Conversion of Quinine Derivatives into Biologically Active Ionic Liquids: Advantages, Multifunctionality, and Perspectives

Abstract

In this study, we demonstrate that quinine with confirmed antiviral and antifeedant activity can be derivatized and formulated as multifunctional ionic liquids which allow one to tune their biological, chemical, and physical properties. Following the optimization of quinine alkylation, pure 1-alkylquinine bromides with alkyl chain length ranging from ethyl to dodecyl were synthesized and extensively characterized. In the next step, these derivatives were combined with counterions of natural origin, which resulted in the formation of naturally derived ionic liquids. Our results indicate that the transformation of quinine into ionic liquids may improve antifeedant properties by 265% compared to the activity of quinine-free base. Moreover, unlike the majority of known cases, the reduction of the alkyl chain length results in a significant increase in this type of biological activity.

Naturally based ionic liquids with indole-3-acetate anions and cations derived from cinchona alkaloids

“…1-Alkylquininium bromides containing substituents ranging from ethyl to dodecyl were synthesized according to a previously disclosed methodology. 35 1-Ethylquinidinium bromide was synthesized via the following method: 0.015 mol of quinidine was placed in a 50 cm 3 EasyMax™ reactor equipped with a stir bar, a condenser, a temperature sensor, and a 9.5 mm AgX probe with a diamond tip connected with a ReactIR™ 15 (Mettler Toledo) FT-IR spectrometer. Then, the reagent was dissolved in 20 cm 3 of DMSO, and a stoichiometric amount of bromoethane was introduced into the reaction system through a dropping funnel.…”

“…All 1alkylquininium indole-3-acetates and 1-ethylquinidinium indole-3-acetate were synthesized according to a previously disclosed methodology. 35 The respective 1-alkylquininium bromide or 1-ethylquinidinium bromide (0.005 mol) was dissolved in ethanol (20 cm 3 ) and introduced into a 50 cm 3 Easy-Max™ reactor. In the next step, 10 cm 3 of the anionic resin AmberTec™ UP550 OH was added in the form of an ethanolic suspension, and the system was stirred for 30 min at 25 C. The resin was ltered off and washed three times with small volumes (5 cm 3 ) of ethanol.…”

“…Two cinchona alkaloids, which are mutual pseudoenantiomers, quinine and quinidine, were chosen as sources of cations. Only a few groups of ILs with quininederived cations have been described thus far, [33][34][35] while there are no literature reports on the preparation of ILs with a quinidine-based cation. According to basic assumptions concerning 3rd generation ILs, the novel forms of IAA designed herein should be characterised by more favourable physicochemical properties compared to the acidic form of IAA.…”

“…According to basic assumptions concerning 3rd generation ILs, the novel forms of IAA designed herein should be characterised by more favourable physicochemical properties compared to the acidic form of IAA. Moreover, it has been conrmed that cations derived from cinchona alkaloids can result in unique changes in the biological activity of the new ILs, 35 which should translate directly into a signicant increase in the potential for application of the active substances.…”

Application of Ionic Liquids for Chemical Demulsification: A Review

“…Ionic liquids were first introduced by Paul Walden in 1914 when he discovered a special chemical-ethyl ammonium nitrate ([EtNH 3 ] [NO 3 ]) with a melting point of 12 °C [ 52 ]. Ionic liquids have been widely used in different fields like pharmaceutical, oil and gas, and chemical industries [ 53 , 54 , 55 , 56 , 57 , 58 ], such as in pharmaceutical products manufacturing [ 59 , 60 , 61 , 62 ], viscosity modifiers [ 63 ], desulfurization of liquid fuels [ 64 ], and liquid-liquid extraction [ 65 , 66 , 67 ]. Several types of ionic liquids, such as polymeric ionic liquids [ 68 , 69 , 70 ], double salt ionic liquids [ 71 ], dicationic ionic liquids [ 72 , 73 , 74 , 75 ], deep eutectic solvents [ 76 , 77 , 78 , 79 ], chiral ionic liquids [ 80 ], and solvate ionic liquids [ 81 , 82 ], have been synthesized for different aforementioned purposes.…”