Understanding and optimizing the structure of novel peptide-based ionic liquids: Water as modulating agent

Choline-peptides ([Ch][Pep]) have recently been presented as a means to advance biocompatible ionic liquids (ILs). Although these ILs found their applications in blends with water, the resulting systems are yet unexplored at the molecular level, a knowledge that is key to understanding and rationalizing novel applications. Thus, building on prior molecular dynamics insights for neat [Ch][Pep], we examined 5 {[Ch][Pep],H2O} binaries with a focus on their nano-structuration. Upon addition, water disperses unevenly within the polar IL network, preferentially near anionic charge centers. With increasing dilution, the ion pairs become progressively isolated and their interactions weakened, yielding five structural regimes with two key transitions: ∼70%n/n (ionic polar network disruption) and ∼95%n/n (ion pair dissociation). For the series of phenylalaninate and di-phenylalaninate-based ILs ([Ch][P] and [Ch][PP]), the apolar domains conformed by phenyl rings (Pher) remain continuous at low dilutions but present different disruption regimes: While the ∼95%n/n dilution of [Ch][PP] is still dominated by a unique aggregate, that of [Ch][P] presents a broken apolar network. In fact, both the uneven breakage of Pher-Pher and Pher-[Ch]+ complexes in [Ch][PP] and a greater and more stretchable polar network lead to an apolar aggregate more regularly distributed at the 96%n/n blend. Greater dilutions do prompt the fracture of the [Ch][PP] Pher-based domain into the small clusters still observable in 99.6%n/n. Overall, this work describes how water reorganizes both polar and apolar motifs in {[Ch][Pep],H2O} and delineates different composition-dependent regimes, insights that can be, for instance, used to sketch more suitable hydrotrope solvents for pharmaceutical formulation.