Studies of Fructus schizandrae. IV. Isolation and determination of the active compounds (in lowering high SGPT levels) of Schizandra chinensis Baill

The alcoholic extracts of the kernels of Schizandra chinensis Baill have been reported to be capable of lowering elevated SGPT levels in mice induced by CCl4 and inhibiting the central nervous system. Seven pharmacological active compounds have been isolated from the alcoholic extracts by column chromatography. Five of them are identified as wuweizisu C (I), wuweizisu B (II), wuweizisu A (III), wuweizichun B (IV) and wuweizichun A (V). They are all derivatives of the dibenzo (a, c) cyclooctene system, among which compounds I and IV have hitherto not been reported in literature. Ozonolysis of III and subsequent oxidation with H2O2 yields meso-3,4-dimethyladipic acid. Pyrolytic syn-elimination of V acetate and oxidation of the resultant olefin (V-4) affords a diketone (V-5) with molecular weight of 446. According to these results and based on the NMR spectra, the two methyl groups at C-6 and C-7 of compound I--V must be cis-oriented.     

Zn-exchange and M?ssbauer studies on the [Fe-Fe] derivatives of the purple acid Fe(III)-Zn(II)-phosphatase from kidney beans

In order to perform M?ssbauer studies, Zn(II) in the Fe(III)-Zn(II) purple acid phosphatase of the red kidney bean has been exchanged by incubating the semiapoenzyme with 57Fe(II). The resulting Fe(III)-57Fe(II) enzyme has 125% activity, compared with that of the Zn(II) enzyme. It can be oxidized by H2O2 or peroxydisulfate to the Fe(III)-57Fe(III) species with a 30-times lower activity. Incubation of the metal-free apoenzyme with 57Fe(II) in the presence of O2 leads to the 57Fe(III)-57Fe(II) species which is stable in dilute solutions, but partially oxidized during the concentration procedure to the 57Fe(III)-57Fe(III) enzyme. Limited reduction of the oxidized enzyme with ascorbate delivers a mixture of the Fe(II)-Fe(II)/Fe(III)-Fe(III) species, but not the mixed valent Fe(III)-Fe(II) species, indicating that after the transfer of the first electron the second electron of the ascorbate radical is immediately transferred to the second Fe(III). The M?ssbauer spectra of the oxidized species show at 4.2 K two quadrupole doublets with delta of 0.51 mm/s and 0.53 mm/s and delta E of 1.46 and 0.96 mm/s indicating high spin Fe(III) in two different binding sites, obviously with a higher asymmetry in the chromophoric Fe(III) site. The values are too low for a mu-oxo bridge. The mixed-valent Fe(III)-Fe(II) species shows two quadrupole doublets with delta values of 0.55 mm/s and 1.14 mm/s and delta E values of 1.43 mm/s and 3.01 mm/s at 70 K for high spin Fe(II) and Fe(III), but the signal of the Fe(II) component shows magnetic patterns at 4.2 K indicating a half-integer spin system with antiferromagnetic coupling. The Fe(II)-Fe(II) system exhibits two quadrupole doublets with delta values of 1.18 mm/s and 1.22 mm/s and with delta E values of 3.69 mm/s and 2.68 mm/s again indicating a higher asymmetry in the originally chromophoric Fe(III)-binding site. Addition of phosphate shows only minor differences in the oxidized enzyme and in the mixed valent Fe(III)-Fe(II) system. Interaction with O2 is discussed.     

A characterization of permolybdate and its effect on cellular tyrosine phosphorylation, gap junctional intercellular communication and phosphorylation status of the gap junction protein, connexin43

Biological and analytical characterizations of permolybdate (a mixture of H2O2 and molybdate) were done. Molybdate (10 mM) and molybdenum(V) chloride (3 mM) did not affect gap junctional intercellular communication (GJIC), phosphorylation status of connexin43 (Cx43) or cellular tyrosine phosphorylation in early passage hamster embryonic cells (mainly fibroblast-like). High concentrations of H2O2 (3-10 mM) affected some of the parameters. Acidified permolybdate was clearly more stable than the unadjusted permolybdate. The maximum biological potency of acidified permolybdate was found at a molar ratio of 2:1 (H2O2:molybdate). The mixtures of molybdenum(V) chloride and H2O2 gave a maximum effect at 4:1 molar ratio (H2O2:molybdenum(V)). This can be explained by decomposition of H2O2 and by the generation of less biologically active compounds. Spectrophotometric analyses of the mixtures corroborated the biological results. The Mo(V) electron spin resonance spectrum disappeared upon addition of H2O2 to Mo(V) solutions, and no spectrum appeared when H2O2 was mixed with Mo(VI). Thus, permolybdate is probably diperoxomolybdate, a Mo(VI) compound. Regardless of the parent metal salt, the H2O2/metal salt mixtures showed concentration-dependent biphasic responses with an initial decrease in GJIC followed by an increase. A dissociation between alteration in Cx43 phosphorylation status and GJIC was obtained under certain conditions. The biological activities of permolybdate were only partially mimicked by phenylarsine oxide, an alternative protein tyrosine phosphatase inhibitor.     

Reactions of bovine liver catalase with superoxide radicals and hydrogen peroxide

The oxidized intermediates generated upon exposure of bovine liver catalase to hydrogen peroxide (H2O2) and superoxide radical (O2-) fluxes were examined with UV-visible spectrophotometry. H2O2 and O2- were generated by means of glucose/glucose oxidase and xanthine/xanthine oxidase systems. Serial overlay of absorption spectra in the Soret (350-450 nm) and visible (450-700 nm) regions showed that three oxidized intermediates, namely Compounds I, II and III, can be observed upon exposure of catalase to enzymatically generated H2O2 and O2-. Compound I is formed during the reaction of native enzyme with H2O2 and disappears in two ways: (i) via the catalytic reaction with H2O2 to restore native catalase and (ii) via the reaction with O2- to form Compound II. At low H2O2 concentrations (< 4.8 x 10(-9) M H2O2), Compound II reverts towards the native state mainly in a direct one-step reaction, whereas at higher H2O2 concentrations the pathway of Compound II back to the native enzyme involves Compound III. Formation of the latter from Compound II and H2O2 is irreversible and the rate constant of this reaction is 6.1 +/- 0.2 x 10(4) M-1 s-1. The formation of Compound III through the direct reaction of O2- with native enzyme has also been observed. Depending on the experimental conditions, the inactivation of catalase by O2- can be due to accumulation of Compound II ("slow" inhibition) or to the formation of Compound III ("rapid" inhibition) part of which leads to a dead end product. Formation of Compound III and of this dead end product are responsible for the irreversible inactivation in presence of an excess of H2O2.     

Heme oxygenase-1, intermediates in verdoheme formation and the requirement for reduction equivalents

Conversion of heme to verdoheme by heme oxygenase-1 (HO-1) is thought to involve alpha-meso-hydroxylation and elimination of the meso-carbon as CO, a reaction supported by both H2O2 and NADPH-cytochrome P450 reductase/O2. Anaerobic reaction of the heme-HO-1 complex with 1 eq of H2O2 produces an enzyme-bound intermediate identified by spectroscopic methods as alpha-meso-hydroxyheme. This is the first direct evidence for HO-1-catalyzed formation of alpha-meso-hydroxyheme. alpha-meso-Hydroxyheme exists as a mixture of Fe(III) phenolate, Fe(III) keto anion, and Fe(II) keto pi neutral radical resonance structures. EPR shows that complexation with CO enhances the Fe(II) pi neutral radical component. Reaction of the alpha-meso-hydroxyheme-HO-1 complex with O2 generates Fe(III) verdoheme, which can be reduced in the presence of CO to the Fe(II) verdoheme-CO complex. Thus, conversion of alpha-meso-hydroxyheme to Fe(III) verdoheme, in contrast to a previous report (Matera, K. M., Takahashi, S., Fujii, H., Zhou, H., Ishikawa, K., Yoshimura, T., Rousseau, D. L., Yoshida, T., and Ikeda-Saito, M. (1996) J. Biol. Chem. 271, 6618-6624), does not require a reducing equivalent. An electron is only required to reduce ferric to ferrous verdoheme in the first step of its conversion to biliverdin.     

Cobalt-mediated generation of reactive oxygen species and its possible mechanism

Electron spin resonance spin trapping was utilized to investigate free radical generation from cobalt (Co) mediated reactions using 5,5-dimethyl-1-pyrroline (DMPO) as a spin trap. A mixture of Co with water in the presence of DMPO generated 5,5-dimethylpyrroline-(2)-oxy(1) DMPOX, indicating the production of strong oxidants. Addition of superoxide dismutase (SOD) to the mixture produced hydroxyl radical (.OH). Catalase eliminated the generation of this radical and metal chelators, such as desferoxamine, diethylenetriaminepentaacetic acid or 1,10-phenanthroline, decreased it. Addition of Fe(II) resulted in a several fold increase in the .OH generation. UV and O2 consumption measurements showed that the reaction of Co with water consumed molecular oxygen and generated Co(II). Since reaction of Co(II) with H2O2 did not generate any significant amount of .OH radicals, a Co(I) mediated Fenton-like reaction [Co(I) + H2O2-->Co(II) + .OH + OH-] seems responsible for .OH generation. H2O2 is produced from O2.- via dismutation, O2.- is produced by one-electron reduction of molecular oxygen catalyzed by Co. Chelation of Co(II) by biological chelators, such as glutathione or beta-ananyl-3-methyl-L-histidine alters, its oxidation-reduction potential and makes Co(II) capable of generating .OH via a Co(II)-mediated Fenton-like reaction [Co(II) + H2O2-->Co(III) + .OH + OH-]. Thus, the reaction of Co with water, especially in the presence of biological chelators, glutathione, glycylglycylhistidine and beta-ananyl-3-methyl-L-histidine, is capable of generating a whole spectrum of reactive oxygen species, which may be responsible for Co-induced cell injury.     

Reaction paths of iron oxidation and hydrolysis in horse spleen and recombinant human ferritins

UV-visible spectroscopy, electrode oximetry, and pH stat were used to study Fe(II) oxidation and hydrolysis in horse spleen ferritin (HoSF) and recombinant human H-chain and L-chain ferritins (HuHF and HuLF). Appropriate test reactions and electrode responses were measured, establishing the reliability of oxygen electrode/pH stat for kinetics studies of iron uptake by ferritin. Stoichiometric ratios, Fe(II)/O2 and H+/Fe(II), and rates of oxygen uptake and proton production were simultaneously measured as a function of iron loading of the protein. The data show a clear distinction between the diiron ferroxidase site and mineral surface catalyzed oxidation of Fe(II). The oxidation/hydrolysis reaction attributed to the ferroxidase site has been determined for the first time and is given by 2Fe2+ + O2 + 3H2O --> [Fe2O(OH)2]2+ + H2O2 + 2H+ where [Fe2O(OH)2]2+ represents the hydrolyzed dinuclear iron(III) center postulated to be a mu-oxo-bridged species from UV spectrometric titration data and absorption band maxima. The transfer of iron from the ferroxidase site to the mineral core has been now established to be [Fe2O(OH)2]2+ + H2O --> 2FeOOH(core) + 2H+. Regeneration of protein ferroxidase activity with time is observed for both HoSF and HuHF, consistent with their having enzymatic properties, and is facilitated by higher pH (7.0) and temperature (37 degreesC) and by the presence of L-subunit and is complete within 10 min. In accord with previous studies, the mineral surface reaction is given by 4Fe2+ + O2 + 6H2O --> 4FeOOH(core) + 8H+. As the protein progressively acquires iron, oxidation/hydrolysis increasingly shifts from a ferroxidase site to a mineral surface based mechanism, decreasing the production of H2O2.     

Adduct formation between alkali metal ions and anionic LV(V)O(2)(-) (L(2-) = tridentate ONS ligands) species: syntheses, structural investigation, and photochemical studies

Syntheses of alkali metal adducts [LVO(2)M(H(2)O)(n)] (1-7) (M = Na(+), K(+), Rb(+), and Cs(+); L = L(1)(-)L(3)) of anionic cis-dioxovanadium(V) species (LVO(2)(-)) of tridentate dithiocarbazate-based Schiff base ligands H(2)L (S-methyl-3-((5-(R-2-hydroxyphenyl))methyl)dithiocarbazate, R = H, L = L(1); R = NO(2), L = L(2); R = Br, L = L(3)) have been reported. The LVO(2)(-) moieties here behave like an analogue of carboxylate group and have displayed interesting variations in their binding pattern with the change in size of the alkali metal ions as revealed in the solid state from the X-ray crystallographic analysis of 1, 3, 6, and 7. The compounds have extended chain structures, forming ion channels, and are stabilized by strong Coulombic and hydrogen-bonded interactions. The number of coordinated water molecules in [LVO(2)M(H(2)O)(n)] decreases as the charge density on the alkali metal ion decreases (n = 3.5 for Na(+) and 1 for K(+) and Rb(+), while, for Cs(+), no coordinated water molecule is present). In solution, compounds 1-7 are stable in water and methanol, while in aprotic solvents of higher donor strengths, viz. CH(3)CN, DMF and DMSO, they undergo photoinduced reduction when exposed to visible light, yielding green solutions from their initial yellow color. The putative product is a mixed-oxidation (mu-oxo)divanadium(IV/V) species as revealed from EPR, electronic spectroscopy, dynamic (1)H NMR, and redox studies.     

The effect of new synthetic cholesterol derivatives on cholesterol metabolism in cultured rabbit hepatocytes

The effects of three novel synthetic derivatives of cholesterol with ethoxy (I), aminoethoxy (II), azidoethoxy (III) and toluenesulfonyloxyethoxy (IV) groups in the 3 beta-hydroxy position of cholesterol on cholesterol synthesis as well as on apolipoprotein B and bile acid secretion in cultured rabbit hepatocytes have been studied. 3 beta-(2-hydroxyethoxy)-cholest-5-en (I) was used as a standard. It was found that the inhibiting effect of these compounds on cholesterol synthesis depends on their structure. Compound II (1 microgram/ml), which inhibited acetate incorporation into cholesterol by 30-50%, appeared to be the most effective among the other compounds tested. This derivative had no effect on the production of bile acids. Compound III was less effective, while compound IV had no effect on cholesterol synthesis. All the compounds under study reduced by 20-36% the secretion of the total apolipoprotein B as measured by the enzyme-linked immunosorbent assay (ELISA). None of the synthetic cholesterol derivatives influenced the leucine incorporation into the total protein fraction. The results obtained indicate that 3 beta-(2-aminoethoxy)cholest-5-en, the most effective compound among other cholesterol derivatives tested in the study, can serve as a basis for synthesizing novel cholesterol derivatives able to inhibit cholesterol biosynthesis in liver cells and to decrease the secretion of very low density lipoproteins in cultured rabbit hepatocytes.     

Site-specific DNA damage induced by NADH in the presence of copper(II): role of active oxygen species

Oxidative DNA damage by NAD(P)H in the presence of metal ions has been characterized by using 32P 5' end-labeled DNA fragments obtained from human p53 tumor suppressor gene and c-Ha-ras-1 protooncogene. NADH, as well as other endogenous reductants, induced DNA damage in the presence of Cu(II). The order of inducing effect on Cu(II)-dependent DNA damage was ascorbate > reduced glutathione (GSH) > NADH > NADPH. Although NADH caused no or little DNA damage in the presence of Fe(III)-EDTA, the addition of H2O2 induced the DNA damage. The Cu(II)-mediated DNA damage induced by NADH was inhibited by catalase and bathocuproine, a Cu(I)-specific chelator; but not by scavengers of hydroxyl free radical (.OH), suggesting the involvement of active species derived from hydrogen peroxide (H2O2) and Cu(I) rather than .OH. The predominant cleavage sites were thymine residues located 5' and/or 3' to guanine. The cleavage pattern was similar to that induced by Cu(II) plus GSH, Cu(II) plus ascorbate, or Cu(I) plus H2O2. Formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine by NADH increased with its concentration in the presence of Cu(II). UV-visible spectroscopy indicated the facilitation of reduction of Cu(II) by NADH under some conditions. ESR spin-trapping experiments and mass spectrometry showed that the carbon-centered radical was formed during the reaction of NADH with Cu(II). These results suggest that optimal molar ratios of DNA/metal ion yield copper with a high redox potential which catalyzes NADH autoxidation to NAD. being further oxidized to NAD+ with generation of superoxide radical and that H2O2 reacts with Cu(I) to form active oxygen species such as copper(I)-peroxide complex causing DNA damage.     

Regulation by cytokines of the inducible nitric oxide synthase promoter in insulin-producing cells

In this article the complexation of anhydrotetracycline (AHTC), the major toxic decomposition product of the antibiotic tetracycline, with Al(III) has been investigated using the AM1 semiempirical and ab initio Hartree-Fock levels of theory. Different modes of complexation have been considered with the structure of tetra- and pentacoordinated complexes being fully optimized. In the gas phase, processes ii and iii, which lead to the complexes with stoichiometry MHL2+, are favored. Structure II ([AlLH2(OH)(H2O)]2+) has the metal coordinated to the O11 and O12 groups and the O3 group protonated and is the global minimum on the potential energy surface for the interaction. In water solution, the Al(III) is predicted to form predominantly a tetracoordinated complex at the Oam and O3 site (V) of the AHTC with the stoichiometry MH2L3+ (process i). The experimental proposal is the complexed form with the metal ion coordinated to the O11-O12 moiety (site II). The intramolecular proton transfer, which leads to the most stable Al(III)-AHTC MHL2+ complex, has not been considered by the experimentalists. The experimental structure was found to be unfavorable in our calculations in both gas phase and water solution. All the semiempirical results are in perfect agreement with the ab initio calculations. So, we suggest that the experimental assignments should be revised, taking into account the results obtained in the present study.     

Resection hip arthroplasty for malignant pelvic tumor. Outcome in 5 patients followed more than 2 years

BACKGROUND: Vasoactive intestinal peptide (VIP) has been reported to have some properties that provide protection from lung injury. Furthermore, its protective effect in cold storage of donor lungs has been confirmed. We examined its effect and the timing of administration in an in vivo rat lung transplantation model. METHODS: All lungs were flushed with low-potassium dextran-1% glucose solution, and orthotopic left lung transplantations were performed. Rats were divided into four groups (n = 6). Group I received no preservation or storage. Groups II, III, and IV grafts were stored for 18 hours at 4 degrees C. Group II received no VIP. Group III received VIP (0.1 g/ml) via the flush solution. Group IV recipients received VIP (3 microg/kg) intravenously just after reperfusion. Twenty-four hours after transplantation, the right main pulmonary artery and right main bronchus were ligated, and the rats were ventilated with 100% O2 for 5 minutes. Mean pulmonary arterial pressure, peak airway pressure, blood gas analysis, serum lipid peroxide level, tissue myeloperoxidase activity, and wet-dry weight ratio were measured. RESULTS: The partial O2 tension values of groups III and IV were better than group II (groups II, III, and IV: 147.4 +/- 71.4, 402.1 +/- 64.8, 373.4 +/- 81.0 mm Hg; p < 0.05). Peak airway pressure was lower in groups III and IV than in group II (groups II, III, and IV: 19.7 +/- 0.8, 16.7 +/- 0.9. and 16.3 +/- 1.0 mm Hg; p < 0.05). Mean pulmonary arterial pressure in group III was lower than group II (groups II and III: 36.3 +/- 3.0 and 22.1 +/- 2.2 mm Hg; p < 0.01). Wet-dry weight ratio in group III was lower than in groups II and IV (group II, III, and IV: 5.2 +/- 0.2, 4.4 +/- 0.2, and 5.2 +/- 0.3; II vs III; p < 0.05, III vs IV; p < 0.01). Serum lipid peroxide levels in groups III and IV were significantly lower (groups II, III, and IV: 2.643 +/- 0.913, 0.455 +/- 0.147, and 0.325 +/- 0.124 nmol/ml; p < 0.01). CONCLUSION: VIP ameliorates reperfusion injury in an in vivo rat lung transplantation model. Either administration of VIP via the flush solution or systemically just after reperfusion was associated with improved pulmonary function.     

Advanced Oxidation of Diuron by Photo-Fenton Treatment as a Function of Operating Parameters

Advanced oxidation of diuron in aqueous solution by photo-Fenton treatment was investigated by batch experiments. Effects of operating parameters, namely, the concentrations of pesticide (diuron), hydrogen peroxide (H2O2), and ferrous ion [Fe (II)] on oxidation of diuron were investigated by using Box-Behnken statistical experiment design and the response surface methodology. Diuron oxidation by photo-Fenton treatment was evaluated by determining the total organic carbon (TOC), diuron, and adsorbable organic halogen (AOX) removals. Concentration ranges of the reagents resulting in the highest level of diuron oxidation were determined. Diuron removal increased with increasing H2O2 and Fe (II) concentrations, up to a certain level. H2O2 concentration had a more profound effect than diuron and Fe (II) on removal of diuron, TOC, and AOX from the aqueous solution. Complete (100%) disappearance of diuron was achieved after a 15?min reaction period. However, 85% of diuron was mineralized after 240?min, indicating a low level of intermediate formation. Optimal H2O2/Fe (II)/diuron ratio resulting in maximum diuron (100%), TOC (85%), and AOX (100%) removals was found to be 267/36/25?(mg?L?1).     

Incorporation of 5-substituted uracil derivatives into nucleic acids. Part IV. The synthesis of 5-ethynyluracil

5-Acetyluracil (I) has been treated with POCI3 to give 5-(1-chlorovinyl)-2,4-dichloropyrimidine (II). Treatment of II with KOEt gave a mixture of 2-ethoxy-5-ethynyl-4 (3H)-pyrimidinone (IIIA) and 4-ethoxy-5-ethynyl-2 (1H)-pyrimidinone (IIIB). IIIA and IIIB were isolated and characterised. The mixture of IIIA and IIIB upon treatment with HCI gave 5(1-chlorovinyl)uracil (IV). Reaction of IV with KOEt gave 5-ethynyluracil (V). 5-Ethynyluracil was more easily obtained by the treatment of II with KOH in aqueous dioxan.     

Spectral and kinetic properties of the Fet3 protein from Saccharomyces cerevisiae, a multinuclear copper ferroxidase enzyme

High affinity iron uptake in Saccharomyces cerevisiae requires Fet3p. Fet3p is proposed to facilitate iron uptake by catalyzing the oxidation of Fe(II) to Fe(III) by O2; in this model, Fe(III) is the substrate for the iron permease, encoded by FTR1. Here, a recombinant Fet3p has been produced in yeast that, lacking the C-terminal membrane-spanning domain, is secreted directly into the growth medium. Solutions of this Fet3p at >1 mg/ml have the characteristic blue color of a type 1 Cu(II)-containing protein, consistent with the sequence homology that placed this protein in the class of multinuclear copper oxidases that includes ceruloplasmin. Fet3p has an intense absorption at 607 nm (epsilon = 5500 M-1 cm-1) due to this type 1 Cu(II) and a shoulder in the near UV at 330 nm (epsilon = 5000 M-1 cm-1) characteristic of a type 3 binuclear Cu(II) cluster. The EPR spectrum of this Fet3p showed the presence of one type 1 Cu(II) and one type 2 Cu(II) (A parallel = 91 and 190 x 10(-4) cm-1, respectively). Copper analysis showed this protein to have 3.85 g atom copper/mol, consistent with the presence of one each of the three types of Cu(II) sites found in multinuclear copper oxidases. N-terminal analysis demonstrated that cleavage of a signal peptide occurred after Ala-21 in the primary translation product. Mass spectral and carbohydrate analysis of the protein following Endo H treatment indicated that the preparation was still 15% (w/w) carbohydrate, probably O-linked. Kinetic analysis of the in vitro ferroxidase reaction catalyzed by this soluble Fet3p yielded precise kinetic constants. The Km values for Fe(II) and O2 were 4.8 and 1.3 microM, respectively, while kcat values for Fe(II) and O2 turnover were 9.5 and 2.3 min-1, consistent with an Fe(II):O2 reaction stoichiometry of 4:1.     

Low-Temperature Oxygen Trap for Maintaining Strict Anoxic Conditions

A low-temperature O2 trap was designed in order to achieve strict anoxic conditions. The work was motivated by observation of slow oxidation of Fe(II) in an anaerobic chamber, leading to an estimated 3.8×10?7?atm O2 (well below the O2 monitor detection limit) despite recirculation of the N2:H2 atmosphere across a Pd catalyst. Very low O2 activity inside an “anaerobic” chamber can result in erroneous conclusions regarding oxidation-reduction reactivities in anoxic environments. The O2 trap consisted of two sequential barrier suspensions with 93.2?mM Fe(III) as ferric hydroxide, 0.90?mM FeCl2, and pH 8.1. The partial pressure of O2 was estimated to be less than 7.5×10?9?atm?O2 when reactors were attached to the traps, based on no observed oxidation of Fe(II).     

Anti-inflammatory drugs interacting with Zn(II), Cd(II) and Pt(II) metal ions

Complexes of Zn(II), Cd(II) and Pt(II) metal ions with the anti-inflammatory drugs, 1-methyl-5-(p-toluoyl)-1H-pyrrole-2-acetic acid (Tolmetin), alpha-methyl-4-(2-methylpropyl)benzeneacetic acid (Ibuprofen), 6-methoxy-alpha-methylnaphthalene-2-acetic acid (Naproxen) and 1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indole-3-acetic acid (indomethacin) have been synthesized and characterized. In the structurally characterized Cd(naproxen)2 complex the anti-inflammatory drugs acts as bidentate chelate ligand coordinatively bound to metal ions through the deprotonated carboxylate group. Crystal data for 1: [C32H26O8Cd], orthorhombic, space group P22(1)2(1), a = 5.693(2) (A), b = 8.760(3) (A), c = 30.74(1) (A), V = 1533(1) A3, Z = 2. Antibacterial and growth inhibitory activity is higher than that of the parent ligands or the platinum(II) diamine compounds.     

Effects of Reagent Concentrations on Advanced Oxidation of Amoxicillin by Photo-Fenton Treatment

The degradation and mineralization of amoxicillin in an aqueous solution was accomplished by using a photo-Fenton treatment. An ultraviolet light source with a 254-nm wavelength was used with hydrogen peroxide (H2O2) and iron(II). The effects of reagent concentrations on amoxicillin degradation and mineralization were investigated systematically by using the Box-Behnken statistical experiment design. Amoxicillin (10–200??mgL-1), H2O2 (10–500??mgL-1), and iron(II) (0–50??mgL-1) concentrations were considered independent variables; the percent amoxicillin degradation and the total organic carbon (TOC) removal (mineralization) were the objective functions to be maximized. Both H2O2 and iron(II) concentrations affected the extent of the amoxicillin degradation and mineralization. The amoxicillin degradation was completed within 2.5?min, and 53% mineralization took place within 60?min. The optimum H2O2∶Fe∶amoxicillin ratio that resulted in complete amoxicillin degradation and 53% mineralization was 100∶40∶105??mgL-1.     

Protein coordination to manganese determines the high catalytic rate of dimanganese catalases. Comparison to functional catalase mimics

Catalysis of hydrogen peroxide dismutation by the dimanganese catalase from Thermus thermophilus has been measured and found to obey Michaelis-Menton kinetics with no evidence for substrate inhibition at concentrations up to 0.45 M H2O2. Comparison among three dimanganese catalases (Thermus thermophilus, Thermoleophilium album, and Lactobacillus plantarum) reveals that their apparent second-order rate constants, Kcat/Km, differ by at most a factor of 5, even though the individual kinetic constants differ by as much as a factor of 20. This similarity suggests that all three enzymes may have the same rate-determining step. For T. thermophilus catalase we find that kcat/Km approximately kbi, the bimolecular rate constant at limiting substrate concentrations. Thus, the rate of the rate-determining step is unaltered over the entire range of substrate concentrations, unlike T. album and L. plantarum catalases where substrate inhibition has been reported. Comparison to structurally characterized dimanganese complexes and dimetalloproteins (arginase, hemerythrin), which are functional, albeit kinetically slow, catalase mimics, reveals that high catalase activity correlates with a greater number of stronger sigma-ligand donors like anionic carboxylatos vs neutral histidines that stabilize the oxidized Mn2(III,III) state over reduced Mn2(II,II). A critical feature for enzymatic functionality in vivo is suppression of one-electron chemistry leading to formation of the mixed-valence forms, Mn2(III,IV) and Mn2(II,III), which are kinetically inactive or precursors to inactive species, respectively. Evidence is presented from model compounds suggesting that the mu-carboxylato bridge between Mn ions in catalase may play the key role in suppressing formation of these detrimental oxidation states through destabilization of these one-electron redox processes.