Hydroxy Acid Conjugation to Lipids Increases Structural and Hydrolytic Stability

Contemporary life requires functional polymers and phospholipid-derived compartmentalization. Mutualistic relationships between compartmentalization and polymerization have never been demonstrated in an abiotic scenario. As both the polymerization of hydroxy acids and the primitive cell-like aggregation of short chain fatty acids are well known, we studied cooperative interactions between compartmentalization and polymerization using these two classes of molecules as a model system. To that end, we explored the formation of various hydroxy acid-decanoic acid conjugates. All reactions produced two types of condensation products: hydroxy acid homoesters and lipid-hydroxy acid heteroesters. We found that conjugation of hydroxy acids to decanoic acid led to the reduction of decanoic acid critical aggregation concentration by an order of magnitude. Furthermore, hydroxy acid oligomers were protected against hydrolysis only upon conjugation to decanoic acid. Our work offers meaningful insights into the role of self-assembly and cooperative chemistry as selective driving forces in lipid-polymer co-evolution.