Robert Bell Hermann

Theory of Hydrophobic Bonding

A method described in a previous paper has been applied here to the calculation of hydrophobic interactions between hydrocarbon pairs and aggregates. Generally a small barrier is found at a distance of less than a water molecule diameter. At minimal contact between hydrocarbon pairs, there is little or no binding energy. Two hydrocarbon chains may be arranged side by side in such a fashion so that binding is substantial, having a maximum upper limit of — 800 cal per ethylene unit pairs. As molecules aggregate binding increases. A model receptor may be constructed by arranging several hydrocarbon chains to form a cleft. The hydrophobic binding between such a cleft and a molecule of ethane is found to be about —2.5 kcal.

Calculation of hydrophobic interactions from molecular dynamics, surface areas, and experimental hydrocarbon solubilities

Using experimental solubilities and partial pressures for hydrocarbon solution in water and molecular dynamics calculations of hydrocarbon water interaction energies, hydrocarbon–water cavity potentials are obtained and then plotted vs. accessible surface area. The data used is mainly for aliphatic hydrocarbons, but benzene is included. Molecular dynamics calculations of pairs of hydrocarbon molecules together with the cavity potential curve are then used to obtain hydrophobic interaction free energies between the hydrocarbon pairs. While the cavity potential change is related to a change in surface area for hydrocarbon systems, the hydrocarbon–water interaction energy is not, so that the hydrophobic binding energy is not. The results are in agreement with previous results by a different method (R.B. Hermann, In Seventh Jerusalem Symposium on Quantum Pharmacology, E. Bergman and B. Pullman, Eds., D. Reidel, Dordrecht, 1974, p. 441) in that there is little or no solvent‐induced binding free energy between small hydrocarbon molecules in a dilute aqueous solution. It is proposed that the cavity potential vs. accessible surface area curve obtained here can be used together with OPLS parameters to calculate both hydrocarbon–water solvation free energies and hydrophobic interactions.