Hydrogen bonding in hydroxyurea: A Raman and density functional theory study

While hydroxyurea (HU) remains an important chemotherapeutic agent, its molecular behavior is strongly affected by its surrounding environment. In this study, we examine how hydrogen bonding and solvent interactions influence the stability and vibrational properties of HU by combining density functional theory (DFT) calculations with Raman and surface-enhanced Raman scattering (SERS) measurements. Computational results show that intermolecular hydrogen bonds promote the solid-state-like self-association of HU, with trans dimers and trimers being 5.8 and 11.3 kcal/mol more stable than the corresponding cis forms. Among the solvents examined, dimethyl sulfoxide (DMSO) provides the highest stabilization, which is consistent with its strong hydrogen-bond acceptor character. Vibrational analysis further reveals that the 976 cm-1 SERS peak, corresponding to the CN symmetric stretching, can be considered a reliable marker in the investigated solvents. The reported results demonstrate how the local molecular environment can govern HU stability and impact its vibrational signatures.