Choline Saccharinate and Choline Acesulfamate:  Ionic Liquids with Low Toxicities

Abstract

Choline saccharinate and choline acesulfamate are two examples of hydrophilic ionic liquids, which can be prepared from easily available starting materials (choline chloride and a non-nutritive sweetener). The (eco)-toxicity of these ionic liquids in aqueous solution is very low in comparison to other types of ionic liquids. A general method for the synthesis and purification of hydrophilic ionic liquids is presented. The method consists of a silver-free metathesis reaction, followed by purification of the ionic liquid by ion-exchange chromatography. The crystal structures show a marked difference in hydrogen bonding between the two ionic liquids, although the saccharinate and the acesulfamate anions show structural similarities. The optimized structures, the energetics, and the charge distribution of cation-anion pairs in the ionic liquids were studied by density functional theory (DFT) and second-order (Møller-Plesset) perturbation theory calculations. The occupation of the non-Lewis orbitals was considered to obtain a qualitative picture of the Lewis structures. The calculated interaction energies and the dipole moments for the ion pairs in the gas phase were discussed.

Ionic Liquids Then and Now: From Solvents to Materials to Active Pharmaceutical Ingredients

“…[59][60][61][62] These were paired with traditional IL-forming counter ions to control physical properties, especially melting point, but with a focus on preparing ILs, not on preparing biologically active salts. In fact only recently, have specific ILs with biologically active ions been prepared and shown to retain their biological activity; specifically, IL salts of anti-bacterial quaternary ammonium cations were shown to be active against various types of bacteria and in some cases, an increased anti-bacterial effect was observed.…”

Theoretical study on the structures and properties of mixtures of urea and choline chloride

“…Thus, ILs have been branded as "environmentally friendly solvents and benign reaction media" [7][8][9]. However, with more thorough development of research on ILs, the potential environmental risks of ILs are being increasingly recognized [10][11][12]. So far, many ILs, such as the traditional imidazolium-based ILs, have been confirmed to possess toxicity and poor biodegradability, which brings environmental risks [10,12].…”

Low melting mixtures in organic synthesis – an alternative to ionic liquids?

“…Choline saccharinate and choline acesulfamate were shown to have a very low ecotoxicity in a standard assay with the crustacean Daphnia magna. 15 The toxicity evaluation of cholinium alkanoates using filamentous fungi as model eukaryotic organisms proved that fungi can actively grow in media up to concentrations in the molar range. 17 Choline is expected to be non-toxic and biodegradable as it is applied as an additive in human nutrition and as animal feed.…”

“…This concept was firstly introduced by Nockemann et al in 2007. 15 They synthesised ionic liquids by a metathesis reaction of choline chloride and the sodium salts of the non-nutritive artificial sweeteners acesulfame and saccharin, followed by purification using ion-exchange chromatography. Also in 2007, Fukaya et al developed room temperature ionic liquids composed of biomaterials, and termed them "bio ionic liquids".…”