Ludwig Gerd, Ranđelović Ivan, Dimić Dušan, Komazec Teodora, Maksimović-Ivanić Danijela, Mijatović Sanja, Rüffer Tobias, Kaluđerović Goran N
Institute of Chemistry, Martin Luther University Halle-Wittenberg, Kurt-Mothes-Straße 2, D-06120 Halle, Germany.
Department of Immunology, Institute for Biological Research "Sinisa Stankovic"-National Institute of the Republic of Serbia, University of Belgrade, Bulevar Despota Stefana 142, 11108 Belgrade, Serbia.
Biomolecules. 2024 Mar 30;14(4):420. doi: 10.3390/biom14040420.
The (pentamethylcyclopentadienyl)chloridoiridium(III) complex bearing a κ,κ-bonded PhPCHCHSPh ligand ([Ir(η-CMe)Cl(PhP(CH)SPh-κκ)]PF, ()] was synthesized and characterized. Multinuclear (H, C and P) NMR spectroscopy was employed for the determination of the structure. Moreover, SC-XRD confirmed the proposed structure belongs to the "piano stool" type. The Hirshfeld surface analysis outlined the most important intermolecular interactions in the structure. The crystallographic structure was optimized at the B3LYP-D3BJ/6-311++G(d,p)(H,C,P,S,Cl)/LanL2DZ(Ir) level of theory. The applicability of this level was verified through a comparison of experimental and theoretical bond lengths and angles, and H and C NMR chemical shifts. The Natural Bond Orbital theory was used to identify and quantify the intramolecular stabilization interactions, especially those between donor atoms and Ir(III) ions. Complex was tested on antitumor activity against five human tumor cell lines: MCF-7 breast adenocarcinoma, SW480 colon adenocarcinoma, 518A2 melanoma, 8505C human thyroid carcinoma and A253 submandibular carcinoma. Complex showed superior antitumor activity against cisplatin-resistant MCF-7, SW480 and 8505C cell lines. The mechanism of tumoricidal action on 8505C cells indicates the involvement of caspase-induced apoptosis, accompanied by a considerable reduction in ROS/RNS and proliferation potential of treated cells.
合成并表征了带有κ,κ-键合的PhPCHCHSPh配体（[Ir(η-CMe)Cl(PhP(CH)SPh-κκ)]PF，()）的（五甲基环戊二烯基）氯铱（III）配合物。采用多核（H、C和P）核磁共振光谱法测定结构。此外，单晶X射线衍射证实所提出的结构属于“钢琴凳”类型。 Hirshfeld表面分析概述了该结构中最重要的分子间相互作用。在B3LYP-D3BJ/6-311++G(d,p)(H,C,P,S,Cl)/LanL2DZ(Ir)理论水平上对晶体结构进行了优化。通过比较实验和理论键长、键角以及H和C核磁共振化学位移，验证了该理论水平的适用性。运用自然键轨道理论识别并量化分子内稳定相互作用，特别是供体原子与Ir(III)离子之间的相互作用。对配合物针对五种人类肿瘤细胞系进行了抗肿瘤活性测试：MCF-7乳腺腺癌、SW480结肠腺癌、518A2黑色素瘤、8505C人甲状腺癌和A253下颌下腺癌。配合物对顺铂耐药的MCF-7、SW480和8505C细胞系表现出优异的抗肿瘤活性。对8505C细胞的杀肿瘤作用机制表明半胱天冬酶诱导的细胞凋亡参与其中，同时伴随着处理细胞的ROS/RNS和增殖潜能的显著降低。
