Dynamics of the excited-state hydrogen transfer in a (dG)·(dC) homopolymer: intrinsic photostability of DNA

Abstract

The intrinsic photostability of nucleic acids is intimately related to evolution of life, while its understanding at the molecular and electronic levels remains a challenge for modern science. Among the different decay pathways proposed in the last two decades, the excited-state hydrogen transfer between guanine-cytosine base pairs has been identified as an efficient non-reactive channel to dissipate the excess of energy provided by light absorption. The present work studies the dynamics of such phenomena taking place in a (dG)·(dC) B-DNA homopolymer in water solution using state-of-the-art molecular modelling and simulation methods. A dynamic effect that boosts the photostability of the inter-strand hydrogen atom transfers, inherent to the Watson-Crick base pairing, is unveiled and ascribed to the energy released during the proton transfer step. Our results also reveal a novel mechanism of DNA decay named four proton transfer (FPT), in which two protons of two adjacent G-C base pairs are transferred to form a biradical zwitterionic intermediate. Decay of the latter intermediate to the ground state triggers the transfer of the protons back to the guanine molecules recovering the Watson-Crick structure of the tetramer. This FPT process is activated by the close interaction of a nearby Na⁺ counterion with the oxygen atoms of the guanine nucleobases and hence represents a photostable channel operative in natural nucleic acids.

Scheme 1. Photostablility and tautomerization mechanisms involved in the ESHT mechanism.,

Fig. 1. (GG/CC)_QM partition of the (dG)·(dC) homopolymer system and atom numbering, of a G–C base pair in the WC arrangement.

Fig. 2. (a) Snapshot of the run b corresponding to the first accessed intersection point (t = 386 fs, ΔE = 0.24 eV), an INT structure with a marked out-of-plane H′41–N′4–C′4–N′3 dihedral angle. The arrows indicate the ground-state tautomeric pathways. (b) Snapshot of the run g corresponding to the first accessed intersection point (t = 30 fs, ΔE = 0.17 eV). The Na⁺ atom is displayed in green. All distances in Å.

Fig. 3. (a) INT biradical intermediate obtained through the ESHT process and (b) INT₂ biradical zwitterionic intermediate yielded by the FPT mechanism in two adjacent G–C pairs A and B. The nearby Na⁺ atom is displayed in green.

Fig. 4. Results of the run g using (a) the (GG/CC)_QM scheme, (b) the (GGGG/CCCC)_QM scheme, and (c) the (GGGG/CCCC)_QM scheme in which the charge of the nearby sodium atom has been switched to 0 (no physical meaning). (d) compares the dipole moment module of the QM systems of the runs shown in (b) and (c).

Fig. 5. Mechanism of the FPT transfer. The red curly arrows denote electron transfer.

Fig. 6. Radial distribution function g(r) of the distance between Na⁺ ions and the O6 atoms of the two central guanine molecules (residues #7 and #8, see Table S1†).