Synthesis and photophysical properties of thioglycosylated chlorins, isobacteriochlorins, and bacteriochlorins for bioimaging and diagnostics

Bioconjug Chem. 2010 Nov 17;21(11):2136-46. doi: 10.1021/bc100356z. Epub 2010 Oct 21.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Fluorescence
  • Humans
  • Mice
  • Molecular Imaging / methods*
  • Molecular Structure
  • NIH 3T3 Cells
  • Photochemistry
  • Porphyrins / chemical synthesis
  • Porphyrins / chemistry*
  • Stereoisomerism
  • Sulfhydryl Compounds / chemical synthesis
  • Sulfhydryl Compounds / chemistry*

Substances

  • Porphyrins
  • Sulfhydryl Compounds
  • bacteriochlorin
  • isobacteriochlorin
  • chlorin