Statistical thermodynamics of aromatic–aromatic interactions in aqueous solution

Abstract

To elucidate the interactions between aromatic rings, which are believed to play essential roles in a variety of biological processes, we analyze the water-mediated interactions between toluene molecules along face-to-face stacked (FF) and point-to-face T-shaped (TS) paths using a statistical-mechanical theory of liquids combined with a molecular model for water. The theory enables us to decompose each interaction into physically insightful components, revealing detailed hydration effects. The dimers (i.e., molecules in contact with each other) formed in the FF and TS paths, which are referred to as “FF stacking” and “TS contact”, respectively, share almost the same stability in vacuum. In water, however, the stability of the FF stacking increases whereas that of the TS contact decreases. By the energetic hydration effect, for the FF stacking, more than half of the London dispersion attractive interaction is cancelled out and the electrostatic repulsive interaction is significantly screened. Importantly, a large gain of water entropy occurs. For the TS contact, the London dispersion interaction is almost completely cancelled out and the electrostatic component of the water-mediated interaction becomes repulsive. It is accompanied by a water-entropy gain. The water-entropy effect is crucially important for the participation of aromatic side chains in the close packing of a protein as well as FF stacked arrangements of aromatic rings in the case of nucleotide base interactions. The term “π–π stacking” is inappropriate for the stacking in aqueous solution, because it sounds as if the London dispersion interaction was the only contributor to it as in vacuum.