMP)(H2O)4]·[Cu2(BDTMP)(H2O)4]0.5·26H2O (1), [Cu2(H4BDTMP)(py)4]·2H2O (2), and [Cu2(H4BDTMP)(phen)2]n·6.6nH2O·1.5nMeOH (3). 1-3 are the first compounds isolated from the Cu(II)-BDTMP family of species. They were characterized by elemental analysis, spectroscopic techniques (FT-IR, UV-vis), magnetic susceptibility, TGA-DTG, cyclic voltammetry, and X-ray crystallography. The lattice in 1 reveals the presence of discrete dinuclear Cu(II) units bound to BDTMP(8-) and water molecules in a square pyramidal geometry. The molecular lattice of 2 reveals the presence of ternary dinuclear assemblies of Cu(II) ions bound to H4BDTMP(4-) and pyridine in a square pyramidal environment. The molecular lattice of 3 reveals the presence of dinuclear assemblies of Cu(II) ions bound to H4BDTMP(4-) and 1,10-phenanthroline in a square pyramidal environment, with the organophosphonate ligand serving as the connecting link to abutting dinuclear Cu(II) assemblies in a ternary polymeric system. The magnetic susceptibility data on 1, 2, and 3 suggest that compounds 1 and 3 exhibit a stronger antiferromagnetic behavior than 2, which is also confirmed from magnetization measurements. The physicochemical profiles of 1-3 (a) earmark the influence of the versatile H8BDTMP ligand as a metal ion binder on the chemical reactivity in binary and ternary systems of Cu(II) in aqueous and nonaqueous media and (b) denote the correlation of ligand hydrophilicity, aromaticity, denticity, charge, and H-bonding interactions with emerging defined Cu(II)-H8BDTMP structures of distinct lattice identity and spectroscopic-magnetic properties. Collectively, such structural and chemical factors formulate the interplay and contribution of binary and ternary interactions to lattice architecture and specified properties of new Cu(II)-organophosphonate materials with defined 2D-3D dimensionality.

Defective dicubanes of Co(II)/Co(III) complexes with triethanolamine and N-donors.

The mixed valence Co(II)/Co(III) tetranuclear clusters [Co(II)2Co(III)2(tea)2(pyr)2(NO3)4]·2CH3CN (1), [Co(II)2Co(III)2(µ3-OH)2(Htea)2(bpy)4](NO3)4 (2), and [Co(II)2Co(III)2(µ3-OH)2(Htea)2(phen)4](NO3)4·2CH3CN·2CH3OH (3) are described where tea and Htea are the fully and the doubly deprotonated form of triethanolamine, while as N-donors are pyridine, 2,2'-bipyridine and 1,10-phenanthroline. Complexes 1-3 contain the Co(II)2Co(III)2O6 core and can be described as defective dicubanes with different imperfectness. In 1, the central rhombic core Co2O2 is occupied by two Co(III) ions while the external cobalt atoms display Co(II) oxidation states; meanwhile 2 and 3 exhibit a reversal in their Co(II)2Co(III)2 oxidation state distribution. Two different theoretical models were used to explain the magnetic behavior: (i) spin-spin interaction model with local anisotropy terms where S = 3/2 for both metal centers and (ii) an anisotropic spin-spin interaction model applicable in the low temperature range (T < 40 K) using effective spins (Seff = 1/2) for both metal centers. For 1 a relatively strong next-nearest-neighbour antiferromagnetic exchange interaction between the Co(II) centers which are connected via diamagnetic Co(III) ion was found while for 2 and 3 the presence of ferromagnetic interaction is confirmed. The fitting results, concerning the first model, gave: J = 2.0(2)/3.2(2)/3.8(2) cm(-1), g = 2.35(1)/2.52(1)/2.57(1) and D = 11.0(1)/8.5(1)/7.8(1) cm(-1) while concerning the second model are: Jz = -7.1(2)/19.2(2)/22.1(2) cm(-1), gz = 6.8(1)/8.1(1)/8.3(1), Jxy/Jz = 0.34(2)/0.11(2)/0.14(2), and gxy/gz = 0.52(2)/0.28(2)/0.36(2) for 1-3. X-Band EPR spectrum of 1 has a very broad derivative centered at g = 5.3 while for 2 and 3 large g-variations were found in the range 20.0-1.0, indicative of an exchange interaction between Co(II) ions.

pH-specific hydrothermal assembly of binary and ternary Pb(II)-(O,N-carboxylic acid) metal organic framework compounds: correlation of aqueous solution speciation with variable dimensionality solid-state lattice architecture and spectroscopic signatures.

Hydrothermal pH-specific reactivity in the binary/ternary systems of Pb(II) with the carboxylic acids N-hydroxyethyl-iminodiacetic acid (Heida), 1,3-diamino-2-hydroxypropane-N,N,N',N'-tetraacetic acid (Dpot), and 1,10-phenanthroline (Phen) afforded the new well-defined crystalline compounds [Pb(Heida)](n)·nH(2)O(1), [Pb(Phen)(Heida)]·4H(2)O(2), and [Pb(3)(NO(3))(Dpot)](n)(3). All compounds were characterized by elemental analysis, FT-IR, solution or/and solid-state NMR, and single-crystal X-ray diffraction. The structures in 1-2 reveal the presence of a Pb(II) center coordinated to one Heida ligand, with 1 exhibiting a two-dimensional (2D) lattice extending to a three-dimensional (3D) one through H-bonding interactions. The concurrent aqueous speciation study of the binary Pb(II)-Heida system projects species complementing the synthetic efforts, thereby lending credence to a global structural speciation strategy in investigating binary/ternary Pb(II)-Heida/Phen systems. The involvement of Phen in 2 projects the significance of nature and reactivity potential of N-aromatic chelators, disrupting the binary lattice in 1 and influencing the nature of the ultimately arising ternary 3D lattice. 3 is a ternary coordination polymer, where Pb(II)-Dpot coordination leads to a 2D metal-organic-framework material with unique architecture. The collective physicochemical properties of 1-3 formulate the salient features of variable dimensionality metal-organic-framework lattices in binary/ternary Pb(II)-(hydroxy-carboxylate) structures, based on which new Pb(II) materials with distinct architecture and spectroscopic signature can be rationally designed and pursued synthetically.

pH-Specific structural speciation of the ternary V(V)-peroxido-betaine system: a chemical reactivity-structure correlation.

Vanadium involvement in cellular processes requires deep understanding of the nature and properties of its soluble and bioavailable forms arising in aqueous speciations of binary and ternary systems. In an effort to understand the ternary vanadium-H(2)O(2)-ligand interactions relevant to that metal ion's biological role, synthetic efforts were launched involving the physiological ligands betaine (Me(3)N(+)CH(2)CO(2)(-)) and H(2)O(2). In a pH-specific fashion, V(2)O(5), betaine, and H(2)O(2) reacted and afforded three new, unusual, and unique compounds, consistent with the molecular formulation K(2)[V(2)O(2)(O(2))(4){(CH(3))(3)NCH(2)CO(2))}]·H(2)O (1), (NH(4))(2)[V(2)O(2)(O(2))(4){(CH(3))(3)NCH(2)CO(2))}]·0.75H(2)O (2), and {Na(2)[V(2)O(2)(O(2))(4){(CH(3))(3)NCH(2)CO(2))}(2)]}(n)·4nH(2)O (3). All complexes 1-3 were characterized by elemental analysis; UV/visible, FT-IR, Raman, and NMR spectroscopy in solution and the solid state; cyclic voltammetry; TGA-DTG; and X-ray crystallography. The structures of 1 and 2 reveal the presence of unusual ternary dinuclear vanadium-tetraperoxido-betaine complexes containing [(V(V)═O)(O(2))(2)] units interacting through long V-O bonds. The two V(V) ions are bridged through the oxygen terminal of one of the peroxide groups bound to the vanadium centers. The betaine ligand binds only one of the two V(V) ions. In the case of the third complex 3, the two vanadium centers are not immediate neighbors, with Na(+) ions (a) acting as efficient oxygen anchors and through Na-O bonds holding the two vanadium ions in place and (b) providing for oxygen-containing ligand binding leading to a polymeric lattice. In 1 and 3, interesting 2D (honeycomb) and 1D (zigzag chains) topologies of potassium nine-coordinate polyhedra (1) and sodium octahedra (3), respectively, form. The collective physicochemical properties of the three ternary species 1-3 project the chemical role of the low molecular mass biosubstrate betaine in binding V(V)-diperoxido units, thereby stabilizing a dinuclear V(V)-tetraperoxido dianion. Structural comparisons of the anions in 1-3 with other known dinuclear V(V)-tetraperoxido binary anionic species provide insight into the chemical reactivity of V(V)-diperoxido systems and their potential link to cellular events such as insulin mimesis and anitumorigenicity modulated by the presence of betaine.

A unique dinuclear mixed V(V) oxo-peroxo complex in the structural speciation of the ternary V(V)-peroxo-citrate system. potential mechanistic and structural insight into the aqueous synthetic chemistry of dinuclear V(V)-citrate species with H2O2.

Diverse vanadium biological activities entail complex interactions with physiological target ligands in aqueous media and constitute the crux of the undertaken investigation at the synthetic level. Facile aqueous redox reactions, as well as nonredox reactions, of V(III) and V(V) with physiological citric acid and hydrogen peroxide, under pH-specific conditions, led to the synthesis and isolation of a well-formed crystalline material upon the addition of ethanol as the precipitating solvent. Elemental analysis pointed to the molecular formulation (NH4)4[(VO2){VO(O2)}(C6H5O7)2]·1.5H2O (1). Complex 1 was further characterized by Fourier transform infrared (FT-IR) spectroscopy, nuclear magnetic resonance (NMR), Raman spectroscopy, cyclic voltammetry, and X-ray crystallography. The crystallographic structure of 1 reveals the presence of the first dinuclear V(V)-citrate complex with non-peroxo- and peroxo-containing V(V) ions, concurrently present within the basic VV2O2 core. The nonperoxo unit VO2+ and the peroxo unit VO(O2)+ are each coordinated to a triply deprotonated citrate ligand in a distinct coordination mode and coordination geometry around the V(V) ions. These units are similar to those in homodinuclear complexes bearing oxo or peroxo groups. The unique assembly of both units in the anion of 1 renders the latter as a potential intermediate in the peroxidation process, from [V2O4(C6H5O7)2]4­ to [V2O2(O2)2(C6H6O7)2]2­. The transformation reactions of 1 establish its connection with several V(V) and V(IV) dinuclear species present in the aqueous distribution of the V(IV,V)-citrate systems. The shown position of 1 as an intermediate in the mechanism of H2O2 addition to dinuclear V(V)-citrate species portends its role in the complex aqueous distribution of species in the ternary V(V)-peroxo-citrate system and its potential reactivity in (bio)chemically relevant media.

Ferromagnetic and antiferromagnetic copper(II) complexes: counterplay between zero-field effects of the quartet ground state and intermolecular interactions.

The linear trinuclear Cu(II) complexes [Cu(3)(L(1))(4)(H(2)tea)(2)] (1), [Cu(3)(L(2))(4)(H(2)tea)(2)]·2CH(3)CN (2), [Cu(3)(L(2))(4)(H(2)tea)(2)] (3), [Cu(3)(L(1))(2)(H(2)tea)(2)(NO(3))(2)] (4) and the dinuclear complex [Cu(2)(L(1))(2)(H(2)tea)(2)] (5), where L(1) = 2-thiophene carboxylate, L(2) = 2-(thiophen-2-yl)-acetate and H(2)tea = the single deprotonated form of triethanolamine have been prepared and characterised while the crystal structures of 1-4 have been determined. The variable-temperature magnetic susceptibilities of complexes 1-5 have been measured in the range 2-300 K under various external fields in the range 0.02-1.0 T. X-band EPR spectra of 1-5 compounds were recorded at 4-100 K. Complexes 1, 2 and 3 found to have the same J = 33 cm(-1) and g values 2.16(1), 2.20(1) and 2.16(1) respectively while for 5 J = 15 cm(-1) and g = 2.06(1) revealing a clear ferromagnetic exchange between Cu(II) ions. Complex 4 was found to be antiferromagnetic with J = -28 cm(-1) and g = 2.21(1). The polycrystalline powder X-band EPR spectrum of complexes 1, 2, and 3 at 4 K are dominated by a transition at 1600 G (g = 4.3) which unambiguously identifies the spin of the ground multiplet (S = 3/2) while the antiferromagnetic complex 4 has a derivative centered at g = 2.1 indicative of a ground doublet (S = 1/2). Concerning complex 5 a spectrum of a dominant derivative centered at g = 2.06(1) is observed with a very weak half field transition (ca. 1500 G) indicative of the ferromagnetic nature of the system. Furthermore, for complexes 2 and 3 a strong temperature dependence of this spectroscopic g-factor is revealed and change of the g(eff) from the liquid helium temperature to the room temperature is almost 2 units.

Preparation and pharmacochemical evaluation of mixed ligand copper(II) complexes with triethanolamine and thiophenyl-2 saturated carboxylic acids.

The dinuclear complex [Cu(2)(L(1))(2)(H(2)tea)(2)] (1) as well as the linear trinuclear complexes [Cu(3)(L(1))(4)(H(2)tea)(2)] (2), [Cu(3)(L(2))(4)(H(2)tea)(2)] (3) and [Cu(3)(L(1))(2)(H(2)tea)(2)(NO(3))(2)] (4) where L(1) = 2-thiophene carboxylato, L(2) = 2-thiophene acetato and H(2)tea = the single deprotonated form of triethanolamine have been prepared and pharmacochemically studied. The crystal structure of 1 is also reported. In vitro antioxidant activity of free ligands and their respective copper complexes includes: a) interaction with 1,1-diphenyl-2-picrylhydrazyl stable free radical, b) the ΗΟ˙ mediated oxidation of DMSO, c) scavenging of superoxide anion radicals, d) inhibition of lipid peroxidation and e) soybean lipoxygenase inhibition. The results indicate selectivity of the complexes to different free radicals as a consequence of their physichochemical features. The majority of the complexes 1, 2, 3, 4 effectively inhibit lipid peroxidation. The trinuclear complex 3 is by far the most active with IC(50)=10 µM, within the set, followed by complexes 1 and 2. The complexes were evaluated for their efficacy as anticancer agents against different cancer and normal human cell lines. Results showed that, these compounds mediate a moderate cytotoxic response to normal and cancer cell lines tested and induce cell cycle arrest in G2/M phase of the cell cycle. Flow cytometric analysis suggested that the tested compounds can induce apoptosis.

Hydrothermal synthesis and characterization of 2D M(II)-Quinate (M = Co,Zn) metal-organic lattice assemblies: solid-state solution structure correlation in M(II)-hydroxycarboxylate systems.

Co(II) and Zn(II) ions exhibit variable reactivity toward O-containing ligands in aqueous media, affording isolable materials with distinct solid-state lattice properties. d-(-)-quinic acid is a cellular α-hydroxycarboxylate metal ion binder, which reacts with Co(II) and Zn(II) under pH-specific hydrothermal conditions, leading to the isolation of two new species [Co(2)(C(7)H(11)O(6))(4)](n)·nH(2)O (1) and [Zn(3)(C(7)H(11)O(6))(6)](n)·nH(2)O (2). Compound 1 was characterized by elemental analysis, spectroscopic techniques (FT-IR, UV-visible, EPR), magnetic studies, and X-ray crystallography. Compound 2 was characterized by elemental analysis, spectroscopic techniques (FT-IR, ESI-MS), and X-ray crystallography. The 2D molecular lattices in 1 and 2 reveal the presence of octahedral M(II) units bound exclusively to quinate in a distinct fashion, thereby projecting a unique chemical reactivity in each investigated system. The magnetic susceptibility and solid-state/frozen solution EPR data on 1 support the presence of a high-spin octahedral Co(II) in an oxygen environment, having a ground state with an effective spin of S = 1/2. Concurrent aqueous speciation studies on the binary Zn(II)-quinate system unravel the nature and properties of species arising from Zn(II)-quinate interactions as a function of pH and molar ratio. The physicochemical profiles of 1 and 2, in the solid state and in solution, earmark the importance of (a) select synthetic hydrothermal reactivity conditions, affording new well-defined lattice dimensionality and nuclearity M(II)-quinate materials, (b) structural speciation approaches delineating solid state-aqueous solution correlations in the binary M(II)-quinate systems, and (c) pH-specific chemical reactivity in binary M(II)-quinate systems reflecting structurally unique associations of simple aqueous complexes into distinctly assembled 2D crystalline lattices.

Synthetic, structural and solution speciation studies on binary Al(III)-(carboxy)phosphonate systems. Relevance to the neurotoxic potential of Al(III).

Efforts to delineate the interactions of neurotoxic Al(III) with low molecular mass substrates relevant to neurodegenerative processes, led to the investigation of the pH-specific synthetic chemistry of the binary Al(III)-[N-(phosphonomethyl) iminodiacetic acid] (Al-NTAP), Al(III)-[nitrilo-tris(methylene-phosphonic acid)] (Al-NTA3P), and Al(III)-[1-hydroxy ethylidene-1,1-diphosphonic acid] (Al-HEDP) systems, in correlation with solution speciation studies. Reaction of Al(NO(3))(3).9H(2)O with NTAP at pH 7.0 and 4.0 afforded the new species (CH(6)N(3))(4)[Al(2)(C(5)H(6)NPO(7))(2)(OH)(2)].8H(2)O (1) and (NH(4))(2)[Al(2)(C(5)H(6)NPO(7))(2)(H(2)O)(2)].4H(2)O (2), while reaction of Al(NO(3))(3).9H(2)O with NTA3P led to K(8)[Al(2)(C(3)H(6)NP(3)O(9))(2)(OH)(2)].20H(2)O (3). Complexes 1-3 were characterized by elemental analysis, FT-IR, (13)C, (31)P, (1)H NMR (for 1-2 solid state and solution NMR where feasible), and X-ray crystallography. The structures of 1-3 reveal the presence of uniquely defined dinuclear complexes of octahedral Al(III) bound to fully deprotonated phosphonate ligands, water and hydroxo moieties. The aqueous solution speciation studies on the aforementioned binary systems project a clear picture of the binary Al(III)-(carboxy)phosphonate interactions and species under variable pH-conditions and specific Al(III):ligand stoichiometry. The concurrent solid state and solution work (a) exemplifies essential structural and chemical attributes of soluble aqueous species, reflecting well-defined interactions of Al(III) with phosphosubstrates and (b) strengthens the potential linkage of neurotoxic Al(III) chemical reactivity toward O,N-containing (carboxy)phosphate-rich cellular targets.