Physicochemical properties calculated using DFT method and changes of 5-methyluridine hemihydrate crystals at high temperatures.

5-methyluridine hemihydrate (5 mU) single crystals were synthesized by the slow solvent evaporation method. The physicochemical properties, such as frontier molecular orbitals, global reactivity indices and vibrational were computationally studied through density functional theory (DFT). In addition, structural, vibrational, and thermal properties were obtained by powder X-ray diffraction (PXRD), Raman spectroscopy, thermogravimetric (TG) analysis and differential scanning calorimetry (DSC). PXRD evaluated the structural behavior of 5 mU crystal in the temperature range of 300-460 K. The high-temperature PXRD results suggested that the crystal undergoes two dehydration processes, being a first occurring from the orthorhombic structure (P21212) to triclinic (P1), in which the water losses occurred around 380 K. A second dehydration triggers the change from the triclinic structure to monoclinic (P21) within the 420-435 K temperature range. Furthermore, after this temperature, the anhydrous 5 mU suffers a melting process near 460 K, which is remarkably characterized as an irreversible process. Raman spectroscopy was carried out to identify the vibrational modes linked to the water molecule and the noticeable changes in these bands due to high-temperature effects around 380 K and 410 K. Indeed, changes on Raman bands, such as intensity inversion, the disappearance of bands associated with the hydrogen bonds formed from the water molecules and uracil group, and the ribose group were observed. Finally, this study provided details on the structural and vibrational changes caused by the dehydration of 5 mU crystals and the importance of hydrogen bonds for understanding the intermolecular interactions of the 5 mU, a methylated nucleoside with important biological functions.