69819-89-2Relevant articles and documents
Models for the inhibition of dithiol-containing enzymes by organoarsenic compounds: synthetic routes and the structure of [PhAs(HlipS2)] (HlipS22- = reduced lipoic acid)
Von Doellen, Angelika,Strasdeit, Henry
, p. 61 - 66 (2007/10/03)
The arsenic(III) dithiolate [PhAs(HlipS2)] (1, HlipS22- = 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-NH2C6H4)As(HlipS2)] (2) from (4-NH2C6H4)AsO(OH)2. rac-Dihydrolipoic acid and Me2-AsO(OH) react to give [(Me2As)2(HlipS2)] (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. (2RS,4RS)-1, which is the isomer found in the crystal, is thermodynamically more stable than the diastereomeric (2SR,4RS)-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.
