Unveiling Repulsion in Intramolecular H-Bonded Systems.

Area of Science:

• Chemistry
• Molecular Biology
• Physical Chemistry

Background:

• Intramolecular hydrogen bonds are crucial for molecular structure and function in various chemical and biological processes.
• Classical models like Hammett analysis fail to fully explain the impact of ortho-substituents on H-bond energetics.
• Understanding these interactions is vital for rational drug design, catalysis, and supramolecular chemistry.

Purpose of the Study:

• To investigate the influence of ortho-substituents on the energetics of intramolecular hydrogen bonds.
• To challenge the conventional understanding of attractive forces in close molecular contacts.
• To provide a new framework for predicting substituent effects on H-bond strength and molecular conformation.

Main Methods:

• Utilized synthetic molecular balances to experimentally measure H-bond energetics.
• Employed computational chemistry to dissect the contributions of attractive and repulsive forces.
• Analyzed trends to correlate substituent properties with observed H-bond behavior.

Main Results:

• Ortho-substituents significantly influence intramolecular H-bond energetics by competing with external interactions.
• Repulsive HO···R interactions, rather than stabilizing OH···R bonds, are often the dominant factor.
• Experimental trends defied predictions based on classical Hammett analysis.

Conclusions:

• A novel framework is presented for understanding ortho-substituent effects on intramolecular H-bonds and molecular conformation.
• The study highlights the critical, often overlooked, role of repulsion in molecular interactions and design.
• Findings challenge intuitive assumptions about attractive forces in close molecular contacts, offering new insights for chemical design.