Enthalpy–Entropy Interplay in π-Stacking Interaction of Benzene Dimer in Water

Abstract

Aromatic groups can engage in an interesting class of noncovalent interactions termed π−π interactions, which play a pivotal role in stabilizing a variety of molecular architectures, including nucleic acids, proteins, and supramolecular assemblies. When the aromatic compounds interact with each other in an aqueous environment, their association is facilitated by the hydrophobic effect−the trend of nonpolar solutes to aggregate in a polar solution. To develop an indepth understanding of hydrophobic association, we investigate in the present work π−π interactions in water, employing as a paradigm the benzene dimer. Using DFT-CES, a mean-field QM/MM method recently developed by our group, we describe the benzene solute at a quantum-mechanical level. Full consideration of detailed solute-electron density enables an optimal description of the solute−solvent interactions, leading to an accurate prediction of hydration free energies. In π-stacking of benzene, we find an entropic stabilization associated with the shrinkage of the solvent-excluded volume, which agrees with the theory of hydrophobic effect at subnanoscales. However, at the equilibrium binding distance of the benzene dimer, we find that the entropic stabilization nearly cancels out due to the enthalpic cost required for dewetting the internal space. Such an enthalpy−entropy compensation leads the association free energy to be predominantly dictated by the solute− solute interaction enthalpy. The present work offers new insight into the mechanistic role of water and the primary thermodynamic driving force of hydrophobic association.

Molecular photoswitches in aqueous environments

“…Here, D is the water/octanol distribution coefficient that considers a sum of the concentration of all species of the compound, both dissociated and non-disassociated, in each phase, at a given pH: where c o is the concentration of a given specific species in octanol and c w is the concentration of a given species in water. Also, the propensity to form stabilizing interactions with water, such as hydrogen bonding, 39 halogen bonding, 65 electrostatic interactions, 66 polar π interaction 67 and van der Waals interactions, 68 differs between charged and non-charged compounds. Specifically, ionic compounds interact by coulombic interactions and their dissolution benefits from the high dielectric constant of water ( ε = 80 at 20 °C), 69 which reduces the coulombic forces within ionic molecules and stabilizes the ions in the aqueous solution.…”

Structure, Dynamics, and Wettability of Water at Metal Interfaces

“…Here, we investigate the water/metal interface by employing our recently developed first-principles-based multiscale simulation method (Fig. 1), which is called the density functional theory in classical explicit solvents (DFT-CES) 5–8 . Using the mean-field coupling of electrostatics between the DFT and classical molecular dynamics, DFT-CES efficiently describes both the structural and dynamical properties of liquid water and the full electronic details and surface polarization of the metal surface.…”

Progressive Hydrophobicity of Fluorobenzenes

“…Recently, it has been reported that the dimerization of benzene in water at a fixed dimer orientation is driven by the enthalpy of intersolute interaction using QM/ MM calculations. 41 The global minimum in the PMF of the It is interesting to note that the global minima corresponding to the contact pair for all the fluorobenzenes considered in the present investigation are in the region of 0.52−0.57 nm, which is associated with a small energy dispersion of 0.5 kJ mol −1 (−2.8 to −3.3 kJ mol −1 ) with an exception of the Bz2F dimer. The solvent-separated minima are shallow and gradually increase to a larger distance with the increase in the number of fluorine atoms.…”