Pyridoxine‐Derived Organoselenium Compounds with Glutathione Peroxidase‐Like and Chain‐Breaking Antioxidant Activity. Issue 39 (14th August 2014)

• Record Type: Journal Article
• Authors: Singh, Vijay P.; Poon, Jia‐fei; Butcher, Ray J.; Engman, Lars
• Is Part Of: Chemistry. Volume 20:Issue 39(2014)
• Page Start: 12563
• Page End: 12571
• Publication Date: 2014-08-14
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201403229
• Languages: English
• ISSNs: 0947-6539

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>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<sub>4</sub>‐reduction. After work‐up, selone <bold>7</bold> 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<bold>⋅⋅⋅</bold>H distance in the crystal structure is likely to provide extra stabilization to the compound. Computational studies showed that selone <bold>7</bold> is more stable than the corresponding selenol tautomer by 12.2 kcal mol<sup>−1</sup>. Hydrogen peroxide oxidation of the selone <bold>7</bold> afforded diselenide <bold>12</bold>, and, on further oxidation, seleninic acid <bold>13</bold>. Treatment of the seleninic acid with thiophenol provided an isolable selenosulfide <bold>14</bold>. The glutathione peroxidase‐like properties of the pyridoxine‐derived compounds were assessed by using the coupled reductase method. Seleninic acid <bold>13</bold> 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 <italic>N</italic>‐acetylcysteine as a thiol reducing agent. Diselenide <bold>15</bold> could match α‐tocopherol when it comes to reactivity towards peroxyl radicals and inhibition time.</p> </abstract>