A review of NIR dyes in cancer targeting and imaging.

Metal Complexes as Photo- and Radiosensitizers

Photodynamic therapy (PDT) is an emerging treatment modality for a range of disease classes, both cancerous and noncancerous. This has brought about an active pursuit of new PDT agents that can be optimized for the unique set of photophysical characteristics that are required for a successful clinical agent. We now describe a totally new class of PDT agent, the BF2-chelated 3,5-diaryl-1H-pyrrol-2-yl-3,5-diarylpyrrol-2-ylideneamines (tetraarylazadipyrromethenes). Optimized synthetic procedures have been developed to facilitate the generation of an array of specifically substituted derivatives to demonstrate how control of key therapeutic parameters such as wavelength of maximum absorbance and singlet-oxygen generation can be achieved. Photosensitizer absorption maxima can be varied within the body's therapeutic window between 650 and 700 nm, with high extinction coefficients ranging from 75,000 to 85,000 M(-1) cm(-1). Photosensitizer singlet-oxygen generation level was modulated by the exploitation of the heavy-atom effect. An array of photosensitizers with and without bromine atom substituents gave rise to a series of compounds with varying singlet-oxygen generation profiles. X-ray structural evidence indicates that the substitution of the bromine atoms has not caused a planarity distortion of the photosensitizer. Comparative singlet-oxygen production levels of each photosensitizer versus two standards demonstrated a modulating effect on singlet-oxygen generation depending upon substituent patterns about the photosensitizer. Confocal laser scanning microscopy imaging of 18a in HeLa cervical carcinoma cells proved that the photosensitizer was exclusively localized to the cellular cytoplasm. In vitro light-induced toxicity assays in HeLa cervical carcinoma and MRC5-SV40 transformed fibroblast cancer cell lines confirmed that the heavy-atom effect is viable in a live cellular system and that it can be exploited to modulate assay efficacy. Direct comparison of the efficacy of the photosensitizers 18b and 19b, which only differ in molecular structure by the presence of two bromine atoms, illustrated an increase in efficacy of more than a 1000-fold in both cell lines. All photosensitizers have very low to nondeterminable dark toxicity in our assay system.

In vitro demonstration of the heavy-atom effect for photodynamic therapy.

Phthalocyanines: old dyes, new materials. Putting color in nanotechnology

7.1. Synthesis 306 7.2. Spectroscopic and Redox Properties 307 7.2.1. Optical Spectroscopy 307 7.2.2. Redox Properties 310 7.2.3. Other Characterization Methods 312 8. seco-Porphyrazines 312 8.1. Synthesis 312 8.2. Spectroscopic and Redox Properties 312 8.2.1. Optical Spectroscopy 312 8.2.2. Redox Properties 313 8.2.3. Other Characterization Methods 313 9. Conclusions 313 10. Abbreviations 314 11. Acknowledgments 314 12. References 314

Low Symmetry Phthalocyanines and Their Analogues

A series of benzyl-substituted phthalonitriles, substituted at the 3-, 4-, and 4,5-positions, underwent varied condensations with phthalonitrile to give a series of protected (monohydroxy- and polyhydroxyphthalocyaninato)zinc(II) derivatives which were readily cleaved to give several hydroxyphthalocyanines (ZnPc) (phthalocyanine phenol analogues). Their efficacy as sensitizers for the photodynamic therapy (PDT) of cancer was evaluated on the EMT-6 mammary tumor cell line. In vitro, the 2-hydroxy ZnPc (32) was the most active, followed by the 2,3- and 2,9-dihydroxy ZnPc (39 and 45), with the 2,9,16-trihydroxy ZnPc (33) exhibiting the least activity. In vivo, the monohydroxy derivative 32 and the 2,3-dihydroxy derivative 39 were both efficient in inducing tumor necrosis at 1 micromol kg-1, but complete tumor regression was poor, even at 2 micromol/kg. In contrast, the 2,9-dihydroxy isomer 45, at 2 micromol kg-1, induced tumor necrosis in all animals treated, with 75% complete regression. These results underline the importance of the position of the substituents on the Pc macrocycle to optimize tumor response and confirm the PDT potential of the unsymmetrical Pcs bearing functional groups on adjacent benzene rings.

Hydroxyphthalocyanines as potential photodynamic agents for cancer therapy

2,9,16,23-Tetra-p-n-butylbenzyloxy-, 2,9,16,23-tetradiphenylmethoxy-, 2,9,16,23-tetramethoxymethoxy-, and 1,8,15,22-tetra-p-n-butylbenzyloxyphthalocyanines were synthesized from the appropriate phthalonitriles. Metal-free phthalocyanines were converted to their zinc derivatives. Cleavage from the appropriate precursor with trifluoroacetic acid produced 2,9,16,23-tetrahydroxyphthalocyanine and 1,8,15,22-tetrahydroxyphthalocyanine and their zinc derivatives. NMR spectroscopy revealed that all the 2,9,16,23-tetrasubstituted phthalocyanines are the usual mixtures of the 2,9,16,23, 2,9,16,24, 2,9,17,24, and 2,10,16,24 isomers, but the two 1,8,15,22-tetrasubstituted phthalocyanines were formed as pure single isomers.

The syntheses of 2,9,16,23- and 1,8,15,22-tetrahydroxyphthalocyanines

The Syntheses of 2,9,16-23- and 1,8,15,22-Tetrahydroxyphthalocyanines. C.C. Leznoff, M. Hu, C.R. McArthur

The spectral and electrochemical properties of tetrabenzo[5,10,15]triazaporphine (TBTAP) and its magnesium derivatives having a long alkyl chain attached to the meso carbon have been studied. Both ...

Mougang Hu

Papers

Hydroxyphthalocyanines as potential photodynamic agents for cancer therapy

The syntheses of 2,9,16,23- and 1,8,15,22-tetrahydroxyphthalocyanines

The Syntheses of 2,9,16-23- and 1,8,15,22-Tetrahydroxyphthalocyanines. C.C. Leznoff, M. Hu, C.R. McArthur

Electrochemistry and spectroelectrochemistry of substituted tetrabenzotriazaporphine

The synthesis of phthalocyanines at room temperature