Predicting electronic properties and behaviour of pharmaceutical compounds in their environment.

B. Courcot^a, D. Firley^a, A. Spasojevic-de Biré^a, J.M. Gillet^a, N.E. Ghermani^a,c and P. Becker^a.

^a Laboratoire SPMS (UMR 8580) CNRS - Ecole Centrale Paris, Grande Voie des Vignes, 92295 Châtenay-Malabry, France

^cLaboratoire PPB (UMR 8612), CNRS - Université Paris-Sud, Faculté de Pharmacie, 92296 Châtenay-Malabry, France

The Cluster Partitionning Method (CPM) aims at an approximated prediction of the 1- Particule Reduced Density Matrix for complex systems (1).

The CPM has so far been validated for simple periodic systems such ionic solids or hydrogen bonded molecular crystals.

Our purpose is to extend this approach to the case of pharmaceutical molecules in a given biological environment.

The description of a crystalline environment is of course essential for comparison with experimentally determined electron density and allows for an accurate calibration of the method.

However, the encapsulated gallenic form as well as a fair account of the biological media are going to be of primary importance.

For large pharmaceutical molecules, additional compromises are obviously to be made. We intend to report on our preliminary results in testing different strategies for positionning and simulating a given environment emphasizing the limits due to long range interactions and basis set effects.

(1) S. Ragot, JM. Gillet, P.J. Becker, Physical Review B : 65 (2002) 235115.