Different Dynamic Behavior of Methyl Groups in Crystalline Carbimazole as Revealed by a Multitechnique Experimental and Theoretical Approach

Dynamic properties of carbimazole (a drug used in hyperthyroidism treatment) were thoroughly investigated by combining solid-state nuclear magnetic resonance spectroscopy and quasielastic neutron scattering with periodic density functional theory (plane-wave DFT) and molecular dynamics simulations. These complementary methods allowed the full description of internal carbimazole motions. Particularly, in crystalline carbimazole, only the reorientations of the two methyl groups were found to be active in the explored timescale. The combination of different techniques allowed the quantitative characterization of the two methyl reorientations, which differ by almost 2 orders of magnitude in the timescale, in agreement with results previously reported in the literature for methyl groups in similar chemical environments. These results could also assume a particular relevance considering the role of methyl groups in determining the biochemical and biological activities of active pharmaceutical ingredients.