Expanding the solvent chemical space for self-assembly of dipeptide nanostructures

Nanostructures composed of short, noncyclic peptides represent a growing field of research in nanotechnology due to their ease of production, often remarkable material properties, and biocompatibility. Such structures have so far been almost exclusively obtained through self-assembly from aqueous solution, and their morphologies are determined by the interactions between building blocks as well as interactions between building blocks and water. Using the diphenylalanine system, we demonstrate here that, in order to achieve structural and morphological control, a change in the solvent environment represents a simple and convenient alternative strategy to the chemical modification of the building blocks. Diphenylalanine (FF) is a dipeptide capable of self-assembly in aqueous solution into needle-like hollow micro- and nanocrystals with continuous nanoscale channels that possess advantageous properties such as high stiffness and piezoelectricity and have so emerged as attractive candidates for functional nanomaterials. We investigate systematically the solubility of diphenylalanine in a range of organic solvents and probe the role of the solvent in the kinetics of self-assembly and the structures of the final materials. Finally, we report the crystal structure of the FF peptide in microcrystalline form grown from MeOH solution at 1 Å resolution and discuss the structural changes relative to the conventional materials self-assembled in aqueous solution. These findings provide a significant expansion of the structures and morphologies that are accessible through FF self-assembly for existing and future nanotechnological applications of this peptide. Solvent mediation of molecular recognition and self-association processes represents an important route to the design of new supramolecular architectures deriving their functionality from the nanoscale ordering of their components.