Interactions of Antithyroid Drugs and Their Analogues with Halogens and their Biological Implications

The selenium analogue of antithyroid drug methimazole (MSeI) reacts with molecular bromine to produce two different types of novel complexes depending upon the molar ratio of MSeI to Br2 in the reaction medium. Dicationic diselenide complex with two Br– ions as counterions is produced in the reaction of MSeI with 0.5 equiv of Br2 (MSeI/Br2, 1.0:0.5), whereas a stable 10-Se-3 hypervalent “T-shaped” complex featuring a linear Br–Se–Br moiety was produced when MSeI was treated with Br2 in an equimolar ratio (MSeI/Br2, 1.0:1.0). A substitution at the free N–H group in MSeI alters its reactivity toward iodine/bromine. For example, the N,N-disubstituted selones exclusively produce the corresponding 10-Se-3 hypervalent “T-shaped” complexes in the reaction with I2. In the presence of the lectoperoxidase/H2O2/I– system, N,N-dimethylimidazole-2-selone produces the corresponding dicationic diselenide with two I– counterions as the final metabolite. The formation of ionic species in these reactions is confirmed by single crystal X-ray diffraction studies and in some cases by Fourier transform-Raman spectroscopic investigations.