Understanding Stacking Interactions between an Aromatic Ring and Nucleobases in Aqueous Solution: Experimental and...

Area of Science:

• Biophysical Chemistry
• Molecular Recognition
• Nucleic Acid Chemistry

Background:

• Stacking interactions between aromatic compounds and nucleobases are vital for nucleotide and nucleic acid recognition.
• A comprehensive understanding of the strength and selectivity of these interactions in aqueous solution remains challenging.

Purpose of the Study:

• To experimentally determine stacking free energies between five nucleobases and anthracene.
• To evaluate three different experimental methods for quantifying these interactions.
• To compare experimental results with theoretical predictions using DFT calculations.

Main Methods:

• Design and analysis of model complexes.
• Thermodynamic double mutant cycles for experimental free energy determination.
• Density Functional Theory (DFT) calculations for theoretical analysis.

Main Results:

• Experimental stacking free energies were determined for guanine (G), thymine (T), uracil (U), cytosine (C), and adenine (A) with anthracene.
• The binding preference order was G > T > U > C > A (kcal/mol).
• DFT calculations showed a trend correlating with experimental findings.

Conclusions:

• Stacking interactions are dominant over hydrophobic effects in aqueous solutions.
• DFT calculations can accurately predict these stacking interactions.
• This work provides crucial insights into the molecular recognition of nucleic acids.