Supramolecular interaction between berberine hydrochloride and baicalin in aqueous solution: Reaction kinetics, spectral analysis and dynamic simulation

The current study presents a comprehensive investigation on the precipitation reaction and supramolecular interactions between berberine hydrochloride (BBR) and baicalin (BA) in an aqueous system. Utilizing a combination of multi-spectral analytical techniques and molecular dynamic simulations, we elucidated the mechanism of the complexion process. The precipitate formation was observed within a drug concentration range of 0.1–1.0 mM, and a 1:1 stoichiometry ratio of BBR to BA was established by the Job's plot method. Morphological and structural characterizations of the precipitates were conducted using DSC, FTIR and PXRD. Additionally, UV–Vis absorption and 1H NMR spectroscopy were employed to compare the spectral characteristics of the precipitates with those of individual drug solution. Molecular dynamic simulations further dissected the intermolecular interactions and self-assembly mechanisms. The precipitates formed were amorphous microparticles with an average diameter of approximately 20 μm, primarily stabilized by hydrogen bonding and π–π stacking. This study contributes foundational insights into the supramolecular interactions between BBR and BA, therefore facilitated a better understanding of the precipitation process involving flavonoid-alkaloid pairs in mixed aqueous solutions.