Department of Chemistry, Faculty of Science, Cairo University, Gamma Street, Giza, Cairo 12613, Egypt.
Institut für Anorganische Chemie, Julius-Maximilians-Universität Würzburg, Am Hubland, D-97074 Würzburg, Germany.
Dalton Trans. 2020 Apr 7;49(14):4491-4501. doi: 10.1039/d0dt00451k.
Reaction between 2-(2'-pyridyl)benzimidazole derivatives and [{IrCl(η5-C5Me5)}2(μ-Cl)2] afforded mono- and binuclear "piano-stool" Ir(iii) compounds of type [IrnCln(η5-C5Me5)n(L)]Cln (n = 1, L = LET (1) and LSO3H (2); n = 2, L = LBN (3)), which were fully characterized, including the X-ray crystallographic analysis of 1. While the free ligands and compound 3 exhibited no toxicity to the tested microbes, compound 1 was highly potent against bacteria (MIC = 12.9-25.8 nM) and fungi (MIC < 0.40 nM). However, complex 1 induced damage to non-malignant cell lines (human embryonic kidney (HEK293), CC50 = 0.995 μg mL-1) and human RBCs (HC10 = 10.9 μg mL-1 and HC50 > 32 μg mL-1). Interestingly, complex 2, bearing the benzimidazole ligand with an alkylated sulfonate side chain (LSO3H), was selectively potent against C. neoformans with MIC value of 11.2 nM and was non-toxic to HEK293. According to DNA binding studies, compounds 1-3 could be considered as moderate metallo intercalators with a binding constant of 5.0 × 104-1.0 × 105 M-1. Alternatively, evidence was obtained, from ESI-MS measurements, for the non-covalent mode of binding of 2 to hen egg white lysozyme, while compounds 1 and 3 decomposed during the interaction with that protein. This may be attributed to the electrostatic and H-bonding interactions between the polar sulfonate group and charged protein side-chains.
2-(2'-吡啶基)苯并咪唑衍生物与[{IrCl(η5-C5Me5)}2(μ-Cl)2]反应，得到单核和双核“钢琴凳”型 Ir(iii)化合物[IrnCln(η5-C5Me5)n(L)]Cln(n=1,L=LET(1)和 LSO3H(2);n=2,L=LBN(3))，它们均经过了充分的表征，包括 1 的 X 射线晶体结构分析。虽然游离配体和化合物 3 对测试的微生物没有毒性，但化合物 1 对细菌（MIC=12.9-25.8 nM）和真菌（MIC<0.40 nM）具有很高的活性。然而，化合物 1 对非恶性细胞系（人胚肾（HEK293），CC50=0.995 μg mL-1）和人红细胞（HC10=10.9 μg mL-1 和 HC50>32 μg mL-1）造成损伤。有趣的是，带有烷化磺酸盐侧链（LSO3H）的苯并咪唑配体的 2 对 C. neoformans 具有选择性的高活性，MIC 值为 11.2 nM，对 HEK293 无毒。根据 DNA 结合研究，化合物 1-3 可以被认为是具有中等金属插入能力的化合物，其结合常数为 5.0×104-1.0×105 M-1。或者，通过 ESI-MS 测量获得了 2 与鸡卵清溶菌酶非共价结合的证据，而化合物 1 和 3 在与该蛋白相互作用时分解。这可能归因于极性磺酸盐基团与带电荷的蛋白质侧链之间的静电和氢键相互作用。
