Hypericin, an intriguing internally heterogenous molecule, forms a covalent intramolecular hydrogen bond

Our ab initio computations suggest that the anomalous solvent effects and ground state heterogeneity of hypericin, a potent antiviral and antitumor agent, could be due to a low-barrier hydrogen bond in the bay region of the deprotonated hypericin. Solvent-caused asymmetry presumably locks the deprotonated hypericin in a conformation where at least one of the peri hydrogen bonds becomes delocalized. A delocalized hydrogen bond, hopping between the five strong intramolecular hydrogen bonds of the deprotonated hypericin, provides a consistent explanation for both the observed ground state heterogeneity and the unusual solvent insensitivity of the excited state proton transfer.