# Predicting Melting Points of Biofriendly Choline-Based Ionic Liquids with Molecular Dynamics
## 5 Conclusions  
This work introduces an MD-based method for estimating the melting points of ILs. While the method is suitable for any ionic compound, we have focused on the melting point of biofriendly choline ILs. Application of these liquids requires them to be liquid at ambient temperature, yet most of them tend to be solid. We have tested the developed method on 15 ILs comprising of choline cation and various biofriendly anions. Compared to previously published methods, the accuracy of our method is excellent with a root-mean-square error of only 18-24 K. Moreover, compared to other approaches, our method has a relevant advantage--it does not require the knowledge of the crystal structure nor does it depend on the choice of a training set as QSPR-based methods do. Hence, our method is useful for the discovery of ionic compounds for example, for computational screening and characterization of novel biofriendly ILs prior to their synthesis. Instead of replicating an experimental crystal, the solid phases in our method are constructed with the help of Coulombic potential wells. The potential well positions are systematically varied for each IL to create optimal structures which are then melted in annealing simulations. Melting point is then determined via analysis of the \(D-T\) dependence of the annealing simulation. Direct melting point determination methods such as ours have previously received criticism that they suffer from overheating due to hysteresis resulting in overestimated melting points. On varying the temperature rate of melting simulations, we observed no clear overheating tendency. However, we did observe significant overestimation of predicted melting points when inaccurate charges partial charge distribution was used, for example, when charges were extracted from the DFT calculations of single ions. We obtained significantly better melting point predictions only after using partial charges extracted from semi-empirical calculations of condensed phase. This indicates that both the effective ionic charges and the charge distributions within ions are detrimental for accurate simulation of ILs. The publicly available automated workflow in Reference [25], which implements the developed method, can be readily extended to other ILs and their mixtures. As similar calculations are readily parallelizable, the only practical limitation is the availability of the force fields. We believe that that disadvantage is minor, as it is being eliminated with the development of novel transferable force field parameters. **Supplementary Materials:** The following are available online at [[http://www.mdpi.com/2076-3417/9/24/5367/s1](http://www.mdpi.com/2076-3417/9/24/5367/s1)]([http://www.mdpi.com/2076-3417/9/24/5367/s1](http://www.mdpi.com/2076-3417/9/24/5367/s1)), Figure S1: \(D\)-\(T\) dependence of Choline Acetate, Figure S2: \(D\)-\(T\) dependence of Choline Acetslander, Figure S3: \(D\)-\(T\) dependence of Choline Acetylsalicylicate, Figure S4: \(D\)-\(T\) dependence of Choline Benzoate, Figure S5: \(D\)-\(T\) dependence of Choline Citrate, Figure S6: \(D\)-\(T\) dependence of Choline Glutamate, Figure S7: \(D\)-\(T\) dependence of Choline Ibuprofen, Figure S8: \(D\)-\(T\) dependence of Choline Isobutanoate, Figure S9: \(D\)-\(T\) dependence of Choline Isovalerate, Figure S10: \(D\)-\(T\) dependence of Choline Lactate, Figure S11: \(D\)-\(T\) dependence of Cholineionate, Figure S12: \(D\)-\(T\) dependence of Choline 2-Methylbutanoate, Figure S13: \(D\)-\(T\) dependence of Choline Saccharinate, Figure S14: \(D\)-\(T\) dependence of Choline Salicylate, Figure S15: \(D\)-\(T\) dependence of Choline TFSI, Table S1 Experimental, predicted and extrapolated melting points. **Author Contributions:** Conceptualization, K.P.-E. and V.I. ; methodology, K.K. ; software, K.K. ; validation, F.E., K.K. ; formal analysis, K.K. ; investigation, F.E. and K.K. ; resources, K.P.-E. and V.I. ; data curation, K.K. ; writing-original draft preparation, F.E. and K.K. ; writing-review and editing, K.P.-E. and V.I. ; visualization, K.K.