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 CH 3 (CH 2 ) 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.

New Crystal Forms for Biologically Active Compounds. Part 1: Noncovalent Interactions in Adducts of Nevirapine with XB Donors

“…(Figure 2). Almost the same supramolecular features can be found in NVP (PABHIJ [53] and PABHIJ01 [58]) crystals as well as in numerous crystals of nevirapine solvates (GIRWUA [54], KACPAH [55], OKETII [57], TISJEL [59], TISJEL01, YIVQIE, YIVQOK, YIVQUQ [58]) and adducts (LATQOO, LATQUU [56], ZEYSAA [60] (Figure 2 (Figure 2). Note that the simultaneous formation of HBs and XBs with the I atoms in 1,4-FIB was previously reported by us [42].…”

“…In addition to antiviral activity, it has been reported to bind to CYP3A4 and CYP2B6 cytochromes [49] and to display some anticancer activity [50][51][52]. Various crystal structures of NVP have been described [53][54][55][56][57][58][59][60]. In the majority of these structures, the NVP molecule acts as an HB donor (via the N-H motif) and an HB acceptor (via the carbonyl O and pyridine N atoms).…”

Crystal Forms of Anti-HIV Drugs: Role of Recrystallization

“…The effect of series of alcohols on solvate formation capability of nevirapine molecule has also been illustrated by Caira et al (Caira et al, 2010). The structures of all the solvates were www.intechopen.com based on a common isostructural framework comprising centrosymmetric hydrogenbonded nevirapine dimers and contain a common channel parallel to the crystal b-axis in the series which accommodates the various solvent molecules.…”

Interplay of thermochemistry and Structural Chemistry, the journal (volume 21, 2010) and the discipline

“…Systematic investigation by X-ray structural and thermal analysis of solvates of nevirapine used in combination with other antiretroviral drugs to treat HIV-1 infection and AIDS, with the homologous series of primary alcohols CH 3 (CH 2 ) n OH with n = 2-7 is then reported by Steiger et al [198]. Nevirapine is a tetraaza derivative of dibenzosuberane.…”