Darstellung und Eigenschaften der α‐halogenierten Thioäther

Böhme, Horst; Fischer, Harriet; Frank, Ronald

doi:10.1002/jlac.19495630107

Cited by 174 publications

(20 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It was shown that for hydrolysis in 5 M water in dioxane at 25 °C, the phenylthiomethyl chloride (chloromethyl phenyl sulfide, 1 ) reacted about 200 times slower than chloromethyl methyl sulfide [24]. The effect of the introduction of meta - and para - substituents into the aromatic ring of 1 has been studied [25] in 50% dioxane at 35 °C.…”

Section: Introductionmentioning

confidence: 99%

“…In a study with thioethers [24], it was found that the solvolyses of CH 3 SCH 2 Cl in 1 M water in dioxane at 25 °C increased in rate by a factor of 500 on the introduction of a methyl group into the chloromethyl, to give CH 3 SCH(CH 3 )Cl. If, in turn, the introduced methyl group was replaced by a phenyl group, it was found that, for reaction with 0.2 M water in dioxane at 25 °C, there was a further 140 fold increase in rate.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Nucleophilic Participation in the Solvolyses of (Arylthio)methyl Chlorides and Derivatives: Application of Simple and Extended Forms of the Grunwald-Winstein Equations

Kevill¹,

Park²,

Park³

et al. 2012

COC

View full text Add to dashboard Cite

The specific rates of solvolysis of chloromethyl phenyl sulfide [(phenylthio)methyl chloride] and its p-chloro-derivative have been determined at 0.0 °C in a wide range of hydroxylic solvents, including several containing a fluroalcohol. Treatment in terms of a two-term Grunwald-Winstein equation, incorporating terms based on solvent ionizing power (YCl) and solvent nucleophilicity (NT) suggest a mechanism similar to that for the solvolyses of tert-butyl chloride, involving in the rate-determining step a nucleophilic solvation of the incipient carbocation in an ionization process. A previous suggestion, that a third-term governed by the aromatic ring parameter (I) is required, is shown both for the new and for the previously studied related substrates to be an artifact, resulting from an appreciable degree of multicollinearity between I values and a linear combination of NT and YCl values.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Nucleophilic Participation in the Solvolyses of (Arylthio)methyl Chlorides and Derivatives: Application of Simple and Extended Forms of the Grunwald-Winstein Equations

Kevill¹,

Park²,

Park³

et al. 2012

COC

View full text Add to dashboard Cite

show abstract

“…For instance, with CH 2 BrCl, the product is GSCH 2 Cl, which will readily hydrolyze to HCHO (regardless of whether Br or Cl is present), but GSCH 2 Cl might have different properties than GSCH 2 Br in reacting with DNA. The details of these differences are still not particularly clear, due to the difficulty in studying the reactive GSCH 2 X compounds (8)(9)(10)(11)44). 2 However, we have shown that GSCH 2 CH 2 Cl is more mutagenic than GSCH 2 CH 2 Br when added to S. typhimurium cells (21), probably because of stability (GSCH 2 H 2 F is even more mutagenic).…”

Section: Discussionmentioning

confidence: 90%

Analysis of the Kinetic Mechanism of Haloalkane Conjugation by Mammalian θ-Class Glutathione Transferases

Guengerich

McCormick

Wheeler

2003

Chem. Res. Toxicol.

View full text Add to dashboard Cite

Glutathione (GSH) transferases (GSTs) catalyze the conjugation of small haloalkanes with GSH. In the case of dihalomethanes and vic-1,2-dihaloalkanes, the reaction leads to the formation of genotoxic GSH conjugates. A generally established feature of the reaction of the mammalian theta-class GSTs, which preferentially catalyze these reactions, is the lack of saturability of the rate with regard to the substrate concentration. However, the bacterial GST DM11 catalyzes the same reactions with a relatively low K(m). Recently, DM11 has been shown to exhibit burst kinetics, with a rate-determining k(off) rate for product (Stourman et al. (2003) Biochemistry 42, 11048-11056). We examined rat GST 5-5 and human GST T1-1 and did not detect any burst kinetics in the conjugation of C(2)H(5)Cl, CH(2)Br(2), or CH(2)Cl(2), distinguishing these enzymes from GST DM11. The kinetic results were fit to a minimal mechanism in which the rate-limiting step is halide displacement. The differences in the steady state kinetics of conjugations catalyzed by bacterial GST DM11 and the mammalian GSTs 5-5 and T1-1 are concluded to be the result of differences in the rate-limiting steps and not to inherent enzyme affinity for the haloalkanes. The results may be interpreted in the context of a model in which the halide order affects the rate of carbon-halogen bond cleavage of all such reactions catalyzed by the GSTs. With GST DM11, the halide order is manifested in the K(m) parameter but not k(cat). With mammalian GSTs, the high K(m) is difficult to estimate. With all of the GSTs, the halide order is seen in the enzyme efficiency, k(cat)/K(m), with C-Br cleavage approximately 10-fold faster than C-Cl cleavage. The ratio k(cat)/K(m) is the most relevant parameter for issues of risk assessment.

show abstract

“…70,72,76 A conjugação do diclorometano (CH 2 Cl 2 ) ou de outros dialoalcanos se dá, inicialmente, pela substituição nucleofílica de um dos áto-mos de cloro por glutationa (GSH), fornecendo o aduto Sclorometilglutationa (52). 77 O aduto S-clorometilglutationa 52 é instável e reativo, 78,79 sendo que evidências diretas de sua formação só foram possíveis utilizando-se ressonância magnética nuclear de 19 F e clorofluorometano (CH 2 ClF) como substrato para as glutationa transferases (GSTs). 80 A interceptação do aduto 52 por nucleofílos biológicos, como as bases nitrogenadas do DNA, gera inicialmente o aduto 53, seguida da despurinação do DNA com formação de 54, podendo levar à morte da célula.…”

Section: Figura 8 Algumas Etapas Da Biossíntese Da Testosteronaunclassified

Glutationa e enzimas relacionadas: papel biológico e importância em processos patológicos

Huber¹,

Almeida²,

Fátima³

2008

Quím. Nova

121

View full text Add to dashboard Cite

Recebido em 22/2/07; aceito em 6/9/07; publicado na web em 9/4/08 GLUTATHIONE AND RELATED ENZYMES: BIOLOGICAL ROLES AND IMPORTANCE IN PATHOLOGICAL PROCESSES. Glutathione (GSH) and related enzymes are pivotal for the normal functioning of several important biological processes. In this review we discuss the biosynthesis and the catalytic cycles of glutathione as well as the major GSH-related enzymes. We also present how glutathione and enzymes are involved in cancer and the chromatographic and non-chromatographic methods used to analyze glutathione and/or its derivatives.Keywords: glutathione; oxidative stress; cancer. INTRODUÇÃOA glutationa (GSH, 1, Figura 1), possui papel central na biotransformação e eliminação de xenobióticos e na defesa das cé-lulas contra o estresse oxidativo.1 Este tripeptídeo é encontrado intracelularmente em altas concentrações, essencialmente em todos os organismos aeróbicos. Nota-se a ligação γ-peptídica pouco usual, a presença da porção γ-glutamil e do grupo α-carboxilato livre prevenindo a hidrólise da GSH pelas peptidases celulares que degradam outros peptídeos pequenos. A GSH é o mais abundante tiol celular de baixa massa molecular; a sua concentração é ~ 2mM e mais de 10 mM em eritrócitos humanos e hepatócitos, respectivamente.1 Face à potencialidade de inibidores das enzimas relacionadas à GSH como alvo para o desenvolvimento de substâncias candidatas a fármacos, nesta revisão serão apresentados aspectos importantes do papel fisiológico da glutationa (GSH) e sua implicação em patologias. Considerando esta abordagem, ênfase especial será dada às glutationas transferase e redutase. Uma vez que a investigação do envolvimento da GSH em processos fisiopatológicos requer sua detecção e quantificação em diferentes matrizes, também serão abordados os principais métodos de análise deste tripeptídeo e derivados.Muitas das reações da GSH envolvem o grupo sulfidrila (SH), altamente polarizável, tornando-o um bom nucleófilo para reações com compostos químicos eletrofílicos. Esta habilidade de doar elé-trons a outros compostos também faz da glutationa um bom redutor. A combinação de sua abundância nos organismos aeróbicos e das propriedades químicas do grupo sulfidrila suporta a proposta de que a GSH surgiu na evolução bioquímica como uma proteção contra espécies reativas de oxigênio e compostos eletrofílicos gerados por processos oxidativos, tanto no organismo quanto no ambiente em que este vive. BiossínteseA biossíntese da GSH ocorre no meio intracelular (exceto em células epiteliais), pela ação consecutiva de duas enzimas. Na primeira reação, é formada uma ligação peptídica entre os aminoácidos glutâmico (2, Figura 2) e cisteína (3), catalisada pela enzima γ-glutamilcisteína sintetase, levando à γ-L-glutamil-L-cisteína (4). Este dipeptídeo é então ligado à glicina pela ação da glutationa sintetase. Estas etapas requerem ATP e Mg +2 . A γ-glutamilcisteína sintetase sofre regulação pela GSH através de um feedback negativo, o que previne a produção excessiva desta ou o acúmulo do intermediário...

show abstract

Darstellung und Eigenschaften der α‐halogenierten Thioäther

Cited by 174 publications

References 22 publications

Nucleophilic Participation in the Solvolyses of (Arylthio)methyl Chlorides and Derivatives: Application of Simple and Extended Forms of the Grunwald-Winstein Equations

Nucleophilic Participation in the Solvolyses of (Arylthio)methyl Chlorides and Derivatives: Application of Simple and Extended Forms of the Grunwald-Winstein Equations

Analysis of the Kinetic Mechanism of Haloalkane Conjugation by Mammalian θ-Class Glutathione Transferases

Glutationa e enzimas relacionadas: papel biológico e importância em processos patológicos

Contact Info

Product

Resources

About