Folic Acid Tetramers: Robust Yet Dynamic Supramolecular Polymers Reinforced by Salting Out with External Kosmotropic Salts

Abstract

Folic acid (FA), a naturally occurring biomolecule, is vital in biological processes. Conventionally recognized for its limited affinity towards common metal ions like Na+/K+ and restricted tetramer-tetramer interactions, this study reveals its exceptional capacity to form highly stable FA-tetramers when guided by coinage metal ions (M+). These FA4.M+ tetramers spontaneously assemble into extended, robust, one-dimensional supramolecular polymers (SPs) through a process called slipped-stacking, resulting in thermally stable self-healing supergels. These SPs exhibit resilience to temperature variations and dilution while possessing unique dynamic characteristics, setting them apart from typical supramolecular assemblies. This research introduces robust SPs and self-healing gels based on biomolecules, underscoring their potential for biological applications due to their inherent biological functionalities. Additionally, the study unveils a crucial finding: the stability of FA-quartet-based SPs is not solely contingent on the internal M+ ion. The stability is notably reinforced by introducing external kosmotropic anions while concurrently reducing solubility, mimicking the 'salting out' behavior observed in proteins and covalent polymers. The M+ ions-driven FA-tetramer stabilization offers new prospects for crafting functional supramolecular assemblies, and the resulting SP gel, combining robustness with dynamism, shows potential for applications in biology and materials that demand increased stability.