The photodynamic drug, hypericin, is studied in fetal rat neurons using flu
orescence microscopy. Hypericin has an extremely high affinity for the cell
membrane and is found to a smaller extent in the nucleus. Fluorescent exci
tation of hypericin is shown to cause irreversible damage to the cell membr
anes of living neurons. Fixed cells were used to make ultrafast time-resolv
ed measurements to avoid the deleterious effects of long-term exposure to i
ntense light and room temperatures. To our knowledge, these are the first u
ltrafast time-resolved measurements of the fluorescence lifetime of hyperic
in in a subcellular environment. Nonexponential fluorescence decay is obser
ved in hypericin in the neurons. This nonexponential decay is discussed in
terms of other examples where nonexponential decay is induced in hypericin
upon its binding to biomolecules. The nonradiative processes giving rise to
the nonexponential hypericin decay are attributed to excited-state electro
n transfer, excited-state proton transfer or both.