Paitandi Rajendra Prasad, Mukhopadhyay Sujay, Singh Roop Shikha, Sharma Vinay, Mobin Shaikh M, Pandey Daya Shankar
Department of Chemistry, Institute of Science, Banaras Hindu University , Varanasi 221005, Uttar Pradesh, India.
Inorg Chem. 2017 Oct 16;56(20):12232-12247. doi: 10.1021/acs.inorgchem.7b01693. Epub 2017 Sep 28.
A pyrazole-appended quinoline-based 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (L1, BODIPY) has been synthesized and used as a ligand for the preparation of iridium(III) complexes [Ir(phpy)(L1)]PF (1; phpy = 2-phenylpyridine) and [(η-CMe)Ir(L1)Cl]PF (2). The ligand L1 and complexes 1 and 2 have been meticulously characterized by elemental analyses and spectral studies (IR, electrospray ionization mass spectrometry, H and C NMR, UV/vis, fluorescence) and their structures explicitly authenticated by single-crystal X-ray analyses. UV/vis, fluorescence, and circular dichroism studies showed that complexes strongly bind with calf-thymus DNA and bovine serum albumin. Molecular docking studies clearly illustrated binding through DNA minor grooves via van der Waals forces and their electrostatic interaction and occurrence in the hydrophobic cavity of protein (subdomain IIA). Cytotoxicity, morphological changes, and apoptosis have been explored by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and Hoechst 33342 staining. IC values for complexes (1, 30 μM; 2, 50 μM) at 24 h toward the human cervical cancer cell line (HeLa) are as good as that of cisplatin (21.6 μM) under analogous conditions, and their ability to kill cancer cells lies in the order 1 > 2. Because of the inherent emissive nature of the BODIPY moiety, these are apt for intracellular visualization at low concentration and may find potential applications in cellular imaging and behave as a theranostic agent.
一种吡唑连接的喹啉基4,4-二氟-4-硼-3a,4a-二氮杂-s-茚（L1，BODIPY）已被合成，并用作配体制备铱（III）配合物[Ir(phpy)(L1)]PF（1；phpy = 2-苯基吡啶）和[(η-CMe)Ir(L1)Cl]PF（2）。配体L1以及配合物1和2已通过元素分析和光谱研究（红外光谱、电喷雾电离质谱、氢和碳核磁共振、紫外/可见光谱、荧光光谱）进行了细致表征，其结构通过单晶X射线分析得到明确验证。紫外/可见光谱、荧光光谱和圆二色性研究表明，这些配合物能与小牛胸腺DNA和牛血清白蛋白强烈结合。分子对接研究清楚地表明，它们通过范德华力和静电相互作用通过DNA小沟结合，并存在于蛋白质的疏水腔（亚结构域IIA）中。通过3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）测定法和Hoechst 33342染色研究了细胞毒性、形态变化和细胞凋亡。在24小时时，配合物（1，30 μM；2，50 μM）对人宫颈癌细胞系（HeLa）的半数抑制浓度（IC值）与类似条件下顺铂（21.6 μM）的相当，且它们杀死癌细胞的能力顺序为1 > 2。由于BODIPY部分固有的发光性质，这些配合物适合在低浓度下进行细胞内可视化，可能在细胞成像中找到潜在应用，并可作为一种诊疗试剂。
