Preparation and in vitro photodynamic activity of amphiphilic zinc(II) phthalocyanines substituted with 2-(dimethylamino)ethylthio moieties and their N-alkylated derivatives

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal

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Author(s)

  • Wubiao Duan
  • Pui-Chi Lo
  • Lei Duan
  • Wing-Ping Fong
  • Dennis K.P. Ng

Detail(s)

Original languageEnglish
Pages (from-to)2672-2677
Journal / PublicationBioorganic and Medicinal Chemistry
Volume18
Issue number7
Publication statusPublished - 1 Apr 2010
Externally publishedYes

Abstract

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)2·2H2O 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 μM. 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. © 2010 Elsevier Ltd. All rights reserved.

Research Area(s)

  • Photodynamic therapy, Photosensitizers, Phthalocyanines, Singlet oxygen

Citation Format(s)

Preparation and in vitro photodynamic activity of amphiphilic zinc(II) phthalocyanines substituted with 2-(dimethylamino)ethylthio moieties and their N-alkylated derivatives. / Duan, Wubiao; Lo, Pui-Chi; Duan, Lei; Fong, Wing-Ping; Ng, Dennis K.P.

In: Bioorganic and Medicinal Chemistry, Vol. 18, No. 7, 01.04.2010, p. 2672-2677.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal