Crystal structure and Hirshfeld surface analysis of the methanol solvate of sclareol, a labdane-type diterpenoid

The key interactions in the extended structure of the title solvate are O—H⋯O hydrogen bonds, which generate [010] chains.


Chemical context
Sclareol, a labdane diterpene, is an important component of Salvia sclarea L., commonly known as clary sage, a medicinal herb mostly found in Mediterranean countries and southern Europe (Kouzi & McChesney, 1990;Acimovic et al., 2018). Sclareol is also reported from Cleome spinose B, Cistus creticus C, and Nicotiana glutinosa S (Caniard et al., 2012). Labdanes show various biological and pharmacological activities , including antifungal, antibacterial, growth-regulating activity, and cytostatic and cytotoxic effects against HL60 human leukemic cell lines (Kouzi et al., 1993;Dimas et al., 2001). Sclareol is also used commercially as a fixative in perfumery and as a flavouring agent in the tobacco industry (Kouzi & McChesney, 1990). ISSN 2056-9890 The presence of solvent molecules of crystallization (Aitipamula et al., 2012) can significantly influence the geometry of the respective pharmaceutical molecule (Chen et al., 2017). The crystal structure of sclareol (orthorhombic, space group P2 1 2 1 2 1 ) has been described (Nagashima et al., 1997). We now describe the crystal structure of the methanol solvate of sclareol (1), which results in a change of space group to triclinic P1. Leishmaniasis is a major infectious disease caused by various species of the genus Leishmania. Currently there is no effective drug or vaccine against leishmanicidal disease commercially available (Tavares et al., 2018). In the current study, the anti-leishmanial activity of 1 was also investigated.
The Hirshfeld surface (Spackman & Jayatilaka, 2009;Capozzi et al., 2019) mapped over d norm for 1 is shown in Fig. 4; red spots indicate the areas of the molecular surfaces where strong interactions occur. The two-dimensional fingerprint Table 1 Hydrogen-bond geometry (Å , ).     The molecular structure of 1 with displacement ellipsoids drawn at the 30% probability level. plots (Fig. 5)

Crystallization
Purified sclareol was taken from the molecular bank facility of the Dr Panjwani Center for Molecular Medicine and Drug Research, ICCBS, University of Karachi, Pakistan. The procedure for isolation and purification has already been described (Shawl et al., 1999). Crystallization was carried out in a 1:1 solvent mixture of acetonitrile and methanol. Colourless blocks of 1 were obtained by slow evaporation at 277 K after two weeks

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 2. All the C-bound H atoms were located with idealized geometry and refined with C-H = 0.95-1.00 Å , having U iso (H) = 1.5U eq (CH 3 ) and 1.2U eq (CH 2 , CH). The O-bound H atoms were found in difference-Fourier maps and their positions freely refined with U iso (H) = 1.2U eq (O).

Funding information
The research leading to these results has, in part, received funding from UK Research and Innovation via the Global Hirshfeld surface mapped over d norm of 1 with neighboring molecules linked via O-HÁ Á ÁO hydrogen bonds (dashed lines).

Figure 5
Two-dimensional Hirshfeld fingerprint plots for 1.  Data collection: APEX2 (Bruker, 2012); cell refinement: SAINT (Bruker, 2012); data reduction: SAINT (Bruker, 2012); program(s) used to solve structure: SHELXT2014/5 (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2016/6 (Sheldrick, 2015b); molecular graphics: SHELXTL (Sheldrick, 2015); software used to prepare material for publication: SHELXTL (Sheldrick, 2015b).  Special details Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.