Solid-state cocrystal formation between acyclovir and fumaric acid: Terahertz and Raman vibrational spectroscopic studies

•Raman and THz-TDS vibrational spectra of acyclovir and its cocrystal formed with fumaric acid are reported.•The major vibrational modes of starting components and cocrystal are obtained and assigned based on DFT results.•Raman and THz-TDS spectroscopic techniques are potential to monitor cocrystal formation and analysis molecular structure changes.

The vibrational spectra of solid-state acyclovir, fumaric acid and their cocrystal have been investigated by using terahertz time-domain spectroscopy (THz-TDS) and Raman spectroscopy at room temperature. In experimental THz spectra, the cocrystal has absorption peaks in 0.65, 0.94 and 1.10 THz respectively, while the raw materials are absolutely different in this region. Raman spectra also show similar results about differences between the cocrystal and raw materials. Density functional theory (DFT) was performed to simulate vibrational modes of different theoretical forms between acyclovir and fumaric acid. The calculation of theoretical THz spectra shows that O8C7N1H27 and the carboxyl group COOH establish a dimer theoretical cocrystal form by the hydrogen bonding effect, which makes contributions to the formation of absorption peaks in 0.70, 1.01 and 1.34 THz, and agrees well with experimental observations. The theoretical Raman result also indicates that this dimer form matches with experimental results. The characteristic bands of the cocrystal between acyclovir and fumaric acid are also assigned based on the simulation results from the DFT calculation.

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