Kinetics and Mechanism of the Oxidation of Sugars and Nucleotides by Oxoruthenium(IV): Model Studies for Predicting Cleavage Patterns in Polymeric DNA and RNA

Neyhart, Gregory A.; Cheng, Chin‐Chi; Thorp, H. Holden

doi:10.1021/ja00110a001

Cited by 72 publications

(92 citation statements)

References 2 publications

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“…Oxochromium(V) complexes efficiently cleave ss-DNA predominantly through oxidation of deoxyribose, since 5-MF, an oxidation product of the sugar, was formed in this reaction (8)(9)(10)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38). Oxidation of DNA is accompanied by release of the four bases.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, other stable (or metastable) oxometal centers must be used to determine the redox chemistry of metal ions and nucleic acids. Oxoruthenium(IV) and oxoosmium(IV) complexes have thus been utilized in oxidation of calf thymus DNA and synthetic oligonucleotides by Thorp and co-workers (8)(9)(10). These authors reported that ruthenium(IV) complexes cleave DNA primarily through oxidation of the ribose and guanine base.…”

Section: Introductionmentioning

confidence: 99%

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Mechanisms of DNA damage by chromium(V) carcinogens

Bose

Fonkeng

Moghaddas

et al. 1998

Nucleic Acids Research

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Reactions of bis(2-ethyl-2-hydroxy-butanato)oxochromate(V) with pUC19 DNA, single-stranded calf thymus DNA (ss-ctDNA), a synthetic oligonucleotide, 5'-GATCTATGGACTTACTTCAAGGCCGGGTAATGCTA-3' (35mer), deoxyguanosine and guanine were carried out in Bis-Tris buffer at pH 7.0. The plasmid DNA was only nicked, whereas the single-stranded DNA suffered extensive damage due to oxidation of the ribose moiety. The primary oxidation product was characterized as 5-methylene-2-furanone. Although all four bases (A, C, G and T) were released during the oxidation process, the concentration of guanine exceeds the other three. Orthophosphate and 3'-phosphates were also detected in this reaction. Likewise, the synthetic oliogomer exhibits cleavage at all bases with a higher frequecncy at G sites. This increased cleavage at G sites was more apparent after treating the primary oxidation products with piperidine, which may indicate base oxidation as well. DNA oxidation is shown to proceed through a Cr(V)-DNA intermediate in which chromium(V) is coordinated through the phosphodiester moiety. Two alternative mechanisms for DNA oxidation by oxochromate(V) are proposed to account for formation of 5-methylene-2-furanone, based on hydrogen abstraction or hydride transfer from the C1' site of the ribose followed by hydration and two successive beta-eliminations. It appears that phosphate coordination is a prerequisite for DNA oxidation, since no reactions between chromium(V) and deoxyguanosine or guanine were observed. Two other additional pathways, hydrogen abstraction from C4' and guanine base oxidation, are also discussed.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mechanisms of DNA damage by chromium(V) carcinogens

Bose

Fonkeng

Moghaddas

et al. 1998

Nucleic Acids Research

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“…Oxidation of DNA deoxyribose at the C1′ position plays an important role in the chemistry of DNA damage by a variety of agents, such as (1,10-phenanthroline) copper complex [(OP) 2 Cu] (1-8), enediyne antibiotics (9)(10)(11)(12), cationic manganese porphyrins (13,14), chromium (V) complexes (15,16), oxoruthenium complexes (17), UV light (18), and ionizing radiation (19)(20)(21)(22). As shown in Scheme I, 2′ -deoxyribonolactone (dL), an alkaline-labile lesion that is structurally related to an abasic site, is believed to be an intermediate of the C1′ pathway.…”

Section: Introductionmentioning

confidence: 99%

The Release of 5-Methylene-2-Furanone from Irradiated DNA Catalyzed by Cationic Polyamines and Divalent Metal Cations

et al. 2005

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Release of 5-methylene-2-furanone (5-MF), a characteristic marker of DNA deoxyribose oxidative damage at the C1′ position, was observed in significant quantities from X-irradiated DNA. This observation, which held for DNA irradiated either in aqueous solution or as a film, requires postirradiation treatment at 90° C in the presence of polyamines and divalent metal cations at biological pH. The 5-MF product was quantified by using reverse-phase HPLC. The radiation chemical yield of 5-MF comprised more than 30% of the yield of total unaltered base release. Polylysine, spermine and Be(II) showed the strongest catalytic effect on 5-MF release, while Zn(II), Cu(II), Ni(II), putrescine and Mg(II) were substantially less efficient. We have hypothesized that the 5-MF release from irradiated DNA occurs through catalytic decomposition of the 2′ -deoxyribonolactone (dL) precursor through two consecutive β -and δ -phosphate elimination reactions. A stepwise character of the process was indicated by the S-shaped time course of 5-MF accumulation. If dL proves to be the precursor to 5-MF formation, it would then follow that dL is a very important lesion generated in DNA by ionizing radiation.

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“…In most of these studies, the complexes mediated single-and double-strand cleavage of plasmid DNA, leading to relaxed open circular (form II) and linear forms (form III), respectively [25 -29]. In some cases, Ru II polypyridyl complexes were found to photocleave DNA by sensitization of singlet oxygen ( 1 O 2 ) [15]. In others, 1 O 2 and superoxide anion radical (O .À 2 ) may play an important role in the photocleavage [9] [10] [30].…”

Section: (Dppz)]mentioning

confidence: 99%

Synthesis, Structure, DNA‐Binding Properties, and Cytotoxicity of Ruthenium(II) Polypyridyl Complexes

Liu¹,

Zeng²,

Jiang³

et al. 2010

Chemistry & Biodiversity

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Many ruthenium(II) complexes show high antitumor activities, and the in vitro antitumor activities are usually related to DNA binding. We designed and synthesized two Ru(II) polypyridyl complexes, [Ru(dmp)2(fpp)]2+ (dmp=2,9-dimethyl-1,10-phenanthroline; fpp=2-[3,4-(difluoromethylenedioxy)phenyl]imidazo[4,5-f] [1,10]phenanthroline and [Ru(phen)(2)(fpp)]2+ (phen=1,10-phenanthroline). The DNA-binding properties of these complexes have been investigated by spectroscopic titration, DNA melting experiments, viscosity measurements, and photoactivated cleavage. The mechanism studies of photocleavage revealed that singlet oxygen (1O2) and superoxide anion radical (O2(.-)) may play an important role in the photocleavage. The cytotoxicity of complexes 1 and 2 have been evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) method; complex 2 shows slightly higher anticancer potency than 1 does against all the cell lines screened.

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Kinetics and Mechanism of the Oxidation of Sugars and Nucleotides by Oxoruthenium(IV): Model Studies for Predicting Cleavage Patterns in Polymeric DNA and RNA

Cited by 72 publications

References 2 publications

Mechanisms of DNA damage by chromium(V) carcinogens

Mechanisms of DNA damage by chromium(V) carcinogens

The Release of 5-Methylene-2-Furanone from Irradiated DNA Catalyzed by Cationic Polyamines and Divalent Metal Cations

Synthesis, Structure, DNA‐Binding Properties, and Cytotoxicity of Ruthenium(II) Polypyridyl Complexes

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