Timothy E. Cummings

Electrochemical reduction of uracil in dimethyl sulfoxide: Autoprotonation of the anion radical

The electrochemical redi the apparent number of electrons transferred (n) decreases from one at infiiite dilution to one-half at concentrations above 1 mM. The concentration dependent n-value is due to proton transfer by the parent compound to the radical anion Formed on reduction. Such a proton transfer, which has been observed for 2-hydroxypyrimidine, deactivates part of the uracil, which would otherwise be available for reduction, by formation of the more difficultly reducible conjugate base. The uracil anion forms insoluble mercury salts, producing two oxidation waves (El12 of -0.1 and -0.3 V); the latter wave is due to formation of a passivating film on the eiectrode. Digital simulations indicate that the protonation rate exceeds 105 M--ls--1 and that, at low uracil concentration, some of the free radical formed on protonation is further reduced. At concentrations exceeding 1 m.M, all of the free radical dime&es. The effect of added acids and base on the electrochemical behavior is described.

Adsorption of adenine at an aqueous solution|/mercury interface☆

Abstract The faradaic and non—faradaic capacitive currents and other behavioral manifestations seen for a 10 μM solution of adenine in pH 4.8 mcilvaine buffer (0.5 M ionic strength) on d.c. polarography, phase—selective a.c. polarography, normal pulse polarography, and rapid scan—rate cyclic voltammetry (including linear potential sweep amperometry) at dropping mercury and hanging mercury drop electrodes, have been analyzed in terms of the adsorptive behavior of the adenine and of chemical reactions coupled to the adsorption of adenine and its faradaic reduction in the adsorbed and unadsorbed states. Important variables included the prepolarization potential, i.e., the potential at which the electrode was held prior to initiation of a perturbation in terms of an increase in potential, and the periods of time for which the prepolarization potential was maintained and during which the potential perturbation occurred, as well as the period of time before the current was sampled after the perturbation was applied.

Construction, operation and evaluation of a rapid-response potentiostat

Abstract Factors involved in construction and utilization of an inexpesive, rapid-response potentiostat with 50 mA current capabilities are discussed. The potentiostat can be used with ancillary units, eg function generators, for a variety of rapid pertubation approaches, eg cyclic voltammetry at scan rates to 4000 V/s or greater, potential-step chronoamperometry with data acquisition after 40 μs or less, pulse polarography at millisecond or shorter discharge times, and phase-selective ac polarography at frequencies to at least 15 kHz. Examination of the Fe(III/II) couple reversibility in oxalate media, the adsorption of adenine, and the dimerization of the NAD free radical are described.

Adenine and cytosine: Basic polarographic behavior and its interpretation☆

Abstract The basic information concerning the behavior on electrochemical reduction in aqueous media at mercury electrodes of cytosine, adenine, model compounds, their nucleosides and nucleotides, and their simpler polymers, is summarized and interpreted with particular reference to the effects of the addition of sugar and sugar—phosphate substituents on the course of the faradaic redox process, intermediate chemical steps in that process, the kinetics and energetics of individual steps, association in solution, and adsorption at the solution|electrode interface and association in the adsorbed state. Since cytosine and adenine are the only two nucleic acid bases, which are normally electrochemically reducible in aqueous media, it is hoped that the discussion will provide the background necessary for the interpretation of the observed behavior on electrochemical reduction ( e.g. , at dropping and hanging drop mercury electrodes) of polymeric species as in the polarographic studies of DNA and RNA, and synthetic polynucleotides.

Electrochemical reduction of uridine in dimethyl sulfoxide: effect of the ribose group

Abstract The easier electrochemical reduction of uridine (1-β-D-ribofuranosyluracil) in dimethyl sulfoxide as compared to uracil (2, 4-dihydroxypyrimidine) by ca. 0.1 V is explicable on the basis of the electron-withdrawing effect of the ribose group. This effect and possible steric hindrance by the ribose group markedly affect the reaction sequence following the initial one-electron reduction to generate a radical anion, which abstracts a proton from the parent uridine (father—son reaction) to form the neutral uridine free radical and the uridine anion. With increasing uridine concentration, further reduction and protonation reactions are favored, resulting in an increase in the effective faradaic n from ca. 0.5 to 0.8. The availability of only one proton-donating site on uridine, ie, that on N(3), allows explication of the behavior of other hydroxypyrimidines such as uracil.

The systemic effect of burn injury and trauma on muscle and bone mass and composition

Background: By understanding the global inflammatory effects on distant myopathies, surgeons can better guide the rehabilitative process for burn patients. The authors tested the systemic effect of burn injury on distant injured muscle and native bone using immunohistochemistry and validated a new morphometric analytic modality to reproducibly quantify muscle atrophy using computed tomographic imaging. Methods: In vivo studies were performed on C57/BL6 mice using an Achilles tenotomy with concurrent burn injury model. Total muscle and bone (tibia and fibula) volume/density were quantified near the site of Achilles tenotomy using micro–computed tomography at 5, 7, and 9 to 12 weeks after surgery. The impact of burn injury on the inflammatory cascade [nuclear factor (NF)-&kgr;B, p-NF-&kgr;B] and the interconnected protein catabolism signaling pathway (Atrogin-1) was assessed by immunohistochemistry. Results: Muscle volume and density at the site of Achilles tenotomy in burned mice were significantly diminished compared with nonburned mice at 5 weeks and 9 to 12 weeks. Similar decreases in muscle volume and density were observed when comparing tenotomy to no tenotomy. Cortical bone health remained stable in burn/tenotomy mice compared with tenotomy. Muscle atrophy was associated with up-regulation of p-NF-&kgr;B, NF-&kgr;B, and Atrogin-1 assessed by immunohistochemistry. Conclusions: Burn injury significantly decreases muscle volume and density. Increased muscle atrophy using our computed tomographic morphometric analysis correlated with a significant increase in intramuscular inflammatory markers and proteolysis enzymes. This study demonstrates a unique characterization of how burn injuries may worsen local myopathy. Moreover, it provides a novel approach for quantifying muscle atrophy over an expanded period.

Calculation of adsorption-related parameters from a.c. polarographic data:: Basis and Computer Programs

Abstract Phase-selective alternating current polarography can be advantageously used for the observation and quantitative description of adsorption at a solution—electrode interface; for example, in the absence of a faradaic process, the quadrature current component is simply related to the interfacial differential capacity. Such a.c. measurements are especially advantageous for the occasional investigation of adsorption. The basis of using such measurements is considered; the data analysis is examined; specifics for computer calculation of differential capacity, surface charge density, and relative surface excess, and the requirements for data smoothing are described. The computer programs developed are sufficiently general for handling special situations.