Intramolecular Electrostatic Interactions Regulate Reactivity of Zwitterionic Functionalities in Amphiphilic Assemblies

The consequences of intramolecular ionic interactions in determining the reactivity of functional groups are of interest because they provide insights into how nature deploys seemingly reactive functionalities to be rather ubiquitous. Of specific interest are the quaternary ammonium ions in lipids. In this work, we investigate the effect of intramolecular electrostatic interactions in zwitterionic functionalities by judiciously incorporating them as leaving groups at the alpha-position of alpha,beta-unsaturated ester-based lipid head groups. We find that electrostatic stabilization indeed plays a critical role in both the reaction kinetics with nucleophiles and the thermodynamics of lipid formation. We further leverage these findings to fabricate both triggerable assembly and disassembly of liposomal supramolecular assemblies in the presence of nucleophiles. Intramolecular electrostatic stabilization in zwitterionic moieties plays a critical role in their reactive stability. The stabilization potential is demonstrated to have a unique spatial orientation dependence in zwitterionic head groups of surfactants and lipids. This feature has been used to generate triggerable supramolecular assembly formation and their disassembly. image