Solid‐State NMR‐Assisted Dynamic Characterization of two Isostructural Solvates of 5α‐Bromo‐6β,19‐Epoxy‐Androstan‐3β,17β‐Diol Diacetate

Abstract

AbstractThe study reports on the rotational dynamics of acetone‐d6 (Form II) and DMSO‐d6 (Form III) within the crystalline structures of two solvates of 5α‐bromo‐6β,19‐epoxy‐androstan‐3β,17β‐diol diacetate (Compound 1) by means of solid‐state Nuclear Magnetic Resonance through the quadrupolar 2H spin‐echo technique. The spectral data allowed the determination of the activation barriers (Ea) for rotation of the solvent molecules, with 6.24 kcal mol−1 for deuterated acetone in the Form II‐d6 and 8.19 kcal mol−1 for the case of deuterated dimethylsulfoxide in Form III‐d6. The use of calculations and the Transition State theory through the linear Eyring equation suggested that although the acetone molecules experience a low activation energy (Ea = 6.24 kcal mol−1), a highly ordered transition state during the molecular motion reduces its rotational rate. Conversely, the DMSO molecules, with a higher activation barrier (Ea = 8.19 kcal mol−1) attributed to a denser packing coefficient, have faster motional rates. Based on complementary X‐ray and NMR spectroscopy techniques, this work provides detailed insights into the mechanistic phenomena involved in the mobility of small molecules inside crystalline arrangements.