Liposome Destabilization by a 2,7-Diazapyrenium Derivative Through Formation of Transient Pores in the Lipid Bilayer

Romina Zappacosta 1, Monica Semeraro 2, Massimo Baroncini 2, Serena Silvi 2, Massimiliano Aschi 3, Alberto Credi 2 *, Antonella Fontana 1 *

1Dipartimento di Scienze del Farmaco Università G. d'Annunzio Via dei Vestini, 66013 Chieti (Italy) 2Dipartimento di Chimica G. Ciamician Università degli Studi di Bologna Via Selmi 2, 40126 Bologna (Italy) 3Dipartimento di Chimica Ingegneria Chimica e Materiali Università degli Studi de L'Aquila Via Vetoio (Coppito II), 67010 Coppito, L'Aquila (Italy)

email: Alberto Credi (alberto.credi@unibo.it) Antonella Fontana (fontana@unich.it)

^*Correspondence to Alberto Credi, Dipartimento di Chimica G. Ciamician Università degli Studi di Bologna Via Selmi 2, 40126 Bologna (Italy).

^*Correspondence to Antonella Fontana, Dipartimento di Scienze del Farmaco Università G. d'Annunzio Via dei Vestini, 66013 Chieti (Italy).

FULL TEXT

The effect of the luminescent heteroaromatic electron acceptor N,N-dimethyl-2,7-diazapyrenium dichloride (DM-DAP2+) on the stability of 1-palmitoyl-2-oleoylphosphatydilcholine (POPC) liposomes is determined on the basis of the rate of release of different fluorescent probes entrapped within the liposome. The experiments show that DM-DAP2+ exerts a substantial destabilizing action on the liposomal bilayer, particularly at low concentrations. Molecular dynamics simulations suggest that the activity of DM-DAP2+ is related to its tendency to surround itself with water molecules, conceivably favoring the formation of transient pores across the bilayer.

Received: 11 December 2009