Synthesis and Photophysical Properties of Thioglycosylated Chlorins, Isobacteriochlorins, and Bacteriochlorins for Bioimaging and Diagnostics

The facile synthesis and photophysical properties of three nonhydrolyzable thioglycosylated porphyrinoids are reported. Starting from meso-perfluorophenylporphyrin, the nonhydrolyzable thioglycosylated porphyrin (PGlc(4)), chlorin (CGlc(4)), isobacteriochlorin (IGlc(4)), and bacteriochlorin (BGlc(4)) can be made in 2-3 steps. The ability to append a wide range of targeting agents onto the perfluorophenyl moieties, the chemical stability, and the ability to fine-tune the photophysical properties of the chromophores make this a suitable platform for development of biochemical tags, diagnostics, or as photodynamic therapeutic agents. Compared to the porphyrin in phosphate buffered saline, CGlc(4) has a markedly greater absorbance of red light near 650 nm and a 6-fold increase in fluorescence quantum yield, whereas IGlc(4) has broad Q-bands and a 12-fold increase in fluorescence quantum yield. BGlc(4) has a similar fluorescence quantum yield to PGlc(4) (<10%), but the lowest-energy absorption/emission peaks of BGlc(4) are considerably red-shifted to near 730 nm with a nearly 50-fold greater absorbance, which may allow this conjugate to be an effective PDT agent. The uptake of CGlc(4), IGlc(4), and BGlc(4) derivatives into cells such as human breast cancer cells MDA-MB-231 and K:Molv NTH 3T3 mouse fibroblast cells can be observed at nanomolar concentrations. Photobleaching under these conditions is minimal.