Synthesis of hydrophilic conjugated porphyrin dimers for one-photon and two-photon photodynamic therapy at NIR wavelengths
- 9 January 2009
- journal article
- research article
- Published by Royal Society of Chemistry (RSC) in Organic & Biomolecular Chemistry
- Vol. 7 (5) , 874-888
- https://doi.org/10.1039/b814789b
Abstract
We report the synthesis of a series of hydrophilic butadiyne-linked conjugated zinc porphyrin dimers (1–7), designed as photodynamic therapy (PDT) agents. These porphyrin dimers exhibit exceptionally high two-photon absorption cross sections (δmax≈ 8,000–17,000 GM) and red-shifted linear absorption spectra (λmax≈ 700–800 nm) making them ideal candidates for one-photon and two-photon excited photodynamic therapy. Four polar triethyleneglycol substituents are positioned along the sides of each dimer, but, on their own, these TEG chains do not confer sufficient solubility in aqueous physiological media for reproducible delivery into live cells. Charged cationic (methylpyridinium and trimethylammonium) and anionic (sulfonate and carboxylate) substituents have been appended to the meso-positions of porphyrin dimers using three synthetic strategies: 1) Suzuki coupling, 2) Sonogashira coupling, and 3) nucleophilic Senge arylation. Approaches 1 and 3 both allow attachment of aromatic substituents directly to the meso-positions of porphyrins. Approach 2 provides a route to hydrophilic porphyrin dimers with an ethyne link between the porphyrin and the polar aromatic substituent. The palladium-catalysed approaches 1 and 2 allow the synthesis of a broader range of meso-capped porphyrins, as many aryl halides are available. However the synthesis of the intermediate required for these routes necessitates a statistical reaction step, which decreases the overall yield. On the other hand, Senge-arylation provides highly regioselective nucleophilic aromatic substitution, and offers higher overall yield than the other routes. All these charged dimers exhibit good solubility in polar solvents (e.g. methanol) and aqueous solvent mixtures (aqueous DMSO or DMF).Keywords
This publication has 76 references indexed in Scilit:
- Determination of the triplet state energies of a series of conjugated porphyrin oligomersPublished by Springer Nature ,2007
- Two-Photon Absorption in Tetraphenylporphycenes: Are Porphycenes Better Candidates than Porphyrins for Providing Optimal Optical Properties for Two-Photon Photodynamic Therapy?Journal of the American Chemical Society, 2007
- Synthesis and cellular studies of PEG-functionalized meso-tetraphenylporphyrinsJournal of Photochemistry and Photobiology B: Biology, 2006
- Bioconjugatable Porphyrins Bearing a Compact Swallowtail Motif for Water SolubilityBioconjugate Chemistry, 2006
- 5,10,15,20-Tetrakis(N-Methyl-4-Pyridyl)-21H,23H-Porphine (TMPyP) as a Sensitizer for Singlet Oxygen Imaging in Cells: Characterizing the Irradiation-dependent Behavior of TMPyP in a Single Cell†Photochemistry and Photobiology, 2006
- Lifetime and Diffusion of Singlet Oxygen in a CellThe Journal of Physical Chemistry B, 2005
- Application of an ex ovo chicken chorioallantoic membrane model for two-photon excitation photodynamic therapy of age-related macular degenerationJournal of Biomedical Optics, 2003
- Water-Soluble 99mTc-Labeled Dendritic Novel Porphyrins Tumor Imaging and DiagnosisBiochemical and Biophysical Research Communications, 2001
- Ring-sidearm cooperativity in cation inclusion complexes of 12-membered ring lariat ethers: effect of sidearm chain length and a clarification of long-sidearm binding strengthsThe Journal of Organic Chemistry, 1988
- Measurements on the depth of penetration of light (0.35?1.0 m) in tissueRadiation and Environmental Biophysics, 1977