Quantum mechanical study of tautomerism of methimazole and the stability of methimazole–I2 complexes

DFT and ab initio theoretical methods were used to calculate the relative stability of tautomers in the methimazole (MMI). The calculations show that the thione form of MMI 1 is more stable than the thiol tautomer in good agreement with the experimental results. The DFT and ab initio calculations were also used to determine the stability of MMI–I₂ complexes. All methods suggest that the methimazole in the MMI–I₂ complex exists almost exclusively as the thione tautomer. The Gibbs free energy difference between planar and perpendicular forms of thione tautomer of MMI–I₂ complex indicates that the planar form is the predominant complex. The counterpoise corrected Gibbs free energy also shows that the MMI–I₂(plan.) complex is more stable than the MMI–I₂(perp.) complex. These predictions are in good agreement with the experimental results. By using the natural bond orbital (NBO) approach, the effects of charge transfer interactions on the stability of MMI–I₂ complexes were investigated. The LP₃(S)→σ*(I–I) and LP₃(I)→σ*(N–H) charge transfer interactions may be very important in the stability of the planar form. The results show that the LP₃(S)→σ*(I–I) charge transfer interaction causes a greater increase in the σ*(I–I) antibond occupation number, and concomitantly, a greater increase in the corresponding I–I bond length in the planar complex with respect to the perpendicular complex. The LP₃(S)→σ*(I–I) charge transfer interaction is assisted by NHI intermolecular hydrogen bonding. The atom in molecule (AIM) analysis shows that the charge density and its Laplacian at the SI bond critical point of the planar complex is greater than the perpendicular complex.