| 1. |
- Eriksson, Emma S. E., et al.
(författare)
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Properties and Permeability of Hypericin and Brominated Hypericin in Lipid Membranes
- 2009
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Ingår i: Journal of Chemical Theory and Computation. - : American Chemical Society (ACS). - 1549-9618 .- 1549-9626. ; 5:12, s. 3139-3149
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 2. |
- Eriksson, Emma S. E., et al.
(författare)
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Redox and debromination reactions of brominated hypericin
- 2008
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Ingår i: International Journal of Quantum Chemistry. - New York : Wiley. - 0020-7608 .- 1097-461X. ; 108:11, s. 1921-1929
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Tidskriftsartikel (refereegranskat)abstract
- Phototoxic and radical-generating debromination reactions of monobrominated hypericin with bromine at one of four possible positions were investigated using density functional theory. The study was performed on two closely lying conformational isomers, differing in the relative orientations of the two anthracene units of the hypericin core. Calculated adiabatic electron affinities show that the molecules have the ability to, in aqueous solution, extract an electron from the surrounding. The electron might then be passed on to molecular oxygen, forming reactive superoxide radical anions. If electron extraction from the molecule does not occur in this step, the molecule might dissociate, generating a negatively charged bromine as a leaving group and a hypericin radical capable of forming direct binding to biological molecules. This reaction was found possible for those species substituted by Br at two of the four positions, with barriers of 13 kcal/mol in aqueous solution. Debromination was not found energetically possible for neither the neutral ground state compounds nor the bay-deprotonated species.
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