Structure and molecular interactions of anti-thyroid drugs. Part 2. Electron donor properties of carbimazole1

Abstract

The electron donor properties of the anti-thyroid drug carbimazole towards the soft Lewis acid I₂ and the hard hydrogen-bond donor 4-fluorophenol are studied. Diiodine forms only a sulfur coordinated charge-transfer complex with carbimazole (formation constant ca. 1400 dm³ mol^–1 in CCl₄), while 4-fluorophenol forms both sulfur and carbonyl hydrogen-bonded complexes (formation constants respectively ca. 21 and 5 dm³ mol^–1 in CCl₄). The lesser hard basicity of carbimazole, and probably also propylthiouracil, compared to methimazole might validate the inactivation of thyroid peroxidase by means of a competitive coordination of these drugs to the ferric site of the enzyme.