(524b) How Much Do Disorder and Entropy Matter in Molecular Systems?

In this talk, I survey our recent work using molecular dynamics to examine the free energy differences between enantiotropic crystalline systems, where the approximation that the lowest lattice energy crystal is the most stable must necessarily break down. We have found that although small rigid crystals are well-described by quasiharmonic approximations, even moderately conformationally flexible molecules can have extremely complex potential energy surfaces, making it hard to find appropriate structures from which to compute quasiharmonic approximations. We also find that many of these minima are accessible at room temperature and that proper annealing can help identify appropriate ensembles of structures to use for quasiharmonic analysis. Finally, we describe new approximations that make it easier to estimate the free energy difference between crystal polymorphs, including entropic effects, at a level that may be useful for large-scale screening of potential crystal structures.