Synthesis, aggregation and cellular investigations of porphyrin-cobaltacarborane conjugates
Synthesis, aggregation and cellular investigations of porphyrin-cobaltacarborane conjugates
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DOI：
10.1002/chem.200700752
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发表时间：
2007-01-01
影响因子：
4.3
通讯作者：
Vicente, M. Graca H.
中科院分区：
文献类型：
--
作者：
Hao, Erhong;Sibrian-Vazquez, Martha;Vicente, M. Graca H.
通过两性离子三碳硼烷钴[3，3 ′-Co（8-C_4H_8 O_2 - 1，2-C_2B_9 H_（10）（1 ′，2 ′-C_2B_9 H_（11））]的开环反应，以优良的产率（90-97%）制备了一系列新的卟啉-三碳硼烷钴共轭物（1-5）。本文给出了一个共轭化合物（3）的X射线结构。这些共轭物的聚集特性进行了研究，通过使用吸收和荧光分光光度计，并通过使用原子力显微镜捕获的微晶形成的阶段。发现所有缀合物在水溶液中聚集，以形成宽分散度的粒度。在人癌HEp 2细胞中评价了这一系列缀合物的细胞摄取、细胞毒性和亚细胞定位的优先位点。结合物细胞摄取的程度取决于卟啉周围的钴碳硼烷单元的数量、它们的分布和结合物聚集行为。共轭物2和4，承载两个相邻的或三个3，5-二钴碳硼烷苯基基团，在HEp 2细胞内积累最多，因此，是最有前途的硼中子捕获治疗剂。所有共轭物显示出非常低的黑暗和光毒性，可能是由于其在水溶液中聚集的强烈倾向，并在一定程度上与细胞溶酶体相关的囊泡内亚细胞定位。
A new series of porphyrin-cobaltacarborane conjugates (1-5) that contain four to sixteen carborane clusters per porphyrin macrocycle, were prepared in excellent yields (90-97%) by means of a ring-opening reaction of the zwitterionic cobaltacarborane [3,3'Co(8-C4H8O2--1,2-C2B9H10)(1',2'- C2B9H11)]. The X-ray structure of one conjugate (3) is presented. The aggregation properties of these conjugates were investigated by using absorption and fluorescence spectrophotometry, and the stages of microcrystal formation were captured by using atomic force microscopy. All conjugates were found to aggregate in aqueous solutions, to form a broad dispersity of particle sizes. The cellular uptake, cytotoxicity, and preferential sites of subcellular localization of this series of conjugates were evaluated in human carcinoma HEp2 cells. The extent of conjugate cellular uptake depends on the number of cobaltacarborane units at the porphyrin periphery, their distribution, and the conjugate aggregation behavior. Conjugates 2 and 4, bearing either two adjacent or three 3,5-dicobaltacarboranephenyl groups, accumulated the most within HEp2 cells and are, therefore, the most promising boron neutron capture therapy agents. All conjugates showed very low dark-and photo-toxicity, probably due to their strong tendency for aggregation in aqueous solutions, and localized subcellularly within vesicles that correlated, to some extent, with the cell lysosomes.