Surprising Conformers of the Biologically Important A·T DNA Base Pairs: QM/QTAIM Proofs.

For the first time novel high-energy conformers-A·T(wWC ) (5.36), A·T(wrWC ) (5.97), A·T(wH ) (5.78), and A·T(wrH ) (ΔG = 5.82 kcal·mol-1 ) (See Graphical Abstract ) were revealed for each of the four biologically important A·T DNA base pairs - Watson-Crick A·T(WC), reverse Watson-Crick A·T(rWC), Hoogsteen A·T(H) and reverse Hoogsteen A·T(rH) at the MP2/aug-cc-pVDZ//B3LYP/6-311++G(d,p) level of quantum-mechanical theory in the continuum with ε = 4 under normal conditions. Each of these conformers possesses substantially non-planar wobble (w) structure and is stabilized by the participation of the two anti-parallel N6H/N6H'…O4/O2 and N3H…N6 H-bonds, involving the pyramidalized amino group of the A DNA base as an acceptor and a donor of the H-bonding. The transition states - TSA·T(WC)↔A·T(wWC) , TSA·T(rWC)↔A·T(wrWC) , TSA·T(H)↔A·T(wH) , and TSA·T(rH)↔A·T(wrH) , controlling the dipole-active transformations of the conformers from the main plane-symmetric state into the high-energy, significantly non-planar state and vice versa , were localized. They also possess wobble structures similarly to the high-energy conformers and are stabilized by the participation of the N6H/N6H'…O4/O2 and N3H…N6 H-bonds. Discovered conformers of the A·T DNA base pairs are dynamically stable short-lived structures [lifetime τ = (1.4-3.9) ps]. Their possible biological significance and future perspectives have been briefly discussed.