Hetero-ring-expansion design for adenine-based DNA motifs: evidence from DFT calculations and molecular dynamics simulations.

The design of new DNA motifs is at present a very interesting topic. Recent progress indicates that the hetero-ring-expanded guanine (G) analogues possess enhanced properties compared with natural guanine. In this work, a series of hetero-ring-expanded adenine (A) analogues are designed, and their structures and electronic properties are investigated by means of density functional calculations and molecular dynamics simulations. The results indicate that the designed A-analogues can form stable base pairs with natural counterpart, and the pairing energetics for the Watson-Crick hydrogen-bonded dimers between the expanded A-analogues and natural T exhibit similarity to natural AT. Their tautomeric preferences are close to natural A, too. Furthermore, compared with natural ones, most size-expanded adenines and corresponding base pairs have smaller ionization potentials. In particular, several designed A analogues have ionization potentials even lower than natural G. The electron affinities of these modified A are comparable with that of natural A. The HOMO-LUMO gaps also behave with sensible trends. Most of A-analogues and their interrelated base pairs possess smaller gaps than the corresponding natural base and base pairs. Further, molecular dynamics simulations show the sufficient stabilities of the DNA analogues (dnA.dT)(12) (where nA represents the size-expanded A-analogues designed here) when forming duplexes as the natural one does. Clearly, these observations imply their promising applications as molecular wires and new DNA motifs.