Substituent\nEffects on Cooperativity in Three-Component\nH‑Bond Networks Involving Phenol–Phenol Interactions

Cooperativity between\nH-bonding interactions in networks is a fundamental\naspect of solvation and self-assembly in molecular systems. The interaction\nof a series of bisphenols, which make an intramolecular H-bond between\nthe two hydroxyl groups, and quinuclidine was used to quantify cooperativity\nin three-component networks. The presence of the intramolecular H-bond\nin the bisphenols was established by using <sup>1</sup>H NMR spectroscopy\nin solution and X-ray crystallography in the solid state. The interactions\nwith quinuclidine were investigated using UV–vis and <sup>1</sup>H NMR titrations, which show that the intramolecular hydrogen bonds\npersist in the 1:1 complexes. By varying substituents on one of the\nphenol groups, it was possible to measure the effect of changing the\nstrength of the intramolecular H-bond between the hydroxyl groups\non the strength of the intermolecular H-bond with quinuclidine. Strong\npositive cooperativity was observed between the two interactions,\nwith increases in binding free energy of up to 16 kJ mol<sup>–1</sup>. By varying substituents on the other phenol group, which makes\nboth an intramolecular H-bond and an intermolecular H-bond in the\ncomplex, it was possible to measure how the properties of this central\nhydroxyl group modulate cooperativity between the interactions with\nthe other two functional groups. Changing the polarity of this phenol\nhad no effect on the measured cooperativity. The results indicate\nthat cooperativity in H-bond networks can be understood as a polar\ninteraction between two remote functional groups that is damped by\na central functional group. The extent of damping is quantified by\ncooperativity parameter κ, which is 0.33 for the hydroxyl group\nand appears to be an intrinsic property of the geometry or polarizability\nof the functional group rather than polarity.