Computational design of ring-expanded pyrimidine-based DNA motifs with improved conductivity.

Motivated by a promising expansion of the genetic alphabet and a successful design of conductive DNA bases justified from the hetero-ring-expanded purine base (G and A) analogs, we extend our hetero-ring expansion scheme to the pyrimidine bases (C and T) to examine the ring-expansion effects on various properties of these single-ring bases with a comparison with those in the double-ring purine case. Four kinds of the hetero-rings are considered to expand C and T, forming the C and T analogs (nC and nT), respectively. The relevant structures and properties were investigated by means of quantum calculations and molecular dynamics simulations. The results reveal that all the modified bases can form base pairs specifically with their natural counterparts and assemble duplex helices which have comparable stability to native ones. The HOMO-LUMO gaps of G-nC and A-nT are smaller than those of the natural pairs, and the assembled duplex helices ((G-nC)(12) and (A-nT)(12)) are diameter-enlarged but with smaller rise and twist, both of which favor DNA-conduction, as confirmed by ionization potentials and spin density distributions. In addition, the hetero-ring expansion can lower the activation barriers and reduce the reaction heats of the inter-base double proton transfers. In particular, as evidenced by NMR parameters and the excited states, the hetero-ring expansion leads to an enhancement of the transverse electronic communication between two pairing bases, clearly facilitating the conduction along the helices. Furthermore, the hetero-ring expansion effect on the pyrimidine bases is larger than that on the purine bases. In summary, this work presents clear theoretical evidence for the possibility of hetero-ring expanded pyrimidine bases as promising candidates for the motifs of the genetic alphabet and DNA nanowires.