Investigation of 5-Fluorouracil Cocrystals by Low-Frequency Vibrational Spectroscopy and Solid-State Density Functional Theory

Cocrystallization of dissimilar organic molecules plays an important role in the design and improvement of solid-state pharmaceuticals. The combined approach of terahertz and Raman spectroscopies, augmented with solid-state density functional theory, offers a powerful method for studying the distinct low-frequency vibrational spectra of these novel solids and the energetic factors involved in cocrystal formation. Here, 5-fluorouracil (a chemotherapy agent) and its 1:1 cocrystals with urea and thiourea are investigated. The first goal is to understand the two polymorphs of 5-fluorouracil and to accurately model the fluorine-fluorine interactions between molecules. In addition to pure 5-fluorouracil, the effects of sulfur and oxygen on the hydrogen bonding networks within the cocrystalline solids is also considered, and how these modify the low-frequency vibrations.