Terahertz and Raman vibrational spectroscopy detection and structural analysis of acyclovir hydrate polymorphs

Drug and water molecules combine in different proportions and arrangements in the crystal lattice, forming hydrated polymorphs with unique physicochemical properties due to intermolecular interaction variations. In this experiment, we successfully prepared two hydrated forms of acyclovir(ACV) under controlled conditions and characterized them using terahertz(THz) and Raman spectroscopy. Significant differences were observed in THz spectra, while Raman differences were minor. To investigate their vibrational modes, we performed simulations on multiple structural fragments using Gaussian software and conducted solid-state density functional theory(DFT) calculations with the Crystal software. Analysis showed similar internal packing modes, explaining the Raman similarity. Furthermore, vibrational mode assignment revealed the considerable impact of intermolecular hydrogen bonds on ACV molecular structure and vibrational modes during crystallization. This study offers a new perspective on ACV hydrate polymorphism and important theoretical support for drug development and quality control.