Solvent Inclusion by the Anti-HIV Drug Nevirapine: X-Ray Structures and Thermal Decomposition of Representative Solvates

The preparation, X-ray crystal structures, and thermal analyses of five solvates of the non-nucleoside reverse transcriptase inhibitor Nevirapine are reported. Thermogravimetric traces for the solvates indicated the following compositions (N = nevirapine): N·(ethyl acetate) 0.5 ( 1 ), N·(dichloromethane) 0.5 ( 2 ), N·(toluene) 0.5 ( 3 ), N·(water) 0.5 ( 4 ), and N·(1,4-dioxane) 1.5 ( 5 ). Centrosymmetric, hydrogen-bonded nevirapine dimers occur in the crystals of 1 – 3 and in a previously characterized, unsolvated form of the drug 6 . In crystals of 4, drug molecules are linked by a single N–H···O═C hydrogen bond only, whereas solvate 5 contains noncentrosymmetric nevirapine dimers. Solvent molecules in 1 – 3 occupy channels, whereas the water molecules in 4 occupy isolated sites and 1,4-dioxane molecules in 5 occupy layers. These inclusion modes are described with reference to the thermal behaviors of the solvates recorded in TGA and DSC.