Models for in Vivo Deiodination of 2-Iodohistidine

✍ Scribed by E.R. Goldberg; L.A. Cohen

• Book ID: 102563784
• Publisher: Elsevier Science
• Year: 1993
• Tongue: English
• Weight: 377 KB
• Volume: 21
• Category: Article
• ISSN: 0045-2068
• DOI: 10.1006/bioo.1993.1006

✦ Synopsis

A variety of simple thiols fully deiodinate 2 -iodohistidine within (24 \mathrm{~h}) at (25^{\circ} \mathrm{C}) (at (\mathrm{pH} 7.2); (t_{12}=23.5 \mathrm{~min}) ). Deiodination of 2,4-diiodoimidazoles occurs specifically at C-2, but at (\frac{1}{6}) the rate for the 2-iodo compound, while 4-iodoimidazoles are completely stable. (\mathrm{N})-alkylation does not prevent deiodination but strong electronegative substituents at (\mathrm{C}-4) or (\mathrm{C}-5) do block the reaction. Bromoimidazoles are totally stable under the specified conditions. The proposed mechanism involves a nucleophilic attack by the soft mercaptide ion on the soft iodine in the protonated imidazole, with the imidazole ylid-carbene as the leaving group. This facile nonenzymatic deiodination provides an explanation for the failure of 2-iodohistidine to maintain its strong antimalarial activity in owl monkeys beyond a 24-h period. O 1993 Academic Press. Inc.