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Models for the Inhibition of Dithiol‐Containing Enzymes by Organoarsenic Compounds: Synthetic Routes and the Structure of [PhAs(HlipS 2 )] (HlipS 2 2− = Reduced Lipoic Acid)
Author(s) -
von Döllen Angelika,
Strasdeit Henry
Publication year - 1998
Publication title -
european journal of inorganic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.667
H-Index - 136
eISSN - 1099-0682
pISSN - 1434-1948
DOI - 10.1002/(sici)1099-0682(199801)1998:1<61::aid-ejic61>3.0.co;2-#
Subject(s) - chemistry , lipoic acid , dithiol , epimer , diastereomer , stereochemistry , crystal structure , enzyme , catalysis , cofactor , crystallography , organic chemistry , antioxidant
The arsenic(III) dithiolate [PhAs(HlipS 2 )] ( 1 , HlipS 2− 2 = reduced rac ‐lipoic acid) has been obtained via three different routes: (A) from (PhAsO) n and rac ‐dihydrolipoic acid, (B) from (AsPh) 6 and rac ‐lipoic acid, and (C) from PhAsO(OH) 2 and rac ‐dihydrolipoic acid. The latter method is also suitable for the preparation of [(4‐NH 2 C 6 H 4 )As(HlipS 2 )] ( 2 ) from (4‐NH 2 C 6 H 4 )AsO(OH) 2 . rac ‐Dihydrolipoic acid and Me 2 AsO(OH) react to give [(Me 2 As) 2 (HlipS 2 )] ( 3 ). These reactions indicate pathways by which mono‐ and diorganoarsenic compounds of various As oxidation states (I, III, and V) may inhibit enzymes that contain lipoic acid as a cofactor. X‐ray structure analysis shows that 1 is a 2,4‐disubstituted 1,3,2‐dithiarsinane, i. e. a six‐membered heterocycle. The phenyl group at the 2‐position (As) adopts the axial orientation. (2 RS ,4 RS )‐ 1 , which is the isomer found in the crystal, is thermodynamically more stable than the diastereomeric (2 SR ,4 RS )‐ 1 by 4.3 ± 0.8 kJ/mol (25°C). In solution, the epimerization by inversion of configuration at the ψ‐tetrahedrally coordinated As atom is faster than expected, with acid catalysis (COOH groups!) being a possible cause.