Lipid-Hydroxy acids Conjugates as Novel Prebiotic Amphiphiles

Rotem Edri^a and Moran Frenkel-Pinter^a,b

^a  Institute of Chemistry, The Hebrew University of Jerusalem, Israel 9190401

^b The Center for Nanoscience and Nanotechnology, The Hebrew University of Jerusalem, Israel 9190401

Compartmentalization is one of the essential properties of living systems. The role of compartmentalization in today’s biology is exclusively fulfilled by complex lipid amphiphiles. While complex biological lipids such as phospholipids are believed to be a product of prolonged chemical evolution, it is generally accepted that simpler lipids, such as short-chain fatty acids, have exhibited primitive cell-like structures. Early Earth was abundant with molecularly diverse molecules, among them are fatty acids, fatty alcohols, and hydroxy acids (HAs). HAs were reported to catalyze peptide bond formation via ester-amide exchange reactions when mixed with amino acids in dried conditions. Nonetheless, the role of HAs was not studied in the context of primordial amphiphiles.

In this work we tested the hypothesis that HAs can react with simple lipids and form novel functional lipid-HA conjugates. To that end, we studied the formation of HA-lipid conjugates under plausible prebiotic conditions using a set of four hydroxy acids and two lipids. The resulting products were characterized using LC-MS, NMR, light microscopy, DLS, and cryo-TEM. We found that all tested HA-lipid combinations produced modified amphiphiles that contained ester bonds. Prominent results were obtained with lactic acid and phenyllactic acid that formed various products in high yield. Rehydration of the reaction products resulted in the formation of assembled structures including vesicles, micelles, and oil droplets, depending on the solution pH and amphiphile.

Our results suggest that HA-lipid conjugates are plausible prebiotic amphiphiles exhibiting a diverse array of assemblies and unique chemical nature that give rise to promising functionalities.