Glycosylated zinc(II) phthalocyanines as efficient photosensitisers for photodynamic therapy. Synthesis, photophysical properties and in vitro photodynamic activity.
Treatment of 3- or 4-nitrophthalonitrile with 1,2:5,6-di-O-isopropylidene-alpha-d-glucofuranose or 1,2:3,4-di-O-isopropylidene-alpha-d-galactopyranose in the presence of K(2)CO(3) gave the corresponding glycosubstituted phthalonitriles. These precursors underwent self-cyclisation, or mixed-cyclisation with the unsubstituted phthalonitrile, to afford the tetra- or mono-glycosylated zinc(ii) phthalocyanines, respectively. As shown by absorption spectroscopy, these compounds were not significantly aggregated in organic solvents, giving a weak to moderate fluorescence emission. Upon irradiation these compounds could sensitise the formation of singlet oxygen in DMF, with quantum yields in the range of 0.40-0.66. The in vitro photodynamic activities of these compounds against HepG2 human hepatocarcinoma and HT29 human colon adenocarcinoma cells were also studied. The mono-glycosylated phthalocyanines exhibited significantly higher photocytotoxicity compared with the tetra-alpha-glycosylated analogues, having IC(50) values down to 0.9 muM. The tetra-beta-glycosylated counterparts were essentially inactive. The lower photocytotoxicities of the tetra-glycosylated phthalocyanines are in line with their lower cellular uptake and/or higher aggregation tendency as reflected by weaker intracellular fluorescence, and lower efficiency at generating intracellular reactive oxygen species. For the mono-glycosylated phthalocyanines, the higher uptake can be attributed to their hydrophilic saccharide units, which increase the amphiphilicity of the macrocycles.
Choi
Chi-Fung
CF
Department of Chemistry and Centre of Novel Functional Molecules, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China. dkpn@cuhk.edu.hk
Huang
Jian-Dong
JD
Lo
Pui-Chi
PC
Fong
Wing-Ping
WP
Ng
Dennis K P
DK
D045744:Cell Line, Tumor; D006031:Glycosylation; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology*; D054833:Isoindoles; D009682:Magnetic Resonance Spectroscopy; D009942:Organometallic Compounds / Q000737:chemistry / Q000494:pharmacology*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry / Q000494:pharmacology*; D013050:Spectrometry, Fluorescence; D021241:Spectrometry, Mass, Electrospray Ionization; D013056:Spectrophotometry, Ultraviolet; D017967:Zinc Compounds
D007211:Indoles; D054833:Isoindoles; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; D017967:Zinc Compounds; C052159:Zn(II)-phthalocyanine