Photophysics and mechanism of photoinduced antiviral action of the natural products, hypericin and hypocrellin A

Fehr, Michael
Major Professor
Jacob W. Petrich
Committee Member
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Hypericin, a naturally occurring polycyclic quinone in the flower, St. John's Wort, has been shown to inactivate retroviruses such as Equine Infectious Anemia Virus (EIAV) and Human Immunodeficiency Virus (HIV). This inactivation has been shown to depend on the absorption of a photon of light by hypericin. Hypericin is closely related to stentorin, the chromophore of stentor coerulus. Stentorin is thought to be responsible for the photophobic and phototactic response of stentor coerulus. High levels of light have been shown to be toxic to stentor coerulus, but low levels of light do not have a negative effect;We have examined the photophysics of hypericin using ultrafast pump probe techniques and have found evidence for an excited state intramolecular proton transfer which occurs in 6 to 12 ps depending on solvent. We have examined the solvent dependence of the proton transfer and found that the proton transfer times do not correlate well to macroscopic parameters with the exception of solvent polarity (E[subscript] T30);Hypericin's antiviral activity has been ascribed to the production of the toxic factor singlet oxygen. We, however, have shown that singlet oxygen is not necessary for hypericin to be an effective antiviral agent. We have proposed that other excited-state processes are responsible for hypericin's antiviral activity and have observed an excited-state deprotonation which results in an acidification of the surrounding medium. This deprotonation occurs from the triplet state of the molecule and may also occur from the singlet state; however, at this point we are unable to observe deprotonations on this time scale because of the limited time resolution of the instrument;We have also proposed methods for generating light within the human body using the luciferin/luciferase system and have shown that the light available from this system is sufficient for hypericin to confer its photosensitizing effects on EIAV;Hypocrellin A occurs naturally in parasitic fungus in the Peoples Republic of China and Sri Lanka. It is structurally similar to hypericin and has been reported to undergo similar ultrafast photophysical processes. It also has been shown to inactivate HIV;We have investigated the oxygen dependence of hypocrellin A's antiviral activity and find it to be strikingly different from hypericin in that it requires oxygen to inactivate retroviruses. We also observe no excited-state deprotonation of hypocrellin A and are currently investigating other excited-state processes that are important in hypocrellin A.