Green Synthesis of Quinoline-Based Ionic Liquid

The monumental growth in the world population accounts for a tremendous increment in the consumption of a vast array of commodities over the past few years, including food, medicaments, as well as other crucial products for the sustenance of mortal organisms. This has invigorated the quest for novel chemical compounds with exceptionally specialized, ecologically sound, and beneficial properties worldwide. Ionic Liquids (ILs) have proved to be felicitous in this regard. The implication of these compounds in the scientific domain has bolstered new ventures in research in contemporary chemical technologies¹. In contrast to the conventional approaches, the utilization of ILs not only facilitates progressive reaction conditions but also promotes a customized strategy to get to grips with various biochemical challenges related to experimental research and development².

Typically, ILs are stable salts constituting cations (organic) and anions (inorganic), possessing a melting point below 100 °C³. Abiding by the 12 principles of green chemistry, empirically, these are convincing substitutes to the customary organic solvents⁴. The astounding properties associated with the utilization of these compounds encompass great intrinsic conductivity, polarity, solvating tendency, thermal stability, non-volatility, acidity/basicity, hydrophilicity/ hydrophobicity, and tunability, making ILs best suited for experimental research⁵.

Apart from the expansive applications of various classes of ILs in modern organic synthesis⁶, catalysis⁷, and various electrochemical processes involving sensors⁸, actuators⁹, batteries¹⁰, and fuel cells¹¹, over the past few years, this class of compounds has been given momentous recognition in the field of biomedicine in light of AMR. Current probations reveal that ILs based on imidazolium, pyridine, choline, and pyrrole are extremely effective as therapeutic agents owing to their high charge and hydrophobicity¹². However, quinoline-based counterparts are still considered to be most potent against the pathogenic microbes¹². Additional biomedical applications accompanying this class of ILs include artificial chaperone activity¹³, cytotoxicity against cancerous cells¹⁴ as well as an excellent drug-carrying capacity¹⁵.

Conventionally, the fabrication of ILs involves the utilization of highly toxic solvent mediums such as dichloromethane, benzene, carbon tetrachloride, dichloroethylene, etc.¹⁶, hindering the biocompatibility and elevating the toxicity of the compound, making them undesirable for biological use. Additionally, the use of harmful solvents in the reaction media not only slows down the reaction time but also increases the unintentional production of waste byproducts released into the environment¹⁷. Moreover, the dissolvent used in the reaction media also influences the pH of the final product; hence, its removal at the end of the reaction is vital, especially when the desired compound is intended to be used for protein-related biological systems. Hence, keeping away from the usage of such solvent is favorable in the realm of green chemistry.

In this study, we report the one-pot synthesis of a biocompatible and non-toxic¹³ IL, namely, 1-Hexadecylquinolin-1-ium bromide, using a greener route. The present strategy omits the utilization of a molecular solvent, leveraging the self-solvating ability of the IL formed within the reaction mixture, promoting high reaction efficiency and chemical yield. Menschutkin reaction¹⁸forms the basis of the current synthesis methodology. The purity of the synthesized compound is probed using NMR and IR spectroscopy. The pharmacokinetic profile of the compound and toxicity were investigated through the ADMET studies. Furthermore, the antimicrobial potential of the synthesized IL against the pathogenic Candida albicans strain has also been demonstrated in the study.