Mechanism of terahertz low-frequency vibrational spectral absorption in zidovudine and its derivatives under active excitation.

This study utilized terahertz time-domain spectroscopy (THz-TDS) combined with dispersion-corrected density functional theory (DFTD3, Grimme' s D3 dispersion correction) to systematically examine the absorption characteristics of adenosine, vidarabine, and zidovudine in the 0.3 to 2.0 THz range. Experimental and simulated results showed excellent agreement, collectively revealing the characteristic absorption spectra of zidovudine and its derivatives in this frequency region. Potential energy distribution (PED) analysis was applied to identify vibrational modes: adenosine primarily exhibits dihedral angle torsions, whereas vidarabine and zidovudine involve both dihedral angle torsion and out-of-plane bending vibrations. Weak interactions were visualized using the interaction region indicator (IRI) and the independent gradient model based on Hirshfeld partition (IGMH) methods, which helped identify the locations and types of these interactions. Compared to the holistic perspective provided by IRI, the IGMH approach allows precise characterization of weak interactions between specific molecular pairs. Results indicate that van der Waals (vdW) interactions dominate the weak interactions in all three molecules. Energy decomposition analysis based on forcefields (EDA-FF) further revealed that attractive electrostatic and dispersion contributions are largely counterbalanced by steric effects. These findings confirm that THz spectroscopy can effectively differentiate isomers and serve as a key tool for elucidating intermolecular interactions and the associated THz absorption mechanisms.