Ab Initio and Density Functional Studies of Substituent Effects of an A−U Base Pair on the Stability of Hydrogen Bonding

Systematic substituent effects on the stability of the hydrogen bonding between 9-methyladenine (A) and 1-methyluracil derivatives (U X ) having various substituent groups were studied. The hydrogen bond stability of mismatched base pairs between 9-methylguanine (G) and the tautomeric enol structures (U X‘ ) of U X was also estimated. Geometry optimization of these bases and their base pairs using the 6-31G* basis set was carried out by Hartree−Fock (HF) self-consistent field (SCF) and the density functional theory (DFT) using Becke's three-parameter hybrid method with Predew/Wang 91 expression (B3PW91). The strength of hydrogen bonding was evaluated at the HF level and the second-order Møller−Plesset correlation energy correction (MP2) level in some cases. The calculated values for the hydrogen bonding strength using DFT were situated between those obtained by using HF and MP2 but closer to the latter than the former. Introduction of an electron-withdrawing group (EWG) into the uracil ring resulted in the formation of more stable hydrogen bonding. These results indicate that the hydrogen bond between 3 H of U and N 1 of A is crucial for the A−U base pairing.