Molecular geometries of the reagents, reaction intermediates, QST-3 transition states and products were optimized using DFT/B3LYP level of theory. Frequency calculations were performed on all optimized structures to ensure that the reactants and products have only positive frequencies and a single negative imaginary frequency in the case of the transition states. The electronic properties and the quantum chemical descriptors for the frontier molecular orbitals of all the antisense modifications were derived and compared. The basis set 6-311+G(d,p) was used for the other atoms. Thermochemical data and temperature corrections were calculated at 298.15 K for all optimized geometries. An IRC scan based on the Gonzalez-Schegel method, which computes the minimum energy reaction pathway (MERP) in massweighted cartesian coordinates between the transition state and its reactants and products, was performed for each of the transition states with maxpoints=20 and recalculation at every 3 points for both the forward and backward trajectories. All energies were corrected by zero-point vibrational energies and all calculations were performed using the Gaussian09 software.