CAROTENOHEMATOPORPHYRINS AS TUMOR-IMAGING DYES - SYNTHESIS AND IN-VITRO PHOTOPHYSICAL CHARACTERIZATION

Multichromophoric dyes for use in tumor imaging have been synthesized and photophysically characterized. Structurally, these dyes are dyads and triads that consist of one or two carotenoid polyenes covalently a ttached to hematoporphyrin (HP) or hematoporphyrin dimethyl ester (HPD ME) moieties via ester linkages. The groundstate absorption of each co mpound shows that the electronic interaction between the chromophores is small. The fluorescence quantum yield for the dyad monocaroteno-HPD ME is 0.033 and the dicaroteno-HPDME triads have yields between 0.016 and 0.007, all of which are reduced with respect to the parent compoun d HPDME (0.09), Global analysis of the transient fluorescence decays o f the dyads and triads requires two exponential components (similar to 5-6 ns and similar to 1-2 ns) to fit the data, while a single exponen tial component with a lifetime of 9.3 ns describes the decay data of t he parent HPDME, Possible mechanisms for the observed porphyrin fluore scence quenching by the nearby carotenoid are discussed. Nanosecond tr ansient absorption reveals a carotene triplet with maximum absorption at 560 nm and a 5.0 us lifetime. No transient was detected at 450 nm, indicating rapid (less than or equal to 10 ns) triplet energy transfer from the hematoporphyrin to the carotenoid moieties in fluid as well as in rigid media. The yield of triplet energy transfer from the porph yrin to the carotenoid moiety is unity. Singlet oxygen, O-2((1)Delta(g )), studies support the transient absorption data, as none of these co mpounds is capable of sensitizing O-2((1)Delta(g)). Liposome vesicles were used to study the photophysical characteristics of the dyes in ph ospholipid membranes. Singlet oxygen was not sensitized by the dyads a nd triads in liposomes, Transient absorption measurements suggest that the triads are substantially aggregated within the phospholipid bilay er, whereas aggregation in the dyads is less severe.