title: Thermodynamic investigations of [(phen)2Ru(tatpp)Ru(phen)2](4+) interactions with B-DNA.
abstract: While the antitumor activity of P(4+) is relatively well understood, the binding mechanism and thermodynamics for formation of (P(4+)·DNA) complexes remain in question. The thermodynamic parameters (Ka, ΔG, ΔH, and -TΔS) for formation of DNA complexes of the ruthenium dimer, [(phen)2Ru(tatpp)Ru(phen)2](4+) (abbreviated as P(4+)), where phen is 1,10-phenanthroline and tatpp is 9,11,20,22-tetraazatetrapyrido[3,2-a:2',3'-c:3″,2″-1:2‴,3‴-n]-pentacene, were determined using isothermal titration calorimetry. Calorimetric and spectroscopic titration experiments were performed in which P(4+) was added to three duplex DNAs of different lengths. We determined that P(4+) binds to duplex DNA at 298 K with modest affinity (Ka ≈ 3.8 × 10(5) M(-1), ΔG ≈ -7.6 kcal/mol), that the enthalpy change is unfavorable (ΔH ≈ +2.1 kcal/mol), and that complex formation is driven by a large favorable change in entropy (-TΔS ≈ -9.7 kcal/mol). These thermodynamic values were found to be approximately independent of the length of the DNA, and the stoichiometry of the (P(4+)·DNA) complexes was determined to be 1 P(4+)/2 DNA bp, at least for the two shorter DNAs. On the basis of the thermodynamic parameters, and the binding stoichiometry (verified in ESI-MS experiments), we conclude that P(4+) is intercalating between two adjacent DNA base pairs and that the neighbor sites on either side of the bound ligand are excluded from binding additional P(4+).
authors.affiliation: Department of Chemistry and Biochemistry, University of Texas at Arlington , Arlington, Texas 76019, United States.
authors.forename: Vu H
authors.initials: VH
authors.lastname: Le
authors.forename: Matthew R
authors.initials: MR
authors.lastname: McGuire
authors.forename: Pooja
authors.initials: P
authors.lastname: Ahuja
authors.forename: Frederick M
authors.initials: FM
authors.lastname: MacDonnell
authors.forename: Edwin A
authors.initials: EA
authors.lastname: Lewis
mesh_terms: D000818:Animals; D002151:Calorimetry; D002417:Cattle; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry*; D006576:Heterocyclic Compounds, 4 or More Rings / Q000737:chemistry*; D009942:Organometallic Compounds / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization; D013816:Thermodynamics
chemical_list: C500978:((Phen)(2)Ru(tatpp)Ru(phen)(2)); D006576:Heterocyclic Compounds, 4 or More Rings; D009942:Organometallic Compounds; D004247:DNA; C427203:calf thymus DNA