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

Abstract

The 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 (E_a) 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 (E_a = 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 (E_a = 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.