Dasari Srikanth, Singh Swati, Abbas Zafar, Sivakumar Sri, Patra Ashis K
Department of Chemistry, Indian Institute of Technology Kanpur, Kanpur 208016, UP, India.
Department of Chemical Engineering and Center for Environmental Science and Engineering, Indian Institute of Technology Kanpur, Kanpur 208016, UP, India.
Spectrochim Acta A Mol Biomol Spectrosc. 2021 Jul 15;256:119709. doi: 10.1016/j.saa.2021.119709. Epub 2021 Mar 18.
We report here a series of coordinatively-saturated and thermodynamically stable luminescent [Ln(dtntp)(HO)] [Ln(III) = Eu (1), Tb (2), Gd (3), Sm (4) and Dy (5)] complexes using an aminophenyl-terpyridine appended-DTPA (dtntp) chelating ligand as cell imaging and photocytotoxic agents. The N,N″-bisamide derivative of HDTPA named as dtntp is based on 4'-(4-aminophenyl)-2,2':6',2″-terpyridine conjugated to diethylenetriamine-N,N',N″-pentaacetic acid. The structure, physicochemical properties, detailed photophysical aspects, interaction with DNA and serum proteins, and photocytotoxicity were studied. The intrinsic luminescence of Eu(III) and Tb(III) complexes due to f → f transitions used to evaluate their cellular uptake and distribution in cancer cells. The solid-state structure of [Eu(dtntp)(DMF)] (1·DMF) shows a discrete mononuclear molecule with nine-coordinated {EuNO} distorted tricapped-trigonal prism (TTP) coordination geometry around the Eu(III). The {EuNO} core results from three nitrogen atoms and three carboxylate oxygen atoms, and two carbonyl oxygen atoms of the amide groups of dtntp ligand. The ninth coordination site is occupied by an oxygen atom of DMF as a solvent from crystallization. The designed probes have two aromatic pendant phenyl-terpyridine (Ph-tpy) moieties as photo-sensitizing antennae to impart the desirable optical properties for cellular imaging and photocytotoxicity. The photostability, coordinative saturation, and energetically rightly poised triplet states of dtntp ligand allow the efficient energy transfer (ET) from Ph-tpy to the emissive excited states of the Eu(III)/Tb(III), makes them luminescent cellular imaging probes. The Ln(III) complexes show significant binding tendency to DNA (K ~ 10 M), and serum proteins (BSA and HSA) (K ~ 10 M). The luminescent Eu(III) (1) and Tb(III) (2) complexes were utilized for cellular internalization and cytotoxicity studies due to their optimal photophysical properties. The cellular uptake studies using fluorescence imaging displayed intracellular (cytosolic and nuclear) localization in cancer cells. The complexes 1 and 2 displayed significant photocytotoxicity in HeLa cells. These results offer a modular design strategy with further scope to utilize appended N,N,N-donor tpy moiety for developing light-responsive luminescent Ln(III) bioprobes for theranostic applications.
我们在此报告了一系列配位饱和且热力学稳定的发光[Ln(dtntp)(HO)] [Ln(III)=铕(1)、铽(2)、钆(3)、钐(4)和镝(5)]配合物，这些配合物使用一种 appended-DTPA（dtntp）螯合配体作为细胞成像和光细胞毒性剂，该配体为氨基苯基 - 三联吡啶连接的二乙三胺五乙酸（HDTPA）的 N,N″-双酰胺衍生物（命名为 dtntp），其基于 4'-(4 - 氨基苯基)-2,2':6',2″-三联吡啶与二乙三胺 - N,N',N″-五乙酸共轭。研究了其结构、物理化学性质、详细的光物理特性、与 DNA 和血清蛋白的相互作用以及光细胞毒性。铕(III)和铽(III)配合物由于 f→f 跃迁产生的固有发光用于评估它们在癌细胞中的细胞摄取和分布。[Eu(dtntp)(DMF)] (1·DMF)的固态结构显示出一个离散的单核分子，在铕(III)周围具有九配位的{EuNO}扭曲三帽三棱柱（TTP）配位几何结构。{EuNO}核心由三个氮原子、三个羧酸根氧原子以及 dtntp 配体酰胺基团的两个羰基氧原子组成。第九个配位点由作为结晶溶剂的 DMF 的一个氧原子占据。所设计的探针具有两个芳香侧基苯基 - 三联吡啶（Ph - tpy）部分作为光敏天线，以赋予细胞成像和光细胞毒性所需的光学性质。dtntp 配体的光稳定性、配位饱和以及能量合适的三重态允许从 Ph - tpy 到铕(III)/铽(III)发射激发态的有效能量转移（ET），使其成为发光细胞成像探针。Ln(III)配合物显示出与 DNA（K10 M）和血清蛋白（牛血清白蛋白和人血清白蛋白）（K10 M）有显著的结合倾向。发光的铕(III)（1）和铽(III)（2）配合物因其最佳的光物理性质被用于细胞内化和细胞毒性研究。使用荧光成像的细胞摄取研究显示在癌细胞中有细胞内（细胞质和细胞核）定位。配合物 1 和 2 在 HeLa 细胞中显示出显著的光细胞毒性。这些结果提供了一种模块化设计策略，还有进一步利用连接的 N,N,N - 供体 tpy 部分开发用于治疗诊断应用的光响应发光 Ln(III)生物探针的空间。
