Interaction of methimazole with I2: X-ray crystal structure of the charge transfer complex methimazole-I2. implications for the mechanism of action of methimazole-based antithyroid drugs

J Med Chem. 2008 Jul 10;51(13):4050-3. doi: 10.1021/jm8001857. Epub 2008 Jun 5.

Abstract

The antithyroid drug methimazole (MMI) reacts with molecular iodine to form, in a multistep process, 1-methylimidazole as final product. In this process, the charge transfer complex MMI-I 2 and the ionic disulfide [(C 4H 6N 2S-) 2] (2+) ( 1, dication MMI disulfide) have been isolated and their X-ray crystal structures solved. Dication MMI disulfide perchlorate acts effectively both in reducing I 2 to I (-) ions and in showing antioxidant properties in inactivating the enzyme lactoperoxidase compound I.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antithyroid Agents / chemistry*
  • Antithyroid Agents / pharmacology*
  • Catalysis
  • Crystallography, X-Ray
  • Disulfides / chemistry
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Iodine / chemistry*
  • Ions / chemistry
  • Lactoperoxidase / antagonists & inhibitors
  • Lactoperoxidase / metabolism
  • Methimazole / chemistry*
  • Methimazole / pharmacology*
  • Models, Molecular
  • Molecular Structure
  • Oxidation-Reduction
  • Spectrophotometry
  • Structure-Activity Relationship

Substances

  • Antithyroid Agents
  • Disulfides
  • Enzyme Inhibitors
  • Ions
  • Methimazole
  • Iodine
  • Lactoperoxidase