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Pyridoxine‐Derived Organoselenium Compounds with Glutathione Peroxidase‐Like and Chain‐Breaking Antioxidant Activity
Author(s) -
Singh Vijay P.,
Poon Jiafei,
Butcher Ray J.,
Engman Lars
Publication year - 2014
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201403229
Subject(s) - chemistry , thiol , diphenyl diselenide , diselenide , ascorbic acid , hydrogen peroxide , medicinal chemistry , antioxidant , organic chemistry , stereochemistry , selenium , food science
One of the vitamin B6 vitamers, pyridoxine, was modified to incorporate selenium in various oxidation states in place of the methyl group in position 2. Such compounds were conveniently accessed by treatment of bis‐4,5‐(carboethoxy)‐2‐iodo‐3‐pyridinol with disodium diselenide and LiAlH 4 ‐reduction. After work‐up, selone 7 was isolated in good yield as an air‐stable crystalline material. Hydrogen bonding to the neighboring hydroxyl group, as revealed by the short intramolecular Se ⋅⋅⋅ H distance in the crystal structure is likely to provide extra stabilization to the compound. Computational studies showed that selone 7 is more stable than the corresponding selenol tautomer by 12.2 kcal mol −1 . Hydrogen peroxide oxidation of the selone 7 afforded diselenide 12 , and, on further oxidation, seleninic acid 13 . Treatment of the seleninic acid with thiophenol provided an isolable selenosulfide 14 . The glutathione peroxidase‐like properties of the pyridoxine‐derived compounds were assessed by using the coupled reductase method. Seleninic acid 13 was found to be twofold more active than ebselen. The chain‐breaking capacity of the pyridoxine compounds were studied in a water/chlorobenzene membrane model containing linoleic acid as an oxidizable substrate and N ‐acetylcysteine as a thiol reducing agent. Diselenide 15 could match α‐tocopherol when it comes to reactivity towards peroxyl radicals and inhibition time.