Channel inclusion of primary alcohols in isostructural solvates of the antiretroviral nevirapine: an X-ray and thermal analysis study

Abstract

X-ray structural and thermoanalytical data for a series of solvates 2–7 of the anti-HIV drug nevirapine containing primary alcohols CH₃(CH₂) _n OH with n = 2–7 are reported. The structures of 2–7 are based on a common isostructural framework comprising centrosymmetric hydrogen-bonded nevirapine dimers and contain a common channel parallel to the crystal b-axis whose repeat length spans a narrow range (~8.43–8.52 Å) in the series and accommodates the various solvent molecules in 2–7. Thermogravimetry yielded a guest–host ratio close to 0.5 for the 1-butanol solvate 3 and a steady decrease in this ratio from 0.43 to 0.32 for the solvates 4–7. This anomalous stoichiometric variation was resolved following successful X-ray analysis of solvate 3 which revealed that the length spanned by the disordered 1-butanol molecule is commensurate with the channel periodicity b, resulting in a stoichiometric compound. Instead, solvates 5–7, for which single crystal X-ray data were available, showed significant disorder for the solvent molecules, attributed to their increasing chain lengths being incommensurate with the parameter b.