Geometry and cooperativity effects in adenosine-carboxylic acid complexes

Area of Science:

• Biophysical Chemistry
• Molecular Biophysics
• Chemical Physics

Background:

• Hydrogen bonding in nucleoside-carboxylic acid complexes is crucial for molecular recognition.
• Understanding these interactions informs drug design and nucleic acid structure studies.

Purpose of the Study:

• To investigate hydrogen bonding between adenine nucleosides and carboxylic acids using NMR.
• To elucidate the structural and electronic properties of these complexes in solution.
• To explore the impact of different carboxylic acids and binding sites on complex stability.

Main Methods:

• Nuclear Magnetic Resonance (NMR) spectroscopy with 1- and 7-15N-labeled adenine nucleosides.
• Cryogenic conditions (down to 123 K) in freon solvents (CDClF2, CDF3) to achieve slow hydrogen bond exchange.
• Quantum chemical calculations for geometries and chemical shifts.

Main Results:

• Chloroacetic acid forms distinct ion-pairing Watson-Crick complexes with displaced protons.
• Calculated and experimental proton chemical shifts agree well when considering vibrational averaging and solvent effects.
• Binding a second ligand at the Hoogsteen site weakens the Watson-Crick hydrogen bond.
• Replacing a carboxylic acid with adenine in trimolecular complexes leads to cooperative binding at both Watson-Crick and Hoogsteen faces.

Conclusions:

• The study provides detailed insights into the structural dynamics of hydrogen-bonded nucleoside-acid complexes.
• Solvent and ligand identity significantly modulate hydrogen bond strength and complex formation.
• Cooperative binding mechanisms are identified, relevant for understanding supramolecular assembly in biological systems.