Electron density analysis of tautomeric mechanisms of adenine, thymine and guanine and the pairs of thymine with adenine or guanine

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 ⇌ A ∗ – T ∗ and G ∗ – T ⇌ 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.