Hydrogen-atom abstraction from the adenine-uracil base pair

Area of Science:

• Computational Chemistry
• Molecular Biology
• Quantum Chemistry

Background:

• The adenine-uracil (AU) base pair is fundamental in nucleic acids.
• Understanding radical formation in DNA/RNA is crucial for radiation chemistry and biology.

Purpose of the Study:

• To investigate the energetics and structural properties of hydrogen-abstracted radicals in the adenine-uracil base pair.
• To identify the most stable radical intermediates and their dissociation pathways.

Main Methods:

• Density Functional Theory (DFT) calculations using the B3LYP/DZP++ level of theory.
• Analysis of radical structures, energies, and dissociation energies.

Main Results:

• The A(N9)-U and A-U(N1) radicals were found to be the lowest-lying among nine studied radicals.
• Radical A(N6a)-U, from adenine amino hydrogen abstraction, exhibited the smallest base-pair dissociation energy (5.9 kcal mol(-1)).
• A uracil N3 hydrogen abstraction resulted in a stable radical (12.9 kcal mol(-1) dissociation energy) with a significant C-H...O hydrogen bond.

Conclusions:

• Hydrogen abstraction from N-H bonds generally yields more stable radicals than from C-H bonds in the AU base pair.
• The A(N9)-U radical is prone to dissociation, while the uracil N3-H abstracted radical shows remarkable stability due to electron density transfer.