Ground State Properties of the Nucleic Acid Constituents Studied by Density Functional Calculations. 2. Comparison between Calculated and Experimental Vibrational Spectra of Uridine and Cytidine

Abstract

Vibrational spectra of two ribonucleosides containing pyrimidine bases, i.e., uridine and cytidine, were analyzed in the solid state at low temperature by neutron inelastic scattering (NIS) and in an aqueous solution at room temperature by Raman scattering and Fourier transform infrared absorption (FT-IR). Analysis of all these experimental spectra, measured on both native and deuterated (on labile hydrogens) species, allows a complete set of information on the vibrational modes arising from the base residues and ribose to be obtained. To interpret the vibrational spectra, a harmonic force field has been estimated for isolated ribonucleosides at the Hartree-Fock (HF) and density functional theory (DFT) levels. All these calculations have been performed by means of the Becke-Lee-Yang-Parr (B3LYP) local exchange and correlation functional (for DFT calculations) and the split valence basis sets, 631G (*) , including nonstandard polarization functions on heavy atoms (for DFT and HF calculations). The lowest energy conformers of these ribonucleosides, i.e., C3′-endo/ anti and C2′-endo/anti have been used in the vibrational mode calculations, where C3′-endo and C2′-endo refer to the N-type and S-type ribose puckering, respectively, and anti designates the orientation of base with respect to the sugar. The absence of any imaginary frequencies in the vibrational calculations confirms that the optimized geometry of the ribonucleosides well corresponds to their local mimima. The addition of the zero-point vibrational energy (ZPVE) to the electronic energy does not, however, change the energy order of the conformers. In both ribonucleosides, the C3′-endo/anti conformer has a lower energy than the C2′-endo/ anti one. It has been shown that NIS intensities calculated at the DFT/B3LYP/631G (*) level account more accurately for the characteristics of the experimental spectra. Therefore, the assignment of the observed vibrational modes has been extensively discussed in this paper on the basis of the results calculated by means of the DFT method. On the other hand, comparison between observed and calculated NIS spectra of native and deuterated species can give insight on the effect of intermolecular hydrogen bonding in the solid phase. Finally, the calculated results seem to be able to interpret the Raman marker shifts observed upon the A-Z helix transitions of poly- and oligonucleotides (C3′-endo/anti to C2′-endo/anti conformational transition of the cytosine residue), as well as those related to the UUCG tetraloop hairpin, involving C2′-endo/anti uridine and cytidine residues found in the middle positions of this highly stable tetraloop.