Influence of Charge Density on Host–Guest Interactions within Amphiphilic Polymer Assemblies in Apolar Media

The effects of charge density on supramolecular host–guest interactions between peptides and reverse micelles are studied using an amphiphilic random copolymer scaffold. While our classical understanding of polyvalent electrostatic interactions suggests that the binding capacity should increase with charge density, our results indicate that this correlation does not necessarily hold within the nanoscale environment of reverse micelles. Using four series of different polymers, we show that peptide binding efficiency depends on the presence of an optimum charge density inside the reverse micelles. Interestingly, the distribution of charges does not have a significant effect on binding. Reverse micelle stability at high charge densities can be regained by tuning the hydrophilic–lipophilic balance of the polymer, yet an optimal density dependence remains. Our findings improve our understanding of host–guest chemistry in confined aqueous environments.