Polarisation effects on the H-bond acceptor properties of secondary amides.

H-bonding interactions in networks are stabilised by cooperativity, but the relationship between the chemical structures of the interacting functional groups and the thermodynamic consequences is not well-understood. We have used compounds with an intramolecular H-bond between a pyridine H-bond acceptor and an amide NH group to quantify cooperative effects on the H-bond acceptor properties of the amide carbonyl group. H NMR experiments in -octane confirm the presence of the intramolecular H-bond and show that this interaction is intact in the 1 : 1 complex formed with perfluoro--butanol (PFTB). UV-vis absorption titrations were used to measure the relationship between the association constant for formation of this complex and the H-bond acceptor properties of the pyridine involved in the intramolecular H-bond. Electron-donating substituents on the pyridine increase the strength of the intermolecular H-bond between PFTB and the amide. There is a linear relationship between the H-bond acceptor parameter measured for the amide carbonyl group and the H-bond acceptor parameter for the pyridine. The cooperativity parameter determined from this relationship is 0.2, for an amide carbonyl group is increased by one fifth of the value of of an acceptor that interacts with the NH group. This result is reproduced by DFT calculations of H-bond parameters for the individual molecules in the gas phase, which implies that the observed cooperativity can be understood as polarisation of the electron density in the amide π-system in response to formation of a H-bond. The cooperativity parameter measured for the secondary amide H-bond donor and H-bond acceptor is identical, which implies that polarisation of an amide mediates the interaction between an external donor or acceptor in a reciprocal manner.