Using dynamic combinatorial chemistry to construct novel thioester and disulfide lipids

Abstract

Given the involvement of sulfur containing compounds in pre-biotic chemistry, the synthesis of sulfur containing lipids that are analogues in structure to phospholipids has been attempted. This thesis details the potential of trans-thioesterification and thiol-disulfide interchange reactions in creating new types of sulfur-containing lipids. The resulting supramolecular structures they formed were both sized, and studied, to give possible indication of biological application. Previous work has shown successful trans-thioesterification reactions of 2-nitro-4-(palmitoylthio)benzoic acid. Using this, several thioester lipids that are analogues in structure to phospholipids were successfully synthesised. Successful synthesis was achieved by the trans-thioesterification between di-thiol substituents (2,3)-dimercapto-1-propanol and (2,3)-dimercapto-propanesulfonic acid and thioester lipids 2-nitro-4-(palmitoyl thio)benzoic acid and 2-nitro-4-(stearoylthio)benzoic acid. Several of the thioester lipids generated were observed to self-assemble into supramolecular structures that display unilamellar morphology, along with being in the size range of large vesicles. Analytical studies showed the resulting vesicle structures displayed an affiliation to encapsulate compounds of hydrophilic nature, along with excellent stability in aqueous conditions.

Date of Award	3 Jan 2018
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Simon Webb (Supervisor), Roger Whitehead (Supervisor) & Laura Nunns (Supervisor)