Negative cooperativity in the formation of two H-bonds with an oxygen H-bond acceptor

TL;DR

This study shows that when a phosphoryl oxygen forms two hydrogen bonds, the second bond is weaker due to repulsion between the two donors.

Contribution

The paper reveals negative cooperativity in hydrogen bonding involving a phosphoryl oxygen and two donors.

Findings

Electron-withdrawing substituents strengthen the intramolecular H-bond but weaken the intermolecular H-bond.

A linear relationship exists between H-bond acceptor and donor parameters, with a negative cooperativity parameter (κ = −0.82).

Negative cooperativity is attributed to electrostatic repulsion between the two H-bond donors.

Abstract

Cooperative effects in H-bond networks can be quantified by measuring the effect of an intramolecular H-bond on the association constant for formation of a second intermolecular H-bond with the same functional group. This approach has been used to quantify the cooperativity associated with the interaction of a phosphoryl oxygen with two H-bond donors. A series of compounds that have an intramolecular H-bond between a phosphinamide oxygen and a phenol hydroxyl group were prepared, using substituents on the phenol to vary the strength of the intramolecular H-bond. The presence of the intramolecular interaction was confirmed by NMR spectroscopy in n-octane solution, and titrations were used to measure the association constants for formation of an intermolecular H-bond with perfluoro-t-butanol in n-octane. Electron-withdrawing substituents on the phenol, which increase the strength of the intramolecular H-bond, were found to decrease the strength of the intermolecular H-bond between the phosphoryl oxygen and perfluoro-t-butanol. The results were used to determine the H-bond acceptor parameters for the phosphinamides, β, and there is a linear relationship between the values of β and the H-bond donor parameter of the phenol involved in the intramolecular H-bond, α. The slope of this relationship was used to determine the cooperativity parameter (κ = −0.82), which quantifies the negative allosteric cooperativity between the two H-bonding interactions. Polarisation models for cooperativity in H-bond networks would predict positive cooperativity for this system, due to an increase in the polarity of the phosphorus–oxygen bond. The observation of substantial negative cooperativity suggests that the effects observed are due to secondary electrostatic interactions between the two H-bond donors that make through-space repulsive interactions with one another.

When a phosphoryl oxygen interacts with two H-bond donors, the strength of the second H-bonding interaction much weaker than the first interaction, due to electrostatic repulsion between the two donors.

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