Millán Gonzalo, Nieddu Mattia, López Icíar P, Ezquerro Cintia, Berenguer Jesús R, Larráyoz Ignacio M, Pichel José G, Lalinde Elena
Departamento de Química-Centro de Síntesis Química de La Rioja, (CISQ), Universidad de La Rioja, 26006, Logroño, Spain.
Chair of Biogenic Functional Materials, Technical University of Munich, Schulgasse, 22, Straubing 94315, Germany.
Dalton Trans. 2023 May 16;52(19):6360-6374. doi: 10.1039/d3dt00028a.
By using ,-dibutyl-2,2'-bipyridine-4,4'-dicarboxamide as a diimine () and distinctive cyclometalated groups, this work reports a new family of cationic phosphorescent Ir(III) cyclometalated [Ir(C^N)(N^N)]X compounds [C^N = difluorophenylpyridine (dfppy) a, 2,6-difluoro-3-(pyridin-2-yl)benzaldehyde (CHO-dfppy) b, and 2,6-difluoro-3-pyridin-2-yl-benzoic acid (COOH-dfppy) c; X = Cl2a,b,c-Cl; X = PF2b,c-PF6]. For comparative purposes, the related complex [Ir(dfppy)(Hdcbpy)] (3a-PF6) incorporating 3,3'-dicarboxy-2,2'-bipyridine as an auxiliary ligand (N^N = Hdcbpy) is also presented. All complexes have been fully characterized and their photophysical properties were investigated in detail. The theoretically calculated results obtained by density functional theory (DFT) and time-dependent density functional theory (TD-DFT) studies indicate that luminescence is derived from mixed ML'CT (Ir → N^N)/LL'CT (C^N → N^N) excited states with the predominant metal-to-diimine charge transfer character. Their antineoplastic activity against tumour cell lines A549 (lung carcinoma) and HeLa (cervix carcinoma), as well as the nontumor BEAS-2B (bronchial epithelium) cell line was assessed and fluorescence microscopy studies were performed for their cellular localization. Among them, 2a-Cl exhibited the most potent anticancer activity, being higher than cisplatin. However, 2b-Cl and 2c-Cl,-PF6 were the least toxic, while 2b-PF6 and 3a-PF6 exhibited only moderate activity. Confocal microscopy studies for 2a-Cl suggest that complexes localize preferentially in the lysosomes and to a lesser extent in the cytoplasm, but ultimately causing damage to the mitochondria. Finally, the potential photodynamic behaviour of scarcely toxic complexes 2b-Cl, 2b-PF6, 2c-Cl and 3a-PF6 was also studied.
通过使用α,ω-二丁基-2,2'-联吡啶-4,4'-二甲酰胺作为二亚胺（N^N）以及独特的环金属化基团，本研究报道了一类新型的阳离子磷光铱（III）环金属化[Ir(C^N)(N^N)]X化合物[C^N = 二氟苯基吡啶（dfppy）a、2,6-二氟-3-（吡啶-2-基）苯甲醛（CHO-dfppy）b和2,6-二氟-3-吡啶-2-基苯甲酸（COOH-dfppy）c；X = Cl（2a、b、c-Cl）；X = PF6（2b、c-PF6）]。为作比较，还展示了相关配合物[Ir(dfppy)(Hdcbpy)]（3a-PF6），其包含3,3'-二羧基-2,2'-联吡啶作为辅助配体（N^N = Hdcbpy）。所有配合物均已得到充分表征，并对其光物理性质进行了详细研究。通过密度泛函理论（DFT）和含时密度泛函理论（TD-DFT）研究获得的理论计算结果表明，发光源自混合的ML'CT（Ir→N^N）/LL'CT（C^N→N^N）激发态，主要具有金属到二亚胺的电荷转移特性。评估了它们对肿瘤细胞系A549（肺癌）和HeLa（宫颈癌）以及非肿瘤BEAS-2B（支气管上皮）细胞系的抗肿瘤活性，并对其细胞定位进行了荧光显微镜研究。其中，2a-Cl表现出最有效的抗癌活性，高于顺铂。然而，2b-Cl和2c-Cl、-PF6毒性最小，而2b-PF6和3a-PF6仅表现出中等活性。对2a-Cl的共聚焦显微镜研究表明，配合物优先定位于溶酶体，在细胞质中的定位程度较小，但最终会对线粒体造成损伤。最后，还研究了低毒配合物2b-Cl、2b-PF6、2c-Cl和3a-PF6的潜在光动力行为。
