We report a kinetics and mechanistic study on the O-1(2) oxidation of 9-methylguanine (9MG) and the cross-linking of the oxidized intermediate 2-amino-9-methyl-9H-purine-6,8-dione (9MOG(OX)) with N-alpha-acetyl-lysine-methyl ester (abbreviated as LysNH(2)) in aqueous solutions of different pH. Experimental measurements include the determination of product branching ratios and reaction kinetics using mass spectrometry and absorption spectroscopy, and the characterization of product structures by employing collision-induced dissociation. Strong pH dependence was revealed for both 9MG oxidation and the addition of nucleophiles (water and LysNH(2)) at the CS position of 9MOG(OX). The O-1(2) oxidation rate constant of 9MG was determined to be 3.6 x 10(7) M-1.s(-1) at pH 10.0 and 0.3 x 10(7) M-1.s(-1) at pH 7.0, both of which were measured in the presence of 15 mM LysNH(2). The omega B97XD density functional theory coupled with various basis sets and the SMD implicit solvation model was used to explore the reaction potential energy surfaces for the O-1(2) oxidation of 9MG and the formation of C5-water and C5-LysNH(2) adducts of 9MOG(OX). Computational results have shed light on reaction pathways and product structures for the different ionization states of the reactants. The present work has confirmed that the initial O-1(2) addition represents the rate-limiting step for the oxidative transformations of 9MG. All of the downstream steps are exothermic with respect to the starting reactants. The C5-cross-linking of 9MOG(OX) with LysNH(2) significantly suppressed the formation of spiroiminodihydantoin (9MSp) resulting from the C5-water addition. The latter became dominant only at the low concentration (similar to 1 mM) of LysNH(2).