Elucidation of complexation mechanism of rosmarinic acid and berberine

Abstract

Polyphenols are known to form complexes with various organic compounds. This ability can may change the chemical or physical properties of the compounds involved and may even affect their efficacy in the case of drugs. Our research revealed that mixing solutions of the polyphenol rosmarinic acid (RA) and berberine (Ber), a widely used and pharmacologically important isoquinoline alkaloid, resulted in the formation of a precipitate of the RA–Ber complex at a molar ratio of 1:1. This was confirmed using ¹H NMR and Fourier Transform Infrared Spectroscopy. To elucidate the formation mechanism of the precipitate, the behavior of RA and Ber in an aqueous solution was examined using ¹H NMR, indicating the formation of the RA–Ber complex at a molar ratio of 1:1, consistent with the results of precipitation. Additionally, we investigated the steric structure of the RA–Ber complex in an aqueous solution using molecular modeling calculations. These calculations suggested the existence of seven types different steric structures of the RA–Ber complex, primarily stabilized by π–π interactions. Based on these results, we concluded that mixing RA and Ber solutions in an aqueous environment results in the formation of RA–Ber complexes with seven types different steric structures at a molar ratio of 1:1. The precipitate forms because these complexes are less water-soluble than either RA or Ber alone.