Hierarchical Self-Assembly in Minimalistic Diacetylenes: From Coacervates to Fibers

Recent advancements in the chemical and biological sciences have revealed admirable success in understanding the phenomenon of liquid-liquid phase separation (LLPS), resulting in coacervation. Tremendous efforts have been invested in designing small molecules capable of undergoing LLPS under physiological conditions. LLPS is gaining increasing importance due to its role in the origin of life and as arbiters of chemical reactions. The fundamental chemical logic from molecular structure to LLPS formation is not fully known. Therefore, rational design of short molecules for LLPS formation is at its infancy. This work presents the synthesis of four designer diacetylenes and their unique topochemical reactivity and ability towards environment dependent coacervation. Here, we propose diacetylene scaffold as an excellent spacer for creating diverse morphology as illustrated with molecules that assemble to coacervates and fibers. Diacetylene with an ortho-pyridyl substituent functions as a pH-responsive molecular switch, reversibly transitioning between autofluorescent coacervates and fibrillar assemblies. This presents a rare example of a minimalistic chemical system that correlates morphology, LLPS and polymerization. Additionally, we observed two different mechanisms of fibrillation of diacetylenes. DA1 and DA4 form fibrillar aggregates directly from monomers. DA3 undergoes LLPS to form condensates before transitioning to fibers closely coinciding with the recently proposed condensation mechanism of amyloid assembly.