Heteroassembly Ability of Dicationic Ionic Liquids and Neutral Active Pharmaceutical Ingredients

[Image: see text] Extensive investigation of interactions and aggregation properties of IL + API systems is necessary to apply ionic liquids (ILs) with different hydrophobic characteristics to drug delivery or in active pharmaceutical ingredient (API) formulations. Therefore, this study aims to investigate the heteroassembly between dicationic ILs ([BisOct(MIM)(2)][2X], in which X is Br or BF(4), and [BisOct(BnIM)(2)][2Br]), both in the absence and the presence of neutral APIs (salicylic acid, ibuprofen, and paracetamol) with different functional groups. Isothermal titration calorimetry results demonstrate that IL–API associations occur at very low concentrations of IL. These results were reinforced by electrospray ionization mass spectrometry with variable collision-induced dissociation, in which the IL dication interactions with APIs were detected. The strength of the dication–API interaction was determined from E(cm,1/2) data. The aggregation parameters (cac, ΔG(agg)(°), and K) between ILs and APIs were evaluated by conductivity. The (1)H NMR data showed that differences in chemical shifts provided relevant insights about interaction sites in both components.