Solvent-induced-effects: self-association of positively charged pi systems

Eric Buisine (1) , Katherine de Villiers (2) , Timothy J. Egan (2) , Christophe Biot (3)

1 UMR CNRS 8009 - Laboratoire de Chimie Organique et Macromoleculaire
2 Department of Chemistry
3 UCCS - Unité de Catalyse et Chimie du Solide - UMR 8181

Antimalarial cationic drugs, such as chloroquine (CQ) and ferroquine (FQ), form stable dimer structures not only in the solid state but also in solution. The short distances (3.3-3.5 Å) observed between the positively charged quinolinium rings suggest that this self-association process is driven by pi/pi stacking interactions. Nevertheless, the strength of these dispersive forces is likely not sufficient to overcome the strong repulsive +/+ electrostatic effects. The question of the exact role of the environment, particularly the solvent, is clearly raised here. Characterization of these unconventional stabilizing nonbonding interactions which we have named +-pi/+-pi is therefore of great importance. In the present work, we describe theoretical calculations and NMR experiments undertaken to probe the nature and the strength of +-pi/+-pi interactions occurring upon self-association of FQ and CQ molecules in water.

Domaines: Chimie thérapeutique

Eric Buisine, Katherine de Villiers, Timothy J. Egan, Christophe Biot. Solvent-induced-effects: self-association of positively charged pi systems. Journal of the American Chemical Society, 2006, 128, pp.12122. ⟨10.1021/ja061755u⟩. ⟨hal-00098658⟩