Crystal and molecular structure of ostarine and andarine

Abstract

In recent years, an increasing focus has been given to the study of selective androgen receptor modulators (SARMS) due to the fewer side effects they exhibit compared to anabolic androgenic steroids. The crystal structure of ostarine (Os) and andarine (AND) has been determined by X-ray single crystal diffraction. It was found that ostarine crystallizes in the monoclinic system, P21 space group with Z = 2 and one molecule in the asymmetric unit, while andarine crystallizes in the tetragonal system, P42212 space group with Z = 8 and one molecule per asymmetric unit. A polymorph of ostarine (Os–P1) has been identified as being monoclinic, space group P21, Z = 2 with two molecules in the asymmetric unit and has been solved by X-ray powder diffraction using Parallel tempering Monte Carlo technique and refined by Rietveld method. This polymorph has been obtained by phase change as a result of heating. All studied compounds were further characterized by IR spectroscopy, differential thermal analysis (DTA) and thermogravimetric analysis (TGA). The molecular self-assembly architectures are built by hydrogen bonds as O–H⋯N and N–H⋯O in ostarine, respectively O–H⋯O, N–H⋯O in andarine. Crystal packing energies were calculated using atom-atom force field method (London-Coulomb-Pauli, CLP) which involves the evaluation of Coulombic, polarization, dispersion and repulsion terms. Furthermore, Hirshfeld surface and fingerprint plot analysis was carried out in order to understand the presence of different intermolecular interactions and how hydrogen bonding holds the stability of the crystal structure.