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

Gebze Institute of Technology, Department of Chemistry, P.O. Box 141, Gebze, 41400, Kocaeli, Turkey.
Dalton Transactions (Impact Factor: 4.2). 12/2010; 40(16):4067-79. DOI: 10.1039/c0dt01260b
Source: PubMed


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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    • "The triethyleneglycol-substituted Zn(II) phthalocyanine (ZnPc) was firstly synthesized using 3-(2-[2-(2-hydroxyethox- y)ethoxy]ethoxy)phthalonitrile according to the method reported by Ahsen and coworkers [29]. The synthesis of RGO–ZnPc hybrid material is based on the initial covalent linkage of ZnPc to GO by an esterification reaction and subsequent in situ reduction of GO moiety to RGO during mild thermal treatment in DMF solvent. "
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    ABSTRACT: A reduced graphene oxide-zinc phthalocyanine (RGO-ZnPc) hybrid material with good dispersibility has been prepared by covalent functionalization method, based on the initial covalent linkage of ZnPc to GO and subsequent in situ reduction of GO moiety to RGO during mild thermal treatment in DMF solvent. The microscopic structure, morphology and photophysical properties of resultant RGO-ZnPc hybrid are characterized. The nonlinear optical (NLO) properties of the RGO-ZnPc hybrid are also investigated using the Z-scan technique at 532 nm with 4 ns laser pulses. The results show that the efficient functionalization and reduction of GO make RGO-ZnPc hybrid possess much larger NLO properties and optical limiting performance than those of individual GO, ZnPc and the GO-ZnPc hybrid. It can be ascribed to a combination of different NLO absorption mechanisms for RGO-ZnPc hybrid, including two-photon absorption originating from the sp(3) domains, saturable absorption from the sp(2) carbon clusters and excited state absorption from numerous localized sp(2) configurations in RGO moiety, reverse saturable absorption arising from ZnPc moiety and the contribution of efficient photo-induced electron transfer or energy transfer process between ZnPc and RGO.
    Full-text · Article · Oct 2014 · Carbon
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    • "So far, most studies that attach functional groups to phthalocyanines to improve their water solubility have focused on the synthesis of sulfonated phthalocyanine. However, sulfonation had resulted in the reduction of singlet oxygen generation [12], [13]. Therefore, functionalization of phthalocyanine with other hydrophilic moieties to improve its aqueous solubility while maintaining its biological activity is needed. "
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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.
    Full-text · Article · May 2014 · PLoS ONE
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    • "To overcome these problems, possible strategies are the substitution of Pc with bulky and polar groups such as polyoxyethylene, or conjugation of Pc macrocycle to biomolecules [1] [14] [15]. Our ongoing investigations focus on the preparation of new water soluble phthalocyanine derivatives which have potential to be used as PDT agents [4] [14]. For this purpose, tetra-peripherally substituted low symmetrical Zn (II) Pc derivatives substituted by bulky polyoxyethylene groups reducing aggregation, and by amino function for enhanced water solubility were designed and synthesized. "
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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.
    Full-text · Article · May 2013 · Journal of Photochemistry and Photobiology A: Chemistry
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