Origin of the Thermodynamic Stability of the Polymorph IV of Crystalline Barbituric Acid: Evidence from Solid-State NMR and Electron Density Analyses

In this contribution, the origin of the stability of the polymorph IV (enol form) of crystalline barbituric acid relative to the polymorph II (keto form) is investigated using solid-state NMR spectroscopy and electron density analysis. Electron density analysis reveals differences in the nature of the intermolecular contacts in the different polymorphs of barbituric acid. Comparing the properties of hypothetical single molecules of barbituric acid with cluster models shows that the electronic and magnetic properties of polymorphs of barbituric acid can be employed to measure the strengths of the intermolecular interactions. Changes in the magnitudes of the NMR chemical shift tensors are also shown to be parallel to the intermolecular delocalization index of Quantum Theory of Atoms in Molecules, which measures the covalency of an intermolecular interaction.