Local thermodynamics of alcohols from THz-calorimetry: Spectroscopic fingerprints of entropic loss and enthalpic gain

Hydration free energies are dictated by a subtle balance of hydrophobic and hydrophilic interactions. which is crucial for many biological processes and technological applications, such as protein folding and molecular recognition. Whereas so far the overall entropy and enthalpy are experimentally determined based on equilibrium measurements using a calorimeter, we present here a pure spectroscopic access to these important observables, which give direct access to the underlying molecular mechanism that determines these driving forces. Using THz calorimetry the contributions due to cavity formation and hydrophilic interactions can be traced back to changes in the intermolecular hydrogen bond stretching region around 150-200 cm−1 and spectroscopic changes due to strong solute-water interactions in the frequency range of the librational modes, i.e. between 540 and 600 cm−1. Thus, we are able to link the thermodynamic model of the Lum-Chandler-Weeks theory, which was a pure ”Gedankenexperiment”, directly to experimental observables. We show that alcohol hydration can be described by a sum of a free energy cost of forming and wrapping a cavity around the solute (which is entropic for small alcohols) and an enthalpic gain due to the hydrogen bonds formed between the alcohol OH group and bound water molecules around it. In the future, our approach will allow to quantify entropic cost and enthalpic gain not only in equilibrium but also in non-equilibrium processes.