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Eukaryotic Cell Toxicity and HSA Binding of [Ru(Me(4)phen)(bb(7))](2+) and the Effect of Encapsulation in Cucurbit[10]uril
The toxicity (IC(50)) of a series of mononuclear ruthenium complexes containing bis[4(4′-methyl-2,2′-bipyridyl)]-1,n-alkane (bb(n)) as a tetradentate ligand against three eukaryotic cell lines—BHK (baby hamster kidney), Caco-2 (heterogeneous human epithelial colorectal adenocarcinoma) and Hep-G2 (li...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6287197/ https://www.ncbi.nlm.nih.gov/pubmed/30560120 http://dx.doi.org/10.3389/fchem.2018.00595 |
Sumario: | The toxicity (IC(50)) of a series of mononuclear ruthenium complexes containing bis[4(4′-methyl-2,2′-bipyridyl)]-1,n-alkane (bb(n)) as a tetradentate ligand against three eukaryotic cell lines—BHK (baby hamster kidney), Caco-2 (heterogeneous human epithelial colorectal adenocarcinoma) and Hep-G2 (liver carcinoma)—have been determined. The results demonstrate that cis-α-[Ru(Me(4)phen)(bb(7))](2+) (designated as α-Me(4)phen-bb(7), where Me(4)phen = 3,4,7,8-tetramethyl-1,10-phenanthroline) showed little toxicity toward the three cell lines, and was considerably less toxic than cis-α-[Ru(phen)(bb(12))](2+) (α-phen-bb(12)) and the dinuclear complex [{Ru(phen)(2)}(2){μ-bb(12)}](4+). Fluorescence spectroscopy was used to study the binding of the ruthenium complexes with human serum albumin (HSA). The binding of α-Me(4)phen-bb(7) to the macrocyclic host molecule cucurbit[10]uril (Q[10]) was examined by NMR spectroscopy. Large upfield (1)H NMR chemical shift changes observed for the methylene protons in the bb(7) ligand upon addition of Q[10], coupled with the observation of several intermolecular ROEs in ROESY spectra, indicated that α-Me(4)phen-bb(7) bound Q[10] with the bb(7) methylene carbons within the cavity and the metal center positioned outside one of the portals. Simple molecular modeling confirmed the feasibility of the binding model. An α-Me(4)phen-bb(7)-Q[10] binding constant of 9.9 ± 0.2 × 10(6) M(−1) was determined by luminescence spectroscopy. Q[10]-encapsulation decreased the toxicity of α-Me(4)phen-bb(7) against the three eukaryotic cell lines and increased the binding affinity of the ruthenium complex for HSA. Confocal microscopy experiments indicated that the level of accumulation of α-Me(4)phen-7 in BHK cells is not significantly affected by Q[10]-encapsulation. Taken together, the combined results suggest that α-Me(4)phen-7 could be a good candidate as a new antimicrobial agent, and Q[10]-encapsulation could be a method to improve the pharmacokinetics of the ruthenium complex. |
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