Protein binding by dinuclear polypyridyl ruthenium(ii) complexes and the effect of cucurbit[10]uril encapsulation

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dc.contributor.authorLi, F.
dc.contributor.authorFeterl, M.
dc.contributor.authorWarner, J.
dc.contributor.authorDay, A.
dc.contributor.authorKeene, F.
dc.contributor.authorCollins, J.
dc.date.issued2013
dc.description.abstractThe effect of human serum on the minimum inhibitory/bactericidal concentrations of the potential antimicrobial agents ΔΔ-[{Ru(phen)₂}₂(μ-bb(n))]⁴⁺ {ΔΔ-Rubb(n); where phen = 1,10-phenanthroline, bb(n) = 1,n-bis[4(4′-methyl-2,2′-bipyridyl)]-alkane for n = 12 and 16} against four strains of bacteria – Gram positive Staphylococcus aureus and methicillin-resistant S. aureus (MRSA), and Gram negative Escherichia coli and Pseudomonas aeruginosa – has been determined. The results demonstrated that the ruthenium(II) complexes have significantly decreased in vitro activity in serum. Fluorescence spectroscopy was used to confirm that the decrease in antimicrobial activity was due to the strong binding of the ruthenium complexes with the serum proteins human serum albumin (HSA) and transferrin. A series of ruthenium complexes showed stronger binding to HSA than apo-transferrin but comparable or less than with holo-transferrin, with the binding affinity to all three proteins decreasing in the order trinuclear > dinuclear > mononuclear. The dinuclear complex ΔΔ-Rubb₁₂ displaced warfarin from HSA, tentatively suggesting that the ruthenium complexes bind at or near the warfarin-binding site, Sudlow's site 1. The binding of ΔΔ-Rubb₁₂ and ΔΔ-Rubb₁₆ to the macrocyclic host molecule cucurbit[10]uril (Q[10]) was examined by NMR spectroscopy. The large upfield ¹H NMR chemical shift changes observed for the methylene protons in the bridging ligands upon addition of Q[10], coupled with the observation of a range of intermolecular ROEs in ROESY spectra, indicated that the dinuclear complexes bound Q[10] with the bridging ligand within the cavity and the metal centres positioned outside the portals. NMR and fluorescence spectroscopy demonstrated that the Q[10]-encapsulated ruthenium complexes directly bound HSA, and with similar affinity to the corresponding free metal complexes.
dc.description.statementofresponsibilityFangfei Li, Marshall Feterl, Jeffrey M. Warner, Anthony I. Day, F. Richard Keene and J. Grant Collins
dc.identifier.citationDalton Transactions: an international journal of inorganic chemistry, 2013; 42(24):8868-8877
dc.identifier.doi10.1039/c3dt50551k
dc.identifier.issn1477-9226
dc.identifier.issn1477-9234
dc.identifier.orcidKeene, F. [0000-0001-7759-0465]
dc.identifier.urihttp://hdl.handle.net/2440/79009
dc.language.isoen
dc.publisherRoyal Soc Chemistry
dc.relation.grantARC
dc.rightsCopyright status unknown
dc.source.urihttps://doi.org/10.1039/c3dt50551k
dc.subjectHumans
dc.subjectPseudomonas aeruginosa
dc.subjectEscherichia coli
dc.subjectStaphylococcus aureus
dc.subjectRuthenium
dc.subjectImidazoles
dc.subjectWarfarin
dc.subjectDoxycycline
dc.subjectSerum Albumin
dc.subjectTransferrin
dc.subjectAnti-Infective Agents
dc.subjectSpectrometry, Fluorescence
dc.subjectMagnetic Resonance Spectroscopy
dc.subjectMicrobial Sensitivity Tests
dc.subjectBinding Sites
dc.subjectMolecular Conformation
dc.subjectProtein Binding
dc.subjectModels, Chemical
dc.subjectMethicillin-Resistant Staphylococcus aureus
dc.subjectBridged-Ring Compounds
dc.titleProtein binding by dinuclear polypyridyl ruthenium(ii) complexes and the effect of cucurbit[10]uril encapsulation
dc.typeJournal article
pubs.publication-statusPublished

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