The prototropism in canonic adenine (A), thymine (T) and guanine (G), isolated or monohydrated, to yield the non-canonical tautomers A*, T* or G* was analyzed using theoretical methods along the potential energy surface. The A-T reversible arrow A*-T* and G*-T reversible arrow G-T* equilibria were also studied. Whereas formation of A*-T* is an unfavorable process without transition state, formation of G-T* involves a transition state and a +2.1 kcal/mol tautomerization energy. Several electron density descriptors were analyzed along the reaction mechanisms. The atomic interactions clearly indicate the synchronous nature of tautomerization of isolated or monohydrated bases and an asynchronous mechanism to form the G-T* mispair. (C) 2009 Elsevier B. V. All rights reserved.