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通过与联吡啶和菲咯啉配体结合的[Au(N N)Cl(NHC)][PF]配合物进行生物膜破坏;靶向膜脂的强效抗菌剂。

Biofilm Demolition by [Au(N N)Cl(NHC)][PF] Complexes Fastened with Bipyridine and Phenanthroline Ligands; Potent Antibacterial Agents Targeting Membrane Lipid.

作者信息

Sahu Priyanka, Chakraborty Sourav, Isab A A, Mandal Santi M, Dinda Joydev

机构信息

Department of Chemistry, Utkal University, Vani Vihar, Bhubaneswar, Odisha, 751004, India.

Department of Bioscience and Biotechnology, Indian Institute of Technology Kharagpur, Kharagpur, West Bengal, 721302, India.

出版信息

Chempluschem. 2025 Jan;90(1):e202400543. doi: 10.1002/cplu.202400543. Epub 2024 Nov 13.

DOI:10.1002/cplu.202400543
PMID:39434616
Abstract

The development of new antibacterial drugs is essential for staying ahead of evolving antibiotic resistant bacterial (ARB) threats, ensuring effective treatment options for bacterial infections, and protecting public health. Herein, we successfully designed and synthesized two novel gold(III)- NHC complexes, [Au(1)(bpy)Cl][PF] (2) and [Au(1)(phen)Cl][PF] (3) based on the proligand pyridyl[1,2-a]{2-pyridylimidazol}-3-ylidene hexafluorophosphate (1⋅HPF) [bpy=2,2'-bipyridine; phen=1,10-phenanthroline]. The synthesized complexes were characterized spectroscopically; their geometries and structural arrangements were confirmed by single crystal XRD analysis. Complexes 2 and 3 showed photoluminescence properties at room temperature and the time-resolved fluorescence decay confirmed the fluorescence lifetimes of 0.54 and 0.62 ns respectively; which were used to demonstrate their direct interaction with bacterial cells. Among the two complexes, complex 3 was found to be more potent against the bacterial strains (Staphylococcus aureus, Gram-positive and Pseudomonas aeruginosa, Gram-negative bacteria) with the MIC values of 8.91 μM and 17.82 μM respectively. Studies revealed the binding of the complexes with the fundamental phospholipids present in the cell membrane of bacteria, which was found to be the leading cause of bacterial cell death. Cytotoxicity was evaluated using an MTT assay on 293 T cell lines; emphasizing the potential therapeutic uses of the Au(III)-NHC complexes to control bacterial infections.

摘要

开发新型抗菌药物对于应对不断演变的抗生素耐药细菌(ARB)威胁、确保细菌感染的有效治疗选择以及保护公众健康至关重要。在此,我们基于前体配体吡啶基[1,2-a]{2-吡啶基咪唑}-3-亚基六氟磷酸盐(1·HPF)[bpy = 2,2'-联吡啶;phen = 1,10-菲咯啉]成功设计并合成了两种新型金(III)-NHC配合物,[Au(1)(bpy)Cl][PF](2)和[Au(1)(phen)Cl][PF](3)。通过光谱对合成的配合物进行了表征;通过单晶XRD分析确认了它们的几何形状和结构排列。配合物2和3在室温下表现出光致发光特性,时间分辨荧光衰减分别证实了荧光寿命为0.54和0.62 ns;这些用于证明它们与细菌细胞的直接相互作用。在这两种配合物中,发现配合物3对细菌菌株(金黄色葡萄球菌,革兰氏阳性菌和铜绿假单胞菌,革兰氏阴性菌)更有效,MIC值分别为8.91 μM和17.82 μM。研究揭示了配合物与细菌细胞膜中存在的基本磷脂的结合,这被发现是细菌细胞死亡的主要原因。使用MTT法在293 T细胞系上评估了细胞毒性;强调了金(III)-NHC配合物在控制细菌感染方面的潜在治疗用途。

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