Hydrated electrons induce the formation of interstrand cross-links in DNA modified by cisplatin adducts.

Double-stranded oligonucleotides containing cisplatin adducts, with and without a mismatched region, were exposed to hydrated electrons generated by gamma-rays. Gel electrophoresis analysis demonstrates the formation of cisplatin-interstrand crosslinks from the cisplatin-intrastrand species. The rate constant per base for the reaction between hydrated electrons and the double-stranded oligonucleotides with and without cisplatin containing a mismatched region was determined by pulse radiolysis to be 7 × 109 and 2 × 109 M-1 s-1, respectively. These results provide a better understanding of the radiosensitizing effect of cisplatin adducts in hypoxic tumors and of the formation of interstrand crosslinks, which are difficult for cells to repair.

Pulse radiolysis study on the reactivity of NO3˙ radical toward uranous(iv), hydrazinium nitrate and hydroxyl ammonium nitrate at room temperature and at 45 °C.

Concentrated nitric acid solutions subjected to radiation produce radicals of extreme importance in the reprocessing of spent nuclear fuel. Knowledge of the different rate constants of the reactions involved in this chemistry is needed to improve the efficiency of the process and to define safe operating practices. Pulse radiolysis measurements are performed to find the rate constant of the reaction between NO3˙ radicals and U(iv) in highly concentrated nitrate solution. The optimal stabilization conditions toward thermal oxidation are defined for the considered solutions at room temperature and at 45 °C by adding anti-nitrous agents such as hydrazinium nitrate (HN) and hydroxyl ammonium nitrate (HAN). The decay of the NO3˙ radical is monitored and its reaction rates with HN, HAN and U(iv) are found to be 1.3 × 105, 1.5 × 107 and 1.6 × 106 M-1 s-1 at room temperature. The latter value is more than 10 times lower than the one currently used in numerical codes for simulation of the long-term radiolytic degradation associated with the reprocessing and storage of spent nuclear waste. At 45 °C, conditions similar to the reprocessing of spent fuel, the values of the rate constants of NO3˙ radical toward HN, HAN and U(iv) increase and are found to be 2.6 × 105, 2.9 × 107 and 9.3 × 106 M-1 s-1.

Transient electrochemistry: beyond simply temporal resolution.

Some physicochemical intrigues for which transient electrochemistry was necessary to solve the problem are summarized in this feature article. First, we highlight the main constraints to be aware of to access to low time scales, and particularly focus on the effects of stray capacitances. Then, the electron transfer rate constant measured for redox molecules in a self-assembled monolayer configuration is compared to the conductance measured through the same systems, but at the single molecule level. This evidences strong conformational changes when molecules are trapped in the nanogap created between both electrodes. We also report about dendrimers, for which a short electrochemical perturbation induces creation of a diffusion layer within the molecule, allowing the electron hopping rate to be measured and analyzed in terms of molecular motions of the redox centers. Finally, we show that transient electrochemistry provides also useful information when coupled to other methodologies. For example, when an ultrasonic field drives very fast movements of a bubble situated above the electrode surface, the motion can be detected indirectly through a modification of the diffusion flux. Another field concerns pulse radiolysis, and we describe how the reactivity (at the electrode or within the solution) of radicals created by a radiolytic pulse can be quantified, widening the possibilities of electrochemistry to operate in biological media.

Radiosensitization of DNA by Cisplatin Adducts Results from an Increase in the Rate Constant for the Reaction with Hydrated Electrons and Formation of Pt(I).

Pulse radiolysis measurements of the decay of hydrated electrons in solutions containing different concentrations of the oligonucleotide GTG with and without a cisplatin adduct show that the presence of a cisplatin moiety accelerates the reaction between hydrated electrons and the oligonucleotide. The rate constant of the reaction is found to be 2.23 × 10(10) mol(-1) L s(-1), which indicates that it is diffusion controlled. In addition, we show for the first time the formation of a Pt(I) intermediate as a result of the reaction of hydrated electrons with GTG-cisplatin. A putative reaction mechanism is proposed, which may form the basis of the radiosensitization of cancer cells in concomitant chemoradiation therapy with cisplatin.

Guanosine radical reactivity explored by pulse radiolysis coupled with transient electrochemistry.

We follow the reactivity of a guanosine radical created by a radiolytic electron pulse both by spectroscopic and electrochemical methods. This original approach allows us to demonstrate that there is a competition between oxidation and reduction of these intermediates, an important result to further analyse the degradation or repair pathways of DNA bases.

One-electron oxidation and reduction of glycosaminoglycan chloramides: a kinetic study.

Hypochlorous acid and its acid-base counterpart, hypochlorite ions, produced under inflammatory conditions, may produce chloramides of glycosaminoglycans, these being significant components of the extracellular matrix (ECM). This may occur through the binding of myeloperoxidase directly to the glycosaminoglycans. The N-Cl group in the chloramides is a potential selective target for both reducing and oxidizing radicals, leading possibly to more efficient and damaging fragmentation of these biopolymers relative to the parent glycosaminoglycans. In this study, the fast reaction techniques of pulse radiolysis and nanosecond laser flash photolysis have been used to generate both oxidizing and reducing radicals to react with the chloramides of hyaluronan (HACl) and heparin (HepCl). The strong reducing formate radicals and hydrated electrons were found to react rapidly with both HACl and HepCl with rate constants of 1-1.7 × 10(8) and 0.7-1.2 × 10(8)M(-1)s(-1) for formate radicals and 2.2 × 10(9) and 7.2 × 10(8)M(-1)s(-1) for hydrated electrons, respectively. The spectral characteristics of the products of these reactions were identical and were consistent with initial attack at the N-Cl groups, followed by elimination of chloride ions to produce nitrogen-centered radicals, which rearrange subsequently and rapidly to produce C-2 radicals on the glucosamine moiety, supporting an earlier EPR study by M.D. Rees et al. (J. Am. Chem. Soc.125: 13719-13733; 2003). The oxidizing hydroxyl radicals also reacted rapidly with HACl and HepCl with rate constants of 2.2 × 10(8) and 1.6 × 10(8)M(-1)s(-1), with no evidence from these data for any degree of selective attack on the N-Cl group relative to the N-H groups and other sites of attack. The carbonate anion radicals were much slower with HACl and HepCl than hydroxyl radicals (1.0 × 10(5) and 8.0 × 10(4)M(-1)s(-1), respectively) but significantly faster than with the parent molecules (3.5 × 10(4) and 5.0 × 10(4)M(-1)s(-1), respectively). These findings suggest that these potential in vivo radicals may react in a site-specific manner with the N-Cl group in the glycosaminoglycan chloramides of the ECM, possibly to produce more efficient fragmentation. This is the first study therefore to conclusively demonstrate that reducing radicals react rapidly with glycosaminoglycan chloramides in a site-specific attack at the N-Cl group, probably to produce a 100% efficient biopolymer fragmentation process. Although less reactive, carbonate radicals, which may be produced in vivo via reactions of peroxynitrite with serum levels of carbon dioxide, also appear to react in a highly site-specific manner at the N-Cl group. It is not yet known if such site-specific attacks by this important in vivo species lead to a more efficient fragmentation of the biopolymers than would be expected for attack by the stronger oxidizing species, the hydroxyl radical. It is clear, however, that the N-Cl group formed under inflammatory conditions in the extracellular matrix does present a more likely target for both reactive oxygen species and reducing species than the N-H groups in the parent glycosaminoglycans.