Assessing the Experimental Hydrogen Bonding Energy of the Cyclic Water Dimer Transition State with a Cyclooctatetraene-Based Molecular Balance

We have conducted an experimental and computational study of cyclooctatetraene-1,4/1,6-dimethanol (1,4 and 1,6) as a molecular balance with the goal in mind to determine the otherwise inaccessible hydrogen bonding energy (HBE) of the cyclic water dimer, which constitutes a transition state. The 1,4/1,6 folding equilibrium is governed by an intramolecular hydrogen bond in the folded 1,6-isomer, in which the OH groups adopt a cyclic planar geometry, akin to the structure of the cyclic water dimer transition state. We characterized hydrogen bonding in 1,6 and reference complexes utilizing SAPT2 + (3)δMP2/aug-cc-pVTZ and selected quantum theory of atoms in molecule descriptors at M06-2XD3(0)/ma-def2-TZVPP. Additionally, we computed HBEs at the DLPNO-CCSD(T)/aug-cc-pVQZ level of theory. We find that hydrogen bonding in 1,6 is very similar to the interaction in the Ci symmetric cyclic water dimer TS, both in magnitude and character. We experimentally determined the Gibbs free energy of the folding process (ΔGeq) in a variety of organic solvents via nuclear magnetic resonance spectroscopy measurements at room temperature. By combining experimentally obtained ΔGeq values with corrections derived from accurate computational methods, we provide estimates for the HBE of cyclic water dimers and the cyclic water dimer TS, as the most stable cyclic water dimer.