107-07-3Relevant articles and documents
-
Gebauer-Fuelnegg,Moffett
, p. 2009 (1934)
-
An Ultrasensitive Fluorescence Assay for the Detection of Halides and Enzymatic Dehalogenation
Aslan-üzel, A?k?n S.,Beier, Andy,Ková?, David,Cziegler, Clemens,Padhi, Santosh K.,Schuiten, Eva D.,D?rr, Mark,B?ttcher, Dominique,Hollmann, Frank,Rudroff, Florian,Mihovilovic, Marko D.,Bury?ka, Tomá?,Damborsky, Ji?í,Prokop, Zbyněk,Badenhorst, Christoffel P. S.,Bornscheuer, Uwe T.
, p. 2032 - 2039 (2020)
Halide assays are important for the study of enzymatic dehalogenation, a topic of great industrial and scientific importance. Here we describe the development of a very sensitive halide assay that can detect less than a picomole of bromide ions, making it very useful for quantifying enzymatic dehalogenation products. Halides are oxidised under mild conditions using the vanadium-dependent chloroperoxidase from Curvularia inaequalis, forming hypohalous acids that are detected using aminophenyl fluorescein. The assay is up to three orders of magnitude more sensitive than currently available alternatives, with detection limits of 20 nM for bromide and 1 μM for chloride and iodide. We demonstrate that the assay can be used to determine specific activities of dehalogenases and validate this by comparison to a well-established GC-MS method. This new assay will facilitate the identification and characterisation of novel dehalogenases and may also be of interest to those studying other halide-producing enzymes.
Structure-Reactivity Effects in the Breakdown of Hemiacetals of α-Bromoacetophenone. Change in Rate-Limiting Step for Base Catalysis
Soerensen, Poul E.,Pedersen, K. J.,Pedersen, P. R.,Kanagasabapathy, V. M.,McClelland, Robert A.
, p. 5118 - 5123 (1988)
Kinetics of breakdown are reported for the ethyl, methyl, 2-chloroethyl, and 2,2,2-trifluoroethyl hemiacetals of α-bromoacetophenone, the hemiacetals being generated by the aqueous bromination of the appropriate α-alkoxystyrene.Acid catalysis is characterized by a Broensted α value of 0.6 and a β1g (for H+) of 0.3.With these values the transition state has been located on a reaction coordinate diagram for the class e mechanism of acid catalysis and a comparison made with positions of transition states for acetaldehyde and formaldehyde hemiacetals.With changing electrophilicity of the carbonyl there is a consistent shift in the position of the transition state, but the effect is relatively small.The base-catalyzed breakdowns of the ethyl and 2-chloroethyl hemiacetals have β vlues near 0.7, significantly higher than the values associated with analogous formaldehyde and acetaldehyde hemiacetals.The difference can be explained in terms of the reaction coordinate diagram of the class n base mechanism, recognizing the decreased susceptibility of the ketone to nucleophilic addition.With the trifluoroethyl hemiacetal, buffer dilution plots are curved and there is a downward break in the rate-pH profile.These are explained by a mechanism-hemiacetal hemiacetal anion -> product-where at low buffer concentrations or low H+ concentration the deprotonation step is rate-limiting.As shown through a kinetic analysis, rate-limiting proton transfer is a result of a large rate constant for anion breakdown (ca. 8E8 s-1).Thus, at low buffer concentration breakdown occurs more quickly than reprotonation.The curvature arises because the buffer acid provides efficient protonation.At high buffer concentration the deprotonation step is (approaching) a rapid equilibrium preceding rate-limiting breakdown.Comparison with the other two hemiacetals shows that the behavior of the trifluoroethyl compound is predictable on the basis of structure-reactivity correlations.A reaction with rate-limiting proton transfer is enforced by the very short lifetime of the hemiacetal anion.
Characterization of transition states by isotopic mapping and structure-reactivity coefficients: Solvent and secondary deuterium isotope effects for the base-catalyzed breakdown of acetaldehyde hemiacetals
Coleman, Charolotte A.,Murray, Christopher J.
, p. 1677 - 1684 (1991)
Rate constants and structure-reactivity coefficients for the breakdown of acetaldehyde and acetaldehyde-d4 hemiacetals were determined in water and deuterium oxide by trapping the acetaldehyde formed with α-effect nucleophiles. General-base catalysis by substituted acetate and cacodylate ion catalysts represents equilibrium ionization of the hemiacetal CL3CL(OL)OR (L = H or D) to form the hemiacetal anion, CL3CL(O-)OR followed by rate-determining general-acid catalysis of the cleavage of the hemiacetal anion to form acetaldehyde and ROL. Solvent isotope effects for the catalytically active proton kpBH/kpBD = 0.9-2.5 do not change significantly with changes in the pK of the catalyst or the leaving group alcohol. The increase in the secondary αβ-deuterium isotope effects kαβH/kαβD = 1.21-1.30 with decreases in the pK of the leaving group alcohol can be described by the interaction coefficient pyy′ = ?ρn/-?pK1g = -0.069. The increase in Br?nsted β = 0.48-0.72 with decreases in the pK of the leaving group alcohol in water can be described by the interaction coefficient pxy′, = ?β/-?pK1g = 0.090 and in D2O by pxy′ = 0.078. The interaction coefficients and the observation of both solvent and secondary deuterium isotope effects are consistent with a coupling between proton transfer to the leaving group oxygen and changes in hybridization about the central carbon in the transition state for cleavage of the hemiacetal anion. The results are discussed in the context of proposals for stable hydrogen-bonded protons in concerted acid- and base-catalyzed reactions in water.
Synthesis of Oxochromium(VI) Alkoxides via Epoxide Cleavage. Structure, Reactivity, and Mechanism
Limberg, Christian,Wistuba, Tobias
, p. 6169 - 6176 (1999)
In an NMR spectroscopic study the cleavage of epoxides [ethylene, propylene, and cis/trans-butylene oxide] by chromyl chloride giving access to oxochromium(VI) alkoxides was shown to proceed via a bimolecular rate-determining step where two molecules of a complex CrO2Cl2...epoxide collide. Subsequently one Cl ligand at the first Cr center attacks the backside of an epoxide molecule complexed at the Cr center of a second CrO2Cl2...epoxide molecule and vice versa. The trans-opening of the epoxides was proved by determining the configuration of the chlorohydrins resulting from hydrolysis of the corresponding alkoxide products in the cases of cis- and trans-butylene oxide. The NMR data provide evidence that each oxochromium(VI) alkoxide adopts one preferred conformation in solution although DFT calculations did not indicate any special stabilizing effects. The product formation was rationalized by DFT calculations concerning the thermodynamics of the reactions.
Effects of Volume and Surface Property in Hydrolysis by Acetylcholinesterase. The Trimethyl Site
Cohen, Saul G.,Elkind, Jerome L.,Chishti, S. Bano,Giner, Jose-L. P.,Reese, Heide,Cohen, Jonathan B.
, p. 1643 - 1647 (1984)
β-Substituted ethyl acetates, XCH2CH2OCOCH3, have been prepared, and their hydrolysis by acetylcholinesterase has been studied.Log of enzymic reactivity, normalized for intrinsic reactivity in hydrolysis by hydroxide, log(kcat/Km)n, rises linearly with increasing refraction volume, MR (or RD25), for substrates with β-X = H, Cl, Br, CH3CH2, (CH3)2CH, (CH3)2S+, (CH3)3N+, and (CH3)3C.Larger substituents may by accommodated, (CH3)3Si and (CH3CH2)3N+, with no further increase in rate.Substrates with β-substituents CH3S, CH3S(O), (CH3)3N+(OH), and CH3S(O2) are less reactive than consistent with the relation with MR by factors of 5-40, indicating that hydrophobic surface and desolvation of the substrate-enzyme interface may be necessary for maximum reactivity correlated with MR.Values of log (kcat/Km)n for substrates with β-substituents X = CH3S, Cl, Br, CH3CH2, (CH3)2CH, (CH3)3C, and (CH3)3Si rise linearly with increasing hydrophobicity, ?, but reactivity of substrates with X = (CH3)3N+ and (CH3)2S+ are more reactive than consistent with a relation to ? by factors of 300 and 40 and with X = CH3S(O2), CH3S(O), and (CH3)2N+(OH), by factors of 7-100.Reactivity appears related to (i) volume of the β-substituent and its fit in its subsite, which is trimethyl rather than anionic, and (ii) the hydrophobicity of its surface.
STEREOSELECTIVE OLIGOMERIZATIONS CATALYZED BY LIPASES IN ORGANIC SOLVENTS.
Margolin, Alexey L.,Crene, Jean-Yves,Klibanov, Alexander M.
, p. 1607 - 1610 (1987)
Lipases have been found to act as stereoselective catalysts in polycondensation reactions between racemic diesters and achiral diols (or vice versa) in organic solvents.Optically active trimers and pentamers have been formed as a result.
Chlorine kinetic isotope effects on the haloalkane dehalogenase reaction
Lewandowicz,Rudzinski,Tronstad,Widersten,Ryberg,Matsson,Paneth
, p. 4550 - 4555 (2001)
We have found chlorine kinetic isotope effects on the dehalogenation catalyzed by haloalkane dehalogenase from Xanthobacter autotrophicus GJ10 to be 1.0045 ± 0.0004 for 1,2-dichloroethane and 1.0066 ± 0.0004 for 1-chlorobutane. The latter isotope effect approaches the intrinsic chlorine kinetic isotope effect for the dehalogenation step. The intrinsic isotope effect has been modeled using semiempirical and DFT theory levels using the ONIOM QM/QM scheme. Our results indicate that the dehalogenation step is reversible; the overall irreversibility of the enzyme-catalyzed reaction is brought about by a step following the dehalogenation.
-
Sroog et al.
, p. 1710 (1949)
-
Chloroethylating and methylating dual function antineoplastic agents display superior cytotoxicity against repair proficient tumor cells
Zhu, Rui,Baumann, Raymond P.,Patridge, Eric,Penketh, Philip G.,Shyam, Krishnamurthy,Ishiguro, Kimiko,Sartorelli, Alan C.
, p. 1853 - 1859 (2013)
Two new agents based upon the structure of the clinically active prodrug laromustine were synthesized. These agents, 2-(2-chloroethyl)-N-methyl-1,2- bis(methylsulfonyl)-N-nitrosohydrazinecarboxamide (1) and N-(2-chloroethyl)-2- methyl-1,2-bis(methylsulfonyl)-N-nitrosohydrazinecarboxamide (2), were designed to retain the potent chloroethylating and DNA cross-linking functions of laromustine, and gain the ability to methylate DNA at the O-6 position of guanine, while lacking the carbamoylating activity of laromustine. The methylating arm was introduced with the intent of depleting the DNA repair protein O6-alkylguanine-DNA alkyltransferase (AGT). Compound 1 is markedly more cytotoxic than laromustine in both AGT minus EMT6 mouse mammary carcinoma cells and high AGT expressing DU145 human prostate carcinoma cells. DNA cross-linking studies indicated that its cross-linking efficiency is nearly identical to its predicted active decomposition product, 1,2-bis(methylsulfonyl) -1-(2-chloroethyl)hydrazine (90CE), which is also produced by laromustine. AGT ablation studies in DU145 cells demonstrated that 1 can efficiently deplete AGT. Studies assaying methanol and 2-chloroethanol production as a consequence of the methylation and chloroethylation of water by 1 and 2 confirmed their ability to function as methylating and chloroethylating agents and provided insights into the superior activity of 1.
-
McBay,Tucker
, p. 869,878,880 (1954)
-
Method for producing chloroethanol and dichloroethane through ethylene glycol chlorination
-
Paragraph 0029-0076, (2021/08/11)
The invention relates to a method for producing chloroethanol and dichloroethane through ethylene glycol chlorination. According to the method, ethylene glycol is taken as a raw material, a cobalt compound, a manganese compound and an iron compound are taken as active components, and a zinc compound is taken as an active catalyst of an active auxiliary agent, so that the reaction of chloroethanol and dichloroethane can be effectively catalyzed, and high chloroethanol yield is obtained. The method solves the problems of poor selectivity and difficulty in organic acid catalyst recovery in the chloroethanol and dichloroethane preparation reaction in the prior art, and also avoids the problems of high ethylene oxide production cost, difficulty in storage and transportation and the like in the chloroethanol process taking ethylene oxide as a raw material.
High-purity chlorohydrin and its preparation method
-
Paragraph 0026; 0027, (2017/02/09)
The invention relates to the field of synthesis of chemical raw materials, and discloses a method for preparing high-purity chlorohydrins. The preparation method comprises the following steps: a, mixing a raw material 1, 4-dichloro-2-butene and an ozonization reaction solvent; agitating; charging ozone to perform ozonization reaction; tracking the reaction through gas chromatography; and stopping the ozonization reaction until raw materials disappear; and b, charging nitrogen to remove the ozone from a reaction flask; adding a reducing agent to reduce at -10-30 DEG C; agitating; recovering the solvent under a normal pressure condition; and distilling and collecting fractions under normal pressure to obtain the high-purity chlorohydrins. The preparation method is simple and convenient in process route, small in pollution, high in yield, fast in reaction speed, and simple in post-treatment; the chlorohydrins have the purity exceeding 99%, and thus the industrial value is relatively high.