Ab Initio GB Study of Methylation Reaction of Adenine, Cytosine, Guanine, and Thymine by Methanediazonium Ion

Methylation reaction at ten nucleophilic sites in four DNA base molecules by methanediazonium ion (N2Me+) was examined by ab initio MO/GB calculation which includes the solvent effect with the continuum model using the generalized Born formula. The stabilization energy of the ion–dipole complex as well as the energy of the transition state are roughly consistent with the experimental fraction of methylation by N -methyl-N -nitrosourea. For the guanine N7 site, which is the principal site of methylation, the stabilization energy is the largest and the energy of the transition state is low. The reactions at the guanine O6 and N7 sites were analysed by drawing the potential energy surface with respect to two parameters, the O6–C(Me) distance and the N7–C(Me) distance. The methylation reactions of the guanine O6 and N7 sites begin from the common geometry, the global minimum in the two-dimensional potential energy surface.