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DOI: 10.1039/A803002B (Paper) Reference Section for: J. Chem. Soc., Perkin Trans. 2, 1998, 1545-1552

Structure and molecular interactions of anti-thyroid drugs. Part 3.1 Methimazole: a diiodine sponge

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Christian Laurence, Mohamed J. El Ghomari, Jean-Yves Le Questel, Michel Berthelot and Rachid Mokhlisse

Abstract

The anti-thyroid drug methimazole functions as a diiodine sponge. Its thione tautomer forms with diiodine a very stable electron donor–acceptor complex (Kf = 36 600 l mol–1 in CCl4), stabilized in a more polar medium (Kf = 92 400 l mol–1 in CH2Cl2). Two stereoisomeric complexes, one planar on the non-bonding sulfur lone pair and the other perpendicular on the sulfur π electrons, are found in solution to be under steric control. The position of the charge-transfer band of many diiodine complexes of thioamides and thioureas allows the prediction of their geometry. The sulfur–iodine coordination is assisted by intramolecular hydrogen bonding NH[hair space][hair space]· · ·[hair space][hair space]I. This iodine amphoterism is explained by the anisotropy of its electrostatic potential surface. Hard and soft acid–base chemistry might explain the two mechanisms of action of anti-thyroid drugs, the inhibition of thyroid peroxidase via coordination to the hard heme group and the trapping of oxidized iodides via complexation of soft iodinated Lewis acids.

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