Reactivity of the drug methimazole and its iodine adduct with elemental zinc

Abstract

The reactivity of zinc complexes with N,S-donor molecules may be of relevance to the study of Zn-metalloproteins and -metalloenzymes. In this context, the zinc complex [Zn(MeImSH)₂I₂] was synthesised by the reaction of zinc powder with the 1 : 1 iodine adduct of the drug methimazole [(MeImSH)·I₂]. The molecular structure of the complex, elucidated by X-ray diffraction analysis, showed a tetrahedral zinc(II) centre coordinated by two neutral methimazole units (through the sulfur atoms) and two iodides. From the reaction of MeImSH and Zn powder, the complex [Zn(MeImSH)(MeImS)₂] (MeImS = deprotonated form of methimazole) was separated and characterised. An analysis of the crystal packing of the neutral complexes [Zn(MeImSH)₂X₂] (X = I, Br and Cl) and the ionic complex [Zn(MeImSH)₃I]I showed that in all of the complexes the sulfur atom, in addition to binding to the metal centre, contributes to the formation of 1-D chains built via C(4)–H⋯S and N–H⋯X interactions in the neutral complexes, and via C(4)–H⋯S and N–CH₃⋯S interactions in the ionic complex [Zn(MeImSH)₃I]I. The deprotonation/protonation of the coordinated methimazole units can modulate the coordination environment at the Zn core. From the reaction of complex [Zn(MeImSH)₃I]I with a strong non-coordinating organic base, we have shown that, as a consequence of the NH deprotonation of methimazole S-coordinated to zinc(II), the ligand coordination mode changes from S-monodentate to N,S-bridging. Correspondingly, in the complex [Zn(MeImSH)(MeImS)₂], the MeImS that displays the N,S-bridging mode at zinc can be N-protonated and thereby changes to the S-monodentate coordination.