Antioxidant and cellular activities of anthocyanins and their corresponding vitisins A - studies in platelets, monocytes, and human endothelial cells

During red wine aging, there is a loss of anthocyanins and the formation of various other pigments, so-called vitisins A, which are formed through the chemical interaction of the original anthocyanins with pyruvic acid. The objective of this study was to investigate the antioxidant activities of the most abundant anthocyanins present in red wine (glycosides of delphinidin, petunidin, and malvidin) and their corresponding vitisins A. Anthocyanins exhibited a higher iron reducing as well as 2,2'-azinobis (3-ethyl-benzothiazoline-6-sulfonate) and peroxyl radical scavenging activity than their corresponding vitisins A. Delphinidin showed the highest antioxidant effect of the tested compounds in all of the assays used. Furthermore, we studied the effect of anthocyanins and vitisins A on platelet aggregation and monocyte and endothelial function. Anthocyanins and vitisins did not affect nitric oxide production and tumor necrosis factor-alpha (TNF-alpha) secretion in lipopolysaccharide plus interferon-gamma-activated macrophages. Furthermore, anthocyanins and vitisins did not change collagen-induced platelet aggregation in vitro. However, anthocyanins and to a lesser extent vitisins exhibited protective effects against TNF-alpha-induced monocyte chemoattractant protein production in primary human endothelial cells.

Theoretical studies of the interface between water and Langmuir films of aliphatic alcohols

The interface between water and Langmuir films of long chain aliphatic molecules is investigated using accurate intermolecular potentials. The stabilities of various ice structures which could form at the interface are examined. Antiferroelectric ice is found to be the most stable, but this stability depends crucially on the first layer of water. Ferroelectric structures are found to collapse upon relaxation. Our model was not able to differentiate between the different nucleation properties of C31H63OH and C30H61OH. A better description of the alcohol–water interaction is probably required to account for this difference.

Kinetic studies of reactions of the nitrate radical (NO3) with peroxy radicals (RO2): an indirect source of OH at night?

A discharge-flow system, coupled to cavity-enhanced absorption spectroscopy (CEAS) detection systems for NO3 at lambda = 662 nm and NO2 at lambda = 404 nm, was used to investigate the kinetics of the reactions of NO3 with eight peroxy radicals at P similar to 5 Torr and T similar to 295 K. Values of the rate constants obtained were (k/10(-12) cm(3) molecule(-1) s(-1)): CH3O2 (1.1 +/- 0.5), C2H5O2 (2.3 +/- 0.7), CH2FO2 (1.4 +/- 0.9), CH2ClO2 (3.8(-2.6)(+1.4)), c-C5H9O2 (1.2(-0.5)(+1.1)), c-C6H11O2 (1.9 +/- 0.7), CF3O2 (0.62 +/- 0.17) and CF3CFO2CF3 (0.24 +/- 0.13). We explore possible relationships between k and the orbital energies of the reactants. We also provide a brief discussion of the potential impact of the reactions of NO3 with RO2 on the chemistry of the night-time atmosphere.

Diorganoruthenium complexes incorporating noninnocent [C6H2(CH2ER2)2-3,5]22-(E = N, P) Bis-Pincer bridging ligands: synthesis, spectroelectrochemistry, and DFT studies

The dinuclear complex [(tpy)Ru-II(PCP-PCP)Ru-II(tPY)]Cl-2 (bridging PCP-PCP = 3,3',5,5'-tetrakis(diphenylphosphinomethyl)biphenyl, [C6H2(CH2PPh2)(2)-3,5](2)(2-)) was prepared via a transcyclometalation reaction of the bis-pincer ligand [PC(H)P-PC(H)P] and the Ru(II) precursor [Ru(NCN)(tpy)]Cl (NCN = [C6H3(CH2NMe2)(2)-2,6](-)) followed by a reaction with 2,2':6',2 ''-terpyridine (tpy). Electrochemical and spectroscopic properties of [(tpy)Ru-II(PCP-PCP)Ru-II(tPY)]Cl-2 are compared with those of the closely related [(tpy)Ru-II(NCN-NCN)Ru-II(tpy)](PF6)(2) (NCN-NCN = [C6H2(CH2- NMe2)(2)-3,5](2)(2-)) obtained by two-electron reduction of [(tpy)Ru-III(NCN-NCN)Ru-III(tpy)](PF6)(4). The molecular structure of the latter complex has been determined by single-crystal X-ray structure determination. One-electron reduction of [(tpy)Ru-III(NCN-NCN)Ru-III(tpy)](PF6)(4) and one-electron oxidation of [(tpy)Ru-II(PCP-PCP)RUII(tpy)]Cl-2 yielded the mixed-valence species [(tpy)Ru-III(NCN-NCN)RUII(tpy)](3+) and [(tpy)Ru-III(PCP-PCP)RUII(tpy)](3+), respectively. The comproportionation equilibrium constants K-c (900 and 748 for [(tpy)Ru-III(NCN-NCN)Ru-III(tpy)](4+) and [(tpy)Ru-II(PCP-PCP)RUII(tpy)](2+), respectively) determined from cyclic voltammetric data reveal comparable stability of the [Ru-III-Ru-II] state of both complexes. Spectroelectrochemical measurements and near-infrared (NIR) spectroscopy were employed to further characterize the different redox states with special focus on the mixed-valence species and their NIR bands. Analysis of these bands in the framework of Hush theory indicates that the mixed-valence complexes [(tpy)Ru-III(PCP-PCP)RUII(tpy)](3+) and [(tpy)Ru-III(NCN-NCN)RUII(tpy)](3+) belong to strongly coupled borderline Class II/Class III and intrinsically coupled Class III systems, respectively. Preliminary DFT calculations suggest that extensive delocalization of the spin density over the metal centers and the bridging ligand exists. TD-DFT calculations then suggested a substantial MLCT character of the NIR electronic transitions. The results obtained in this study point to a decreased metal-metal electronic interaction accommodated by the double-cyclometalated bis-pincer bridge when strong sigma-donor NMe2 groups are replaced by weak sigma-donor, pi-acceptor PPh2 groups

Gas-phase kinetics of chlorosilylene reactions II. ClSiH + C2H4: absolute rate measurements and quantum chemical and RRKM calculations for the prototype pi addition reaction

Time-resolved studies of chlorosilylene, ClSiH, generated by the 193 nm laser flash photolysis of 1-chloro-1-silacyclopent-3-ene, are carried out to obtain rate constants for its bimolecular reaction with ethene, C2H4, in the gas-phase. The reaction is studied over the pressure range 0.13-13.3 kPa (with added SF6) at five temperatures in the range 296-562 K. The second order rate constants, obtained by extrapolation to the high pressure limits at each temperature, fitted the Arrhenius equation: log(k(infinity)/cm(3) molecule(-1) s(-1))=(-10.55 +/- 0.10) + (3.86 +/- 0.70) kJ mol(-1)/RT ln10. The Arrhenius parameters correspond to a loose transition state and the rate constant at room temperature is 43% of that for SiH2 + C2H4, showing that the deactivating effect of Cl-for-H substitution in the silylene is not large. Quantum chemical calculations of the potential energy surface for this reaction at the G3MP2//B3LYP level show that, as well as 1-chlorosilirane, ethylchlorosilylene is a viable product. The calculations reveal how the added effect of the Cl atom on the divalent state stabilisation of ClSiH influences the course of this reaction. RRKM calculations of the reaction pressure dependence suggest that ethylchlorosilylene should be the main product. The results are compared and contrasted with those of SiH2 and SiCl2 with C2H4.

NMR studies of the conformational effect of single and double 3'-S-phosphorothiolate substitutions within deoxythymidine trinucleotides

NMR spectroscopy has been used to investigate the conformational effects of single and two consecutive 3′-S-phosphorothiolate modifications within a deoxythymidine trinucleotide. The presence of a single 3′-phosphorothioate modification shifts the conformation of the sugar ring it is attached to, from a mainly south to north pucker; this effect is also transmitted to the 3′-neighbour deoxyribose. This transmission is thought to be caused by favourable stacking of the heterocyclic bases. Similar observations have been made previously by this group. When two adjacent modifications are present, the conformations of the attached deoxyribose rings are again shifted almost completely to the north, however, there is no transmission to the 3′ deoxyribose ring. Base proton chemical shift analysis and molecular modelling have been used to aid elucidation of the origin of this feature. The observation for the dimodified sequence is consistent with our previously reported results for a related system in which spaced modifications are more thermodynamically stable than consecutive ones.

Self-assembled molecular complexes and coordination polymers of CdII, hexamine, and monocarboxylates: structural analysis and theoretical studies of supramolecular interactions

Four new cadmium(II) complexes [Cd-2(bz)(4)(H2O)(4)(mu 2-hmt)]center dot Hbz center dot H2O (1), [Cd-3(bz)(6)(H2O)(6)(mu 2-hmt)(2)]center dot 6H(2)O (2), [Cd(pa)(2)(H2O)(mu(2)-hmt)](n) (3), and {[Cd-3(ac)(6)(H2O)(3)(mu(3)-hmt)(2)]center dot 6H(2)O}(n) (4) with hexamine (hmt) and monocarboxylate ions, benzoate (bz), phenylacetate (pa), or acetate (ac) have been synthesized and characterized structurally. Structure determinations reveal that 1 is dinuclear, 2 is trinuclear, 3 is a one-dimensional (1D) infinite chain, and 4 is a two-dimensional (2D) polymer with fused hexagonal rings consisting of Cd-II and hmt. All the Cd-II atoms in the four complexes (except one CdII in 2) possess seven-coordinate pentagonal bipyramidal geometry with the various chelating bidentate carboxylate groups in equatorial sites. One of the CdII ions in 2, a complex that contains two monodentate carboxylates is in a distorted octahedral environment. The bridging mode of hmt is mu 2- in complexes 1-3 but is mu 3- in complex 4. In all complexes, there are significant numbers of H-bonds, C-H/pi, and pi-pi interactions which play crucial roles in forming the supramolecular networks. The importance of the noncovalent interactions in terms of energies and geometries has been analyzed using high level ab initio calculations. The effect of the cadmium coordinated to hmt on the energetic features of the C-H/pi interaction is analyzed. Finally, the interplay between C-H/pi and pi-pi interactions observed in the crystal structure of 3 is also studied.

A dialkylborenium ion via reaction of N-heterocyclic carbene–organoboranes with Brønsted acids—synthesis and DOSY NMR studies

A dialkylborenium ion stabilized by an N-heterocyclic carbene has been prepared for the first time by reaction of IMes-9-BBN-H with triflic acid. The ion-separated nature of the borenium ion was confirmed by 1H and 19F diffusion ordered NMR spectroscopy.

Nickel(II) and copper(II) complexes of Schiff base ligands containing N4O2 and N4S2 donors with pyrrole terminal binding groups: synthesis, characterization, X-ray structures, DFT and electrochemical studies

A series of hexadentate ligands, H2Lm (m = 1−4), [1H-pyrrol-2-ylmethylene]{2-[2-(2-{[1H-pyrrol-2-ylmethylene]amino}phenoxy)ethoxy]phenyl}amine (H2L1), [1H-pyrrol-2-ylmethylene]{2-[4-(2-{[1H-pyrrol-2-ylmethylene]amino}phenoxy)butoxy]phenyl}amine (H2L2), [1H-pyrrol-2-ylmethylene][2-({2-[(2-{[1H-pyrrol-2-ylmethylene]amino}phenyl)thio]ethyl}thio)phenyl]amine (H2L3) and [1H-pyrrol-2-ylmethylene][2-({4-[(2-{[1H-pyrrol-2-lmethylene]amino}phenyl)thio]butyl}thio) phenyl]amine (H2L4) were prepared by condensation reaction of pyrrol-2-carboxaldehyde with {2-[2-(2-aminophenoxy)ethoxy]phenyl}amine, {2-[4-(2-aminophenoxy)butoxy]phenyl}amine, [2-({2-[(2-aminophenyl)thio]ethyl}thio)phenyl]amine and [2-({4-[(2-aminophenyl)thio]butyl}thio)phenyl]amine respectively. Reaction of these ligands with nickel(II) and copper(II) acetate gave complexes of the form MLm (m = 1−4), and the synthesized ligands and their complexes have been characterized by a variety of physico-chemical techniques. The solid and solution states investigations show that the complexes are neutral. The molecular structures of NiL3 and CuL2, which have been determined by single crystal X-ray diffraction, indicate that the NiL3 complex has a distorted octahedral coordination environment around the metal while the CuL2 complex has a seesaw coordination geometry. DFT calculations were used to analyse the electronic structure and simulation of the electronic absorption spectrum of the CuL2 complex using TDDFT gives results that are consistent with the measured spectroscopic behavior of the complex. Cyclic voltammetry indicates that all copper complexes are electrochemically inactive but the nickel complexes with softer thioethers are more easily oxidized than their oxygen analogs.

Molecular modelling studies of binding of DACD derivatives into G-Quadruplex DNA: comparison of force field and quantum polarized ligand docking methods

The DNA G-qadruplexes are one of the targets being actively explored for anti-cancer therapy by inhibiting them through small molecules. This computational study was conducted to predict the binding strengths and orientations of a set of novel dimethyl-amino-ethyl-acridine (DACA) analogues that are designed and synthesized in our laboratory, but did not diffract in Synchrotron light.Thecrystal structure of DNA G-Quadruplex(TGGGGT)4(PDB: 1O0K) was used as target for their binding properties in our studies.We used both the force field (FF) and QM/MM derived atomic charge schemes simultaneously for comparing the predictions of drug binding modes and their energetics. This study evaluates the comparative performance of fixed point charge based Glide XP docking and the quantum polarized ligand docking schemes. These results will provide insights on the effects of including or ignoring the drug-receptor interfacial polarization events in molecular docking simulations, which in turn, will aid the rational selection of computational methods at different levels of theory in future drug design programs. Plenty of molecular modelling tools and methods currently exist for modelling drug-receptor or protein-protein, or DNA-protein interactionssat different levels of complexities.Yet, the capasity of such tools to describevarious physico-chemical propertiesmore accuratelyis the next step ahead in currentresearch.Especially, the usage of most accurate methods in quantum mechanics(QM) is severely restricted by theirtedious nature. Though the usage of massively parallel super computing environments resulted in a tremendous improvement in molecular mechanics (MM) calculations like molecular dynamics,they are still capable of dealing with only a couple of tens to hundreds of atoms for QM methods. One such efficient strategy that utilizes thepowers of both MM and QM are the QM/MM hybrid methods. Lately, attempts have been directed towards the goal of deploying several different QM methods for betterment of force field based simulations, but with practical restrictions in place. One of such methods utilizes the inclusion of charge polarization events at the drug-receptor interface, that is not explicitly present in the MM FF.

Application of the BRAFO-tiered approach for benefit-risk assessment to case studies on natural foods

There is evidence that consumption of fish, especially oily fish, has substantial beneficial effects on health. In particular an inverse relationship of oily fish intake to coronary heart disease incidence has been established. These beneficial effects are ascribed to fish oil components including long chain ω-3 polyunsaturated fatty acids. On the other hand it should be noted that oily fish also contains hazardous substances such as dioxins, PCBs and methylmercury. Soy consumption has been associated with potential beneficial and adverse effects. The claimed benefits include reduced risk of cardiovascular disease; osteoporosis, breast and prostate cancer whereas potential adverse effects include impaired thyroid function, disruption of sex hormone levels, changes in reproductive function and increased breast cancer risk The two cases of natural foods highlight the need to consider both risks and benefits in order to establish the net health impact associated to the consumption of specific food products. Within the Sixth Framework programme of the European Commission, the BRAFO project was funded to develop a framework that allows for the quantitative comparison of human health risks and benefits in relation to foods and food compounds. This paper describes the application of the developed framework to two natural foods, farmed salmon and soy protein. We conclude that the BRAFO methodology is highly applicable to natural foods. It will help the benefit-risk managers in selecting the appropriate dietary recommendations for the population.

Unraveling the electronic structures of low-valent naphthalene and anthracene iron complexes: x-ray, spectroscopic, and density functional theory studies

Naphthalene and anthracene transition metalates are potent reagents, but their electronic structures have remained poorly explored. A study of four Cp*-substituted iron complexes (Cp* = pentamethylcyclopentadienyl) now gives rare insight into the bonding features of such species. The highly oxygen- and water-sensitive compounds [K(18-crown- 6){Cp*Fe(η4-C10H8)}] (K1), [K(18-crown-6){Cp*Fe(η4-C14H10)}] (K2), [Cp*Fe(η4-C10H8)] (1), and [Cp*Fe(η4-C14H10)] (2) were synthesized and characterized by NMR, UV−vis, and 57Fe Mössbauer spectroscopy. The paramagnetic complexes 1 and 2 were additionally characterized by electron paramagnetic resonance (EPR) spectroscopy and magnetic susceptibility measurements. The molecular structures of complexes K1, K2, and 2 were determined by single-crystal X-ray crystallography. Cyclic voltammetry of 1 and 2 and spectroelectrochemical experiments revealed the redox properties of these complexes, which are reversibly reduced to the monoanions [Cp*Fe(η4-C10H8)]− (1−) and [Cp*Fe(η4-C14H10)]− (2−) and reversibly oxidized to the cations [Cp*Fe(η6-C10H8)]+ (1+) and [Cp*Fe(η6-C14H10)]+ (2+). Reduced orbital charges and spin densities of the naphthalene complexes 1−/0/+ and the anthracene derivatives 2−/0/+ were obtained by density functional theory (DFT) methods. Analysis of these data suggests that the electronic structures of the anions 1− and 2− are best represented by low-spin FeII ions coordinated by anionic Cp* and dianionic naphthalene and anthracene ligands. The electronic structures of the neutral complexes 1 and 2 may be described by a superposition of two resonance configurations which, on the one hand, involve a low-spin FeI ion coordinated by the neutral naphthalene or anthracene ligand L, and, on the other hand, a low-spin FeII ion coordinated to a ligand radical L•−. Our study thus reveals the redox noninnocent character of the naphthalene and anthracene ligands, which effectively stabilize the iron atoms in a low formal, but significantly higher spectroscopic oxidation state.

Steric effects on uranyl complexation: synthetic, structural, and theoretical studies of carbamoyl pyrazole compounds of the uranyl(VI) ion

New bifunctional pyrazole based ligands of the type [C3HR2N2CONR'] (where R = H or CH3; R' = CH3, C2H5, or (C3H7)-C-i) were prepared and characterized. The coordination chemistry of these ligands with uranyl nitrate and uranyl bis(dibenzoyl methanate) was studied with infrared (IR), H-1 NMR, electrospray-mass spectrometry (ES-MS), elemental analysis, and single crystal X-ray diffraction methods. The structure of compound [UO2(NO3)(2)(C3H3N2CON{C2H5}(2))] (2) shows that the uranium(VI) ion is surrounded by one nitrogen atom and seven oxygen atoms in a hexagonal bipyramidal geometry with the ligand acting as a bidentate chelating ligand and bonds through both the carbamoyl oxygen and pyrazolyl nitrogen atoms. In the structure of [UO2(NO3)(2)(H2O)(2)(C5H7N2CON {C2H5}(2))(2)], (5) the pyrazole figand acts as a second sphere ligand and hydrogen bonds to the water molecules through carbamoyl oxygen and pyrazolyl nitrogen atoms. The structure of [UO2(DBM)(2)C3H3N2CON{C2H5}(2)] (8) (where DBM = C6H5COCHCOC6H5) shows that the pyrazole ligand acts as a monodentate ligand and bonds through the carbamoyl oxygen to the uranyl group. The ES-MS spectra of 2 and 8 show that the ligand is similarly bonded to the metal ion in solution. Ab initio quantum chemical studies show that the steric effect plays the key role in complexation behavior.

Environmental oestrogens and breast cancer: long-term low-dose effects of mixtures of various chemical combinations

The incidence of breast cancer has risen worldwide to unprecedented levels in recent decades, making it now the major cancer of women in many parts of the world.1 Although diet, alcohol, radiation and inherited loss of BRCA1/2 genes have all been associated with increased incidence, the main identified risk factors are life exposure to hormones including physiological variations associated with puberty/pregnancy/menopause,1 personal choice of use of hormonal contraceptives2 and/or hormone replacement therapy.3–6 On this basis, exposure of the human breast to the many environmental pollutant chemicals capable of mimicking or interfering with oestrogen action7 should also be of concern.8 Hundreds of such environmental chemicals have now been measured in human breast tissue from a range of dietary and domestic exposure sources7 ,9 including persistent organochlorine pollutants (POPs),10 polybrominated diphenylethers and polybromobiphenyls,11 polychlorinated biphenyls,12 dioxins,13 alkyl phenols,14 bisphenol-A and chlorinated derivatives,15 as well as other less lipophilic compounds such as parabens (alkyl esters of p-hydroxybenzoic acid),16 but studies investigating any association between raised levels of such compounds and the development of breast cancer remain inconclusive.7–16 However, the functionality of these chemicals has continued to be assessed on the basis of individual chemicals rather than the environmental reality of long-term low-dose exposure to complex mixtures. This misses the potential for individuals to have high concentrations of different compounds but with a common mechanism of action. It also misses the complex interactions between chemicals and physiological hormones which together may act to alter the internal homeostasis of the oestrogenic environment of mammary tissue.