MECHANISM OF THE REDUCTION OF WATER BY REDUCED METHYL VIOLOGEN MEDIATED BY PLATINIZED ALUMINA - H/D ISOTOPE EFFECTS

The rate of oxidation of reduced methyl viologen (MV+4) by water, catalyzed by colloidal Pt/Al2O3, is reduced by a factor of congruent-to 5 when D2O is used as a solvent rather than H2O in the presence of a pH 4.40 acetate buffer. In contrast, the rate measured in the presence of a pH 3.05 buffer is reduced only slightly when D2O replaces H2O. H/D isotope separation factors for the methyl viologen mediated reduction of water to hydrogen catalyzed by Pt/Al2O3 are 4.22 (+/- 0.15) at pH 4.40 and 5.99 (+/- 0.11) at pH 3.05, at 25-degrees-C. These data are interpreted in terms of the electrochemical model for metal-catalyzed redox reactions with a pH-dependent mechanism for the hydrogen-evolving reaction. It is proposed that hydrogen atom combination on the catalyst surface is the rate-limiting step at pH 4.40, whereas at pH 3.05 diffusion of MV2+4 is rate limiting and hydrogen evolution proceeds via the electrochemical reaction between a surface-adsorbed hydrogen atom and a solution-phase proton.

Photoelectrochemistry with quinone radical anions: Kinetics of homogeneous redox catalysis

Cyclic voltammograms of quinones were recorded in acetonitrile in the presence of various substrates: carbonyl compounds, halobenzenes, Methyl Viologen and Neutral Red. When illuminated with light of λ >410 nm, catalytic waves were observed. From the ratio of the catalysed to uncatalysed peak current, electron transfer rate constants were calculated using the working curves of Saveant and coworkers. The values of these rate constants were compared with the values obtained by Shukla and Rusling for different systems using a similar method and with quenching rate constants calculated using Rehm-Weller-Marcus theory.

Photoelectrochemistry using quinone radical anions

The photoelectrochemistry of quinone radical anions has been demonstrated qualitatively by the photoassisted reduction of methyl viologen with benzoquinone and of neutral red with chloranil. Data were then collected for the estimation of quenching rate constants using Marcus-Weller theory. Reduction potentials of seven quinones were obtained in four solvents (and two aqueous mixtures) by cyclic voltammetry. The solvent effects on these potentials were studied by fitting them to the Taft relationship. The effects of proton donors were also noted. Absorption spectra of the radical anions were measured and the solvent effects noted and commented upon. From the molar absorption coefficients of the radical anions, the mean lifetimes of the excited states were estimated. Fluorescence spectra were obtained for anthraquinone and naphthaquinone radical anions and excitation energies were calculated. These values were estimated for the other quinones. Values of redox potentials for the excited radical anions were thence obtained. The Gibbs energies of the electron transfers between the excited quinone radical anions and the various substrates were obtained and hence the Gibbs energies of activation were calculated using the Marcus equation. The quenching rate constants were calculated using the Rehm-Weller equation and plotted vs. ΔG giving a characteristic Marcus plot including some data in the inverted region. The significance of the inverted region is discussed.

In vitro phototoxicity of 5-aminolevulinic acid and its methyl ester and the influence of barrier properties on their release from a bioadhesive patch.

opical administration of excess exogenous 5-aminolevulinic acid (ALA) leads to selective accumulation of the potent photosensitiser protoporphyrin IX (PpIX) in neoplastic cells, which can then be destroyed by irradiation with visible light. Due to its hydrophilicity, ALA penetrates deep lesions, such as nodular basal cell carcinomas (BCCs) poorly. As a result, more lipophilic esters of ALA have been employed to improve tissue penetration. In this study, the in vitro release of ALA and M-ALA from proprietary creams and novel patch-based systems across normal stratum corneum and a model membrane designed to mimic the abnormal stratum corneum overlying neoplastic skin lesions were investigated. Receiver compartment drug concentrations were compared with the concentrations of each drug producing high levels of PpIX production and subsequent light-induced kill in a model neoplastic cell line (LOX). LOX cells were found to be quite resistant to ALA- and M-ALA-induced phototoxicity. However, drug concentrations achieved in receiver compartments were comparable to those required to induce high levels of cell death upon irradiation in cell lines reported in the literature. Patches released significantly less drug across normal stratum corneum and significantly more across the model membrane. This is of major significance since the selectivity of PDT for neoplastic lesions will be further enhanced by the delivery system. ALA/M-ALA will only be delivered in significant amounts to the abnormal tissue. PpIX will only then accumulate in the neoplastic cells and the normal surrounding tissue will be unharmed upon irradiation.

Influence of plasticizer type and storage conditions on properties of poly(methyl vinyl ether-co-maleic anhydride) bioadhesive films

Poly(methyl vinyl ether-co-maleic anhydride) formed films from aqueous formulations with characteristics that are ideal as a basis for producing a drug-containing bioadhesive delivery system when plasticized with a monohydroxyl functionalized plasticizer. Hence, films containing a novel plasticizer, tripropylene glycol methyl ether (TPME), maintained their adhesive strength and tensile properties when packaged in aluminized foil for extended periods of time. Films plasticized with commonly used polyhydric alcohols, such as the glycerol in this study, underwent an esterification reaction that led to polymer crosslinking, as shown in NMR studies. These revealed the presence of peaks in the ester/carbonyl region, suggesting that glyceride residue formation had been initiated. Given the polyfunctional nature of glycerol, progressive esterification would result in a polyester network and an accompanying profound alteration in the physical characteristics. Indeed, films became brittle over time with a loss of both the aqueous solubility and bioadhesion to porcine skin. In addition, a swelling index was measurable after 7 days, a property not seen with those films containing TPME. This change in bioadhesive strength and pliability was independent of the packaging conditions, rendering the films that contain glycerol as unsuitable as a basis for topical bioadhesive delivery of drug substances. Consequently, films containing TPME have potential as an alternative formulation strategy.

Large carbon isotope fractionation associated with oxidation of methyl halides by methylotrophic bacteria

The largest biological fractionations of stable carbon isotopes observed in nature occur during production of methane by methanogenic archaea. These fractionations result in substantial (as much as 70) shifts in 13C relative to the initial substrate. We now report that a stable carbon isotopic fractionation of comparable magnitude (up to 70) occurs during oxidation of methyl halides by methylotrophic bacteria. We have demonstrated biological fractionation with whole cells of three methylotrophs (strain IMB-1, strain CC495, and strain MB2) and, to a lesser extent, with the purified cobalamin-dependent methyltransferase enzyme obtained from strain CC495. Thus, the genetic similarities recently reported between methylotrophs, and methanogens with respect to their pathways for C1-unit metabolism are also reflected in the carbon isotopic fractionations achieved by these organisms. We found that only part of the observed fractionation of carbon isotopes could be accounted for by the activity of the corrinoid methyltransferase enzyme, suggesting fractionation by enzymes further along the degradation pathway. These observations are of potential biogeochemical significance in the application of stable carbon isotope ratios to constrain the tropospheric budgets for the ozone-depleting halocarbons, methyl bromide and methyl chloride.

A method for carbon stable isotope analysis of methyl halides and chlorofluorocarbons at pptv concentrations

A pre-concentration system has been validated for use with a gas chromatography/mass spectrometry/isotope ratio mass spectrometer (GC/MS/IRMS) to determine ambient air 13C/12C ratios for methyl halides (MeCl and MeBr) and chlorofluorocarbons (CFCs). The isotopic composition of specific compounds can provide useful information on their atmospheric budgets and biogeochemistry that cannot be ascertained from abundance measurements alone. Although pre-concentration systems have been previously used with a GC/MS/IRMS for atmospheric trace gas analysis, this is the first study also to report system validation tests. Validation results indicate that the pre-concentration system and subsequent separation technologies do not significantly alter the stable isotopic ratios of the target methyl halides, CFC-12 (CCl2F2) and CFC-113 (C2Cl3F3). Significant, but consistent, isotopic shifts of -27.5 to -25.6 do occur within the system for CFC-11 (CCl3F), although the shift is correctible. The method presented has the capacity to separate these target halocarbons from more than 50 other compounds in ambient air samples. Separation allows for the determination of stable carbon isotope ratios of five of these six target trace atmospheric constituents within ambient air for large volume samples (10 L). Representative urban air analyses from Belfast City are also presented which give carbon isotope results similar to published values for 13C/12C analysis of MeCl (-39.1) and CFC-113 (-28.1). However, this is the first paper reporting stable carbon isotope signatures for CFC-11 (-29.4) and CFC-12 (-37.0).

Solvation effects on equilibria: Triazoles and N-methyl piperidinol

We have performed calculations of the solvation effects on a number of equilibrium constants in water using a recently proposed hybrid quantum classical scheme in which the liquid environment is modelled using classical solvent molecules and the solute electronic structure is computed using modern quantum chemical methods. The liquid phase space is sampled from a fully classical simulation. We find that solvation effects on both triazole tautomeric equilibrium constants and piperidinol conformational equilibrium constants can be interpreted in terms of subtle differences in the local environment which can be seen in probability densities and radial distribution functions. Lower level calculations were performed for comparison and we conclude that the solvation thermodynamics can be predicted from a good classical model of solvent and solute molecules, but the implicit models that we tried are less successful.