Crystal structure of naltrexone chloride solvates with ethanol, propan-2-ol, and 2-methylpropan-2-ol

Abstract

Naltrexone [systematic name: 17-(cyclopropylmethyl)-3,14-dihydroxy-4,5α-epoxymorphinan-6-one] is an opioid receptor competitive antagonist that has been widely used to prevent relapse in opioid- and alcohol-dependent subjects. Its chloride salt forms non-isomorphic solvates with ethanol (C20H24NO4+·Cl−·C2H5OH) (I), propan-2-ol (C20H24NO4+·Cl−·C3H7OH) (II), and 2-methylpropan-2-ol (C20H24NO4+·Cl−·C4H9OH) (III). The naltrexone cation can be described as a T-shape made out of two ring systems, a tetrahydro-2H-naphtho[1,8-bc]furan system and a decahydroisoquinolinium subunit, that are nearly perpendicular to one another. The flexible cyclopropylmethyl group can adopt various different conformations in response to its surroundings: an increase of available space around cyclopropylmethyl group may allow it to adopt a more favorable conformation. In all these structures, the alcohol molecules occupy infinite solvent-filled channels. All three compounds described are attractive crystalline forms for unambiguous identification of naltrexone chloride after isolation from a pharmaceutical form. Compound (III) was refined as a two-component twin.

Keywords

• crystal structure
• naltrexone
• chloride
• solvate
• ethanol
• propan-2-ol
• 2-methylpropan-2-ol