H-bond cooperativity: polarisation effects on secondary amides

Area of Science:

• Supramolecular Chemistry
• Organic Chemistry

Background:

• Hydrogen bonds are crucial non-covalent interactions in chemistry and biology.
• Amide groups are fundamental building blocks in peptides and synthetic materials.
• Polarization effects can significantly influence the strength and cooperativity of hydrogen bonds.

Purpose of the Study:

• To quantify the impact of intramolecular hydrogen bonding on the strength of subsequent intermolecular hydrogen bonds formed by amide NH groups.
• To investigate the role of polarization in modulating hydrogen bond donor properties.
• To provide a quantitative basis for understanding cooperativity in complex non-covalent interaction networks.

Main Methods:

• Synthesis of 2-hydroxylbenzamide derivatives with varying substituents.
• Measurement of association constants for 1:1 complex formation with tri-n-butyl phosphine oxide in n-octane solution.
• Comparison of association constants between compounds with and without the 2-hydroxy group to isolate the intramolecular H-bond effect.

Main Results:

• The presence of an intramolecular hydrogen bond in 2-hydroxybenzamides increases intermolecular hydrogen bond strength by over an order of magnitude.
• The enhancement in the amide NH hydrogen bond donor parameter is directly proportional to the donor parameter of the involved phenol OH group.
• Polarization of the amide bond by the intramolecular hydrogen bond is the primary mechanism driving this strengthening.

Conclusions:

• Intramolecular hydrogen bonds act as potent amplifiers of intermolecular hydrogen bond strength through polarization.
• This study provides quantitative evidence for significant cooperativity in systems with networked non-covalent interactions.
• The findings are applicable to understanding complex molecular assemblies and biological systems involving hydrogen bonding networks.