We are convinced that THz calorimetry will open new horizons and will have a broader impact as a cutting-edge experimental tool. We succeeded in establishing a direct connection between thermodynamic quantities – hydration entropy and enthalpy – and spectroscopic observables, i.e. well-defined fingerprints in the THz spectral range. The two spectroscopic fingerprints of the hydration bond network are the "cavity wrap" and "H-bound" hydration water populations, which are makers for hydrophobic and hydrophilic solvation at the surface of biomolecules respectively. It was remarkably and unexpected, that these two hydration water bands a) can be detected, quantified and b) are sufficient to deduce the solvation entropy, enthalpy, etc. and thus monitor these "online" in reactions.
We were able to quantify solvation entropy and enthalpy from the amplitude of the THz bands, and to dissect the hydrophilic and hydrophobic contributions by individually evaluating the amplitude of the wrap and bound THz-fingerprints. Such decomposition goes beyond the state of the art, since it cannot be achieved by standard calorimetry approaches, and represented a long-standing challenged for both theory and experiments.
Our novel THz-calorimetry methodology allowed to experimentally test fundamental theories of hydrophobic solvation, such as the well-established Lum-Chandler-Weeks theory. This was another important achievement, since a connection of this theory to experimental observables was lacking so far and our experimental methodology will help the development and validation of hydrophobic theories.
More importantly, we are now able to use THz fingerprints to map hydrophobic and hydrophilic solvation spots around biomolecules, even during biological processes, e.g. as demonstrated for biomolecular recognition processes, in the DNA ion atmosphere, and liquid-liquid phase separation. This represents a breakthrough in biology, because it paved the way toward a rational control of biological processes based on real time THz spectroscopy screening.
