Fluorinated N-Heterocyclic Carbene Silver(I) Complexes with High Cancer Cell Selectivity

IF 2.5 3区化学 Q2 CHEMISTRY, INORGANIC & NUCLEAR Organometallics Pub Date : 2024-09-19 DOI:10.1021/acs.organomet.4c00292

Oliver S. King, Benjamin J. Hofmann, Aran E. Boakye-Smith, Amy J. Managh, Tameryn Stringer, Rianne M. Lord

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Abstract

This work presents the synthesis of five new functionalized (benz)imidazolium N-heterocyclic (NHC) ligands (L) and four new (benz)imidazole silver(I) NHC (Ag(I)-NHC) complexes of mononuclear [Ag(L)₂](PF₆) or binuclear [Ag₂(L)₂](PF₆)₂ type. The complexes have been fully characterized, including single crystal X-ray diffraction of three new structures. The complexes and their corresponding free NHC ligands have been screened against breast cancer and noncancerous cell lines, showing the mononuclear benzimidazole complex has the highest activity, while the binuclear benzimidazole complex has the highest cancer cell selectivity. The silver uptake was measured by ICP-MS and highlights a strong link between cytotoxicity and cellular uptake. DNA interaction studies, molecular docking, and evaluation of reactive oxygen species (ROS) have been conducted for the most promising complexes to identify modes of action. Overall, the binuclear benzimidazole complex is the most selective and promising candidate against the MDA-MD-231 (breast cancer) cell line and has potential to be developed for treatment of late-stage breast cancers.

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具有高癌细胞选择性的氟化 N-杂环羰基银（I）配合物

本研究合成了五种新的功能化（苯）咪唑鎓 N-杂环（NHC）配体（L）和四种新的（苯）咪唑银（I）NHC（Ag(I)-NHC）单核[Ag(L)2](PF6)或双核[Ag2(L)2](PF6)2 型配合物。这些配合物已得到全面表征，包括三种新结构的单晶 X 射线衍射。这些配合物及其相应的游离 NHC 配体针对乳腺癌和非癌细胞系进行了筛选，结果表明单核苯并咪唑配合物的活性最高，而双核苯并咪唑配合物对癌细胞的选择性最高。银的吸收是通过 ICP-MS 测量的，凸显了细胞毒性与细胞吸收之间的密切联系。对最有前景的复合物进行了 DNA 相互作用研究、分子对接和活性氧（ROS）评估，以确定其作用模式。总之，双核苯并咪唑复合物是对 MDA-MD-231（乳腺癌）细胞系最具选择性和前景的候选化合物，有望开发用于治疗晚期乳腺癌。

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来源期刊

Organometallics 化学-无机化学与核化学

CiteScore

5.60

自引率

7.10%

发文量

382

审稿时长

1.7 months

期刊介绍： Organometallics is the flagship journal of organometallic chemistry and records progress in one of the most active fields of science, bridging organic and inorganic chemistry. The journal publishes Articles, Communications, Reviews, and Tutorials (instructional overviews) that depict research on the synthesis, structure, bonding, chemical reactivity, and reaction mechanisms for a variety of applications, including catalyst design and catalytic processes; main-group, transition-metal, and lanthanide and actinide metal chemistry; synthetic aspects of polymer science and materials science; and bioorganometallic chemistry.

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