Radical-based Oxidation Research Articles

Radical-mediated dimerization and oxidation reactions for the synthesis of complex alkaloids.

Concise and general strategies for radical-based dimerization of cyclotryptamine and cyclotryptophan derivatives in addition to radical-based oxidation of structurally complex diketopiperazines are discussed. The impact of these radical-based chemistries on the rapid generation of molecular complexity is highlighted using representative examples from recent complex homodimeric alkaloid total syntheses. Additionally, a new and general strategy for radical-based directed heterodimerization of cyclotryptamine substructures via solvent-caged unsymmetrical diazene fragmentation is discussed.

Isolation and characterization of α-amylase from thermophilic Geobacillus stearothermophilus

Metabolite formation from radical-based oxidation of the environmental pollutant triclosan (TCS) was compared using an ascomycete (Phoma sp. UHH 5-1-03) and a basidiomycete (Trametes versicolor) laccase, laccase-redox mediator systems, and electrochemical oxidation (EC). Laccase oxidation predominantly yielded TCS di- and trimers, but notably also caused TCS ether bond cleavage. The latter was more prominent during EC-catalysed TCS oxidation, which generally resulted in a broader and more divergent product spectrum. By contrast, only quantitative but not qualitative differences in TCS metabolite formation were observed for the two laccases. Application of the presumable natural laccase redox mediator syringaldehyde (SYD) shifted the TCS-transforming reactions of laccase systems from oligomerization more towards ether bond cleavage. However, the observed rapid removal of SYD from reaction systems caused by predominant adduct formation from SYD and TCS, and concomitant conversion of SYD into 2,6-dimethoxy-1,4-benzoquinone (DMBQ) clearly demonstrates that SYD does not function as a “true” laccase redox mediator in the sense of being recycled during TCS oxidation. Laccase treatment of TCS without SYD decreased the anti-bacterial TCS activity more than treatment employing SYD in addition, indicating that SYD and/or its transformation products contribute to bacterial toxicity. DMBQ was found to be about 80% more active in a bacterial growth inhibition test than its parent compound SYD in terms of IC20 values. These observations establish DMBQ as a potential cause of toxicity effects of SYD-laccase systems. They further illustrate that a natural origin of a redox mediator does not automatically qualify its use as environmentally benign or non-hazardous.

Advanced oxidation of the surfactant SDBS by means of hydroxyl and sulphate radicals

The objective of the present study was to characterize the removal of the model surfactant sodium dodecylbenzene sulfonate (SDBS) from waters using several radical-based water treatment processes. Fenton's reagent has shown high efficacy in surfactant degradation at pH 2 but does not mineralize the dissolved contaminant and is ineffective at pH 7. Due to a low quantum yield ( Φ < 0.12 mol −1 Einstein −1), direct photooxidation is not very effective to remove SDBS from aqueous solutions. The presence of H 2O 2 and K 2S 2O 8 during irradiation generates highly oxidizing radicals that enhance the SDBS degradation rate by radical-based oxidation processes. The UV/K 2S 2O 8 system is the most effective process, because this process can produce the generation of SO 4 − and HO radical for SDBS oxidation. Moreover, the results obtained in the presence of HO radical scavengers could indicate that SO 4 − is more selective than HO radicals. For a UV dose of 400 J m −2 the depletion yields determined were 0.4%, 15.6% and 27.8% for UV, UV/H 2O 2 ([H 2O 2] = 300 μM) and UV/K 2S 2O 8 ([K 2S 2O 8] = 300 μM) respectively, confirming that UV/K 2S 2O 8 process is the most efficient to oxidize SDBS.

Light-induced exacerbation of retinal degeneration in a rat model of Smith–Lemli–Opitz syndrome

Potentiation of retinal degeneration by intense light exposure, and its amelioration by an antioxidant, were studied in a rat model of Smith–Lemli–Opitz syndrome (SLOS), in comparison with normal (control) Sprague–Dawley rats. The SLOS model is created by treating rats with AY9944, a selective inhibitor of cholesterol synthesis at the level of 3β-hydroxysterol-Δ 7-reductase. A subset of rats was treated with dimethylthiourea (DMTU), a synthetic antioxidant, 24 and 1 hr prior to light exposure. Half of the animals (±DMTU) were exposed to intense, constant, green light (24 hr, 1700 lx, 490–580 nm), while the others were maintained in darkness. Subsequently all animals were returned to dim cyclic light (20–40 lx, 12 hr light–12 hr dark) for 2 weeks, after which electroretinograms were recorded. One eye from each rat was taken for histological and quantitative morphometric analyses; sterol analysis was performed on retinas from contralateral eyes. HPLC analysis confirmed the accumulation of 7-dehydrocholesterol (7DHC) in retinas of AY9944-treated rats; cholesterol represented >99% of the sterol in control retinas. Histology of retinas from unexposed, AY9944-treated rats (6-week-old) was normal. In contrast, age-matched, light-exposed rats exhibited massive photoreceptor cell loss in both the superior and inferior hemispheres, and concomitant rod and cone dysfunction. The severity and geographic extent of the damage was far greater than that observed in normal albino rats exposed to the same conditions. DMTU pre-treatment largely prevented these degenerative changes. These findings indicate that the AY9944-induced rat SLOS model is hypersensitive to intense light-induced retinal damage, relative to normal rats. DMTU protection against light-induced damage implicates free radical-based oxidation in the retinal degeneration process. Furthermore, the use of green light (corresponding to the absorption maxima of rhodopsin) implicates rhodopsin in the initiation of the pathobiological mechanism. We propose that generation of cytotoxic oxysterols (by-products of 7DHC oxidation) is an integral part of retinal cell death in the SLOS rat model, which is exacerbated by intense light. Furthermore, the results predict light-dependent potentiation of retinal degeneration in SLOS patients, and the possible ameliorative effects of antioxidant therapy.

Site-Selective Oxidation and Metal-Induced 2-Propynylation of Pyranose Derivatives en route to Tetrodotoxins

The radical-based site-selective oxidation of 2-hydroxyethyl acetals and the metal(Zn,Ti)-induced 2-propynylation of aldehydes can both be carried out successfully on highly functionalized oxygenated substrates, as demonstrated in the context of a synthetic plan for tetrodotoxin and its analogues, for which promising synthetic intermediates were prepared from D-mannopyranoses.

Oxidative catalysis by Mn 4O 46+ cubane complexes

The oxidation of a variety of substrates (thioethers, hydrocarbons, alkenes, benyzl alcohol and benzaldehyde) by t BuOOH catalyzed by Mn 4O 4(O 2PPh 2) 6 ( 1) and Mn 4O 4(O 2P( p-MePh) 2) 6 ( 2) is reported. These reactions illustrate the first examples of oxidative catalysis using a manganese-oxo complex with a Mn 4O 4 cubane core. These uncharged complexes contain Mn ions in a mixed valence oxidation state, formally Mn 4(2III, 2IV), and are bridged by bulky diphenylphosphinate chelates across each of the six faces of the cube. Using this system, methyl phenyl sulfide is selectively mono-oxygenated to methyl phenyl sulfoxide with high catalytic efficiency, and no evidence for further oxidation to the thermodynamically preferred sulfone. Toluene is oxidized to a mixture of benzyl alcohol, benzaldehyde, and benzoic acid with high catalytic efficiencies. Lower catalytic efficiencies are observed in the oxidation of styrene to a mixture of styrene oxide and benzaldehyde, of cyclohexene to a mixture of cyclohexene oxide, 2-cyclohexen-1-ol, and 2-cyclohexen-1-one, and of cyclohexane to a mixture of cyclohexanol and cyclohexanone. The observed product distribution from the oxidation of hydrocarbons has the characteristics of a free radical-based oxidation mechanism. However, the sulfoxidation and epoxidation activity of the 1 / t BuOOH system, as well as the observed steric preferences for less congested substrates, suggest that a metal-oxo centered oxidation mechanism is active in the reactions studied here. An intermediate species, characterized by a UV–VIS band centered at 610 nm is observed in all reaction mixtures, and forms upon reaction of 1 or 2 with t BuOOH . Preliminary evidence suggests this reactive intermediate may correspond to a Mn(V)O species. Kinetic studies suggest two pathways for oxidation: one involving an oxygen atom transfer (two-electron branch), and the other involving a hydrogen atom abstraction (one-electron branch).

Gaulin homogenization: a mechanistic study.

Free radical-based oxidation has been detected in the normal operating regime of the Gaulin homogenizer, demonstrating that cavitation occurs in this important industrial bioprocessing equipment. Free radical generation is suppressed by imposition of back pressure, proving that such cavitation occurs in the impingement section. The calculated value of the cavitation number is consistent with submerged jet cavitation, wherein a high-speed jet exiting from the valve gap accelerates fluid in the impingement region, creating the vacuum conditions for cavitation. Using polysaccharides as a model shear-sensitive compound, their breakage pattern in the homogenizer was characterized by molecular size and polydispersity and compared to those of fluid shear flows in capillary tubes and cavitating flow from a sonic horn. The results indicate that breakage occurs primarily by fluid shear, although a contribution by cavitation is also apparent when back pressure is applied. Because biological molecules can readily react with free radicals and the alterations caused thereby are subtle in nature, a thorough evaluation of the impact of free radicals in upstream homogenization is warranted.