title: The Structure of Linkers Affects the DNA Binding Properties of Tethered Dinuclear Ruthenium(II) Metallo-Intercalators.
abstract: With the long-term aim of enhancing the binding properties of dinuclear RuII-based DNA light-switch complexes, a series of eight structurally related mono- and dinuclear systems are reported in which the linker of the bridging ligand has been modulated. These tethered systems have been designed to explore issues of steric demand at the binding site and the thermodynamic cost of entropy loss upon binding. Detailed spectroscopic and isothermal titration calorimetry (ITC) studies on the new complexes reveal that one of the linkers produces a dinuclear system that binds to duplex DNA with an affinity (Kb>107m-1) that is higher than its corresponding monometallic complex and is the highest affinity for a non-threading bis-intercalating metal complex. These studies confirm that the tether has a major effect on the binding properties of dinuclear complexes containing intercalating units and establishes key design rules for the construction of dinuclear complexes with enhanced DNA binding characteristics.
authors.affiliation: Department of Chemistry, University of Sheffield, Sheffield, S3 7HF, UK.
authors.forename: Hiwa K
authors.initials: HK
authors.lastname: Saeed
authors.affiliation: Physical Organic Chemistry Centre, School of Chemistry, Cardiff University, Main Building Park Place, Cardiff, CF10 3AT, UK.
authors.forename: Ibrahim Q
authors.initials: IQ
authors.lastname: Saeed
authors.affiliation: Physical Organic Chemistry Centre, School of Chemistry, Cardiff University, Main Building Park Place, Cardiff, CF10 3AT, UK.
authors.forename: Niklaas J
authors.initials: NJ
authors.lastname: Buurma
authors.affiliation: Department of Chemistry, University of Sheffield, Sheffield, S3 7HF, UK.
authors.forename: Jim A
authors.identifier: http://orcid.org/0000-0002-8662-7917
authors.initials: JA
authors.lastname: Thomas
mesh_terms: D001665:Binding Sites; D056831:Coordination Complexes / Q000737:chemistry*; D004247:DNA / Q000737:chemistry*; D007364:Intercalating Agents / Q000737:chemistry*; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D012428:Ruthenium / Q000737:chemistry*
chemical_list: D056831:Coordination Complexes; D007364:Intercalating Agents; D008024:Ligands; D012428:Ruthenium; D004247:DNA
keywords: DNA; intercalation; isothermal titration calorimetry (ITC); luminescence; ruthenium