ON THE ORIGINS OF THE HYDROPHOBIC EFFECT - OBSERVATIONS FROM SIMULATIONS OF N-DODECANE IN MODEL SOLVENTS

The importance of the small size of a water molecule as contributing t o the hydrophobic effect is examined from simulations of n-dodecane in different solvents. The earlier observations of the origin of hydroph obicity, derived from cavity formations by Pratt and Pohorille (1992, Proc. Natl. Acad. Sci. USA. 89:2995-2999) and Madan and Lee (1994, Bio phys. Chem. 51:279-289), are shown to be largely consistent for a hydr ocarbon-induced water pocket. In effect, the small size of a water mol ecule limits the probability (and hence free energy) of finding an app ropriate void in the fluid that will accommodate a solute. In this wor k a simulated collapse of an n-dodecane molecule in H2O, CCl4, and a w ater-like Lennard-Jones solvent indicates that the induced entropy and enthalpy changes are qualitatively similar for hydrogen-bonded and Le nnard-Jones water solvents. These results suggest that a large part of the hydrophobic response of solutes in aqueous solutions is due to th e small size of the solvent. Important quantitative differences betwee n the studied water solvents indicate that the hydrogen-bonded propert ies for water are still needed to determine the overall hydrophobic re sponse.