Lu Cuifen, Xu Wan, Shah Harshit, Liu Bingqing, Xu Wei, Sun Liya, Qian Steven Y, Sun Wenfang
Department of Chemistry and Biochemistry, North Dakota State University, Fargo, North Dakota 58108-6050, United States.
Hubei Collaborative Innovation Center for Advanced Organochemical Materials and Ministry-of-Education Key Laboratory for the Synthesis and Application of Organic Functional Molecules, Hubei University, Wuhan 430062, P. R. China.
ACS Appl Bio Mater. 2020 Oct 19;3(10):6865-6875. doi: 10.1021/acsabm.0c00784. Epub 2020 Sep 14.
Three mononuclear or dinuclear bis(terpyridine) (tpy) iridium(III) complexes bearing pyren-1-yl (pyr) group(s) were synthesized. Their photophysical properties in water and in vitro photodynamic therapy (PDT) effects toward the human lung epithelial cancer cell line A549 and the human epidermal skin cancer cell line A431 were investigated to evaluate the effects of dinuclear versus mononuclear complexes and the impact of the oligoether substituent at the ligand. All complexes possessed pyr-tpy ligand-associated charge transfer (CT)/ππ* absorption bands at 350-550 nm, with the dinuclear complex showing the much enhanced absorptivity of this band. These complexes exhibited dual emission upon excitation at >430 nm in most cases, with the emitting states being ascribed to ILCT (intraligand charge transfer) and π,π*/CT states, respectively. All complexes exhibited relatively weak to moderate cytotoxicity in the dark but high photocytotoxicity upon broadband visible light irradiation. Among them, the dinuclear complex showed the highest intracellular reactive oxygen species (ROS) generation and PDT efficiency compared to its mononuclear counterpart Introducing an oligoether substituent on one of the tpy ligands in also improved its intracellular ROS generation and PDT efficacy compared to those induced by . induced both mitochondrial dysfunction and lysosomal damage upon light activation toward both cell lines, whereas and caused both mitochondrial dysfunction and lysosomal damage in A431 cells but only lysosomal damage in A549 cells. The dominant cell death pathway induced by PDT is apoptosis.
合成了三种带有芘-1-基（pyr）基团的单核或双核双（三联吡啶）（tpy）铱（III）配合物。研究了它们在水中的光物理性质以及对人肺上皮癌细胞系A549和人表皮皮肤癌细胞系A431的体外光动力疗法（PDT）效果，以评估双核与单核配合物的效果以及配体上寡醚取代基的影响。所有配合物在350 - 550 nm处都具有与pyr-tpy配体相关的电荷转移（CT）/ππ吸收带，其中双核配合物的该吸收带吸光度显著增强。在大多数情况下，这些配合物在波长>430 nm激发时呈现双重发射，发射态分别归因于配体内电荷转移（ILCT）和π,π/CT态。所有配合物在黑暗中表现出相对较弱至中等的细胞毒性，但在宽带可见光照射下具有高光细胞毒性。其中，与单核对应物相比，双核配合物表现出最高的细胞内活性氧（ROS）生成和PDT效率。在配合物中，在一个tpy配体上引入寡醚取代基也比配合物诱导的细胞内ROS生成和PDT疗效有所提高。在对两种细胞系进行光激活时，配合物诱导了线粒体功能障碍和溶酶体损伤，而配合物和在A431细胞中导致了线粒体功能障碍和溶酶体损伤，但在A549细胞中仅导致了溶酶体损伤。配合物PDT诱导的主要细胞死亡途径是凋亡。
