Spectroscopic Fingerprints of Cavity Formation and Solute Insertion as a Measure of Hydration Entropic Loss and Enthalpic Gain

Abstract

Hydration free energies are dictated by a subtle balance of hydrophobic and hydrophilic interactions. We present here a spectroscopic approach, which gives direct access to the two main contributions: Using THz‐spectroscopy to probe the frequency range of the intermolecular stretch (150–200 cm−1) and the hindered rotations (450–600 cm−1), the local contributions due to cavity formation and hydrophilic interactions can be traced back. We show that via THz calorimetry these fingerprints can be correlated 1 : 1 with the group specific solvation entropy and enthalpy. This allows to deduce separately the hydrophobic (i.e. cavity formation) and hydrophilic contributions to thermodynamics, as shown for hydrated alcohols as a case study. Accompanying molecular dynamics simulations quantitatively support our experimental results. In the future our approach will allow to dissect hydration contributions in inhomogeneous mixtures and under non‐equilibrium conditions.

Local Water Structures Govern the Mixing Thermodynamics of Glycerol-Water Solutions

“…29 In the ~350-600 cm -1 region (i.e., the onset of the water libration band), 𝜀 ℎ𝑦𝑑𝑟𝑎𝑡𝑖𝑜𝑛 increases remarkably with frequency and the steepness of such increase shows a clear and nonmonotonic dependence with Xgly. An 𝜀 ℎ𝑦𝑑𝑟𝑎𝑡𝑖𝑜𝑛 increase at the onset of the libration band is typically observed for bound water molecules interacting with polar solutes, and the steepness of such increase was reported in a previous study 29 to inform on the number of bound water molecules, i.e., the number of water-solute HB in the system. Therefore, such feature is assigned to the formation of HBs between glycerol and bound water molecules.…”

“…Terahertz (THz) absorption spectroscopy has the potential to address this challenge, since it directly probes the collective motions of water and that of the solvation shells, which allow characterizing the complexity of the water-glycerol network in combination with MD simulations. 17, [27][28][29][30] In a recent study of hydrated alcohols, we identified spectroscopic fingerprints in the THz/FIR spectral range that directly probe the distinct structural motifs of HB-network around alcohol solutes. 27 This study showed that water populations close to the hydrophilic and hydrophobic moieties of the alcohol provide two distinct THz/FIR fingerprints that are well distinguished from that of bulk water.…”

“…32 On the other hand, "bound" water molecules H-bonded to the hydrophilic (OH) moieties have their imprint in the 350-600 cm -1 (10-18 THz) frequency range of water's librational mode, originating from steric constraints in water rotational motions induced by the proximity to and direct H-bonding with the solutes, which causes a blue shift. 29 This population informs about the strength and number of attractive interactions that stabilize the solvation of a solute in water. 29 Using THz-calorimetry to relate spectroscopic signatures to thermodynamic quantities, combined with MD simulations to independently quantify the structural aspects of the distinct local contributions of the two identified populations to solvation entropy and enthalpy, we showed that the wrap population carries an entropic cost for (small) alcohol hydration, compensated by an enthalpic gain from the bound water population.…”

“…29 This population informs about the strength and number of attractive interactions that stabilize the solvation of a solute in water. 29 Using THz-calorimetry to relate spectroscopic signatures to thermodynamic quantities, combined with MD simulations to independently quantify the structural aspects of the distinct local contributions of the two identified populations to solvation entropy and enthalpy, we showed that the wrap population carries an entropic cost for (small) alcohol hydration, compensated by an enthalpic gain from the bound water population. 27,33 This concept of spectroscopically distinct hydrophilic and hydrophobic hydration populations is more general and can also be applied to water hydrating other solutes and biomolecules.…”

“…Based on these results, in the following we use the slope to quantify the variations in the number of bound water molecules (𝑁 𝑏𝑜𝑢𝑛𝑑 ) in the glycerol-water mixtures directly from the measured 𝜀 ℎ𝑦𝑑𝑟𝑎𝑡𝑖𝑜𝑛 spectra. 29,36 To this end, we linearly fit the 𝜀 ℎ𝑦𝑑𝑟𝑎𝑡𝑖𝑜𝑛 spectra in the frequency range from 340 cm -1 to 475 cm -1 (blue shaded region in figure 3a), where 340 cm -1 is the turning point at which To further characterize these structural transformations, we performed classical MD simulations and evaluated the relative mole fractions of wrap and bound water populations, as well as of bulk-like water not involved in the hydration of glycerol solutes (denoted hereafter non-shell water) as a function of Xgly. We identify these three populations in the simulations based on structural criteria, i.e., on their proximity with respect to OH and hydrophobic glycerol moieties and their H-bonding properties (see method section and references 27,29 for details).…”