Novel berberine-based pharmaceutical salts with fatty acid anions: Synthesis, characterization, physicochemical properties

Berberine (BBR), a quaternary isoquinoline alkaloid found in a Chinese herb medicine from Berberis species plants, was utilized to synthesize three new biocompatible berberine-based pharmaceutical salts, featuring three mid-chain fatty acid anions derived from animal and vegetable oils. Three salts [BBR][FA] were namely berberine caproate [BBR][CAP], berberine heptylate [BBR][HEP] and berberine octoate [BBR][OCT]. These compounds were characterized using 1 H and 13 C NMR, FTIR, ESI-MS, and thermogravimetric analyses. The solubility and octanol/water partition coefficient were evaluated in water and simulated body fluids (simulated gastric, simulated intestinal and simulated body fluids). The water solubility of [BBR][FA] was higher than that of salt precursor berberine chloride [BBR][Cl]. The minimum inhibitory concentration and minimum bactericidal or fungicidal concentration against three strains ( Staphylococcus aureus , Bacillus subtilis and Candida albicans ) were also examined. The results showed that they have similar antimicrobial activity to [BBR][Cl]. Furthermore, transport and volumetric properties (density and conductivity) were determined to investigate their aggregation and solvation behaviors in aqueous solution. The limiting molar conductivity, Ʌ 0 , critical micelle concentration, cmc , apparent molar volume at infinite dilution, V 2 , φ 0 , the apparent molar expansibility at infinite dilution, E φ 0 , etc for [BBR][FA] were calculated. Effect of the length in alkyl chain of fatty acid anions in [BBR][FA] and temperature on the obtained properties as well as the nature of the interactions in aqueous [BBR][FA] solutions have been discussed.