STRUCTURE AND MOLECULAR-INTERACTIONS OF ANTITHYROID DRUGS - PART 2 - ELECTRON-DONOR PROPERTIES OF CARBIMAZOLE

The electron donor properties of the anti-thyroid drug carbimazole tow ards the soft Lewis acid I, and the hard hydrogen-bond donor 4-fluorop henol are studied. Diiodine forms only a sulfur coordinated charge-tra nsfer complex with carbimazole (formation constant ca. 1400 dm(3) mol( -1) in CCl4), while 4-fluorophenol forms both sulfur and carbonyl hydr ogen-bonded complexes (formation constants respectively ca. 21 and 5 d m(3) mol(-1) in CCl4). The lesser hard basicity of carbimazole, and pr obably also propylthiouracil, compared to methimazole might validate t he inactivation of thyroid peroxidase by means of a competitive coordi nation of these drugs to the ferric site of the enzyme.