期刊
BIOORGANIC & MEDICINAL CHEMISTRY
卷 18, 期 7, 页码 2672-2677出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2010.02.020
关键词
Phthalocyanines; Photodynamic therapy; Photosensitizers; Singlet oxygen
资金
- The Chinese University of Hong Kong
Treatment of 4,5-dichlorophthalonitrile with 2-(dimethylamino)ethanethiol hydrochloride and K2CO3 afforded 4,5-bis[2-(dimethylamino)ethylthio]phthalonitrile or a heterocycle-fused phthalonitrile depending on the reaction temperature. The latter has been spectroscopically and structurally characterized. Both compounds underwent mixed cyclization with 3 equiv of unsubstituted phthalonitrile in the presence of Zn(OAc)(2)center dot 2H(2)O and 1,8-diazabicyclo[5.4.0] undec-7-ene to give the corresponding 2,3-disubstituted zinc(II) phthalocyanines. N-methylation or pentylation of the bis[2-(dimethylamino) ethylthio] substituted analogue resulted in the formation of the respective dicationic phthalocyanines. For comparison, the octa-substituted analogues were also prepared by base and zinc-promoted self-cyclization of 4,5-bis[2-(dimethylamino) ethylthio] phthalonitrile followed by N-methylation. The spectroscopic and basic photophysical properties of these di- and octa-substituted phthalocyanines were examined in N,N-dimethylformamide. All of them remained essentially non-aggregated, showed moderate fluorescence emission, and could generate singlet oxygen, except the heterocycle-fused analogue, of which the singlet excited state was reductively quenched by the amino substituent. The photocytotoxicity of these compounds was also evaluated against HepG2 human hepatocarcinoma cells and HT29 and T84 human colon adenocarcinoma cells. The disubstituted amphiphilic phthalocyanines are particularly potent with IC50 values down to 0.08 mu M. Fluorescence microscopic studies revealed that the non-ionic derivative has selective affinity to the mitochondria of HT29 cells, while its di-N-methylated analogue shows preferential localization in the cell membrane. (C) 2010 Elsevier Ltd. All rights reserved.
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