Properties and behaviour of tetracyclic allopsoralen derivatives inside a DPPC lipid bilayer model

Allopsoralens are angular psoralen derivatives presenting advantages over the parent compound because of monofunctional DNA-photobinding and consequent lower toxicity. Allopsoralen molecules with three different substituents and different protonation states were studied using the molecular dynamics technique. The location of these molecules when inside the lipid bilayer is of major importance because their photochemical properties can change with the environment. Also, the ability of psoralens to form photoadducts with unsaturated phospholipids depends on the preference of the molecules to locate themselves closer to the bilayer middle were the double bond functionality can be found. Herein we show that the allopsoralens tend to accumulate inside the lipid bilayer closer to the water interface when protonated or closer to the interface middle otherwise. Allopsoralens containing one amine terminated carbon chain tend to have different rotational and orientational behaviour and an orientation preference close to the ones shown by the lipids. The size and chemical nature of the substituent also affect the molecular mobility and capacity to interact with water molecules and the nitrogen or phosphorus atoms of the lipids.

Daniel J. V. A. dos Santos*a, Patricia Saenz-Méndez b, Leif A. Eriksson c, Rita C. Guedes a

a iMed.UL, Faculty of Pharmacy, University of Lisbon, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal. E-mail: dsantos@ff.ul.pt; Fax: +351 217946470; Tel: +351 217946477

b Physical Organic Chemistry and Bioprocesses Group, Department of Organic Chemistry, Facultad de Quı´mica, UdelaR, CC1157, Avda. Gral Flores 2124, Montevideo 11800, Uruguay

c School of Chemistry, National University of Ireland, University Road, Galway, Ireland

http://dx.doi.org/10.1039/C0CP02245D

 

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