A set of highly water-soluble tetraethyleneglycol-substituted Zn(II) phthalocyanines: synthesis, photochemical and photophysical properties, interaction with plasma proteins and in vitro phototoxicity.

Gebze Institute of Technology, Department of Chemistry, P.O. Box 141, Gebze, 41400, Kocaeli, Turkey.
Dalton Transactions (Impact Factor: 4.1). 12/2010; 40(16):4067-79. DOI: 10.1039/c0dt01260b
Source: PubMed

ABSTRACT Three Zn(II) phthalocyanines substituted by hydroxyl-terminated tetraethylene glycol chains have been synthesized. In order to evaluate the potential of these highly water-soluble phthalocyanines as type II-photosensitisers for photodynamic therapy, their structure-activity relationship was assessed by determining relevant photophysical and photochemical properties, such as their aggregation behaviour in aqueous buffers, their fluorescence properties and their efficiency with regard to the generation of singlet oxygen. In addition, evidence for a negligible interaction with plasma proteins in undiluted human plasma was obtained using a recently developed bioanalytical method and compared with the fluorescence quenching approach. These results combined with in vitro data regarding the phototoxicity of these phthalocyanines against HT-29 cancer cells provide evidence for the relevance of the non-peripherally substituted derivative for further in vivo investigations.

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    Carbon 10/2014; 77:1020-1030. · 6.16 Impact Factor
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    ABSTRACT: Phthalocyanines are excellent photosensitizers for photodynamic therapy as they have strong absorbance in the near infra-red region which is most relevant for in vivo activation in deeper tissular regions. However, most phthalocyanines present two major challenges, ie, a strong tendency to aggregate and low water-solubility, limiting their effective usage clinically. In the present study, we evaluated the potential enhancement capability of glycerol substitution on the photodynamic properties of zinc (II) phthalocyanines (ZnPc). Three glycerol substituted ZnPc, 1-3, (tetra peripherally, tetra non-peripherally and mono iodinated tri non-peripherally respectively) were evaluated in terms of their spectroscopic properties, rate of singlet oxygen generation, partition coefficient (log P), intracellular uptake, photo-induced cytotoxicity and vascular occlusion efficiency. Tetrasulfonated ZnPc (ZnPcS4) was included as a reference compound. Here, we showed that 1-3 exhibited 10-100 nm red-shifted absorption peaks with higher molar absorptivity, and at least two-fold greater singlet oxygen generation rates compared to ZnPcS4. Meanwhile, phthalocyanines 1 and 2 showed more hydrophilic log P values than 3 consistent with the number of glycerol attachments but 3 was most readily taken up by cells compared to the rest. Both phthalocyanines 2 and 3 exhibited potent phototoxicity against MCF-7, HCT-116 and HSC-2 cancer cell-lines with IC50 ranging 2.8-3.2 µM and 0.04-0.06 µM respectively, while 1 and ZnPcS4 (up to 100 µM) failed to yield determinable IC50 values. In terms of vascular occlusion efficiency, phthalocyanine 3 showed better effects than 2 by causing total occlusion of vessels with diameter <70 µm of the chorioallantoic membrane. Meanwhile, no detectable vascular occlusion was observed for ZnPcS4 with treatment under similar experimental conditions. These findings provide evidence that glycerol substitution, in particular in structures 2 and 3, is able to improve the photodynamic properties of ZnPc.
    PLoS ONE 05/2014; 9(5):e97894. · 3.53 Impact Factor
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    ABSTRACT: Journal of Photochemistry and Photobiology A: Chemistry j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / j p h o t o c h e m Amino-functionalized water-soluble zinc phthalocyanines: Synthesis, photophysical, photochemical and protein binding properties a b s t r a c t Tetra-peripherally substituted symmetrical and low symmetrical Zn (II) phthalocyanines containing 2-[2-(2-ethoxyethoxy)ethoxy]-1-[2-((2-ethoxyethoxy)-ethoxy)ethoxymethyl] ethyloxy and [2-(tert-butoxycarbonyl)amino]ethoxy groups, as well as their deprotected amino-functionalized derivatives were synthesized for the first time. These novel zinc phthalocyanines were characterized by elemen-tal analysis and spectroscopic methods including FT-IR, 1 H and 13 C NMR, MALDI-TOF, UV–vis. Their photophysical (fluorescence quantum yields and lifetimes) and photochemical (singlet oxygen and pho-todegradation quantum yields) properties were investigated in DMSO, in water and in water + triton X-100 solutions for comparison of solvents and aggregation effects. Effects of symmetries of the phthalo-cyanine molecules on these properties were also revealed. The fluorescence quenching of these Zn (II) phthalocyanines upon addition of 1,4-benzoquinone were examined in DMSO. Binding study of these phthalocyanine photosensitizers to bovine serum albumin one of the blood carrier proteins, was also examined in this study.
    Journal of Photochemistry and Photobiology A: Chemistry 05/2013; 266:37-46.