Eukaryotic Cell Toxicity and HSA Binding of [Ru(Me4phen)(bb7)]2+ and the Effect of Encapsulation in Cucurbit[10]uril

Biyun Sun, Ian F Musgrave, Anthony I Day, Kirsten Heimann, F Richard Keene, J Grant Collins

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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 4p hen-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.

Original languageEnglish
Article number595
Number of pages12
JournalFrontiers in Chemistry
Issue numberNOV
Early online date2018
Publication statusPublished - 30 Nov 2018


  • Eukaryotic Cell Toxicity
  • HSA Binding
  • Effect of Encapsulation
  • Cytotoxicity
  • Ruthenium complexes
  • Cucurbit[10]uril
  • HSA binding
  • Supramolecular chemistry


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