The formation of purine and pyrimidine base pairs (BPs), which contributes to shaping of the canonical and noncanonical 3D structures of nucleic acids, is one the most investigated phenomena in chemistry and life sciences. In this contribution, the anatomy of the bond energy (BDE) of the base-pairing interaction in 39 different arrangements found experimentally or predicted for DNA structures containing the four common nucleobases (A, C, G, T) in their neutral or protonated forms is described in light of the theory of interacting quantum atoms within the context of the quantum theory of atoms in molecules. The interplay of individual energy components involved in the three stages of the bond formation process (structural deformation, electron-density promotion, and intermolecular interaction) is studied. We recognized that for the neutral BPs, variations in the kinetic and electrostatic contributions to the BDE are rather negligible, leaving the exchange-correlation energy as the main stabilizing component. It is shown that the contribution of the exchange-correlation term can be recovered by including atoms that are formally assumed to be hydrogen bonded (primary interaction). In contrast, to recover the electrostatic component of interaction, one must consider both the primary and secondary (formally nonbonded atoms) interatomic interactions. The results of our study were employed to design new types of BPs with altered bonding anatomy. We demonstrate that improving the electrostatic characteristics of the BPs does not necessarily result in greater interaction energies if weak secondary hydrogen bonding is destroyed. However, the main tuning factor for systems with conserved interacting faces (primary interactions) is the electrostatic component of the interaction energy resulting from the secondary atom-atom electrostatics.
