Alkane oxygenation with H2O2 catalysed by FeCl3 and 2,2′-bipyridine

The H₂O₂-FeCl₃-bipy system in acetonitrile efficiently oxidises alkanes predominantly to alkyl hydroperoxides. Turnover numbers attain 400 after 1 h at 60 °C. It has been assumed that bipy facilitates proton abstraction from a H₂O₂ molecule coordinated to the iron ion (these reactions are stages in the catalytic cycle generating hydroxyl radicals from the hydrogen peroxide). Hydroxyl radicals then attack alkane molecules finally yielding the alkyl hydroperoxide.     

Two new compounds from Zingiber officinale

A new cyclic diarylheptanoid,1,5-epoxy-3-hydroxy-1-(3-methoxy-4,5-dihydroxyphenyl)-7-(4-hydroxyphenyl)-heptane (1),as well as a new monoterpene,10-O-β-D-glucopyranosyl-hydroxy cineole (2) were isolated from the rhizomes of Zingiber officinale. The structures of compounds 1 and 2 were established based on their spectral data.In addition,the antioxidant activities of these compounds were also measured.     

Catalytic Oxidative Cyclocondensation of o‐Aminophenols to 2‐Amino‐3H‐phenoxazin‐3‐ones

The catalytic oxidative cyclocondensation of the o‐aminophenols 1a–f was investigated. The oxidants used were air/laccase, H₂O₂/horseradish peroxidase, H₂O₂/ebselen (3), and TBHP/diphenyl diselenide 4. The products obtained were 2‐amino‐3H‐phenoxazin‐3‐one—questiomycin A, its derivative 2b, and cinnabarinic acid and actinocin (2c,d). Substrates with methyl groups at 4 and 5 positions of benzene ring were converted to different dihydrophenoxazinones 2g,h. Compounds having chlorine atoms at the same positions underwent oxidation to planar phenoxa-zinones 2e,f with elimination of one hydrochloride molecule.     

Three new monoterpene indole alkaloids from Psychotria umbellata Thonn.

Three new psychollatine-derived monoterpene indole alkaloids were obtained from Psychotria umbellata Thonn.: 3,4-Dehydro-18,19-β-epoxy-psychollatine (2), N⁴-[1-((R)-2-hydroxypropyl)]-psychollatine (3), and N⁴-[1-((S)-2-hydroxypropyl)]-psychollatine (4). Their structures were determined by ¹H and ¹³C NMR spectra, 2D correlations (COSY, HMQC, and HMBC), and mass and UV spectra. Compounds 3 and 4 were synthesized for structural confirmation and for the determination of the stereochemistry of the hydroxyl group.     

致癌性卤代醌类消毒副产物造成 DNA 损伤的分子机理研究

卤代醌是一类卤代芳烃类环境污染物的致癌中间体,也是在饮用水中新发现的氯化消毒副产物。我们最近发现卤代醌和 H₂O₂ 或有机氢过氧化物体系可以不依赖过渡金属离子,而产生高活性的羟基/烷氧自由基和醌氧/醌碳自由基。目前尚不清楚这些卤代醌类致癌物和氢过氧化物共存能否诱导 DNA 产生氧化损伤和修饰,以及其潜在的分子机制是什么。我们的研究发现 DNA 在四氯-1,4-苯醌/H₂O₂体系中可被氧化产生 8-氧脱氧鸟苷、DNA 链断裂和三种甲基氧化产物,这些反应不依赖过渡金属离子,且由于卤代醌与 DNA 的嵌入作用而导致其氧化作用增强。其他卤代醌也观察到了类似的现象,而且通常比经典的 Fenton 体系更有效。我们进一步将研究从纯化的 DNA 扩展到了活细胞的基因组 DNA。同时还发现卤代醌和有机氢过氧化物(如叔丁基过氧化氢或在正常生理条件下产生的 13S-过氧羟基-9Z,11E-十八碳二烯酸(13-HPODE))共存时,可通过独特的醌氧自由基介导机制诱导 DNA 氧化生成致突变性更强的咪唑啉酮类产物 dIz。这些发现为解释普遍存在的卤代醌类致癌中间体和消毒副产物的潜在基因毒性、致突变性和致癌性提供了新思路。     

Three New Monoterpene Alkaloids and a New Caffeic Acid Ester from Incarvillea mairei var. multifoliolata

Three new monoterpene alkaloids, mairine A ( 1 ), mairine B ( 2 ), and mairine C ( 3 ), and a new caffeic acid ester, 2‐(1‐hydroxy‐4,4‐dimethoxycyclohexyl)ethyl caffeate ( 4 ), were isolated from the EtOH extract of the whole plants of Incarvillea mairei var. multifoliolata. The structures of these compounds were established on the basis of 1D‐ and 2D‐NMR and HR‐ESI‐MS analysis.     

Unusual formation of hydroperoxides in the reactions of substituted spiro[pyrazolinecyclopropanes]

3-Cyano- and 3-(alkoxycarbonyl)spiro[2-pyrazoline-5,1’-cyclopropane] and 5-phenylspiro[1-pyrazoline-3,1’-cyclopropane] undergo unusual transformations into 3(5)-substituted 5(3)-(2-hydroperoxyethyl)pyrazoles in the presence of atmospheric oxygen. The conditions for the formation of hydroperoxides (e.g., in oxygen-saturated solutions of spiro[2-pyrazoline-5,1’-cyclopropanes] in CHCl₃) and their conversion into (2-hydroxyethyl)pyrazoles or the corresponding nitrates under the action of nitrosating reagents were considered.__________Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 2160–2164, October, 2004.     

Cholesterol Hydroperoxides as Substrates for Cholesterol‐Metabolizing Cytochrome P450 Enzymes and Alternative Sources of 25‐Hydroxycholesterol and other Oxysterols

The interaction of the primary autoxidation products of cholesterol, namely 25‐ and 20ξ‐hydroperoxides, with the four principal cholesterol‐metabolizing cytochrome P450 enzymes is reported. Addition of cholesterol 25‐hydroperoxide to the enzymes CYP27A1 and CYP11A1 induced well‐defined spectral changes while generating 25‐hydroxycholesterol as the major product. The 20ξ‐hydroperoxides induced spectral shifts in CYP27A1 and CYP11A1 but glycol metabolites were detected only with CYP11A1. CYP7A1 and CYP46A1 failed to give metabolites with any of the hydroperoxides. A P450 hydroperoxide‐shunt reaction is proposed, where the hydroperoxides serve as both donor for reduced oxygen and substrate. CYP27A1 was shown to mediate the reduction of cholesterol 25‐hydroperoxide to 25‐hydroxycholesterol, a role of potential significance for cholesterol‐rich tissues with high oxidative stress. CYP27A1 may participate in the removal of harmful autoxidation products in these tissues, while providing a complementary source of 25‐hydroxycholesterol, a modulator of immune cell function and mediator of viral cell entry.     

Standard operation protocol for analysis of lipid hydroperoxides in human serum using a fully automated method based on solid-phase extraction and liquid chromatography-mass spectrometry in selected reaction monitoring

Standard operating procedures (SOPs) are of paramount importance in the analytical field to ensure the reproducibility of the results obtained among laboratories. SOPs gain special interest when the aim is the analysis of potentially unstable compounds. An SOP for analysis of lipid hydroperoxides (HpETEs) is here reported after optimization of the critical steps to be considered in their analysis in human serum from sampling to final analysis. The method is based on automated hyphenation between solid-phase extraction (SPE) and liquid chromatography-mass spectrometry (LC-MS). The developed research involves: (i) optimization of the SPE and LC-MS steps with a proper synchronization; (ii) validation of the method-viz. accuracy study (estimated as 86.4% as minimum value), evaluation of sensitivity and precision, which ranged from 2.5 to 7.0 ng/mL (0.25-0.70 ng on column) as quantification limit and precision below 13.2%), and robustness study (reusability of the cartridge for 5 times without affecting the accuracy and precision of the method); (iii) stability study, involving freeze-thaw stability, short-term and long-term stability and stock solution stability tests. The results thus obtained allow minimizing both random and systematic variation of the metabolic profiles of the target compounds by correct application of the established protocol.