Solvent Isotope Effect on the Thermodynamics of Complexation with Cyclodextrins and Cucurbiturils: An ITC Study in H2O and D2O.

Determination of supramolecular host-guest complex stability constants often relies on 1H NMR spectroscopy, particularly when it comes to reactants lacking chromophores. This is usually the case for hydrophobically driven complexation, where hosts such as cyclodextrins and cucurbiturils interact with small, scarcely soluble guests in aqueous media. Even sophisticated solvent suppression techniques still require a small percentage of deuterated water, so the reactions are usually affected by the solvent isotope effect, either kinetically or thermodynamically, the latter being significantly less investigated. In this work, we report a systematic calorimetric study of the influence of solvent deuteration on the thermodynamic reaction parameters (ΔrX°, where X = G, H, S, Cp) in 278-338 K temperature range for the reactions involving cyclodextrins and cucurbiturils and two hydrophobic alcohols. In accord with previous systematic investigations carried out solely at 298 K, the complex stability constants did not vary significantly when transferred from H2O to D2O. This was, in the case of cyclodextrins, a consequence of a partial enthalpy-entropy compensation, as the differences between ΔrH° and -TΔrS° in two media were similar in magnitude but opposite in sign (up to 5 kJ mol-1, excluding one outlier). Thus, our finding indicates that differences in the hydration of the hosts and guests in regular and heavy water partially compensate for each other.