Insights Into Guanine Radical Cation Deprotonation Using the Quantum Mechanics and Quantum Mechanics/Molecular Mechanics (<scp>ABEEM</scp>) Methods

ABSTRACT In double‐stranded DNA, a rapid deprotonation of guanine radical cation (G •+ ) hinders the long‐distance transfer of positive charge (hole). It is significant to explore the proton transfer of G •+ for designing other DNA structures with high electrical conductivity. The deprotonation of G •+ is explored in the 1H 2 O, 2H 2 O, 3H 2 O, and 9H 2 O models by quantum mechanics (QM) method. The results indicate that the second hydration shell facilitates proton transfer. The QM/molecular mechanics (MM) (ABEEM) method accurately simulates polarization and charge transfer effects through the implementation of the reactive valence‐state electronegativity piecewise functions and setting local charge conservation conditions. The QM/MM(ABEEM) method has been developed to investigate the 9H 2 O model. The obtained activation energy (16.3 ± 0.8 kJ/mol) through molecular dynamics simulations is consistent with experimental data (15.1 ± 1.5 kJ/mol), demonstrating the accuracy of the QM/MM(ABEEM) method in simulating proton transfer in the DNA system. The deprotonation rate of G •+ in the free base (1.5 × 10 7 s −1 ) is faster than that of G •+ within double‐stranded DNA (10 6 –10 7 s −1 ), which indicates that the free G base is an avoidable participant when designing hole transfer carrier due to its rapid deprotonation rate. Concurrently, the relationship between the proton transfer distance and potential barrier is monotone increasing, meaning that the long‐range proton transfer corresponds to high energy barrier. The molecule involved in long‐range proton transfer of G •+ is more suitable as DNA electronic devices. This research provides valuable microscopic insight into deprotonation to advance the advancement of DNA structures with high electrical conductivity.