Matrinium-based active pharmaceutical ingredient ionic liquids: chain length effect on micellization, bioactivity and thermodynamic behaviors

Abstract

The active pharmaceutical ingredient ionic liquids (API-ILs) obtained from bio-renewable and natural compounds are noted for their good safety and biodegradability. This study focused on the utilization of naturally occurring matrine (Mat) in the synthesis of matrinium-based API-ILs with attractive application potential. Five matrinium-based API-ILs were synthesized by a neutralization reaction between Mat and biodegradable saturated fatty acids (enanthic acid, pelargonic acid, undecanoic acid, tridecanoic acid, and pentadecanoic acid). We typically employed ¹H and ¹³C NMR, FTIR, ESI-MS, and thermogravimetric analysis techniques for characterization of the structural properties of the synthetic API-ILs. Additionally, the n-octanol–water partition coefficient as well as the solubility of these ILs in various mediums were measured. The solvation behavior, association, and aggregation properties were studied through density, conductivity, and fluorescence spectrometry analyses, respectively. Many parameters such as apparent molar volume at infinite dilution (V⁰_2,φ), limiting molar conductivity (Λ₀) and critical micelle concentration (cmc) of MatILs in water, association constant (K_A), and related micellization thermodynamic functions were calculated. The minimum inhibitory concentrations (MICs) of three API-ILs against four strains (Escherichia coli, Staphylococcus aureus, Candida albicans, and Cutibacterium acnes) were determined. The results demonstrated their potent antibacterial efficacy. Through cytotoxicity assays, it was observed that compared to Mat, the synthesized API-ILs exhibited enhanced cytotoxic effects on two human tumor cell lines (A549 and HepG2). Furthermore, we systematically correlated anion alkyl chain length with some of the physicochemical properties and biological activities of ionic liquids to elucidate structure–property relationships.