(457b) Molecular Simulation Study of Ionic Association in Lidocaine Docusate, An Active Pharmaceutical Ingredient Ionic Liquid and Its Derivative

Shah, J. K. - Presenter, University of Notre Dame
Maginn, E. J., University of Notre Dame

Until very recently, the design of so-called first and second generations of ionic liquids focused on tailoring their physical and chemical properties for a specific application. The third generation of ionic liquids is designed to exhibit enhanced biological activity arising from their constituent ions. For example, lidocaine hydrogen chloride is an analgesic while sodium docusate is an emollient. Lidocaine ion when paired with the anion docusate produces a colorless ionic liquid lidocaine docusate that has been shown to prolong analgesic effects. However, it is not clear what the microscopic state of the ions is when dissolved in water. Such questions are vital to understanding how ion pairing might affect biological activity of such an ionic liquid.

In this talk, we elucidate the nature of ionic interactions in water by calculating the potential of mean force from molecular dynamics simulation. First, force field parameters are developed for the ions lidocaine and docusate. Adaptive biasing force methodology is then applied to determine the potential of mean force as a function of the distance between the two ions. The propensity for ionic association is then compared with that for the two derivatives: lidocaine chloride and sodium docusate. In addition, we report the association constants for these ionic liquids and discuss organization of the ions and water in terms of radial distribution functions.