[1–9-NαC]-Linusorb B3 (Cyclolinopeptide A) dimethyl sulfoxide monosolvate

[1–9-NαC]-Linusorb B3 (Cyclolinopeptide A) was extracted from flaxseed oil crystals formed in dimethyl sulfoxide. The molecule has four intramolecular N—H⋯O hydrogen bonds, and the DMSO solvate molecule is bound to the Phe6 amino acid by a fifth N—H⋯O hydrogen bond.

The molecular structure of the title compound is shown in Fig. 1. The cyclic polypeptide or orbitide [1-9-NC]-linusorb B3 (Cyclolinopeptide A; CLP-A) has nine amino acids (Ile1-Leu2-Val3-Pro4-Pro5-Phe6-Phe7-Leu8-Ile9). The nomenclature and amino-acid numbering for orbitides was standardized by Craik et al. (2016). The title compound was first isolated from flax seed by Kaufmann & Tobschirbel (1959). The current method involves the use of silica gel chromatography to extract cyclic peptides from unrefined flaxseed oil, followed by isolation of the orbitide using high performance liquid chromatography (Reaney et al., 2013). The isolated orbitide was then dissolved in dimethyl sulfoxide (DMSO) and stored under ambient conditions. The molecule has four intramolecular N-HÁ Á ÁO hydrogen bonds, and the DMSO solvate molecule is bound to the Phe6 amino acid by an N-HÁ Á ÁO hydrogen bond (Table 1). The packing is shown in Fig. 2. The first crystal structure for CLP-A 2-propanol solvate was published by Di data reports Blasio et al., 1989), followed by the same compound in methanol/2-propanol (Matsumoto et al., 2002), methanol (Quail et al., 2009), and in acetonitrile (Chitanda et al., 2016).
The compound, [1-9-NC]-linusorb B3, has shown to induce potentially beneficial responses in living organisms. The biomolecular interaction with human albumin has been reported by Rempel et al. (2010). It has demonstrated cytoprotective activity in liver cells by inhibiting cholate uptake (Kessler et al., 1986). The title compound has been shown to have immunosuppressive activity, and no toxicity at high doses (Wieczorek et al., 1991;Gaymes et al., 1997).

Synthesis and crystallization
The crystals were found unintentionally after the title compound was dissolved in DMSO, and allowed to evaporate slowly at ambient temperature. Single crystal X-ray diffraction data for the title compound were collected using the Canadian Macromolecular Crystallography Facility CMCF-BM beamline at the Canadian Light Source (CLS), described by Grochulski et al. (2011). The CMCF-BM is a bending magnet beamline equipped with an Si (111) double-crystal monochromator, Rayonix MX300HE CCD detector and MD2 microdiffractometer equipped with Mini Kappa Goniometer Head. Data for the title compound were collected at 18.000 keV (0.68882 Å ) and 100 K.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 2. Cell refinement and data reduction were performed using XDS (Kabsch, 1993). A semi-empirical absorption correction, based on the multiple measurements of equivalent reflections, and merging of data was performed using SADABS (Krause et al., 2015). Data conversion from XDS file format to SADABS file format was performed using XDS2SAD (Sheldrick, 2008a). The space group was confirmed by XPREP routines (Bruker, 2014). The structures were solved by direct-methods and refined by full-matrix least squares and difference-Fourier techniques with SHELXL2016 (Sheldrick, 2015). All non-H atoms were refined by full-matrix least squares with anisotropic displacement parameters. A final verification of possible voids was performed using the VOID routine of PLATON (Spek, 2020). The checkCIF routine and structure-factor analyses were performed by PLATON (Spek, 2020). All publication materials were prepared using LinXTL (Spasyuk, 2009) and Mercury (Macrae et al., 2020). Table 1 Hydrogen-bond geometry (Å , ). Symmetry code: (i) x þ 1; y; z.

Figure 1
The molecular structure of the title compound. Displacement ellipsoids are drawn at 50% probability level. The DMSO solvent molecule is not shown.

Figure 2
View along the b axis showing crystal packing of the title compound. The hydrogen bonds are shown as dashed lines and H atoms have been omitted for clarity.  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. Refinement. The H atoms were generated geometrically (C-H 0.93 to 0.98, N-H 0.86 and O-H 0.82?Å) and were included in the refinement in the riding model approximation; their displacement parameterwere set to 1.5 times those of the equivalent isotropic temperature factors of the parent site (methyl) and 1.2 times for others.