Solid-State Synthesis and Self-Assembly of cyclo(Phe-Gly) Dipeptide

Diketopiperazines, or cyclic dipeptides, represent an important class of biologically active compounds with a broad spectrum of functional properties. Solid-state synthesis of cyclic dipeptides from their linear analogs upon heating is a promising strategy. In this study, the solid-state cyclization of the dipeptide L-phenylalanyl-glycine is investigated for the first time. The structure of the product is determined using a combination of physicochemical methods. A kinetic analysis of this reaction is performed, and the kinetic parameters are determined. Atomic force microscopy demonstrates the effect of solvent on the self-assembly of cyclo(Phe-Gly). These results expand our understanding of the mechanisms of dipeptide cyclization in the solid state and the potential for their use as building blocks for functional and bioinspired materials.