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

Abstract

The facile synthesis and photophysical properties of three non-hydrolysable thioglycosylated porphyrinoids are reported. Starting from meso perfluorophenylporphyrin, the non-hydrolysable 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 nM concentrations. Photobleaching under these conditions is minimal.

Chemical Synthesis and Medicinal Applications of Glycoporphyrins

“…In a similar way, Drain and coworkers extended from previous work on the synthesis of thioglycosylated porphyrins (95 and 91) [247] to form their 1,3-dipolar cycloadducts, i.e. chlorins (542a,a'), isobacteriochlorins (545a,a') and bacteriochlorins (546a,a') via the same procedure [274] . The photophysical properties showed that the lowest energy Q band of 542a is 25 times greater than that of the corresponding porphyrin 91 while that of the isobacteriochlorin 545a is only 5 times greater than 91.…”

“…The photophysical properties showed that the lowest energy Q band of 542a is 25 times greater than that of the corresponding porphyrin 91 while that of the isobacteriochlorin 545a is only 5 times greater than 91. All these compounds were evaluated against MDA-MB-231 and K:Molv NIB 3T3 mouse fibroblast cells [274] . …”

“…Also, the β-Dglucosyl-thio derivatives (91) showed a better photodynamic effect compared to β-D-galactosyl-thio systems in MDA-MB-231 human breast cancer and 3Y1 rat fibroblasts observed by Drain et al [247] . In addition meso substituted chlorins (542a,a'), isobacteriochlorins (545a,a') and bacteriochlorins (546a,a') were evaluated against human breast cancer cells MDA-MB-231 and K:Molv NIB 3T3 mouse fibroblast cell lines [274] . Compound 542a showed a significant red shift compared to 91 however, the bacteriochlorins 546a displayed the greatest red shift near 730 nm and 50 times greater absorbance optimum for PDT.…”

mTHPC – A drug on its way from second to third generation photosensitizer?

“…A potential problem might be the susceptibility of the O-linked conjugates through hydrolysis. Here, thioester linkages have recently been used to prepare more stable derivatives [75].…”

Current Developments in Using MESO-(TETRA) Substituted Porphyrins for PDT

“…81 Compared to the porphyrin 74, 84 exhibited a 6-fold increase in Φ f , 89 a 12-fold increase, 90 had a Φ f similar to 74, however, it also possessed a considerably red-shifted absorbance to 730 nm with a nearly 50-fold greater absorbance. Previous studies with 74 indicated good uptake and photodynamic effects on several cancer cell lines, e.g., K:Molv NIH 3T3 mouse fibroblasts and the MDA-MB-231 breast cancer cell line.…”