The synthesis and characterisation of iridium(III) bis(2-(2,4-difluorophenyl)pyridinato-N, C2')-2(4-carboxylphenyl)imidazo[4,5-f][1,10]phenanthroline perchlorate, [Ir(dfpp)(2)(picCOOH)](+) and its octaarginine conjugate [Ir(dfpp)(2)(picCONH-Arg(8))](9+) are reported. Both complex and conjugate exhibit intense and long-lived luminescence, which is O(2) and pH sensitive. Conjugation to the polyarginine peptide renders the complex very water soluble. The uptake of the parent iridium(III) complex and conjugate are compared in two mammalian cell lines; SP2 myeloma and Chinese hamster ovary (CHO). Both complexes internalise into the cytoplasm, however dye uptake rate and distribution vary with peptide conjugation and with cell identity. Whereas transmembrane transport is thought to have been facilitated by the dimethyl sulfoxide (DMSO) used as co-solvent (0.05% v/v) for the parent complex, the octaarginine, the dye-conjugate (iridium-R(8)) is membrane permeable in water only. Both complexes exhibit high cytotoxicity, evident through blebbing and vacuole formation within living cells, indicative of apoptosis, within 30min of exposure to the probe. The IC(50) recorded for the cells in the dark was independent, in the case of the parent complex, of the identity of the cell, with IC(50) of 84.8μM and 88μM respectively for SP2 and CHO cells. The IC(50) approximately doubled for the polyarginine conjugate and displayed a significant dependence on cell type with IC(50) of 35μM and 54.1μM respectively for SP2 and CHO cells. These IC(50) values were recorded in the dark. However under irradiation cell death is considerably faster. Evidence from imaging suggests that the conjugate penetrates the nucleus whereas the parent does not, indicating that nuclear penetration may play a role in cytotoxicity.

译文

铱 (III) 双 (2-(2,4-二氟苯基) 吡啶-N,C2 ')-2(4-羧基苯基) 咪唑并 [4,5-f][1,10] 菲咯啉高氯酸盐的合成和表征,报道了 [Ir(dfpp)(2)(picCOOH)]() 及其八精氨酸缀合物 [Ir(dfpp)(2)(picCONH-Arg(8))](9)。复合物和缀合物都表现出强烈和长寿命的发光,O(2) 和pH敏感。与聚精氨酸肽的结合使复合物非常水溶性。在两种哺乳动物细胞系中比较了母体铱 (III) 复合物和结合物的吸收; SP2骨髓瘤和中国仓鼠卵巢 (CHO)。两种复合物都内化到细胞质中,然而,染料的吸收速率和分布随肽缀合和细胞特性而变化。而跨膜运输被认为是由用作母体复合物 (八精氨酸) 的共溶剂 (0.05% v/v) 的二甲基亚砜 (DMSO) 促进的。染料偶联物 (铱-R(8)) 仅在水中具有膜渗透性。两种复合物均表现出高细胞毒性,通过活细胞内的起泡和液泡形成明显,表明细胞凋亡,在暴露于探针的30分钟内,在黑暗中记录的细胞的IC(50) 是独立的,在母体复合体的情况下,细胞的身份,对于SP2和CHO细胞,IC(50) 分别为84.8 μ m和88 μ m。对于聚精氨酸缀合物,IC(50) 大约增加了一倍,并且对于SP2和CHO细胞,IC(50) 分别为35 μ m和54.1 μ m的细胞类型显示出显着依赖性。这些IC(50) 值被记录在黑暗中。然而,在辐射下,细胞死亡要快得多。来自成像的证据表明,缀合物穿透细胞核,而亲本没有穿透细胞核,表明核渗透可能在细胞毒性中起作用。

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