Computer Modeling

The promising photosensitizing properties of hypericin, a substituted phenanthroperylene quinone naturally found in Saint John’s wort, has led to the proposal that it can be utilized in photodynamic therapy. Structurally modified derivatives are at the present time being investigated to generate a more effective hypericin photosensitizer. Neither the detailed mechanism behind the powerful action of hypericin, arising as a result of light excitation, nor the intracellular localization and transportation is still fully understood. In the present work, molecular dynamics simulations have been performed to study the properties and the permeability of hypericin and modifications thereof, substituted with one or four bromine atoms, in a dipalmitoylphosphatidylcholine lipid membrane. The molecules were found to accumulate in the most dense region of the lipids due to competing interactions with the hydrophobic lipid interior and the polar aqueous environment. This was confirmed by analyzing the radial distribution functions and by the density profiles of the system components. Calculated free energy profiles display large negative changes in free energy for the transport process of the molecules into the lipids, which also support this finding. Permeability coefficients show overall fastest diffusion in the membrane system for hypericin containing one bromine.

Emma S. E. Eriksson^†‡∥, Daniel J. V. A. dos Santos^§, Rita C. Guedes^§ and Leif A. Eriksson*^†∥

† Örebro Life Science Center, School of Science and Technology, Örebro University.

‡ Modelling and Simulation Research Center; Örebro University.

∥ School of Chemistry, National University of Ireland.

§ iMED.UL, CECF, Department of Pharmacy, University of Lisbon.