(192ag) Differences in Relative Free Energy Versus Temperature Curves for Small Organic Molecules  between Quantum Mechanical and Classical Potentials.

The crystalline packing or polymorphic state of a material can have an effect on many of the physical properties of that material. Traditional crystal structure prediction methods rely on the potential energies of the 0K structures to make determinations about the most stable polymorph at higher temperatures. However, because of entropic effects, this approach may not always yield the correct room temperature structure. In this project, we show the effect of using a quantum mechanical potential on the estimation of the entropic effects in the temperature dependent polymorph stability.

In previous work, we have shown that in some small molecule organic crystals, the entropic effects are large enough to change the ordering of stability in crystal polymorphs between the ordering determined by the 0K structure and by molecular dynamics or the quasiharmonic approximation at room temperature. We have also shown that the potential used has an effect on the ordering of the stability of the polymorphs and the temperature of the temperature mediated transformation of the polymorph. We have determined the free energy versus temperature curves for full molecular dynamics in point charge and polarizable potentials, and their comparison to the quasiharmonic approximation in point charge potentials. To further examine the effect of changing potentials on the temperature mediated transformation of polymorphs, this project uses the quasiharmonic approximation in quantum mechanical potentials and the non-equilibrium work implementation of the Jarzynski equation for to obtain dG versus T stability curves.

In this project, two crystals were studied , benzene and aripiprazole. Benzene is a rigid molecule and aripiprazole has more flexibility. The cp2k package was used, with DFT-D3 corrections and the PBE functional. The vibrational analysis module in cp2k was used to obtain the normal mode frequencies and the corresponding eigenvectors of the two systems, and the Gruneisen parameter approach was used to construct the dG vs T curves for the free energy difference between polymorphs. the We can compute the free energy versus temperature for ab initio quantum mechanical approach by computing the free energy correction from a classical force field to a classical one, and adding this correction to previously computed classical results. We examined the length of switching simulations necessary to efficiently estimate the free energy of switching between potentials.