Broadband terahertz signatures and vibrations of Phe-Phe peptide and its fibrils

In recent years, peptide-based nanomaterials have gained significant attention in drug discovery due to their biocompatibility and promising functionality in biophysical processes. This current study employs terahertz (THz) spectroscopy and density functional theory (DFT) to investigate the vibrational properties of the phenylalanine dipeptide (Phe-Phe), a building block with notable self-assembling properties and potential applications in drug delivery and nanostructured biomaterials. The dynamics of proteins and biomolecules occurring on the picosecond timescale can be probed by THz spectroscopy and is closely related to their functionality. Here, we investigate the low-frequency vibrational modes of Phe-Phe under two different conditions, as crystalline commercial powder and post-self-assembled powder, in the 0.2-4 THz range. The refractive index of pure Phe-Phe, as evaluated from THz spectroscopy, is approximately 1.47, and the THz absorption peaks are observed at 0.55, 0.83, 1.13, 1.40, 1.68, 2.18, 2.71, 3.00, and 3.33 THz. Potential energy distribution (PED) analysis provides a detailed assignment of the observed modes and identifies characteristic vibrational features. The novel thin bi-layer approach for sample preparation employed here proved to be effective in terms of signal-to-noise ratio and in eliminating artifacts possibly originating from the host material. This combined experimental-computational approach not only offers valuable insights into the conformational flexibility and self-assembly potential of Phe-Phe, but also underscores the efficacy of THz spectroscopy and DFT analysis for studying the vibrational properties of peptides, with implications for biophysics, nanotechnology, and biochemistry. Moreover, this study highlights the impact of intermolecular interactions on the vibrational spectra by comparing crystalline powder and self-assembled peptide powder.