title: Targeted guanine oxidation by a dinuclear copper(II) complex at single stranded/double stranded DNA junctions.
abstract: A dinuclear copper(II) complex [Cu(II)2(PD'O-)(H2O)2](ClO4)3 (5) with terminal Cu(II)-H(2)O moieties and a Cu...Cu distance of 4.13 A (X-ray structure) has been synthesized and characterized by EPR spectroscopy (ferromagnetic coupling observed) and cyclic voltammetry. Dizinc(II) and mononuclear copper(II) analogues [Zn(II)2(PD'O-)(H2O)2]3+ (7) and [Cu(II)(mPD'OH)(H2O)]2+ (6), respectively, have also been synthesized and structurally characterized. Reacting 5/MPA/O(2) (MPA = 3-mercaptopropionic acid) with DNA leads to a highly specific oxidation of guanine (G) at a junction between single- and double-stranded DNA. Mass spectrometric analysis of the major products indicates a gain of +18 and +34 amu relative to initial DNA strands. The most efficient reaction requires G at the first and second unpaired positions of each strand extending from the junction. Less reaction is observed for analogous targets in which the G cluster is farther from the junction or contains less than four Gs. Consistent with our previous systems, the multinuclear copper center is required for selective reaction; mononuclear complex 6 is not effective. Hydrogen peroxide as a substitute for MPA/O2 also does not lead to activity. Structural analysis of a [Cu(II)2(PD'O-)(G)]3+ complex (8) and dizinc analogue [Zn(II)(2)(PD'O-)(G)](ClO4)3 (9) (G = guanosine) reveals coordination of the G O6 and N7 atoms with the two copper (or zinc) centers and suggests that copper-G coordination likely plays a role in recognition of the DNA target. The Cu2-O2 intermediate responsible for guanine oxidation appears to be different from that responsible for direct-strand scission induced by other multinuclear copper complexes; the likely course of reaction is discussed.
authors.affiliation: Department of Chemistry, The Johns Hopkins University, Baltimore, MD 21218, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.forename: Narasimha N
authors.initials: NN
authors.lastname: Murthy
authors.forename: Joshua
authors.initials: J
authors.lastname: Telser
authors.forename: Lev N
authors.initials: LN
authors.lastname: Zakharov
authors.forename: Glenn P A
authors.initials: GP
authors.lastname: Yap
authors.forename: Arnold L
authors.initials: AL
authors.lastname: Rheingold
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Karlin
authors.forename: Steven E
authors.initials: SE
authors.lastname: Rokita
mesh_terms: D015097:3-Mercaptopropionic Acid / Q000737:chemistry; D003300:Copper / Q000737:chemistry*; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry*; D004277:DNA, Single-Stranded / Q000737:chemistry*; D004563:Electrochemistry; D004578:Electron Spin Resonance Spectroscopy; D016166:Free Radical Scavengers / Q000737:chemistry; D006147:Guanine / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D010084:Oxidation-Reduction; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D004277:DNA, Single-Stranded; D016166:Free Radical Scavengers; D009942:Organometallic Compounds; D006147:Guanine; D003300:Copper; D004247:DNA; D015097:3-Mercaptopropionic Acid