Oxidative Damage by Ruthenium Complexes Containing the Dipyridophenazine Ligand or Its Derivatives:  A Focus on Intercalation

Delaney, Sarah; Pascaly, Matthias; Bhattacharya, Pratip K.; Han, Koun; Barton, Jacqueline K.

doi:10.1021/ic0111738

Cited by 230 publications

(195 citation statements)

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“…This chemistry was first developed to probe long-range electron transfer in proteins (38). Examining DNA CT using the flash͞quench technique has been particularly advantageous in that the methodology permits both spectroscopic studies to monitor formation of DNA radicals on a short time scale (16,(39)(40)(41) and biochemical analysis to determine the yield of oxidative damage occurring on a longer time scale (39)(40)(41)(42)(43). The flash͞quench experiment for DNA typically is carried out with dipyridophenazine (dppz) complexes of Ru(II), complexes that bind avidly to DNA by intercalation (44 (54).…”

mentioning

confidence: 99%

Protein–DNA charge transport: Redox activation of a DNA repair protein by guanine radical

Yavin

Boal²,

Stemp

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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117

124

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DNA charge transport (CT) chemistry provides a route to carry out oxidative DNA damage from a distance in a reaction that is sensitive to DNA mismatches and lesions. Here, DNA-mediated CT also leads to oxidation of a DNA-bound base excision repair enzyme, MutY. DNA-bound Ru(III), generated through a flash͞ quench technique, is found to promote oxidation of the 1؉ clusters. In ruthenium-tethered DNA assemblies, oxidative damage to the 5-G of a 5-GG-3 doublet is generated from a distance but this irreversible damage is inhibited by MutY and instead EPR experiments reveal cluster oxidation. With rutheniumtethered assemblies containing duplex versus single-stranded regions, MutY oxidation is found to be mediated by the DNA duplex, with guanine radical as an intermediate oxidant; guanine radical formation facilitates MutY oxidation. A model is proposed for the redox activation of DNA repair proteins through DNA CT, with guanine radicals, the first product under oxidative stress, in oxidizing the DNA-bound repair proteins, providing the signal to stimulate DNA repair.electron transfer ͉ iron-sulfur cluster ͉ oxidative DNA damage D NA-mediated charge transport (CT) from a distance to generate oxidative damage was first demonstrated in an assembly containing a tethered metallointercalator (1). In this assembly, photoinduced oxidative damage of the 5Ј-G of 5Ј-GG-3Ј sites was observed; this damage pattern has since become the hallmark of DNA CT chemistry, and long-range oxidative damage has been confirmed by using a variety of pendant oxidants (2-6). Long-range oxidative DNA damage has been demonstrated over a distance of at least 200 Å (7, 8). Indeed, DNA either packaged in nucleosome core particles (9) or inside the cell nucleus (10) has been found to be susceptible to long-range oxidative damage. Chemically well defined assemblies, consisting of DNA duplexes with covalently bound oxidants, have been particularly useful in establishing the sensitivity of DNA CT to base-stacking perturbation (11-16). Recently, analogous studies probing long-range reductive chemistry on DNA has been probed both in solution (17-20) and on DNAmodified surfaces (14,15,21). As with oxidation chemistry, these reactions show only small variations in rate with distance but are remarkably sensitive to perturbations in the intervening base pair stack. Mechanistic descriptions for DNA CT focused first on a mixture of hopping and tunneling. A phonon-assisted polaron model has also been put forth (22). Studies as a function of temperature have shown the CT process to be gated by base pair dynamics; in fact, base pair motions are required for CT (23, 24).We have therefore described DNA CT in the context of transport among delocalized DNA domains formed and dissolved based on sequence-dependent DNA dynamics.Given the exquisite sensitivity of DNA CT to DNA lesions and mismatches, we have recently explored a possible role for DNA CT in repair. We demonstrated that redox activity required DNA binding for MutY (25), a base excision repair (BER) enzyme fr...

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mentioning

confidence: 99%

Protein–DNA charge transport: Redox activation of a DNA repair protein by guanine radical

Yavin

Boal²,

Stemp

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

117

124

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“…λ 2 sinh (λN ) (22) where λ = (k r /k) 1/2 = 2 −1/2 α if expressed in the parameters used in our study. If λ is small, then sinh(λ) ≈ λ and eq 22 turns directly into eq 15a, which describes the same physical situation.…”

Section: Distance Dependencies Of Chemical Yields Under Steady-state mentioning

confidence: 99%

Diffusion Approach to Long Distance Charge Migration in DNA: Time-Dependent and Steady-State Analytical Solutions for the Product Yields

2004

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In this study we report analytical solutions for both time-dependent and steady-state problems of unbiased charge transfer through a regular DNA sequence via a hopping mechanism. The phenomenon is treated as a diffusion of charge in a one-dimensional array of equally spaced and energetically equivalent temporary trapping sites. The solutions take into account the rates of charge hopping (k), side reactions (k r ), and charge transfer to a terminal charge acceptor (k t ). A detailed analysis of the time-dependent problem is performed for the diffusion-controlled regime, i.e., under the assumption that k t ≫ k, which is also equivalent to the fast relaxation limit of charge trapping. The analysis shows that the kinetics of charge hopping through DNA is always multiexponential, but under certain circumstances it can be asymptotically approximated by a single-exponential term. In that case, the efficiency of charge transfer can be characterized by a single rate constant k CT = 1.23kN −2 + k r , where N is the DNA length expressed in terms of the number of equidistant trapping sites and k r is the rate of competing chemical processes. The absolute yield of charge transfer under steady-state conditions in general is obtained as Y ∞ = ω [α sinh(αN) + ω cosh(αN)] −1 , where α = (2k r /k) 1/2 and ω = 2k t /k. For the diffusion-controlled regime and small N, in particular, it turns into the known "algebraic" dependence Y ∞ = [1 + (k r /k)N 2 ] −1 . At large N the solution is asymptotically exponential with the parameter α mimicking the tunneling parameter β in agreement with earlier predictions. Similar equations and distance dependencies have also been obtained for the damage ratios at the intermediate and terminal trapping sites in DNA. The nonlinear least-squares fit of one of these equations to experimental yields of guanine oxidation available from the literature returns kinetic parameters that are in reasonable agreement with those obtained by Bixon et al. [Proc. Natl. Acad. Sci. U.S.A. 1999, 96, 11713-11716] by numerical simulations, suggesting that these two approaches are physically equivalent.

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“…[7] The pharmacological activity has also been found to be highly dependent on the nature of the metal ion and the donor sequence of the ligands as different ligands exhibit different biological properties. [8] There is a great deal of interest in the synthesis and characterization of transition metal complexes of heterocyclic compounds, in particular imidazole derivatives. The heterocyclic moiety benzimidazole plays an important role both in chemical and biological contexts, because it is structurally isostere of naturally occurring nucleotides; hence, it has been extensively utilized as a drug scaffold in the medicinal chemistry.…”

Section: Introductionmentioning

confidence: 99%

Antimicrobial and Spectral Studies of Zinc Metal Complexes Derived From Imidazo [4, 5-F] [1, 10] – Phenanthroline Derivative

Ghanwat¹

2017

WJPPS

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Oxidative Damage by Ruthenium Complexes Containing the Dipyridophenazine Ligand or Its Derivatives: A Focus on Intercalation

Cited by 230 publications

References 62 publications

Protein–DNA charge transport: Redox activation of a DNA repair protein by guanine radical

Protein–DNA charge transport: Redox activation of a DNA repair protein by guanine radical

Diffusion Approach to Long Distance Charge Migration in DNA: Time-Dependent and Steady-State Analytical Solutions for the Product Yields

Antimicrobial and Spectral Studies of Zinc Metal Complexes Derived From Imidazo [4, 5-F] [1, 10] – Phenanthroline Derivative

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