Raza Md Kausar, Gautam Srishti, Garai Aditya, Mitra Koushambi, Kondaiah Paturu, Chakravarty Akhil R
Department of Inorganic and Physical Chemistry and ‡Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science , Bangalore 560012, India.
Inorg Chem. 2017 Sep 18;56(18):11019-11029. doi: 10.1021/acs.inorgchem.7b01346. Epub 2017 Aug 28.
Monofunctional platinum(II) complexes of formulation cis-Pt(NH)(L)Cl, where L is an imidazole base conjugated to 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) with emissive (L in 1) and nonemissive (L in 2) moieties were prepared and characterized, and their singlet oxygen-mediated photoinduced cytotoxicity was studied. The 1-methylimidazole (1-MeIm) complex 3 was prepared as a control and for structural characterization by X-ray crystallography. Complexes 1 and 2 showed strong visible absorption bands at 500 nm (ε = 2.7 × 10 M cm) and 540 nm (1.4 × 10 M cm). Complex 1 is emissive with a band at 510 nm (Φ = 0.09) in 1% dimethyl sulfoxide/Dulbecco's Modified Eagle's Medium (pH 7.2). Singlet oxygen generation upon photoirradiation with visible light (400-700 nm) was evidenced from 1,3-diphenylisobenzofuran titration experiments showing significant photosensitizing ability of the BODIPY complexes. Both 1 and 2 were remarkably photocytotoxic in visible light (400-700 nm, 10 J cm) in skin keratinocyte HaCaT and breast cancer MCF-7 cells giving IC values in nanomolar concentration. The complexes were, however, essentially nontoxic to the cells in the dark (IC > 80 μM). Complex 2 having a diiodo-BODIPY unit is nonemissive but an efficient photosensitizer with high singlet oxygen generation ability in visible light (400-700 nm). Confocal microscopy using the emissive complex 1 showed significant mitochondrial localization of the complex. Cell death via apoptotic pathway was observed from the Annexin-V-FITC/PI assay. The formation of Pt-DNA adducts was evidenced from the binding experiments of the complexes 1 and 2 with 9-ethylguanine as a model nucleobase from H NMR and mass spectral studies.
制备并表征了顺式-Pt(NH)(L)Cl形式的单功能铂(II)配合物，其中L是与4,4-二氟-4-硼-3a,4a-二氮杂-s-茚并[1,2-b]吡咯（BODIPY）共轭的咪唑碱，具有发射性部分（1中的L）和非发射性部分（2中的L），并研究了它们的单线态氧介导的光诱导细胞毒性。制备了1-甲基咪唑（1-MeIm）配合物3作为对照，并通过X射线晶体学进行结构表征。配合物1和2在500 nm（ε = 2.7 × 10 M cm）和540 nm（1.4 × 10 M cm）处显示出很强的可见吸收带。配合物1在1%二甲基亚砜/杜尔贝科改良伊格尔培养基（pH 7.2）中在510 nm处有发射带（Φ = 0.09）。1,3-二苯基异苯并呋喃滴定实验证明了用可见光（400 - 700 nm）光照射时单线态氧的产生，表明BODIPY配合物具有显著的光敏能力。1和2在皮肤角质形成细胞HaCaT和乳腺癌MCF-7细胞中在可见光（400 - 700 nm，10 J cm）下均具有显著的光细胞毒性，其IC值处于纳摩尔浓度。然而，这些配合物在黑暗中对细胞基本无毒（IC > 80 μM）。具有二碘代BODIPY单元的配合物2不发光，但在可见光（400 - 700 nm）下是一种高效的光敏剂，具有高单线态氧产生能力。使用发射性配合物1的共聚焦显微镜显示该配合物在线粒体中有显著定位。通过膜联蛋白-V-异硫氰酸荧光素/碘化丙啶检测观察到细胞通过凋亡途径死亡。配合物1和2与9-乙基鸟嘌呤作为模型核碱基的结合实验通过核磁共振氢谱和质谱研究证明了Pt-DNA加合物的形成。
