DFT Study on the Conformational and Vibrational Properties of 3’-Deoxycytidine and Its Analogues

Impact of saturation of the sugar C(3’)=C(4’) bond of acytidine nucleoside derivative, 3’, 4’-didehydro-3’-deoxycytidine (I) is revealed usingsimulated vibrational spectra, with respect to 3’-deoxycytidine. The density functional theory based calculations found that the C(3’)=C(4’) double bondrestricts the sugar flexibility and affects the sugar-base intramolecular hydrogen bond network. For 3’-dC, two minimal energy conformers are identified on the potential energy surface. The first conformer (IIA) takes anO4’-endo and gauche-gauche (gg) orientation whereas the second (IIB) has a C3’-exo and gauche-trans (gt) orientation in gas phase. The two conformers which have been observed previously in the crystal structure are separated by a low energy barrier. The carbon double bond in the sugar moiety of I confines the pseudorotation of the pentagon ring to be significantly flatter than that of the sugar ring in IIA and IIB. The simulated vibrational spectra, both in gas phase and in solutions, report such structural caused spectral changes with red and blue vibrational frequency shifts.The firsthydration shell of 3’-dC has been also investigated applying hybrid QM/MM molecular dynamic simulation.