# Predicting Melting Points of Biofriendly Choline-Based Ionic Liquids with Molecular Dynamics
## 1 Introduction  
The past decades have seen a steep increase of interest in ionic liquids (IL) such as solvents and electrolytes. ILs are commonly defined as salts that are liquid under 100 \({}^{\circ}\)C and are entirely composed of ions [1]. Due to their ionic character, they exhibit several desirable properties, for example, negligible vapor pressure, tunable polarity and high charge density. Moreover, there is a large number of different ions that can potentially yield an IL, which allows the fine-tuning of its properties for various applications [1]. Due to high thermal and (electro)chemical stability [2; 3; 4] some ILs are especially suitable candidates for energy applications, where higher cell voltage directly translates into increased energy density [5]. Furthermore, ILs are widely utilized as catalysts, lubricants, solvents in organic synthesis and countless other applications [6]. However, common ILs containing imidazolium cations and fluorinated anions are far from being biofriendly, which prevents their use in medicine and biotechnology [7]. For example, there is an increasing interest for usage of electroactive polymer actuators containing IL electrolytes in various medical devices [8; 9; 10].  
On the one hand, it is true that the stability and low volatility of ILs decrease the risk of pollution by evaporation. On the other hand, even ILs of the latest generation are still toxic and often non-biodegradable. For example, fluorinated and cyano-based anions can emit hydrofluoric acid and hydrogen cyanide, respectively [7]. Toxicity depends on both cation and anion and thus less toxic ions have been considered. In case of anion, increase in the hydrophilicity as well as exclusion of fluoride- and cyano-substituents generally results in practically harmless and more biodegradable ILs [7]. In case of cation, toxicity is strongly influenced by alkyl chain length--shorter alkyl chains increase hydrophilicity and result in more benign ILs [7]. [PERSON] et al. showed that choline cation is considerably less toxic than other traditional quaternary nitrogen based cations [11]. The primarydrawback of introducing a more biofriendly ion to an IL composition is the resulting higher melting point; in many cases, the IL turns solid at ambient temperatures [11].  
The experimental data on melting points of the biofriendly choline ILs is scarce and sometimes inconsistent due to variable water content and the presence of anion conjugated acid in the salt [12; 13]. For example, for choline acetate [11; 14; 15] and choline citrate [16; 17] significantly different melting points have been reported. Herewith, any _experimental_ high-throughput characterization of promising ILs is unacceptably time-consuming--evaporation of water in vacuo, extraction or crystallization of ILs require much time and effort. A _computational_ approach to the assessment of ILs properties looks most appealing. Previously, the melting points of ILs were computationally predicted with molecular dynamics (MD) simulations and quantitative structure-activity relationship (QSAR) models [18]. An overview of these methods is given in the discussion section. Their comparison reveals that the most accurate is the so-called pseudo supercritical path (PSCP) method, which has a significant limitation--requirement for the knowledge of the IL crystal structure [19; 20].  
In this study, we have developed simulation-based melting point prediction method for ILs with unknown crystal structure. Using this method, we have computationally investigated fourteen biofriendly, choline cation-based ILs and choline bis[(trifluoromethyl)sulfonyl]imide (TFSI). We have validated the predicted results against experimental melting points, which were available in the literature and/or measured in the current work.