Hashim, R (reprint author), Univ Malaya, Dept Chem, Kuala Lumpur 59100, Malaysia.
; Hashim, Rauzah] Univ Malaya, Dept Chem, Kuala Lumpur 59100, Malaysia
; [Bryce, Richard A.] Univ Manchester, Manchester Pharm Sch, Manchester, Lancs, England
; [ManickamAchari, Vijayan
; Hashim, Rauzah] Chinese Acad Sci, Kavli Inst Theoret Phys China, Beijing, Peoples R China
The rational design of a glycolipid application (e. g. drug delivery) with a tailored property depends on the detailed understanding of its structure and dynamics. Because of the complexity of sugar stereochemistry, we have undertaken a simulation study on the conformational dynamics of a set of synthetic glycosides with different sugar groups and chain design, namely dodecyl beta-maltoside, dodecyl beta-cellobioside, dodecyl beta-isomaltoside and a C12C10 branched beta-maltoside under anhydrous conditions. We examined the chain structure in detail, including the chain packing, gauche/trans conformations and chain tilting. In addition, we also investigated the rotational dynamics of the headgroup and alkyl chains. Monoalkylated glycosides possess a small amount of gauche conformers (similar to 20%) in the hydrophobic region of the lamellar crystal (L-C) phase. In contrast, the branched chain glycolipid in the fluid L-alpha phase has a high gauche population of up to similar to 40%. Rotational diffusion analysis reveals that the carbons closest to the headgroup have the highest correlation times. Furthermore, its value depends on sugar type, where the rotational dynamics of an isomaltose was found to be 11-15% and more restrained near the sugar, possibly due to the chain disorder and partial inter-digitation compared to the other monoalkylated lipids. Intriguingly, the present simulation demonstrates the chain from the branched glycolipid bilayer has the ability to enter into the hydrophilic region. This interesting feature of the anhydrous glycolipid bilayer simulation appears to arise from a combination of lipid crowding and the amphoteric nature of the sugar headgroups.