Crystal Structure Prediction for Six Monosaccharides Revisited

Six monosaccharides were studied as prototypes for flexible molecules, forming crystal structures with complex hydrogen bond patterns. In earlier work the prediction of these crystal structures had been attempted using empirical force fields. Now ab initio energies have been calculated for 20 hypothetical structures of each substance, along with corrections to the free energy at room temperature. Five experimental structures corresponded to the global free energy minimum, the sixth ranking second at a relative free energy of only 1.3 kJ/mol. This strongly suggests that a thermodynamic approach to crystal structure prediction will often be adequate, kinetic effects being dominant only in a minority of cases.