Effects of Morphology and Solvent/Temperature on THz Spectra: Take Nucleosides as Example.

Water molecules were easy to combine with organic molecules and embed into the lattice of solid molecules to form a hydrate. Compared with anhydrous compounds, a hydrate has completely different physical and chemical properties. In this paper, terahertz (THz) spectra of five nucleosides in the solid and liquid phases were studied experimentally by Fourier-transform infrared spectroscopy (FTIR) in the frequency of 0.5-9 THz. In addition, the lattice energy, geometric structure, and vibration spectrum of the molecular crystal of the nucleosides were analyzed theoretically by the generalized energy-based fragmentation approach under periodic boundary conditions (denoted as PBC-GEBF). Furthermore, different nucleoside molecular morphology (monomer, polymer, and crystal), solvent (implicit and explicit water), and temperature/theoretical model effect on the THz spectra were mainly investigated. It was found that in the low-frequency band, the vibrational modes were generally originated from the collective vibration of all molecules involved (more than 99% of them were vibration; only less than 1% of them were rotation and translation), which can reflect the molecular structure and spatial distribution of different substances. The Gibbs free energy of thymidine monomer, dimer, tetramer, and crystal was studied. It was found that the cell-stacking energy had the greatest influence on the spectrum, indicating that only the crystal structure constrained by the periodic boundary conditions could well describe the experimental results. In addition, hydrophobic forces dominated the formation of new chemical bonds and strong inter-molecular interactions; the free water had little contribution to the THz spectrum of nucleosides, while crystalline water had a great influence on the spectrum.

Terahertz spectra and weak intermolecular interactions of nucleosides or nucleoside drugs.

In this paper, terahertz (THz) spectra of four DNA nucleosides (Adenosine, Thymidine, Cytidine and Guanosine) and two nucleoside derivatives (Ribavirin and Entecavir, first time reported) in the solid phase were studied experimentally by Fourier Transform Infrared Spectroscopy (FTIR) in the frequency of 1-10 THz. The lattice energy, geometric structure, vibration spectrum of them were analyzed theoretically by the generalized energy-based fragmentation approach under periodic boundary conditions (denoted as PBC-GEBF) and the density functional theory (DFT). The intra- and inter-molecular weak interactions corresponding to the vibrational modes of the crystal, polymer and monomer were obtained, with the help of the potential energy distribution (PED) and reduced density gradient (RDG) methods. It was found that the sum of electronic and thermal free energies increased from the monomer to polymer, and from the polymer to crystal. For example, the inter-molecular interaction energy from the monomer to dimer of adenosine increased 6.969 kcal/mol, and that from the dimer to crystal (the periodic boundary conditions were considered) increased 666.792 kcal/mol. Therefore, only the crystal structure constrained the periodic boundary conditions could well describe the experimental results, although the former scholars chose the monomer or polymer as the initial configuration due to the limitation of computing resources and methods. In THz band, the vibrational modes were generally originated from the collective vibration (more than 99% of them were vibration, only less than 1% of them were rotation and translation) of all molecules involved, which could reflect the molecular structure and spatial distribution of different substances. In order to accurately identify the spectra, we studied the location, type and contribution of all weak interactions, and found that the strong characteristic peaks corresponding to the strong hydrogen bonds came from inter-molecular, while the weak hydrogen bonds mainly originated from intra- and inter-molecular, the out-of-plane bending made the largest contribution, accounting for more than 90%. Furthermore, taking guanine, guanosine and two guanosine derivatives (Ribavirin and Entecavir) as examples, the differences of weak interaction among them caused by different molecular configuration, arrangement and substituent position were studied, and the fundamental reason of THz spectrum change was found. This research can lay a foundation for crystal engineering, supramolecular chemistry, molecular recognition and self-assembly, protein-ligand interaction, etc.

Terahertz spectra of DNA nucleobase crystals: A joint experimental and computational study.

Terahertz (THz) spectra of DNA nucleobase crystals were experimentally studied by terahertz time domain spectroscopy (THz-TDS), Fourier transform infrared spectroscopy (FTIR), and computationally studied by the generalized energy-based fragmentation approach under periodic boundary conditions (denoted as PBC-GEBF). We analyzed the vibrational spectra of solid-state DNA nucleobases and assigned the corresponding vibrational modes to the main peaks in the experimental spectra with the PBC-GEBF results. The computational results were verified to be in good accordance with the experimental data. Harmonic vibrational frequency results revealed that all the vibrational modes belong to collective vibrational modes, which involve complicated mixtures of inter- and intramolecular displacements, somewhere in the vicinity of 0.5-9THz.