Nanostructured Branched-Chain Carboxylate Ionic Liquids: Synthesis, Characterization, and Extraordinary Solubility for Bioactive Molecules

Abstract

The design of multifunctional ionic liquids (ILs) that integrate different attractive characteristics, such as strong hydrogen-bonding interactions, good lipophilicity, significant nanoscale organization, and low viscosity, in a molecular structure is of great importance for the application of ILs in extraction, biomass conversion, and catalysis but remains challenging. Here, we synthesized a family of novel phosphonium ILs featuring branched chain carboxylate anions with carbon number up to 18 and systematically characterized the physicochemical properties of prepared ILs. The branched chain carboxylate ILs (BCC-ILs) exhibit very strong hydrogen-bond basicity (β = 1.49–1.72, 30 °C) and excellent lipophilicity (π* = 0.73–0.95, 30 °C), and have obvious nanoscale segregation and moderate viscosity (η = 91.8–200.5 mPa, 40 °C). The d value of BCC-ILs ranged from 10.5 to 15.6 Å when the length of alkyl chain in anions or cation rose. These nanostructured solvents can undergo self-assembly processes with typical bioactive molecules of cholesterol to form highly ordered mesoscopic structures through cooperative hydrogen-bond and van der Waals interactions, which enable unprecedented high solubility of cholesterol in BCC-ILs (molar solubilities 0.31–1.12 at 50 °C). Additionally, we found that n-heptane had the significant synergistic effect on the dissolution of cholesterol molecules, and the introduction of n-heptane promoted the formation of highly ordered lamellar liquid crystals in the BCC-IL/cholesterol system. The dissolving mechanism of BCC-ILs for bioactive molecules was explored by experimental studies. This work indicates that the multifunctional BCC-ILs are promising solvents for extractions, catalysis, and biomass conversion.

Design and Characterization of Fatty Acid-Based Amino Acid Ester as a New “Green” Hydrophobic Ionic Liquid for Drug Delivery

“…These multiple hydrogen bond formation between drug and FAAAE-ILs is the driving force in the liquefaction of solid drug in the form of drug–IL complexes, which may be existed at the bound between simple eutectics and partially ionized ILs. These results appear to be in good agreement with the use of CAGE to dissolve the hydrophobic drug nobiletin or other bioactive molecules. − Therefore, it is possible that multiple hydrogen bonding interactions between Ibu and IL contributed to the enhancement of drug solubility.…”

Biocompatible Ionic Liquid Surfactant-Based Microemulsion as a Potential Carrier for Sparingly Soluble Drugs

“…In the past decade, ionic liquid (ILs)-based MEs have been tested as potential nanocarriers for TDD. ILs are tunable designer solvents and play a versatile role in all phases of ME systems by altering water, oil, and surfactant components. − Moniruzzaman et al developed IL-in-oil (IL/O) MEs where IL replaced the water phase for solubilizing sparingly soluble drugs acyclovir (ACV) and methotrexate (MTX) . Subsequently, they evaluated the dermal delivery of 5-fluorouracil through an IL/O system and investigated the influence of the surfactant ratio in an effort to promote their application in pharmaceutics .…”

Aqueous Biphasic Systems Containing Customizable Poly(Ionic Liquid)s for Highly Efficient Extractions

“…Therefore, selective extraction was achieved. With the extension of the alkyl chain in anion, the H‐bond accepting ability became stronger owing to the electron‐donating effect of the alkyl chains, which led to even higher partition coefficients. Second, although the initial concentrations were the same (PIL/K 3 PO 4 /H 2 O=13:25:62 wt %), the difference in their phase separation abilities resulted in different concentrations in the PIL‐rich phase and inorganic‐salt‐rich phase.…”