π-Cooperativity effect on the base stacking interactions in DNA: is there a novel stabilization factor coupled with...

Area of Science:

• Computational Chemistry
• Molecular Biophysics
• DNA Structure and Stability

Background:

• DNA duplex stability is crucial for genetic information storage and replication.
• Base stacking interactions and hydrogen bonding are key determinants of DNA structure.
• The role of proton transfer in DNA base pairing and stacking remains an active area of research.

Purpose of the Study:

• To investigate the impact of double-proton transfer (DPT) on dinucleotide step stacking energies.
• To explore the interplay between intra- and inter-strand base stacking interactions mediated by hydrogen bonds.
• To elucidate novel base pairing rules and assess potential oxidative damage during DPT.

Main Methods:

• Utilized absolutely localized molecular orbital (ALMO)-energy decomposition analysis (EDA) at the M06-2X/cc-pVTZ level.
• Employed ALMO-charge transfer analysis (CTA) to study electronic interactions.
• Analyzed changes in stacking energies and redox properties of nucleobases.

Main Results:

• DPT reactions through H-bonds introduce a significant stabilization or destabilization factor in DNA duplexes.
• Intra- and inter-strand stacking interactions are coupled via H-bridged quasirings.
• Variations in H atom positions alter local base aromaticity, leading to π-cooperativity effects and changes in stacking energies.
• Dispersion forces in dinucleotide steps can drastically alter nucleobase redox properties, particularly for adenine and guanine.

Conclusions:

• DPT is a critical factor influencing DNA stacking energies and overall duplex stability.
• Novel base pairing rules are proposed based on CTA, extending beyond Watson-Crick interactions.
• Additional base pairing via π-stacks during DPT does not induce intrinsic oxidative damage to nucleobases.