Sulfated quaternary amine lipids: a new class of inverse charge zwitterlipids

Abstract

We describe a new class of charge inverted zwitterionic sulfated lipids (AS) with a cationic quaternary amine anchored at the membrane interface and an anionic sulfate moiety extended into the aqueous phase. These lipids have exceptionally high transition temperatures and assemble into lipid aggregates when dispersed in aqueous solutions.

Fig. 1

Differential scanning calorimetry of AS lipids. (A) T_m comparison of all AS lipids in 150 mM NaCl salt. (B) Phase transition temperatures of AS lipids in comparison to other commercially available and inverse charge lipids. PC, phosphatidylcholine; CPe, ethylated inverse PC lipid; PG, phosphatidylglycerol; PS, phosphatidyl serine; BL, betaine-like; SB, inverse sulfobetaine; PE, phosphatidylethanolamine; PA, phosphatidic acid; AS, inverse sulfolipids.

Fig. 2

Differential scanning calorimetry of AS lipids in the presence of additives. Transition temperature reduction using the Hofmeister series of chaotropic salts (NaClO₄ > NaI > NaCl) on (A) DMAS, (B) DPAS, (C) DSAS. (D) Effect of cholesterol on the transition temperature of DSAS.

Fig. 3

TEM images of formulations prepared with DOAS, DMAS, DMAS with 10% tocopherol (DMAS:TC) and DMAS with 10% tocopherol-PEG (DMAS:TC-PEG).

Scheme 1

Synthetic scheme to synthesize a novel series of sulfated quaternary amine charge inverted zwitterionic lipids (AS).