# Predicting Melting Points of Biofriendly Choline-Based Ionic Liquids with Molecular Dynamics
## 4 Discussion  
The prediction of IL melting point was performed before with varying success via quantitative structure-property relationship (QSPR) or MD-based [18] approach. In QSPR methods, several simple descriptors are correlated to the melting point. Numerous QSPR [46; 47; 48; 49; 50; 51; 52] and other statistical models [53; 54] were assembled, with perhaps the most impressive being a work by [PERSON] et al., who report a mean prediction error of only 1.30% [46]. However, the QSPR and QSAR-based models have an intrinsic shortcoming--they are reliable as far as the characterized substances are similar to those of the training set that were used to build the model. Therefore, they are not best suited for screening for novel compounds or for studying more complex systems, for example, mixtures of ILs. There are several MD-based methods for melting point determination such as the free-energy based PSCP method [19; 20; 55], hysteresis method [56], voids method [57; 58] and solid-liquid interface method [59]. They are in principle more reliable and universally applicable than the QSPR methods [18]. In practice, they have a severe limitation--requirement for the crystal structure data. The main motivation for the melting point prediction of ILs is to identify new low melting ILs prior to their synthesis. If the prediction method requires crystal structure data, then it makes synthesis and crystallization of the IL inevitable. At that point, a little effort put in measuring the melting point makes the post-prediction useless. Our method does not require the knowledge of IL crystal structure. Instead, the solid phases are packed with the help of Coulombic potential wells. Differently from the PSCP method [19; 20; 55], where the wells are placed in known lattice vertices, we simulate different lattices and choose the highest melting point. Our analysis of \(D\)-\(T\) dependencies can be considered direct as opposed to constructing phase transition free energy cycles as is done in PSCP. The authors of the PSCP method, [PERSON] and [PERSON] claimed that direct prediction of melting points of ILs is not accurate due to the superheating phenomenon which leads to severe overestimation of the melting points [18]. Contrary to that claim, in our results (Table 2), there is a relatively small skew (2-10 K mean average error) towards higher predicted values. In addition, we did not observe clear superheating hysteresis when changing the temperature rate of annealing simulations (Figure 5). Interestingly, faster temperature rates did yield inaccurate results, but they tended to underestimate rather than overestimate the melting points. This might be happen due to local overheating or problems with the temperature coupling algorithm at more rapid temperature rates. Conducting annealing simulations with different temperature rates also yields a slightly more accurate prediction for most cases. This was shown with the regression lines in Figure 5 via extrapolation towards temperature rate of \(0\) K \(\cdot\) ns\({}^{-1}\), which would correspond to an infinitely slow annealing. Another factor, which did lead to markedly overestimated results for our method, was using inaccurate partial charges. In the work by [PERSON] and [PERSON] [18], the IL force field charges used to test different methods were obtained similarly to our initial DFT CHELPG charges, where the ionic charges are forced to be \(\pm 1\) e. In current work, we observed large errors when using these partial charges (Table 3). The situation improved slightly with scaling the charges \begin{table}
\begin{tabular}{l c c c c} \hline \hline
**Cation: Choline** & **Experimental** & **DFT** & **DFT 0.8** & **GFN2-xTB** \\
**Anion** & \(\mathbf{T_{M}}\) (K) & \(\mathbf{T_{M}}\) (K) & \(\mathbf{T_{M}}\) (K) & \(\mathbf{T_{M}}\) (K) \\ \hline Acetate & 354\({}^{a}\) & 359 & 354 & 330 \\ Benzoate & 320 [14] & 381 & 365 & 335 \\ Salicylate & 323 [40] & 377 & 364 & 343 \\ TFSI & 306 [24] & 348 & 345 & 321 \\ \hline \hline \end{tabular} \({}^{a}\)—this work.  
\end{table}