Synthesis and Evaluation of Trans-bilayer Cross Linking Phospholipids Based on Click (Azide-Alkyne) Chemistry

Abstract

This thesis describes the synthesis of two phosphatidylcholine (PC) derivatives that are capable of coupling with each other from the alkyl chain through click reaction to form bola-PC. Successful coupling of monomeric phosphatidylcholine derivatives would lead to synthesis of corresponding phosphatidylinositol molecules as future work. PC derivatives that were synthesized in this work were phosphatidylcholine containing terminal azide and terminal alkyne on the alkyl chain of sn2 position. Sn-glycero-3-phosphocholine (GPC) was used as glycerol back bone with two available hydroxyl groups for esterification. The first esterification was done using dibutyltin oxide as catalyst and palmitoyl chloride as acylating agent on the primary hydroxyl group, sn1 position. Secondary hydroxyl group in the sn2 position of GPC was esterified by terminal alkyne and terminal azide fatty acids through Steglich esterification. PC analogues with suitable functional groups for click chemistry were, then, incorporated in the 100 nm-vesicles in buffer solution and exposed to copper catalyst/L-histidine complex and sodium ascorbate solution at room temperature. Formation of bola-PC were observed in the hydrophobic core of lipid bilayer and this was the main objective of this study.