Proteogenic Amino Acids: Chiral and Racemic Crystal Packings and Stabilities

Crystal structures of chiral and racemic proteogenic amino acids are compared, over a database of 40 crystal structures and 20 chiral-racemic pairs. Wallach’s rule does not apply. Solubility data show that the racemates tend to be slightly more stable than their chiral counterparts. Lattice energies are calculated by semiempirical PIXEL methods and by several ab initio methods, which also yield molecular energies. Results, especially molecular energies, are sensitive to small structural differences and therefore depend on the crystal structure accuracy. Surface effects in crystals of zwitterionic molecules require special attention. Energy differences between chiral and racemic crystals are typically around 10 kJ mol–1, roughly the limit of our calculations. These suggest, however, that crystal stability tends to increase with decreasing crystal density, a result possibly related to the strong directionality of hydrogen bonds. The analysis of interaction energies between molecules related by specific symmetry operations shows that stabilization in homochiral crystal structures comes mainly from formation of screw-symmetric ribbons, whereas racemic crystal structures preferentially exhibit strongly stabilizing centrosymmetric dimers.