Synthesis and characterization of pyridine N-oxide complexes of manganese, copper and zinc

A series of metal carboxylates containing pyridine N-oxide are prepared via one pot synthesis and solid phase synthesis. The structural variations from metal to metal are observed. In the case of reactions of manganese(II) acetate with pyridine N-oxide in the presence of aromatic carboxylic acids, polymeric complexes with bridging aromatic carboxylate as well as bridging pyridine N-oxide are observed. Whereas, the reaction of copper(II) acetate with pyridine N-oxide in the presence of an aromatic carboxylic acid led to mononuclear or binuclear paddle wheel carboxylate complexes with monodentate pyridine N-oxide. Co-crystal of two neutral complexes having composition [Cu₂(OBz)₄(MeOH)₂][Cu₂(OBz)₄(pyO)₂] (where OBz = benzoate, pyO = pyridine N-oxide) each neutral parts have paddle wheel structure. Solid phase reaction of zinc chloride with sodium benzoate prepared in situ and pyridine N-oxide leads to a tetra-nuclear zinc complex.     

Reduced pyridine nucleotides in Pseudomonas carboxydovorans are formed by reverse electron transfer linked to proton motive force

In cell suspensions of Pseudomonas carboxydovorans pulsed with lithotrophic substrates (CO or H₂) in the presence of oxygen, formation of reduced pyridine nucleotides and of ATP could be demonstrated using the bioluminescent assay. Experiments employing base-acid transition, an uncoupler and inhibitors of ATPase or electron transport enabled us to propose a model for the formation of NAD(P)H in chemolithotrophically growing P. carboxydovorans.The protonophor FCCP (carbonly-p-trifluormethoxyphenylhydrazon) inhibited both, formation of NAD(P)H and of ATP. In the absence of oxygen, a chemical potential imposed by base-acid transition resulted in the formation of NAD(P)H and ATP when electrogenic substrates (CO or H₂) were present. This suggests proton motive force-driven NAD(P)H formation. The proton motive force was generated by oxidation of substrate, and not by ATP hydrolysis, as obvious from NAD(P)H formation during inhibition of ATP synthesis by oligomycin and N,N-dicyclohexylcarbodiimide.That the CO-born electrons are transferred via the ubiquinone 10-cytochrome b region to NADH dehydrogenase functioning in the reverse direction, was indicated by inhibition of NAD(P)H formation by HQNO (2-n-heptyl-4-hydroxyquinoline-N-oxide) and rotenone, and by resistance to antimycin A.We conclude that in P. carboxydovorans, growing with CO or H₂, electrons and a proton motive force, generated by respiration, are required to drive an reverse electron transfer for the formation of reduced pyridine nucleotides.Abbreviations CODH carbon monoxide dehydrogenase - DCCD N,N-dicyclohexylcarbodiimide - FCCP carbonyl-p-trifluormethoxyphenylhydrazon - HQNO 2-n-heptyl-4-hydroxyquinoline-N-oxide - pmf proton motive force     

Application of High Enzyme Activities Present in Clostridium Thermoaceticum for the Efficient Regeneration of NADPH, NADP+, NADH AND NAD+

Crude extracts of Clostridium thermoaceticum DSM 521 contain various AMAPORs (artificial mediator accepting pyridine nucleotide oxidoreductases). The specific activities of this mixture of AMAPORs is about 8-9 U mg^-1 protein (µmoles mg^-1 min^-1) for NADPH and 3-4 U mg^-1 protein for NADH formation with reduced methylviologen (MV⁺⁺) as electron donor. These AMAPOR-activities are only slightly oxygen sensitive. The reoxidation of NADPH and NADH with carboxamido-methylviologen is catalysed by crude extracts with 2.0 and 1.6 U mg^-1 protein, respectively. The same crude extracts also catalyse the dehydrogenation of reduced pyridine nucleotides with suitable quinones such as anthraquinone-2,6-disulphonate. The reduced quinone can be reoxidised by dioxygen.

The K_m-values of these enzymes for the pyridine nucleotides and also for the artificial electron mediators are in a suitable range for preparative transformations.

Furthermore the crude extract of C. thermoaceticum contains about 2.5 U mg^-1 protein of an NADP⁺-dependent formate dehydrogenase (FDH), which is suitable for NADPH and/or MV⁺⁺ regeneration. The regeneration of MV⁺⁺ with FDH and formate as electron donor proceeds with a specific activity of about 5 U mg^-1 protein of the crude extract. The reduced viologen in turn reduces NAD(P)⁺ by AMAPOR. The formate dehydrogenase is sensitive to oxygen.

Examples of compounds which have been prepared by combination of AMAPORs or formate dehydrogenase with an oxidoreductase are: (S)-3-hydroxycarboxylates, esters of (S)-3-hydroxycarboxylates, (1R,2S)-1-hydroxypropane-tricarboxylate (D_s-(+)-isocitrate), L_s-(-)-isocitrate and 6-phosphogluconate.     

Kinetics and mechanism of CO substitution of [η-CpFe(CO)3]PF6 with PPh3 in the presence of substituted pyridine N-oxide

The kinetics of substitution reactions of [η-CpFe(CO)₃]PF₆ with PPh₃ in the presence of R-PyOs have been studied. For all the R-PyOs (R = 4-OMe, 4-Me, 3,4-(CH)₄, 4-Ph, 3-Me, 2,3-(CH)₄, 2,6-Me₂, 2-Me), the reactions yeild the same product [η⁵-CpFe(CO)₂PPh₃]PF₆, according to a second-order rate law that is first order in concentrations of [η⁵-CpFe(CO)₃]PF₆ and of R-PyO but zero order in PPh₃ concentration. These results, along with the dependence of the reaction rate on the nature of R-PyO, are consistent with an associative mechanism. Activation parameters further support the bimmolecular nature of the reactions: ΔH^≠ = 13.4 ± 0.4 kcal mol⁻¹, ΔS^≠ = −19.1 ± 1.3 cal k⁻¹ mol⁻¹ for 4-PhPyO; ΔH^≠ = 12.3 ± 0.3 kcal mol⁻¹, ΔS^≠ = 24.7 ±1.0 cal K⁻¹ mol⁻¹ for 2-MePyO. For the various substituted pyridine N-oxides studied in this paper, the rates of reaction increase with the increasing electron-donating abilities of the substituents on the pyridine ring or N-oxide basicities, but decrease with increasing ¹⁷O chemical shifts of the N-oxides. Electronic and steric factors contributing to the reactivity of pyridine N-oxides have been quantitatively assessed.     

Energy metabolism of autotrophically and heterotrophically grown cells of Nitrobacter winogradskyi

The adenine nucleotide pools and the NADH pool were compared in intact Nitrobacter winogradskyi cells grown under different conditions. The NADH pool was highest in nitrite-grown cells (22.0 nmol/mg N), less high in acetategrown cells (15.1 nmol/mg N),and lowest in pyruvate-grown cells (11.9 nmol/mg N).The adenine nucleotide pools and the NADH pool were determined after the transition from anaerobic to aerobic conditions.In both autotrophically and heterotrophically grown cells the ATP pool decreased within the first second after the addition of oxygen and then increased.In cells grown with nitrite or acetate the NADH pool increased the first second after the addition of oxygen then decreased below the initial value. In pyruvate-grown cells the changes in the NADH pool were less obvious.In the presence of rotenone autotrophic cells were able to generate ATP, but the reverse energy-dependent electron transport was inhibited. Consequently, NADH was not synthesized. N,N-dicyclohexylcarbodiimide an inhibitor of ATPase, prevented both ATP and NADH generation.Abbreviations DCCD N,N-dicyclohexylcarbodiimide     

First novel synthesis of triazole thioglycosides as ribavirin analogues

This study reports a novel and efficient method for the synthesis of the first reported novel class of triazole thioglycosides. These series of compounds were designed through the reaction of potassium cyanocarbonimidodithioate 2 with hydrazine derivatives 3a-d in EtOH at room temperature to give the corresponding potassium 5-amino-1H-1,2,4-triazole-3-thiolates 4a-d. The latter compounds were treated with tetra-O-acetyl-α-D-glucopyranosyl bromide 6a and tetra-O-acetyl-α-D-galactopyranosyl bromide 6b in DMF at room temperature to give in high yields the corresponding triazole thioglycosides 7a-h. Treatment of triazole salts 4a–d with hydrochloric acid afforded the corresponding 3-mercaptotriazoles 5a-d. Compounds 5a-d were then reacted with bromoperacetylated sugars 6a,b in sodium hydride-DMF at ambient temperature to afford the thioglycosyl compounds 7a-h. Ammonolysis of the triazole thioglycosides 7a-h afforded the corresponding free thioglycosides 8a-h. The scope and limitation of the method is demonstrated. The structure of the reaction products was confirmed on the basis of their elemental analysis and spectral data (IR, ¹H NMR, MS and ¹³C NMR).     

Phosphodiesterase inhibitors. Part 6: Design,synthesis, and structure–activity relationships of PDE4-inhibitory pyrazolo[1,5-a]pyridines with anti-inflammatory activity

We previously identified KCA-1490 [(?)-6-(7-methoxy-2-trifluoromethyl-pyrazolo[1,5-a]pyridin-4-yl)-5-methyl-4,5-dihydro-3-(2H)-pyridazinone], a dual PDE3/4 inhibitor. In the present study, we found highly potent selective PDE4 inhibitors derived from the structure of KCA-1490. Among them, N-(3,5-dichloropyridin-4-yl)-7-methoxy-2-(trifluoromethyl)pyrazolo[1,5-a]pyridine-4-carboxamide (2a) had good anti-inflammatory effects in an animal model.     

Biodegradation of pyridine by an isolated bacterial consortium/strain and bio-augmentation of strain into activated sludge to enhance pyridine biodegradation

Pyridine and pyridine based products are of major concern as environmental pollutants due to their recalcitrant, persistent, toxic and teratogenic nature. In this study, we describe biodegradation of pyridine by an isolated consortium/strain under aerobic condition. Batch experiment results reveal that at lower initial pyridine concentrations (1-20 mg l(-1)), almost complete degradation was observed whereas at higher concentration (30-50 mg l(-1)), the degradation efficiency was dropped significantly. This may be due to inhibitory effect of pyridine at higher concentrations. The value of decay and yield coefficient was also determined. Furthermore, the bio-augmentation of isolated consortium/strain into the activated sludge consortium in different quantity has been also done and the effect of bio-augmentation on degradation has been studied. The results reveal that as the quantity of bio-augmentation increases, the degradation of pyridine increases. At 25% bio-augmentation, complete degradation of 20 mg l(-1) of pyridine can be achieved within 96 h of incubation. Thus, the study concluded that the bio-augmentation of the isolated consortium/strain into the sludge enhances the pyridine degradation efficiency of the biomass.     

四种中草药对大鼠半乳糖性白内障氧化还原物质及糖类含量的影响

对正常和半乳糖性白内障及给中草药的大鼠晶状体中某些吡啶核苷酸成分、糖类、非蛋白质巯基的含量进行了比较。结果表明,在白内障晶状体中,NADPH及非蛋白质巯基的含量明显低于正常晶状体的,而NADP、半乳糖及半乳糖醇的含量明显高于正常晶状体的;当注射半乳糖的同时分别用黄岑、石斛、菟丝子及玉蝴蝶四种中草药水煎剂灌胃,上述变化为基本恢复至正常晶状体的水平。表明四种中草药对晶状体中的异常生化变化具有阻止及纠正作用。