Double hydrogen bond interaction in 7-azaindole complexes with protic solvents

Area of Science:

• Computational Chemistry
• Molecular Interactions
• Biophysical Chemistry

Background:

• Hydrogen bonding is crucial for DNA base pairing and mutations.
• 7-azaindole (7AI) serves as a model system for studying tautomeric shifts in DNA bases.
• Understanding solvent effects on hydrogen bonds is key to molecular recognition.

Purpose of the Study:

• To investigate the double hydrogen bond interactions between 7-azaindole and various protic solvents.
• To model mutations arising from tautomeric shifts in DNA.
• To elucidate the nature and strength of these hydrogen bonds using computational methods.

Main Methods:

• Energy Decomposition Analysis (EDA) was employed to quantify interaction energies.
• Analysis of electrostatic and polarization components of hydrogen bonds.
• Calculation of aromaticity indices for 7AI complexes.
• Investigation of spectroscopic shifts (red/blue) associated with hydrogen bonding.

Main Results:

• The 7-azaindole-formic acid (7AI-FA) complex exhibited the strongest electrostatic and polarization energies.
• An inverse correlation between polarization and electrostatic components was observed.
• Most complexes showed red-shifted hydrogen bonds due to hyperconjugation, except 7AI-MeOH.
• Aromaticity analysis indicated changes in 7AI's pentagonal and hexagonal rings.
• The double hydrogen bond in 7AI-FA was identified as the primary driver for 7AI tautomerization.

Conclusions:

• The double hydrogen bond interaction, especially with formic acid, is critical for 7-azaindole tautomerization.
• Solvent interactions significantly influence the electronic properties and hydrogen bond characteristics of 7AI.
• These findings offer a molecular-level understanding of processes relevant to DNA mutations.