Oxidative damage by ruthenium complexes containing the dipyridophenazine ligand or its derivatives: A focus on intercalation

被引:218
作者
Delaney, S [1 ]
Pascaly, M [1 ]
Bhattacharya, PK [1 ]
Han, K [1 ]
Barton, JK [1 ]
机构
[1] CALTECH, Div Chem & Chem Engn, Pasadena, CA 91125 USA
关键词
D O I
10.1021/ic0111738
中图分类号
O61 [无机化学];
学科分类号
070301 ; 081704 ;
摘要
Interactions with DNA by a family of ruthenium(II) complexes bearing the dppz (dppz = dipyridophenazine) ligand or its derivatives have been examined. The complexes include Ru(bPY)(2)(dppX)(2+) (dppx = 7,8-dimethyldipyridophenazine), Ru(bpy)(2)(dpq)(2+) (dpq = dipyridoquinoxaline), and Ru(bpy)(2)(dpqC)(2+) (dpqC = dipyrido-6,7,8,9-tetrahydrophenazine). Their ground and excited state oxidation/reduction potentials have been determined using cyclic voltammetry and fluorescence spectroscopy, An intercalative binding mode has been established on the basis of luminescence enhancements in the presence of DNA, excited state quenching, fluorescence polarization values, and enantioselectivity. Oxidative damage to DNA by these complexes using the flash/quench method has been examined. A direct correlation between the amount of guanine oxidation obtained via DNA charge transport and the strength of intercalative binding was observed. Oxidative damage to DNA through DNA-mediated charge transport was also compared directly for two DNA-tethered ruthenium complexes. One contains the dppz ligand that binds avidly by intercalation, and the other contains only bpy ligands, that, while bound covalently, can only associate with the base pairs through groove binding, Long range oxidative damage was observed only with the tethered, intercalating complex. These results, taken together, all support the importance of close association and intercalation for DNA-mediated charge transport, Electronic access to the DNA base pairs, provided by intercalation of the oxidant, is a prerequisite for efficient charge transport through the DNA pi-stack.
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页码:1966 / 1974
页数:9
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共 68 条
  • [1] SYNTHESIS AND STUDY OF A MIXED-LIGAND RUTHENIUM(II) COMPLEX IN ITS GROUND AND EXCITED-STATES - BIS(2,2'-BIPYRIDINE)(DIPYRIDO[3,2-A, 2',3'-C]PHENAZINE-N4N5)RUTHENIUM(II)
    AMOUYAL, E
    HOMSI, A
    CHAMBRON, JC
    SAUVAGE, JP
    [J]. JOURNAL OF THE CHEMICAL SOCIETY-DALTON TRANSACTIONS, 1990, (06): : 1841 - 1845
  • [2] DESIGNED SYNTHESIS OF MONONUCLEAR TRIS(HETEROLEPTIC) RUTHENIUM COMPLEXES CONTAINING BIDENTATE POLYPYRIDYL LIGANDS
    ANDERSON, PA
    DEACON, GB
    HAARMANN, KH
    KEENE, FR
    MEYER, TJ
    REITSMA, DA
    SKELTON, BW
    STROUSE, GF
    THOMAS, NC
    TREADWAY, JA
    WHITE, AH
    [J]. INORGANIC CHEMISTRY, 1995, 34 (24) : 6145 - 6157
  • [3] High-intensity UV laser photolysis of DNA and purine 2'-deoxyribonucleosides: Formation of 8-oxopurine damage and oligonucleotide strand cleavage as revealed by HPLC and gel electrophoresis studies
    Angelov, D
    Spassky, A
    Berger, M
    Cadet, J
    [J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1997, 119 (47) : 11373 - 11380
  • [4] Rates of DNA-mediated electron transfer between metallointercalators
    Arkin, MR
    Stemp, EDA
    Holmlin, RE
    Barton, JK
    Hormann, A
    Olson, EJC
    Barbara, PF
    [J]. SCIENCE, 1996, 273 (5274) : 475 - 480
  • [5] ENANTIOMERIC RESOLUTION OF RU(PHEN)3(2+) AND RU(BPY)2PPZ2+ ON A DNA HYDROXYLAPATITE COLUMN
    BAKER, AD
    MORGAN, RJ
    STREKAS, TC
    [J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1991, 113 (04) : 1411 - 1412
  • [6] BINDING MODES AND BASE SPECIFICITY OF TRIS(PHENANTHROLINE)RUTHENIUM(II) ENANTIOMERS WITH NUCLEIC-ACIDS - TUNING THE STEREOSELECTIVITY
    BARTON, JK
    GOLDBERG, JM
    KUMAR, CV
    TURRO, NJ
    [J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1986, 108 (08) : 2081 - 2088
  • [7] METALS AND DNA - MOLECULAR LEFT-HANDED COMPLEMENTS
    BARTON, JK
    [J]. SCIENCE, 1986, 233 (4765) : 727 - 734
  • [8] DEOXYNUCLEOSIDE PHOSPHORAMIDITES - A NEW CLASS OF KEY INTERMEDIATES FOR DEOXYPOLYNUCLEOTIDE SYNTHESIS
    BEAUCAGE, SL
    CARUTHERS, MH
    [J]. TETRAHEDRON LETTERS, 1981, 22 (20) : 1859 - 1862
  • [9] Influence of intervening mismatches on long-range guanine oxidation in DNA duplexes
    Bhattacharya, PK
    Barton, JK
    [J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2001, 123 (36) : 8649 - 8656
  • [10] Mutation detection by electrocatalysis at DNA-modified electrodes
    Boon, EM
    Ceres, DM
    Drummond, TG
    Hill, MG
    Barton, JK
    [J]. NATURE BIOTECHNOLOGY, 2000, 18 (10) : 1096 - 1100