Photosensitization by Diporphyrins Joined via Methylene Bridges

Photodynamic and biophysical properties of three porphyrin dimers joined by methylene bridges were examined. Fluorescence emission spectra and fluorescence lifetimes of the methylene‐linked dimers were similar to values obtained with porphyrin monomers. Singlet oxygen quantum yields were not significantly different when the three diporphyrins were compared. The diporphyrins were short‐acting tumor photosensitizers in vivo, and were rapidly cleared from plasma. Of the 3 diporphyrins examined, one was essentially ineffective as a sensitizer in vivo. This could not have been predicted from in vitro studies which indicated photodamage to membrane and mitochondrial loci. The methyiene‐linked diporphyrins were hydrophilic dyes (water/octanol distribution ratio =120–200) and bound mainly to plasma high‐density lipoprotein. In contrast, the more hydrophobic diporphyrin ester/ether fraction from HPD was a long‐persisting photosensitizer in vivo. Compared with hematoporphyrin, this hematoporphyrin derivative (HPD) fraction demonstrated a red‐shift in fluorescence emission and a shortened fluorescence lifetime. These comparisons suggest that ring‐ring interactions occur in the ester/ether‐linked diporphyrins from HPD, but not in the methyiene‐linked diporphyrins.