Solvent Dependence on the Intramolecular Excited-State Proton or Hydrogen Atom Transfer in Hypocrellin

Hypocrellin and its analog, hypericin (Figure 1), are naturally occurring quinones that have been used for centuries as folk medicines in the orient and the occident and that have attracted much interest because of their light-induced toxicity toward the human immunodeficiency virus (HIV).1The structural similarities of hypocrellin and hypericin would seem to suggest that hypocrellin exhibits excited-state and antiviral behavior similar to that of hypericin. Although they both execute excited-state proton or atom transfer2,3between the keto and enol oxygens (Figure 1), there are many important differences between them. Hypocrellin absolutely requires oxygen for antiviral activity whereas hypericin does not.3 Hypocrellin does not provide a lightinduced pH drop of its surroundings under conditions in which hypericin does.4 Here we discuss two other important differences. First, whereas in hypericin the excited-state photophysics depend only negligibly on solvent,2b in hypocrellin there is a very pronounced dependence on the solvent, which is related to bulk viscosity and to polarity in primary alcohols and, perhaps, nitriles. Second, the excited-state transfer process in hypocrellin occurs on a time scale at least 10 times longer than the analogous event in hypericin.2 The elucidation of these primary photophysical processes provides a basis for understanding the different modes of activity of hypocrellin and hypericin and will be significant in the exploitation of their properties against viruses and tumors and in the design of other analogous systems.