The interaction mechanism between zein and folic acid in alkaline aqueous solutions: an experimental and molecular simulation study

Abstract Objectives Folic acid is a vitamin that is not highly soluble in water and is sensitive to the environment. Therefore, it is important to find suitable carriers. This study aimed to exemplify the interaction of folic acid with zein in alkaline aqueous solutions and shed light on how zein can be used as a carrier for folic acid. Materials and Methods Zein and folic acid were separately dissolved in NaOH solutions with a PH of 11.5. Zein solution and folic acid solution were combined in specific ratios. Various methods including multi-spectroscopy, dynamic light scattering, and electron microscopy combining with molecular dynamics simulations were used to study the interaction mechanism between zein and folic acid in alkaline aqueous solutions. Results Fluorescence spectroscopy showed that the quenching of zein by folic acid was mainly static, and the main driving force behind this interaction was van der Waals forces and hydrogen bonds. The formation of zein–folic acid complexes was confirmed by ultraviolet–visible spectroscopy, Fourier transform infrared spectroscopy, and circular dichroism spectroscopy. The results also showed that the structure of zein changed when it interacted with folic acid. Dynamic light scattering analysis revealed that the addition of folic acid caused proteins to aggregate. The aggregates of the complexes had an irregular shape and were large, as observed by scanning electron microscopy and transmission electron microscopy. Molecular simulation was used to further investigate the interaction mechanisms. According to these findings, the folic acid molecule interacted with zein in a shallow recess near the protein surface. The dominant forces at play in the zein–folic acid interaction were van der Waals forces and electrostatic forces, including hydrogen bonding. Conclusion The zein alkali-soluble system is very suitable for folic acid delivery.