Terahertz spectroscopy analysis of L-Phenylalanine and its fluorinated derivatives

3-Fluoro-L-Phenylalanine (3-F-L-Phe) and 4-Fluoro-L-Phenylalanine (4-F-L-Phe) are fluorinated derivatives of L-Phenylalanine (L-Phe) that hold significant medical applications. To investigate the impact of introducing fluorine atoms on the structure of L-Phe, this study employed terahertz (THz) spectroscopy to distinguish three crystal structure differences. A comparative analysis of the absorption peaks of 3-F-L-Phe and 4-F-L-Phe with that of L-Phe revealed varying degrees of red shift and blue shift. The dielectric loss analysis demonstrated that the substitution of fluorine atoms in different positions of the benzene ring changes the crystal structure and electric dipole moment. By combining lattice network and vibration mode comparative analysis, the study concluded that the differences in the spectrum could be attributed to variations in the hydrogen bond network and changes in the unit cell volume. These findings highlight the effectiveness of using terahertz time domain spectroscopy (THz-TDS) and solid-state density functional theory (DFT) as a new method for the qualitative analysis of fluorinated amino acid derivatives.