Investigation of the Effect of Sugar Stereochemistry on Biologically Relevant Lyotropic Phases from Branched-Chain Synthetic Glycolipids by Small-Angle X‑ray Scattering

Synthetic branched-chain glycolipids are suitable as model systems in understanding biological cell membranes, particularly because certain natural lipids possess chain branching. Herein, four branched-chain glycopyranosides, namely, 2-hexyl-decyl-α-d-glucopyranoside (α-Glc–OC10C6), 2-hexyl-decyl-β-d-glucopyranoside (β-Glc–OC10C6), 2-hexyl-decyl-α-d-galactopyranoside (α-Gal–OC10C6), and 2-hexyl-decyl-β-d-galactopyranoside (β-Gal–OC10C6), with a total alkyl chain length of 16 carbon atoms have been synthesized, and their phase behavior has been studied. The partial binary phase diagrams of these nonionic surfactants in water were investigated by optical polarizing microscopy (OPM) and small-angle X-ray scattering (SAXS). The introduction of chain branching in the hydrocarbon chain region is shown to result in the formation of inverse structures such as inverse hexagonal and inverse bicontinuous cubic phases. A comparison of the four compounds showed that they exhibited different polymorphism, especially in the thermotropic state, as a result of contributions from anomeric and epimeric effects according to their stereochemistry. The neat α-Glc–OC10C6 compound exhibited a lamellar (Lα) phase whereas dry α-Gal–OC10C6 formed an inverse bicontinuous cubic Ia3d (QII G) phase. Both β-anomers of glucoside and galactoside adopted the inverse hexagonal phase (HII) in the dry state. Generally, in the presence of water, all four glycolipids formed inverse bicontinuous cubic Ia3d (QII G) and Pn3m (QII D) phases over wide temperature and concentration ranges. The formation of inverse nonlamellar phases by these Guerbet branched-chain glycosides confirms their potential as materials for novel biotechnological applications such as drug delivery and crystallization of membrane proteins.