Department of Chemical Technology of Drugs, Faculty of Pharmacy, Poznan University of Medical Sciences, Grunwaldzka 6, 60-780 Poznan, Poland.
J Inorg Biochem. 2013 Oct;127:62-72. doi: 10.1016/j.jinorgbio.2013.06.012. Epub 2013 Jun 28.
Four novel magnesium(II) and zinc(II) phthalocyanines bearing 1,4,7-trioxanonyl, polyether and/or (2-methyl-5-nitro-1H-imidazol-1-yl)ethoxy, heterocyclic substituents at their non-peripheral positions were synthesized and assessed in terms of physicochemical and biological properties. Magnesium phthalocyanine derivatives bearing polyether substituents (Pc-1), a mixed system of polyether and heterocyclic substituents (Pc-3), and four heterocyclic substituents (Pc-4), respectively, were synthesized following the Linstead macrocyclization reaction procedure. Zinc phthalocyanine (Pc-2) bearing polyether substituents at non-peripheral positions was synthesized following the procedure in n-pentanol with the zinc acetate, and DBU. Novel phthalocyanines were purified by flash column chromatography and characterized using NMR, MS, UV-Vis and HPLC. Moreover, two precursors in macrocyclization reaction phthalonitriles were characterized using X-ray. Photophysical properties of the novel macrocycles were evaluated, including UV-Vis spectra analysis and aggregation study. All macrocycles subjected to singlet oxygen generation and the oxidation rate constant measurements exhibited lower quantum yields of singlet oxygen generation in DMSO than in DMF. In addition, the Pc-2 molecule was found to be the most efficient singlet oxygen generator from the group of macrocycles studied. The photocytotoxicity evaluated on the human oral squamous cell carcinoma cell line, HSC-3, for Pc-3 was significantly higher than that for Pc-1, Pc-2, and Pc-4. Interestingly, Pc-3 was found to be the most active macrocycle in vitro although its ability to generate singlet oxygen was significantly lower than those of Pc-1 and Pc-2. However, attempts to encapsulate phthalocyanines Pc-1-Pc-3 in liposomal membranes were unsuccessful. The phthalocyanine-nitroimidazole conjugate, Pc-4 was encapsulated in phosphatidylglycerol:phosphatidylcholine unilamellar liposomes and subjected to photocytotoxicity study.
四种新型镁（II）和锌（II）酞菁，具有 1,4,7-三氧杂壬基、聚醚和/或（2-甲基-5-硝基-1H-咪唑-1-基）乙氧基、杂环取代基，位于其非外围位置，通过 Linstead 大环化反应程序合成并评估其物理化学和生物性质。带有聚醚取代基的镁酞菁衍生物（Pc-1）、聚醚和杂环取代基的混合体系（Pc-3）和四个杂环取代基（Pc-4）分别通过 Linstead 大环化反应程序合成。具有非外围位置聚醚取代基的锌酞菁（Pc-2）通过醋酸锌和 DBU 在正戊醇中合成。新型酞菁通过快速柱色谱法纯化，并通过 NMR、MS、UV-Vis 和 HPLC 进行表征。此外，在大环化反应中对两个前体酞腈进行了 X 射线表征。评估了新型大环的光物理性质，包括 UV-Vis 光谱分析和聚集研究。所有大环都进行了单线态氧生成和氧化速率常数测量，在 DMSO 中的单线态氧生成量子产率均低于 DMF。此外，在研究的大环中，Pc-2 分子被发现是最有效的单线态氧生成剂。在人口腔鳞状细胞癌细胞系 HSC-3 上评估的光细胞毒性，Pc-3 的光细胞毒性明显高于 Pc-1、Pc-2 和 Pc-4。有趣的是，尽管 Pc-3 生成单线态氧的能力明显低于 Pc-1 和 Pc-2，但它在体外是最活跃的大环。然而，将酞菁 Pc-1-Pc-3 包封在脂质体膜中的尝试均未成功。将酞菁-硝基咪唑缀合物 Pc-4 包封在磷脂酰甘油：磷脂酰胆碱单层脂质体中，并进行光细胞毒性研究。
