Many properties of small organic molecules are dependent on the current crystal packing, or polymorph, of the material, including bioavailability of pharmaceuticals, optical properties of dyes, and charge transport properties of semiconductors. Computational prediction of the most stable crystalline form is done by determining the crystalline form with the lowest relative Gibbs free energy. Effective computational prediction of the most stable polymorph could save significant time and effort in the design of organic solids, especially those which have not been synthesized yet.<br/><br/>In this study, we use multistate reweighting methods to determine the most stable polymorph for three test systems, including small organic molecules and Lennard-Jones spheres across a variety of temperatures and pressures. In order to achieve this, sampling is performed at a selection of temperature and pressure states in the region of interest. Multistate reweighting methods are then employed to determine the reduced free energy differences between T,P states within a polymorph. By combining these reduced free energy differences with a reference Gibbs free energy difference between polymorphs, the relative stability of the polymorphs at the sampled states can be determined and interpolated to create the phase diagram.<br/><br/>We have determined the efficiency of using multistate reweighting for this process by determining the relationship between the size of the system and the number of samples required to obtain a constant uncertainty in the results. Using this analysis, we have shown that the numbers of samples needed as the system size increases scales better than the number of molecules in the system. We have also explored increasing the efficiency of this method by adding Jacobian mapping between states to increase the phase space overlap between adjacent samples and therefore decrease the amount of direct sampling that must be performed. We have thus far shown this to be a feasible method of increasing the spacing between sampled pressures in a system of Lennard-Jones spheres.

Predicting relative polymorph stability using multistate reweighting methods and Jacobian mapping

253rd National Meeting (2017)

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