H-bond cooperativity: polarisation effects on secondary amides

Formation of a H-bond with an amide carbonyl oxygen atom increases the strength of subsequent H-bonds formed by the amide NH, due to polarisation of the bond. The magnitude of this effect has been quantified by measuring association constants for the formation of 1 : 1 complexes of 2-hydroxylbenzamides with tri-n-butyl phosphine oxide. In 2-hydroxybenzamides, there is an intramolecular H-bond between the phenol OH group and the carbonyl oxygen atom. Comparison of the association constants measured for compounds with and without the 2-hydroxy group allows direct quantification of the effect of the intramolecular H-bond on the H-bond donor properties of the amide NH group. Substituents were used to modulate the strength of the intramolecular and intermolecular H-bonds. The presence of an intramolecular H-bond increases the strength of the intermolecular H-bond by more than one order of magnitude in n-octane solution. The increase in the H-bond donor parameter used to describe the amide NH group is directly proportional to the H-bond donor parameter of the phenol OH group that makes the intramolecular H-bond. These polarisation effects will lead to substantial cooperativity in complex systems that feature networks of non-covalent interactions, and the measurements described here provide a quantitative basis for understanding such phenomena.

Automated summary

The formation of a hydrogen bond with an amide carbonyl oxygen atom was found to increase the strength of subsequent hydrogen bonds formed by the amide NH group. This effect was quantified by measuring association constants for the formation of complexes between 2-hydroxybenzamides and tri-n-butyl phosphine oxide. The presence of an intramolecular hydrogen bond was found to significantly enhance the strength of intermolecular hydrogen bonds, with the enhancement effect being directly proportional to the hydrogen bond donor properties of the phenol OH group. These findings provide quantitative insights into the cooperative interactions in complex systems featuring networks of non-covalent interactions.