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Electrophilic Compounds (electrophilic + compound)
Selected AbstractsMechanistic Study of the Reaction of Thiol-Containing Enzymes with ,,,-Unsaturated Carbonyl Substrates by Computation and ChemoassaysCHEMMEDCHEM, Issue 6 2010Alexander Paasche Abstract We investigated the reactions between substituted ,,,-unsaturated carbonyl compounds (Michael systems) and thiols by computations as well as chemoassays. The results give insight into variations in the underlying mechanisms as a function of the substitution pattern. This is of interest for the mechanisms of inhibition of the SARS coronavirus main protease (SARS-CoV Mpro) by etacrynic acid derivatives as well as for the excess toxicity of substituted ,,,-unsaturated carbonyl compounds. This study compares possible reaction courses including 1,4-addition followed by a ketonization step, and underscores the importance of a base-catalyzed step for the reactivity of thiol groups in enzymes. Phenyl and methyl substituents at the Michael system decrease the reactivity of the electrophilic compound, but chlorophenyl substituents partly recover the reactivity. Computations also indicate that electron-pushing substituents lead to a change in the reaction mechanism. The conformation of the Michael system is also found to significantly influence reactivity: the s - cis conformation leads to higher reactivity than the s - trans conformation. The computed data explain the trends in measured inhibition potencies of substituted ,,,-unsaturated carbonyl compounds and of reaction rates in chemical assays. They also indicate that the reversibility of inhibition does not stand in contrast to the formation of a new covalent bond between inhibitor and protease. [source] Synthesis of N -alkoxybenzimidoyl azides and their reactions in electrophilic mediaJOURNAL OF PHYSICAL ORGANIC CHEMISTRY, Issue 3 2010Debra D. Dolliver Abstract A new general route to N -alkoxybenzimidoyl azides [ArC(N3)=NOR] from a reaction of N -alkoxybenzimidoyl bromide [ArC(Br)=NOR] with sodium azide in DMSO is described. These reactions result in the Z -geometric configuration. These compounds show a moderate degree of thermal stability as assessed by differential scanning calorimetry, and lack reactivity in traditional 1,3-dipolar cycloaddition ,click' reactions. Upon exposure to electrophilic compounds (trifluoroacetic acid or acetyl chloride), these azide compounds can react by two pathways: a Schmidt-type rearrangement to form an N -alkoxyurea or an isomerization,cyclization reaction pathway to form an N -alkoxytetrazole. The route of the reaction has no dependence on solvent polarity and appears to depend upon the electrophile (H+vs. CH3CO+): reaction of the azide with trifluoroacetic acid results predominantly in the urea; reaction with acetyl chloride results solely in the tetrazole. Calculations indicate that the urea product is thermodynamically favored over the tetrazole product. They also indicate that both reaction conditions result in an equilibration between the starting azide and the tetrazole with the tetrazole being the major component in this equilibrium mixture. The fact that the azide also undergoes a Schmidt-type rearrangement to form an N -alkoxyurea when treated with trifluoroacetic acid appears to indicate that the barrier for aromatic ring migration is lower in the protonated azide produced on reaction with trifluoroacetic acid than in the acetylated azide produced on reaction with acetyl chloride. Copyright © 2009 John Wiley & Sons, Ltd. [source] The redox-sensing regulator YodB senses quinones and diamide via a thiol-disulfide switch in Bacillus subtilisPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 17 2010Bui Khanh Chi Abstract The MarR/DUF24-type repressor YodB controls the azoreductase AzoR1, the nitroreductase YodC and the redox-sensing regulator Spx in response to quinones and diamide in Bacillus subtilis. Previously, we showed using a yodBCys6-Ala mutant that the conserved Cys6 apparently contributes to the DNA-binding activity of YodB in vivo. Here, we present data that mutation of Cys6 to Ser led to a form of the protein that was reduced in redox-sensing in response to diamide and 2-methylhydroquinone (MHQ) in vivo. DNA-binding experiments indicate that YodB is regulated by a reversible thiol-modification in response to diamide and MHQ in vitro. Redox-regulation of YodB involves Cys6-Cys101' intermolecular disulfide formation by diamide and quinones in vitro. Diagonal Western blot analyses confirm the formation of intersubunit disulfides in YodB in vivo that require the conserved Cys6 and either of the C-terminal Cys101' or Cys108' residues. This study reveals a thiol-disulfide switch model of redox-regulation for the YodB repressor to sense electrophilic compounds in vivo. [source] Considerations for the design of organic mulch permeable reactive barriersREMEDIATION, Issue 1 2007Farrukh Ahmad Organic mulch consists of insoluble carbon biopolymers that are enzymatically hydrolyzed during decomposition to release aqueous total organic carbon (TOC). The released TOC is utilized by microorganisms as an electron donor to transform electrophilic contaminants via reductive pathways. Over the last decade, organic mulch permeable reactive barriers (PRBs), or biowalls, have received increased interest as a relatively inexpensive slow-release electron donor technology for addressing contaminated groundwater. To date, biowalls have been installed to enhance the passive bioremediation of groundwater contaminated with a variety of electrophilic compounds, including chlorinated solvents, explosives, and perchlorate. In addition, several mulch biowall projects are currently under way at several U.S. Department of Defense facilities. However, at the present time, the guidelines available for the design of mulch PRBs are limited to a few case studies published in the technical literature. A biowall design, construction, and operation protocol document is expected to be issued by the Air Force Center for Environmental Excellence in 2007. In this publication, three technical considerations that can have a significant impact on the design and performance of mulch PRBs are presented and discussed. These technical considerations are: (1) hydraulic characteristics of the mulch bed; (2) biochemical characteristics of different types of organic amendments used as mulch PRB fill materials; and (3) a transport model that can be used to estimate the required PRB thickness to attain cleanup standards. © 2007 Wiley Periodicals, Inc. [source] The effect of bacterial glutathione S-transferase on morpholine degradationBIOTECHNOLOGY JOURNAL, Issue 2 2009Giti Emtiazi Professor Abstract Glutathione S-transferases (GSTs) constitute a large family of enzymes that catalyze the addition of glutathione to endogenous, or xenobiotic, often toxic electrophilic compounds. The effect of this enzyme in facilitating polychlorinated biphenyls degradation has been studied previously. Here the effects of induced cell-free extracts of Acinetobacter calcoaceticus and Pseudomonas aeruginosa (grown on hexadecane), and E. coli BL21 (induced with pGEX-2T plasmid on isothiopropylgalactoside) were recruited to facilitate morpholine degradation by Mycobacterium and were compared with non-induced strains. The results showed that all induced strains had significantly more GST activity compared to non-induced ones, and the strain with most GST activity, A. calcoaceticus BS, removed morpholine faster. Eukaryotic GST gene expressed in E. coli BL21 also could facilitate morpholine degradation by Mycobacterium, The same experiments performed with cell-free extracts of non-induced cells did not show any significant effects on morpholine removal. These results showed that there is a correlation between GST activity and acceleration of morpholine degradation. [source] | ||||||||||