Supramolecular Chemistry of Folic Acid — Experimental and Computational Investigation

Supramolecular chemistry of folic acid is studied and revealed by exploring its assembly and disassembly process in a liquid–liquid interface. Experimental and computational studies are conducted to understand the interfacial interactions of folic acid in a oil-in-water interface by investigating the role of folic acid’s critical aggregation concentration (CAC), molecular arrangement, and intermolecular interactions at the molecular level. The folic acid’s CAC, determined from the concentration-dependent UV–vis absorption spectra in water/methanol solvent system, is found to be 2.72[Formula: see text][Formula: see text]M. The sigmoidal behavior of folic acid’s maximum absorbances with respect to different folic acid concentrations reveals the nature of the self-assembly dynamics and aggregative assemblies’ formation by three signature phases, in which CAC lies in the second phase — the growth phase. The computational studies reveal the intermolecular interactions and molecular orientation of folic acid molecules. They interact each other via H2-bonding between carboxylic acid groups in two glutamate units and two amine groups in pteridine units and [Formula: see text]–[Formula: see text] interactions between pteridine units and phenyl units, orienting two units in a parallel stacked arrangement. Correlating the computed intermolecular interactions and structural orientation of folic acid with its solid-state crystal packing structure has provided strong evidence supporting its supramolecular chemistry and assembly dynamics to make nanoassemblies in a liquid–liquid interface.