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A versatile ditopic ligand system for sensitizing the luminescence of bimetallic lanthanide bio-imaging probes

机译:通用的双位配体系统,用于敏化双金属镧系生物成像探针的发光

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The homoditopic ligand 6,6'-[methylenebis(1-methyl-1H-benzimid- azole-5.2-diyl)]bis(4-{2-[2-(2-methoxyethoxy)ethoxy]ethoxylpyridine-2-carboxylic acid) (H2LC2) has been tailored to self-assemble with lanthanide ions (Ln(III)), which results in the formation of neutral bimetallic helicates with the overall composition [Ln(2)(L-C2)(3)] and also provides a versatile platform for further derivatization. The grafting of poly(oxyethylene) groups onto the pyridine units ensures water solubility, while maintaining sizeable thermodynamic stability and adequate antenna effects for the excitation of both visible- and NIR-emitting Ln(III) ions. The conditional stability constants (109023) are close to 25 at physiological pH and under stoichiometric conditions. The ligand triplet state features adequate energy (0-phonon transition at approximate to 21900 cm(-1)) to sensitize the luminescence of Eu-III (Q = 21%) and Tb-III (11%) in aerated water at pH 7.4. The emission of several other VIS- and NIR-emitting ions, such as Sm-III (Q = 0.38%) or Yb-III (0.15%), for which in cellulo luminescence is evidenced for the first time, is also sensitized. The Eu-III emission spectrum arises from a main species with pseudo-D-3 symmetry and without coordinated water. The cell viability of several cancerous cell lines (MCF-7, HeLa, Jurkat and 5D10) is unaffected if incubated with up to 500 mu m [Eu-2(L-C2)(3)] during 24 h. Bright Eu-III emission is seen for incubation concentrations above 10 mu m and after a 15-minute loading time; similar images are obtained with Tb-III and Sm-III. The helicates probably permeate into the cytoplasm of HeLa cells by endocytosis. The described luminescent helical stains are robust chemical species which remain undissociated in the cell medium and in presence of other complexing agents, such as edta, dtpa, citrate or L-ascorbate. Their derivatization, which would open the way to the sensing of targeted in cellulo phenomena, is currently under investigation.
机译:同位异位配体6,6'-[亚甲基双(1-甲基-1H-苯并咪唑-唑基-5.2-二基)]双(4- {2- [2-(2-(2-甲氧基乙氧基)乙氧基]乙氧基吡啶-2-羧酸) (H2LC2)经过定制,可与镧系元素离子(Ln(III))自组装,从而形成具有整体组成[Ln(2)(L-C2)(3)]的中性双金属螺旋结构,并提供进一步衍生化的通用平台。聚(氧乙烯基)基团接枝到吡啶单元上可确保水溶性,同时保持可观的热力学稳定性和足够的天线效应,以激发可见光和近红外发射Ln(III)离子。在生理pH和化学计量条件下,条件稳定性常数(109023)接近25。配体三重态具有足够的能量(在约21900 cm(-1)处有0声子跃迁),可激发pH 7.4的充气水中Eu-III(Q = 21%)和Tb-III(11%)的发光。还首次敏化了一些其他的VIS和NIR发射离子的发射,例如Sm-III(Q = 0.38%)或Yb-III(0.15%)。 Eu-III发射光谱来自具有伪D-3对称性且没有配位水的主要物种。如果在24小时内与最多500μm[Eu-2(L-C2)(3)]孵育,则几种癌细胞系(MCF-7,HeLa,Jurkat和5D10)的细胞生存力不会受到影响。在浓度超过10μm且加载15分钟后,可以看到明亮的Eu-III发射。用Tb-III和Sm-III可获得相似的图像。螺旋藻可能通过内吞作用渗透到HeLa细胞的细胞质中。所描述的发光螺旋染色是坚固的化学物质,其在细胞培养基中以及在其他络合剂例如edta,dtpa,柠檬酸盐或L-抗坏血酸盐的存在下保持未解离。目前正在研究它们的衍生化,这将为感知纤维素现象中的目标开辟道路。

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