Spontaneous Resolution of Chiral Molecules. As a second example of insight that can be gained from large numbers of crystal energy landscapes, we examine the tendency for spontaneous resolution of chiral molecules. It is generally ac- cepted that crystallisation from a racemic solution of a chiral molecule more frequently yields racemic crystals rather than undergoing spontaneous resolution into a mixture of crystals, each containing a single stereoisomer.(66) However, information in structural databases alone is limited: knowing whether crystals were grown from racemic or enantiomerically pure solution is necessary to interpret the incidence rate of spontaneous resolution and the molecular characteristics that influence this behaviour. Furthermore, where enantiomers separate upon crystallisation, it is not possible to grow racemic crystals, so that comparison of racemic vs enantiomerically pure crystal structures is not possible. Computed crystal energy landscapes make it possible to compare the structures and relative energies of the alternative crystallisation outcomes. In Figure , we show the difference in stability and density between the energy minimum across all Sohncke (i.e. enantiopure) space groups and the minimum across enantiogenic (i.e. racemic) space groups for the 356 molecules in our set containing at least one chiral centre. This energy difference represents the propensity for spontaneous resolution of a racemic solution compared to a racemic crystal of both enantiomers. In general, there is a slight but consistent lattice energy penalty to enantiopurity -the average difference in lattice energy between the enantiopure global minimum and the racemic global minimum is 2.7 kJ/mol, favouring the racemate. Of the 356 chiral molecules, racemic crystallisation is preferred in 86% (305) of molecules and spontaneous resolution is predicted to occur for approximately 14% (51) of molecules, although those with small lattice energy differences could be influenced by thermal contributions that are not included here. Moreover, this is accompanied (or perhaps driven) by improved packing in the racemate -on average, optimal enantiopure structures are 2.3% less dense than optimal racemic structures, consistent with the empirical Wallach's rule .