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

• Published in: Bioconjugate chemistry Vol. 21; no. 11; pp. 2136 - 2146
• Main Authors: Singh, Sunaina, Aggarwal, Amit, Thompson, Sebastian, Tomé, João P. C, Zhu, Xianchun, Samaroo, Diana, Vinodu, Mikki, Gao, Ruomei, Drain, Charles Michael
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 17.11.2010
• Subjects: Animals; Biochemistry; Breast cancer; Cell Line, Tumor; Chemical synthesis; Comparative analysis; Fluorescence; Humans; Mice; Molecular Imaging - methods; Molecular Structure; NIH 3T3 Cells; Photochemistry; Physical properties; Porphyrins - chemical synthesis; Porphyrins - chemistry; Rodents; Stereoisomerism; Sulfhydryl Compounds - chemical synthesis; Sulfhydryl Compounds - chemistry
• ISSN: 1043-1802; 1520-4812
• DOI: 10.1021/bc100356z

The facile synthesis and photophysical properties of three nonhydrolyzable thioglycosylated porphyrinoids are reported. Starting from meso-perfluorophenylporphyrin, the nonhydrolyzable thioglycosylated porphyrin (PGlc4), chlorin (CGlc4), isobacteriochlorin (IGlc4), and bacteriochlorin (BGlc4) 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, CGlc4 has a markedly greater absorbance of red light near 650 nm and a 6-fold increase in fluorescence quantum yield, whereas IGlc4 has broad Q-bands and a 12-fold increase in fluorescence quantum yield. BGlc4 has a similar fluorescence quantum yield to PGlc4 (<10%), but the lowest-energy absorption/emission peaks of BGlc4 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 CGlc4, IGlc4, and BGlc4 derivatives into cells such as human breast cancer cells MDA-MB-231 and K:Molv NIH 3T3 mouse fibroblast cells can be observed at nanomolar concentrations. Photobleaching under these conditions is minimal.