Experimental and Theoretical Investigation of the Mechanism of the Reduction of O2 from Air to O22- by VIVO2+-N,N,N-Amidate Compounds and Their Potential Use in Fuel Cells.

The two-electron reductive activation of O2 to O22- is of particular interest to the scientific community mainly due to the use of peroxides as green oxidants and in powerful fuel cells. Despite of the great importance of vanadium(IV) species to activate the two-electron reductive activation of O2, the mechanism is still unclear. Reaction of VIVO2+ species with the tridentate-planar N,N,N-carboxamide (ΗL) ligands in solution (CH3OH:H2O) under atmospheric O2, at room temperature, resulted in the quick formation of [VV(═O)(η2-O2)(κ3-L)(H2O)] and cis-[VV(═O)2(κ3-L)] compounds. Oxidation of the VIVO2+ complexes with the sterically hindered tridentate-planar N,N,N-carboxamide ligands by atmospheric O2 gave only cis-[VV(═O)2(κ3-L)] compounds. The mechanism of formation of [VV(═O)(η2-O2)(κ3-L)(H2O)] (I) and cis-[VV(═O)2(κ3-L)] (II) complexes vs time, from the interaction of [VIV(═O)(κ3-L)(Η2Ο)2]+ with atmospheric O2, was investigated with 51V, 1H NMR, UV-vis, cw-X-band EPR, and 18O2 labeling IR and resonance Raman spectroscopies revealing the formation of a stable intermediate (Id). EPR, MS, and theoretical calculations of the mechanism of the formation of I and II revealed a pathway, through a binuclear [VIV(═O)(κ3-L)(H2O)(η1,η1-O2)VIV(═O)(κ3-L)(H2O)]2+ intermediate. The results from cw-EPR, 1H NMR spectroscopies, cyclic voltammetry, and the reactivity of the complexes [VIV(═O)(κ3-L)(Η2Ο)2]+ toward O2 reduction fit better to an intermediate with a binuclear nature. Dynamic experiments in combination with computational calculations were undertaken to fully elucidate the mechanism of the O2 reduction to O22- by [VIV(═O)(κ3-L)(Η2Ο)2]+. The galvanic cell {Zn|VIII,VII||Id, [VIVO(κ3-L)(H2O)2]+|O2|C(s)} was manufactured, demonstrating the important applicability of this new chemistry to Zn|H2O2 fuel cells technology generating H2O2 in situ from the atmospheric O2.

Insight into the Recent Application of Chemometrics in Quality Analysis and Characterization of Bee Honey during Processing and Storage.

The application of chemometrics, a widely used science in food studies (and not only food studies) has begun to increase in importance with chemometrics being a very powerful tool in analyzing large numbers of results. In the case of honey, chemometrics is usually used for assessing honey authenticity and quality control, combined with well-established analytical methods. Research related to investigation of the quality changes in honey due to modifications after processing and storage is rare, with a visibly increasing tendency in the last decade (and concentrated on investigating novel methods to preserve the honey quality, such as ultrasound or high-pressure treatment). This review presents the evolution in the last few years in using chemometrics in analyzing honey quality during processing and storage. The advantages of using chemometrics in assessing honey quality during storage and processing are presented, together with the main characteristics of some well-known chemometric methods. Chemometrics prove to be a successful tool to differentiate honey samples based on changes of characteristics during storage and processing.

A Combined Experimental and Theoretical Investigation of Oxidation Catalysis by cis-[VIV(O)(Cl/F)(N4)]+ Species Mimicking the Active Center of Metal-Enzymes.

Reaction of VIVOCl2 with the nonplanar tetradentate N4 bis-quinoline ligands yielded four oxidovanadium(IV) compounds of the general formula cis-[VIV(O)(Cl)(N4)]Cl. Sequential treatment of the two nonmethylated N4 oxidovanadium(IV) compounds with KF and NaClO4 resulted in the isolation of the species with the general formula cis-[VIV(O)(F)(N4)]ClO4. In marked contrast, the methylated N4 oxidovanadium(IV) derivatives are inert toward KF reaction due to steric hindrance, as evidenced by EPR and theoretical calculations. The oxidovanadium(IV) compounds were characterized by single-crystal X-ray structure analysis, cw EPR spectroscopy, and magnetic susceptibility. The crystallographic characterization showed that the vanadium compounds have a highly distorted octahedral coordination environment and the d(VIV-F) = 1.834(1) Å is the shortest to be reported for (oxido)(fluorido)vanadium(IV) compounds. The experimental EPR parameters of the VIVO2+ species deviate from the ones calculated by the empirical additivity relationship and can be attributed to the axial donor atom trans to the oxido group and the distorted VIV coordination environment. The vanadium compounds act as catalysts toward alkane oxidation by aqueous H2O2 with moderate ΤΟΝ up to 293 and product yields of up to 29% (based on alkane); the vanadium(IV) is oxidized to vanadium(V), and the ligands remain bound to the vanadium atom during the catalysis, as determined by 51V and 1H NMR spectroscopies. The cw X-band EPR studies proved that the mechanism of the catalytic reaction is through hydroxyl radicals. The chloride substitution reaction in the cis-[VIV(O)(Cl)(N4)]+ species by fluoride and the mechanism of the alkane oxidation were studied by DFT calculations.

Binuclear VIV/V, MoVI and ZnII - hydroquinonate complexes: Synthesis, stability, oxidative activity and anticancer properties.

Since the discovery of the anticancer properties of cis-platin the road for the development of less toxic and more specific metal ion based anticancer drugs has opened. Based on the low toxicity of VIV/V, MoVI and ZnII metal ions, their binuclear hydroquinonate complexes have been synthesized and their biological activity towards their anticancer properties on various cancerous and non-cancerous cell lines has been evaluated. The new complexes of ZnII with the ligands 2,5-bis((bis(pyridin-2-ylmethyl)amino)methyl)benzene-1,4-diol (H2bpymah) and 2,2'-(((2,5-dihydroxy-1,4-phenylene)bis(methylene))bis((carboxymethyl)ammoniumdiyl))diacetate (H6bicah) have been synthesized and characterized by X-ray crystallography in solid state and 1H NMR in aqueous solution. The binuclear nature of the complexes increases their hydrolytic stability in aqueous solutions at pD 7.0, depending on the metal ion. The most hydrolytic stable VV and ZnII hydroquinonate complexes show to activate O2 towards oxidation of mercaptoethanol in aqueous solutions at physiological pHs. Only the strongest oxidant, the VV complex with bicah6-, significantly activates the intracellular radical oxygen species (ROS) generation. Apparently, the mercaptoethanol oxidation experiment vs time can be used as a preliminary experiment for the prediction of the in vitro ROS generation activity of the complexes in aqueous solutions.

Enhancement of the Anti-Inflammatory Activity of NSAIDs by Their Conjugation with 3,4,5-Trimethoxybenzyl Alcohol.

The synthesis of derivatives of three nonspecific COX-1 and COX-2 inhibitors, ibuprofen, ketoprofen, naproxen is presented. These acids were connected via an amide bond with an amino acid (L-proline, L-tyrosine, and beta-alanine) used as a linker. The amino acid carboxylic group was esterified with 3,4,5 trimethoxybenzyl alcohol. The activity of the novel derivatives was examined in vivo on carrageenan-induced inflammation, and in vitro, as cyclooxygenase and lipoxygenase inhibitors. It was found that the new compounds were more potent anti-inflammatory agents than the parent drugs. Thus, the ibuprofen (21) and ketoprofen (16) derivatives reduced rat paw edema by 67 and 91% (the reduction by the relevant NSAIDs was 36 and 47%, respectively). They inhibited COX-2 more than the starting drugs (21 by 67%, ibuprofen 46%, 19 by 94%, ketoprofen 49%). Docking of compounds on the active sites of COX-1 and COX-2 reflects their in vitro activity. Thus, 19 adopts an unfavorable orientation for COX-1 inhibition, but it binds effectively in the binding pocket of COX-2, in agreement with the absence of activity for COX-1 and the high inhibition of COX-2. In conclusion, the performed structural modifications result in the enhancement of the anti-inflammatory activity, compared with the parent NSAIDs.

Synthesis, characterization and pharmacological evaluation of quinoline derivatives and their complexes with copper(ΙΙ) in in vitro cell models of Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disorder of the central nervous system. The main pathophysiological mechanisms involve cholinergic neurotransmission, beta-amyloid (Αß) and Tau proteins, several metal ions and oxidative stress, among others. Current drugs offer only relief of symptoms and not a cure of AD. Accumulating evidence suggests that multifunctional compounds, targeting multiple pathophysiological mechanisms, may have a great potential for the treatment of AD. In this study, we report on the synthesis and physicochemical characterization of four quinoline-based metal chelators and their respective copper(II) complexes. Most compounds were non-toxic at concentrations ≤5 µM. In neuroprotection studies employing undifferentiated and differentiated SH-SY5Y cells, the metal chelator N2,N6-di(quinolin-8-yl)pyridine-2,6-dicarboxamide (H2dqpyca) appeared to exert significant neuroprotection against both, Aß peptide- and H2O2-induced toxicities. The copper(II) complex [CuII(H2bqch)Cl2].3H2O (H2bqch = N,N'-Bis(8-quinolyl)cyclohexane-1,2-diamine) also protected against H2O2-induced toxicity, with a half-maximal effective concentration of 80 nM. Molecular docking simulations, using the crystal structure of the acetylcholinesterase (AChE)-rivastigmine complex as a template, indicated a strong interaction of the metal chelator H2dqpyca, followed by H2bqch, with both the peripheral anionic site and the catalytic active site of AChE. In conclusion, the sufficient neuroprotection provided by the metal chelator H2dqpyca and the copper(II) complex [CuII(H2bqch)Cl2].3H2O along with the evidence for interaction between H2dqpyca and AChE, indicate that these compounds have the potential and should be further investigated in the framework of preclinical studies employing animal models of AD as candidate multifunctional lead compounds for the treatment of the disease.

Synthesis of vitamin E and aliphatic lipid vanadium(IV) and (V) complexes, and their cytotoxic properties.

Novel vitamin E chelate derivatives and their VIV/V complexes have been synthesized and characterized, and their anticancer properties have been evaluated. The new complexes have been designed to exhibit enhanced cytotoxicity by combining high lipophilicity with the properties of vanadium to induce the formation of reactive oxygen species (ROS). In particular, the ß-tocopherol derivatives with iminodiethanol (ß-tocDEA) and dipicolylamine (ß-tocDPA) as well their VV and VIV complexes, [VVO(ß-tocDEA] and [VIVO(ß-tocDPA] have been synthesized and characterized by Nuclear Magnetic Resonance (NMR), Ultra Violet-Visible (UV-Vis) and Electron Paramagnetic Resonance (EPR) spectroscopies. Although the ß-tocopherol compounds exhibit antioxidant activity their complexes induce formation of radicals. In addition, two vanadium amphiphilic complexes of 2,2'-((2-hydroxyoctadecyl)azanediyl)bis(ethan-1-ol) (C18DEA) and 1-(bis(pyridin-2-ylmethyl)amino)octadecan-2-ol (C18DPA) known to activate O2 and produce ROS were synthesized and characterized (C. Drouza, A. Dieronitou, I. Hadjiadamou, M. Stylianou, J. Agric. Food. Chem., vol. 65, 2017, pp. 4942-4951). The four amphiphilic vanadium complexes exhibit enhanced hydrolytic stability. All compounds found to be cytotoxic for cancer cells exhibiting activity similar or higher to cis-platin.

Traditionally Used Sideritis cypria Post.: Phytochemistry, Nutritional Content, Bioactive Compounds of Cultivated Populations.

Sideritis species are recognized as important medicinal plants and their commercial demand is continuously on the rise both in the European and in the global market. Consequently, the cultivation of Sideritis species has been occurred to successfully meet the need for mass production of high-quality plant material. The present study was undertaken in order to investigate the chemical composition of cultivated S. cypria. Infusions of flowers and leaves were prepared separately, according to the European Medicine Agency (EMA) monograph. The infusion of the flowers revealed the presence of four flavones, isoscutellarein-7-O-[6'″-O-acetyl-ß-D-allopyranosyl-(1→2)-ß-D-glucopyranoside, its 4'-O-methyl-derivative, 4'-O-methyl-hypolaetin-7-O-[6'″-O-acetyl-ß-D-allopyranosyl-(1→2)-ß-D-glucopyranoside, and isoscutellarein-7-O-[6'″-O-acetyl-ß-D-allopyranosyl-(1→2)]-6″-O-acetyl-ß-D-glucopyranoside; four phenylethanoid glucosides, acteoside, leucosceptoside A, lamalboside, and leonoside A; one iridoid, melittoside, and one phenolic acid, chlorogenic acid, while the infusion of the leaves of the same population afforded the same first two flavones; five phenylethanoid glucosides, acteoside, leucosceptoside A, lavandulifolioside, leonoside A, and lamalboside; melittoside and chlorogenic acid. The structural elucidation of the isolated compounds was undertaken by high-field NMR spectroscopy. Moreover, the essential oils of the flowers and leaves were studied by GC-MS, separately. In addition, the mineral, bioactive compounds, protein and carbohydrate contents were evaluated for both plant materials.

Investigation of dioxygen activation by copper(ii)-iminate/aminate complexes.

The activation of dioxygen by metal ions is critical in chemical and bio-chemical processes. A scientific challenge is the elucidation of the activation site of dioxygen in some copper metalloproteins, which is either the metal center or the substrate. In an effort to address this challenge, we prepared a series of new copper(ii) complexes (1·2H2O, 2·CH3OH, 3) with bio-inspired amidate ligands and investigated their activity towards dioxygen activation. The secondary amine group ligated to copper(ii) of the complex 1·2H2O in methyl alcohol is oxidized (2e-) by air dioxygen in a stepwise fashion to an imine group, affording complex 2. The copper(ii) complex 2 in methyl alcohol induces the 4e- oxidation by air dioxygen of the imine functionality ligated to copper(ii) to an azinate group, resulting in the isolation of a dinuclear azinate copper(ii) compound (4). Experimental and computational studies, including X-band c. w. EPR, UV-vis and ESI-MS spectroscopy and density functional theory computations, indicate a direct attack of the dioxygen on the -HC[double bond, length as m-dash]N- group ligated to copper(ii), and a possible mechanism of the oxidation of the -HC[double bond, length as m-dash]N- functionality ligated to copper(ii) to an azinate group is provided. This unprecedented activation of dioxygen by a copper substrate paves the way for further exploration of the O2 activation mechanisms in enzymes and the development of effective catalysts in O2-involved green organic synthesis.

Characterization and Botanical Differentiation of Monofloral and Multifloral Honeys Produced in Cyprus, Greece, and Egypt Using Physicochemical Parameter Analysis and Mineral Content in Conjunction with Supervised Statistical Techniques.

Thirty-four honey samples donated by beekeepers and purchased from supermarkets were collected during harvesting years 2010-2014 from Cyprus, Greece, and Egypt. The aims of this study were to characterize honey samples and, if possible, to differentiate honeys according to the honey type on the basis of physicochemical parameter values, mineral content, and their combination using supervised statistical techniques (linear discriminant analysis (LDA)). Physicochemical parameters (colour, pH, free acidity, total dissolved solids, salinity, electrical conductivity, and moisture content) were determined according to official methods, while minerals (Al, As, B, Ba, Be, Ca, Cd, Co, Cr, Cu, Fe, Hg, Mg, Mn, Mo, Ni, P, Pb, Sb, Si, Ti, Tl, V, and Zn) using inductively coupled plasma optical emission spectrometry. The majority of honey samples analyzed met the quality criteria set by the European directive and national decision related to honey. Implementation of multivariate analysis of variance (MANOVA) and LDA on specific physicochemical parameters, minerals, or their combination provided a satisfactory classification of honeys according to floral type. The overall correct classification rate (based on the cross-validation method) was 79.4% using 7 minerals and 91.2% using 8 physicochemical parameters. When the 15 parameters were combined, the classification rate of Egyptian honeys was improved by 25%.

Chemometric characterization of virgin olive oils of the two major Cypriot cultivars based on their fatty acid composition.

The effects of the geographical region and the botanical origin of olive oils on the profile of fatty acids isolated from monovarietal virgin olive oils from Cyprus were investigated, in order to establish, for the first time, promising models for authentication and classification of monovarietal virgin olive oils produced on the island. The two dominant Cypriot olive cultivars, Cypriot (ladoelia), and Koroneiki (lianolia), were analyzed for fatty acid composition by GC/FID after preparation of Fatty Acid Methyl Esters from olive oil, using a cold esterification method. The data obtained were analyzed statistically using multivariate and univariate ANOVA, principal components analysis (PCA) and hierarchical cluster analysis. Results showed that the olive oils can be separated into two distinct groups using the FAME data bank obtained from 225 samples. Significant differences in the proportion of some variables such as polyunsaturated linoleic acid, and the ratio C18:1/C18:2 from oils of different varieties and geographical regions were detected. The ratios C18:1/C18:2 and MUFA/PUFA, as well SFA, ω-9 and PUFA showed the higher discriminant power based on the cultivar.

Investigation of Phenols Activity in Early Stage Oxidation of Edible Oils by Electron Paramagnetic Resonance and 19F NMR Spectroscopies Using Novel Lipid Vanadium Complexes As Radical Initiators.

A novel dynamic method for the investigation of the phenols activity in early stage oxidation of edible oils based on the formation of α-tocopheryl radicals initiated by oil-soluble vanadium complexes is developed. Two new vanadium complexes in oxidation states V and IV were synthesized by reacting 2,2'-((2-hydroxyoctadecyl)azanediyl)bis(ethan-1-ol) (C18DEA) with [VO(acac)2] and 1-(bis(pyridin-2-ylmethyl)amino)octadecan-2-ol (C18DPA) with VOCl2. Addition of a solution of either complex in edible oils resulted in the formation of α-tocopheryl radical, which was monitored by electron paramagnetic resonance (EPR) spectroscopy. The intensity of the α-tocopheryl signal in the EPR spectra was measured versus time. It was found that the profile of the intensity of the α-tocopheryl signal versus time depends on the type of oil, the phenolic content, and the storage time of the oil. The time interval until the occurrence of maximum peak intensity be reached (tm), the height of the maximum intensity, and the rate of the quenching of the α-tocopheryl radical were used for the investigation of the mechanism of the edible oils oxidation. 19F NMR of the 19F labeled phenolic compounds (through trifluoroacetate esters) and radical trap experiments showed that the vanadium complexes in edible oil activate the one electron reduction of dioxygen to superperoxide radical. Superperoxide reacts with the lipids to form alkoperoxyl and alkoxyl lipid radicals, and all these radicals react with the phenols contained in oils.

Synthesis, Bonding, and Reactivity of Vanadium(IV) Oxido-Fluorido Compounds with Neutral Chelate Ligands of the General Formula cis-[V(IV)(═O)(F)(L(N-N))2](+).

Reaction of the oxidovanadium(IV)-L(N-N) species (L(N-N) is bipy = 2,2'-bipyridine or bipy-like molecules) with either BF4(-) or HF and/or KF results in the formation of compounds of the general formula cis-[V(IV)(═O)(F)(L(N-N))2](+). Structural and spectroscopic (electron paramagnetic resonance) characterization shows that these compounds are in the tetravalent oxidation state containing a terminal fluorido ligand. Density functional theory calculations reveal that the V(IV)-F bond is mainly electrostatic, which is reinforced by reactivity studies that demonstrate the nucleophilicity of the fluoride ligand in a halogen exchange reaction and in fluorination of various organic substrates.

Aerial Oxidation of a V(IV)-Iminopyridine Hydroquinonate Complex: A Trap for the V(IV)-Semiquinonate Radical Intermediate.

The reaction of 2,5-bis[N,N'-bis(2-pyridyl-aminomethyl)aminomethyl]-p-hydroquinone (H2bpymah) with VO(2+) salts in acetonitrile or water at a low pH (2.2-3.5) results in the isolation of [{V(IV)(O)(Cl)}2(µ-bpymah)], the p-semiquinonate complex [{V(IV)(O)(Cl)}2(µ-bpymas)](OH), the cyclic mixed-valent hexanuclear compound [{V(V)(O)(µ-O)V(IV)(O)}(µ-bpymah)]3, and [(V(V)O2)2(µ-bpymah)]. [{V(IV)(O)(Cl)}2(µ-bpymas)](OH) is an intermediate of the radical-mediated oxidation of [{V(IV)(O)(Cl)}2(µ-bpymah)] from O2. At lower pH values (2.2), a reversible intramolecular electron transfer from the metal to the ligand of [{V(IV)(O)(Cl)}2(µ-bpymas)](OH) is induced with the concurrent substitution of chlorine atoms by the oxygen-bridging atoms, resulting in the formation of [{V(V)(O)(µ-O)V(IV)(O)}(µ-bpymah)]3. The metal complexes were fully characterized by X-ray crystallography, infrared (IR) spectroscopy, and magnetic measurements in the solid state, as well as by conductivity measurements, UV-vis spectroscopy, and electrochemical measurements in solution. The oxidation states of the metal ions and ligands were determined by the crystallographic data. The [{V(IV)(O)(Cl)}2(µ-bpymah)]-[{V(IV)(O)(Cl)}2(µ-bpymas)](OH) redox process is electrochemically reversible. The V(IV) ion in the semiquinonate compound exhibits a surprisingly low oxophilicity, resulting in the stabilization of OH(-) counterions at acidic pH values. An investigation of the mechanism of this reaction reveals that these complexes induce the reduction of O2 to H2O2, mimicking the activity of enzymes incorporating two redox-active centers (metal-organic) in the active site.

Donor atom electrochemical contribution to redox potentials of square pyramidal vanadyl complexes.

A simple donor atom additivity relationship has been used to calculate the donor atom electrochemical contribution (DEC) of the Oac (acetylacetonate-enolic oxygen), OPh (phenolic oxygen), SPh (mercaptophenol sulfur), Nam (deprotonate amide nitrogen), Nim (imine nitrogen) and Npy (pyridine nitrogen) to the redox processes of the square pyramidal vanadyl complexes. The study focuses on the amidate vanadyl complexes because of (a) their biological interest and (b) the existence of data from plethora complexes studied in great details. The electrochemical contributions for the vanadyl oxidation and reduction processes increase following the same order, OPh~Oac(enolic)

Vanadium(IV/V)-p-dioxolene temperature induced electron transfer associated with ligation/deligation of solvent molecules.

Reaction of an aqueous solution of NaVO3 or a methanol solution of [VO(acac)2] with 2,5-bis((bis(2-hydroxyethyl)amino)methyl)hydroquinone, H6bdeah, results in the formation of two major vanadium species characterized by X-ray crystallography: the [(V(5+)O)2(bdeah)] and the [(V(4.5+)O)2(bdeas)S2] (S = DMSO or MeOH). The vanadium ions in the two species have a trigonal pyramidal and an octahedral coordination sphere respectively. Variable temperature UV-Vis and (51)V NMR spectroscopy as well as EPR and electrochemistry showed a temperature induced electron transfer. The diamagnetic [(V(5+)O)2(bdeah)] is the main species at high temperature. At low temperature one electron is transferred from the bdeah(6-) to the two vanadium centers resulting in the [(V(4.5+)O)2(bdeas)S2] species [H5bdeas = 2,5-bis((bis(2-hydroxyethyl)amino)methyl)-1,4-semiquinone]. The thermodynamic parameters of this intramolecular electron transfer were calculated by UV-Vis (ΔH = -36 ± 2 kJ mol(-1) and ΔS = -129 ± 5 J mol(-1) K(-1)) and (51)V NMR spectroscopy (ΔH = -37 ± 2 kJ mol(-1) and ΔS = -109 ± 5 J mol(-1) K(-1)). The electron transfer is a result of the large change of entropy which is associated with the ligation of the solvent molecules and the geometry change. EPR spectroscopy shows that most of the electron density in [(V(4.5+)O)2(bdeas)S2] is mainly located on the two vanadium ions.

From Blatter radical to 7-substituted 1,3-diphenyl-1,4-dihydrothiazolo[5',4':4,5]benzo[1,2-e][1,2,4]triazin-4-yls: toward multifunctional materials.

A Blatter radical is oxidized to benzotriazin-7(H)-one which after amination and subsequent acyl- and aroylation gives N-(benzotriazin-6-yl)carboxamides that undergo ring closure with P(2)S(5) to afford the corresponding thiazolo[5',4':4,5]benzo[1,2-e][1,2,4]triazin-4-yls. These highly delocalized radicals are air stable and show good reversible electrochemical behavior.

pH-Potentiometric Investigation towards Chelating Tendencies of p-Hydroquinone and Phenol Iminodiacetate Copper(II) Complexes.

Copper ions in the active sites of several proteins/enzymes interact with phenols and quinones, and this interaction is associated to the reactivity of the enzymes. In this study the speciation of the Cu(2+) with iminodiacetic phenolate/hydroquinonate ligands has been examined by pH-potentiometry. The results reveal that the iminodiacetic phenol ligand forms mononuclear complexes with Cu(2+) at acidic and alkaline pHs, and a binuclear O(phenolate)-bridged complex at pH range from 7 to 8.5. The binucleating hydroquinone ligand forms only 2 : 1 metal to ligand complexes in solution. The pK values of the protonation of the phenolate oxygen of the two ligands are reduced about 2 units after complexation with the metal ion and are close to the pK values for the copper-interacting tyrosine phenol oxygen in copper enzymes.

Synthesis, solution, and structural characterization of tetrahydrofuranyl-2,2-bisphosphonic acid disodium salt.

Bisphosphonates are biologically relevant therapeutics for bone disorders and cancer. Reaction of gamma-chlorobutyric acid, phosphorus acid, and phosphorus trichloride without the use of solvent gave the tetrahydrofuranyl-2,2-bisphosphonate sodium salt (Na(2)H(2)L). The Na(2)H(2)L was isolated, characterized in solution by (1)H, (13)C, and (31)P NMR spectroscopy and in solid state by single X-Ray crystallography. The crystal structure showed that the Na(2)H(2)L forms in the crystal infinite two-dimensional sheets stacked one parallel to the other. A comparison of the chelating properties of H(2)L(2-) with similar hydroxyl bisphosphonate ligands shows that the strength of the Na-O(furanyl/hydroxyl) bond is directly related to the total charge of the ligand anion.