Isomerization reactions at aqueous interfaces

A. Pohorille and M. A. Wilson, in Proceedings on the 26 Jerusalem Symposium on Quantum Chemistry and Biochemistry, Reaction Dynamics in Clusters and Condensed Phases, B. Pullman and R. Levine, eds., Kluwer, Dordrecht, 1994, pp 207-226.

Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94143

Abstract:

In this paper we discuss the transfer of small, flexible molecules across the water-hexane interface. The study is motivated by biological and pharmacological importance of this process in water-membrane systems. We focus on three main issues: (a) what are free energy profiles for transferring molecules across the interface, (b) how conformational equilibria at the interface differ from those in the bulk phases, and (c) how the rates of isomerization compare to the rates of transfer across the interface. We investigate these problems by molecular dynamics simulations of two systems - 1,2-dichloroethane and alanine dipeptide. For both molecules, free energy minima at the interface were found. As a consequence, the molecules encounter an apparent ``interfacial resistance'', in violation of the solubility-diffusion model. For 1,2-dichloroethane the relaxation time of the isomerization reaction was calculated from the transition state theory and corrected for dynamic effects which included a contribution from quasi-periodic trajectories. This time was found to be much shorter than the lifetime of the solute at the interface, indicating that the conformational equilibrium in this region is readily reached during the transfer. For alanine dipeptide it was found that conformations present in water and in hexane are all populated at the interface, but energy barriers between them are markedly reduced. The description of the transfer across the interface by a simple diffusion model was tested. The model gives satisfactory results for 1,2-dichloroethane but is less accurate for alanine dipeptide.