Thiiranium ion intermediates in the formation and reactions of S-(2-haloethyl)-l-cysteines |
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| Institution: | 1. Maternal and Fetal Health Research Centre, Institute of Human Development, The University of Manchester, Manchester Academic Health Science Centre, St. Mary''s Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester M13 9WL, United Kingdom;2. School of Nursing, Midwifery and Social Work, The University of Manchester, Jean McFarlane Building, Oxford Road, Manchester M13 9PL, United Kingdom;3. Department of Biology, Ecology and Earth Sciences, University of Calabria, Arcavacata di Rende, CS, Italy;4. Pcovery Aps, Thorvaldsensvej 57, DK-1871 Frederiksberg C, Denmark;1. Department Chemie und Pharmazie, Anorganische und Allgemeine Chemie, Friedrich–Alexander–Universität Erlangen–Nürnberg, Egerlandstr. 1, 91058, Erlangen, Germany;2. Department of Chemistry, University of Zurich, Winterthurerstrasse 190, CH-8057, Zurich, Switzerland;3. Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou 511436, China,;4. Department of Pharmacology, Jiangsu Key Laboratory of Neuropsychiatric Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu 215123, China,;6. Department of Urology, Nanjing Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu 21002, China,;12. Department of Oncology, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China, and;5. Sichuan Kelun Pharmaceutical Co., Ltd., Chengdu, Sichuan 610071, China;1. NMR Laboratory, University of Pannonia, H-8200 Veszprém, Egyetem u. 10, Hungary;2. Department of Organic Chemistry, University of Pannonia, H-8200 Veszprém, Egyetem u. 10, Hungary;1. Laboratory of Organic Chemistry, Wageningen University, Dreijenplein 8, Wageningen 6703 HB, The Netherlands;2. Plant Research International, Bioscience, Droevendaalsesteeg 1, Wageningen 6708 PB, The Netherlands;3. Department of Chemical and Materials Engineering, King Abdulaziz University, Jeddah, Saudi Arabia;4. Department of Chemical Biology and Drug Discovery, Utrecht Institute for Pharmaceutical Sciences and Bijvoet Center for Biomolecular Research, Utrecht University, The Netherlands |
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| Abstract: | Thiiranium ions formed from the cysteine or glutathione conjugates of 1,2-dihaloethanes are believed to be responsible for the genotoxicity of the parent alkyl halides. The conversions of specifically deuterated β-hydroxyethyl sulfides to the corresponding β-haloethyl sulfides are studied to provide direct evidence for the involvement of thiiranium ions in the reactions of the cysteine conjugates of 1,2-dihaloethanes. S-(2-Hydroxyethyl-1, 1-d2)-l-cysteine is converted to an equal mixture of the 1,1-d2 and 2,2-d2 isomers of the corresponding S-(2-haloethyl)-l-cysteines in concentrated hydrochloric, hydrobromic, or hydroiodic acids without detectable formation of the 2,2-d2 isomer of the parent hydroxyethyl derivative. Dissolution of S-(2-hydroxyethyl)-l-cysteine in trifluoromethanesulfonic acid yields a compound with the NMR spectral properties of S-(l-cysteinyl)ethyl thiiranium trifluoromethanesulfonate. The organosoluble S-(2-hydroxyethyl-1,1-d2) benzyl sulfide is converted to an equal mixture of the 1,1-d2 and 2,2-d2 isomers of S-(2-chloroethyl) benzyl sulfide by thionyl chloride or triphenylphosphine: carbon tetrachloride. These results demonstrate the involvement of thiiranium ion intermediates in the conversion of 2-hydroxyethyl sulfides to 2-haloethyl sulfides in halogen acids and a similar symmetrical intermediate in the chlorination reactions effected by thionyl chloride or triphenylphosphine: carbon tetrachloride. |
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