Remarkable preference for di-substitution in self-assembled glycolipids

Abstract

Lipids are known to be amphitropic, exhibiting lyotropic and/or thermotropic liquid crystal mesophases that can exist between the solid and liquid states of matter. In biological systems, naturally occurring lipids can spontaneously create membraneous structures, which can support the formation of micelles and cells that are the encapsulants for biomaterials. It appears that there is a relationship between the structures of natural lipids, and those of the mesophases that they form, with the most common being lipids having two aliphatic chains attached to a polar head group. These architectures allow for self-organization or self-assembly to occur, thereby supporting the formation of columnar or lamellar structures. In this present study we investigate the stability of lamellar liquid crystal phases as a function of the number of aliphatic chains attached to the polar head groups via new glycolipids that we synthesised using click chemistry, and in which triazoles were used to attach the chains to the central sugar scaffolds. Optical microscopy, differential scanning calorimetry and X-ray diffraction were used to study the lamellar liquid crystal behaviour and transition temperatures of these materials; the experimental data indicated that the compound with two chains, derived from trehalose, formed a more ordered lamellar phase than the compounds with one or three chains. DFT calculations gave optimised structures indicating the overall shapes of the isolated molecules. Molecular dynamics simulations enabled us to study the self-assembly of the molecules into lamellar phases. Detailed analyses of these simulations revealed that the molecules with either two or three chains adopted a defined set of folded and extended molecular architectures as the stable lamellar phases formed, providing insight into the relative stability of the phase structure formed by the molecules with two chains.