New Polymorphic Modifications of 6-Methyluracil: An Experimental and Quantum Chemical Study.

Polymorphism of 6-methyluracil, which affects the regulation of lipid peroxidation and wound healing, has been studied by experimental and quantum chemical methods. Two known polymorphic modifications and two new crystalline forms were crystallized and characterized by single crystal and powder X-ray diffraction (XRD) methods as well as by the differential scanning calorimetry (DSC) method and infrared (IR) spectroscopy. The calculations of pairwise interaction energies between molecules and lattice energies in periodic boundary conditions have shown that the polymorphic form used in the pharmaceutical industry and two new forms and , which can be formed due to temperature violations, may be considered as metastable. The centrosymmetric dimer bound by two N-H···O hydrogen bonds was recognized as a dimeric building unit in all of the polymorphic forms of 6-methyluracil. Four polymorphic forms have a layered structure from the viewpoint of interaction energies between dimeric building units. The layers parallel to the (100) crystallographic plane were recognized as a basic structural motif in the , , and crystals. In the structure, a basic structural motif is a layer parallel to the (001) crystallographic plane. The ratio between the interaction energies within the basic structural motif and between neighboring layers correlates with the relative stability of the studied polymorphic forms. The most stable polymorphic form has the most anisotropic "energetic" structure, while the interaction energies in the least stable form are very close in various directions. The modeling of shear deformations of layers in the metastable polymorphic structures has not revealed any possibility of these crystals to be deformed under external mechanical stress or pressure influence. These results allow the use of metastable polymorphic forms of 6-methyluracil in the pharmaceutical industry without any limitations.