X-Ray Crystal Structures and Organogelator Properties of (R)-9-Hydroxystearic Acid

Abstract

(R)-9-hydroxystearic acid, (R)-9-HSA, is a chiral nonracemic hydroxyacid of natural origin possessing interesting properties as an antiproliferative agent against different cancer types. Considering its potential application for medical and pharmaceutical purposes, the structures and rheological properties of (R)-9-HSA were investigated. Oscillatory rheology measurements reveal that (R)-9-HSA gels only paraffin oil, with less efficiency and thermal stability than its positional isomer (R)-12-HSA. Conversely, (R)-9-HSA affords crystals from methanol, acetonitrile, and carbon tetrachloride. The single crystal structures obtained both at 293 K and 100 K show non-centrosymmetric twisted carboxylic acid dimers linked at the midchain OHs into long, unidirectional chains of hydrogen bonds, owing to head-tail ordering of the molecules. Synchrotron X-ray powder diffraction experiments, performed on the solids obtained from different solvents, show the occurrence of polymorphism in paraffin oil and through thermal treatment of the solid from methanol.

(R)-10-Hydroxystearic Acid: Crystals vs. Organogel

“…The CD spectrum displays a signal with a positive sign, similar to the gels of both (R)-9-HSA and (R)-12-HSA in the same solvent. Interestingly, it is more stable in time, at least a few weeks, with respect to the analogous gel of (R)-9-HSA, which flows already after one week since preparation [18].…”

“…They are sparse and coexist with crystals that become more and more abundant, while the spherulites dissolve within about 20 min (Figure S3). On the contrary, spherulites of (R)-9-HSA formed in acetonitrile look very light, float in the solution, and quickly grow in volume and number so that they fill all the space, before giving rise to a precipitate of needlelike crystals [18].…”

“…On the contrary, the higher concentration required to form organogels of the racemic mixture allowed for crystallization and diffraction analysis [15,16], thus apparently confirming the commonplace that "gelation is crystallization gone wrong" [17]. Recently, we solved the X-ray structure of the positional analogue (R)-9-HSA, which showed less organogelator properties with respect to (R)-12-HSA but crystallizes in solvents of variable polarity and hydrogen bonding properties [18]. The crystal structure obtained for this hydroxystearic acid is characterized by a head-to-tail interdigitated arrangement of molecules, with the longest unit cell axis having a value compatible with the length of the molecule.…”

“…The CD spectrum displays a signal with a positive sign, similar to the gels of both (R)-9-HSA and (R)-12-HSA in the same solvent. Interestingly, it is more stable in time, at least a few weeks, with respect to the analogous gel of (R)-9-HSA, which flows already after one week since preparation [18]. In the IR spectrum, the signals of O-H and C=O stretching modes [26] for (R)-10-HSA in the paraffin oil gel occur at the same position and with the same shape as the heat-treated (R)-10-HSA (Figure 3).…”

“…Considering the presence of polymorphs observed for positional isomers of (R)-10-HSA, such as 12-HSA and 9-HSA [7,8,14,18], the compound was crystallized from a supersaturated cyclohexane solution and analyzed using powder diffraction techniques at room temperature (Figure 8, black line). The comparison of the resulting pattern with the simulated pattern obtained from the single-crystal structure at 100 K (Figure 8, blue line) shows a clear similarity between the two forms.…”