Lone-pair-π interactions: analysis of the physical origin and biological implications

Area of Science:

• Biophysical Chemistry
• Computational Chemistry
• Molecular Interactions

Background:

• Lone-pair-π (lp-π) interactions are proposed to stabilize DNA and protein structures.
• Understanding the physical origin of lp-π interactions is crucial for DNA-protein complex formation.
• Previous studies suggested strong charge-transfer (CT) components in some lp-π systems.

Purpose of the Study:

• To theoretically analyze the physical origin of lp-π interactions in biologically relevant systems.
• To compare lp-π interactions in water-indole and water-uracil complexes with a reference system.
• To investigate the contributions of different energy components to these interactions.

Main Methods:

• Theoretical multi-approach analysis.
• Comparison of water-indole and water-uracil complexes with the chloride-tetracyanobenzene (TCB) complex.
• Evaluation of electrostatic, polarization, dispersion, and charge-transfer energy components.

Main Results:

• The charge-transfer (CT) component in lp-π interactions between water and indole/uracil is significantly smaller than in the Cl(-)-TCB system.
• Water-indole and water-uracil interactions are weak forces with smaller contributions from all energy components.
• Indole's π-face has a negative electrostatic potential, favoring O-Hπ hydrogen bonding over lp-π interactions.

Conclusions:

• Lone-pair-π interactions involving water and indole or uracil are weak forces.
• The charge-transfer component is less significant than in systems like Cl(-)-TCB.
• Observed water-tryptophan contacts in proteins may result from O-Hπ hydrogen bonding rather than lp-π interactions.