Catalytic Hydroxylation Research Articles

Egg yolk phosvitin inhibits hydroxyl radical formation from the fenton reaction.

Phosvitin, a phosphoprotein known as an iron-carrier in egg yolk, binds almost all the yolk iron. In this study, we investigated the effect of phosvitin on Fe(II)-catalyzed hydroxyl radical ((.-)OH) formation from H(2)O(2) in the Fenton reaction system. Using electron spin resonance (ESR) with 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) and deoxyribose degradation assays, we observed by both assays that phosvitin more effectively inhibited (.-)OH formation than iron-binding proteins such as ferritin and transferrin. The effectiveness of phosvitin was related to the iron concentration, indicating that phosvitin acts as an antioxidant by chelating iron ions. Phosvitin accelerates Fe(II) autoxidation and thus decreases the availability of Fe(II) for participation in the (.-)OH-generating Fenton reaction. Furthermore, using the plasmid DNA strand breakage assay, phosvitin protected DNA against oxidative damage induced by Fe(II) and H(2)O(2). These results provide insight into the mechanism of protection of the developing embryo against iron-dependent oxidative damage in ovo.

Comparative study of photo- and thermal catalytic hydroxylation of phenol with H2O2over TS-1

The hydroxylation of phenol into catechol (CAT) and hydroquinone (HQ) with hydrogen peroxide and TS-1 catalyst was carried out via both photo- and dark (thermal) reactions. The conversion of phenol and the product ratio of CAT/HQ in the photocatalytic reaction were higher than those in dark (thermal) reaction.

Immobilized Osmium Clusters in the Processes of Liquid-Phase Oxidation of Cycloxehene

The reaction of catalytic hydroxylation of olefins by organic hydroperoxides in the presence of osmium carbonyl clusters supported on polymer matrices is studied. The process occurs with the predominant formation of unsaturated alcohols. The oxidative coupling of olefins with the formation of nonconjugated dienes and in which the double bonds remain intact occurs in parallel. In the course of the reaction, changes in the chemical structures of the initial osmium clusters are not observed.

α-Fe2O3 Nanowires. Confined Synthesis and Catalytic Hydroxylation of Phenol

Abstract α-Fe2O3 nanowires were prepared using mesoporous silica SBA-15 as a template and showed a remarkable catalytic activity for the hydroxylation of phenol with 30% H2O2 in aqueous solution at 343 K.

The 1.5-Å Structure of Chryseobacterium meningosepticum Zinc β-Lactamase in Complex with the Inhibitor, D-Captopril

The crystal structure of the class-B beta-lactamase, BlaB, from the pathogenic bacterium, Chryseobacterium meningosepticum, in complex with the inhibitor, d-captopril, has been solved at 1.5-A resolution. The enzyme has the typical alphabeta/betaalpha metallo-beta-lactamase fold and the characteristic two metal binding sites of members of the subclass B1, in which two Zn2+ ions were identified. d-Captopril, a diastereoisomer of the commercial drug, captopril, acts as an inhibitor by displacing the catalytic hydroxyl ion required for antibiotic hydrolysis and intercalating its sulfhydryl group between the two Zn2+ ions. Interestingly, d-captopril is located on one side of the active site cleft. The x-ray structure of the complex of the closely related enzyme, IMP-1, with a mercaptocarboxylate inhibitor, which also contains a sulfhydryl group bound to the two Zn2+ ions, shows the ligand to be located on the opposite side of the active site cleft. A molecule generated by fusion of these two inhibitors would cover the entire cleft, suggesting an interesting approach to the design of highly specific inhibitors.

Catalytic hydroxylation of benzene and cyclohexane using in situ generated hydrogen peroxide: new mechanistic insights and comparison with hydrogen peroxide added directly

Hydrogen peroxide is considered an ideal “green” oxidant due to its high oxidizing ability and lack of toxic by-products. Herein, we report on an oxidation procedure that couples metallic palladium-catalyzed in situ hydrogen peroxide generation from dihydrogen and dioxygen with a second vanadium or iron catalyst that utilizes the hydrogen peroxide for the hydroxylation of benzene and cyclohexane. Studies indicate that the slow step in the overall reaction is the formation of usable hydrogen peroxide, and the mechanism of hydroxylation by the second catalyst is not affected by the presence of metallic palladium. The reported procedure, which resembles monoxygenases, allows the direct use of dioxygen in catalytic oxidations. Comparisons between the in situ method of hydrogen peroxide generation and hydrogen peroxide added via syringe pump show that the in situ method is more selective. Additionally, new insight into the mechanism of vanadium-catalyzed benzene hydroxylation is reported. Mechanistic investigations include the observation of a high NIH shift, the use of a radical cation rearrangement probe, and the first use of H218O enrichment studies. Based on these, an electron transfer mechanism resulting in a radical cation intermediate is proposed.

Vitamin C (Ascorbic Acid) Induced Hydroxyl Radical Formation in Copper Contaminated Household Drinking Water: Role of Bicarbonate Concentration

We have previously shown that Vitamin C (ascorbic acid) can trigger hydroxyl radical formation in copper contaminated household drinking water. We report here that the capacity of ascorbic acid to catalyze hydroxyl radical generation in the drinking water samples is strongly dependent on the bicarbonate concentration (buffer capacity and pH) of the samples. We found that at least 50 mg/l bicarbonate was required in the water samples to maintain the pH over 5.0 after ascorbic acid addition. At this pH, that is higher than the pKa1 4.25 of ascorbic acid, a hydroxyl radical generating redox cycling reaction involving the mono-anion of vitamin C and copper could take place. The ascorbic acid induced hydroxyl radical generating reaction could easily be mimicked in Milli-Q water by supplementing the water with copper and bicarbonate. Our results demonstrate that ascorbic acid can induce a pH dependent hydroxyl radical generating reaction in copper contaminated household tap water that is buffered with bicarbonate. The impact of consuming ascorbic acid together with copper and bicarbonate containing drinking water on human health is discussed.

Liquid-Phase Catalytic Hydroxylation of Phenol Using Cu(II), Ni(II) and Zn(II) Complexes of Amidate Ligand Encapsulated in Zeolite-Y as Catalysts

Copper(II), nickel(II) and zinc(II) complexes of amidate ligand 1,2-bis(2-hydroxybenzamido)ethane(H2hybe) encapsulated in the super cages of zeolite-Y have been prepared and characterized by spectroscopic studies and thermal as well as X-ray diffraction (XRD) patterns. These complexes catalyze the liquid-phase hydroxylation of phenol with H2O2 to catechol as a major product and hydroquinone as a minor product. Considering the concentration of substrate and oxidant, amount of catalyst, temperature of the reaction and volume of solvent, a best-suited reaction condition has been optimized to get maximum hydroxylation. Under the optimized reaction conditions, [Cu(hybe)]-Y has shown the highest conversion of 40% after 6 h, which is followed by [Ni(hybe)]-Y with 37% conversion and [Zn(hybe)]-Y has shown the poorest performance with 33% conversion. All these catalysts are more selective towards catechol formation (∼90%), irrespective of their catalytic performance.

Catalytic hydroxylation of phenol over CuM(II)M(III) ternary hydrotalcites, where M(II) = Ni or Co and M(III) = Al, Cr or Fe

In large-scale industry, the WGS reaction is the most widely used method for the purification of hydrogen obtained from natural gas. This is a process that hinges on factors such as temperature, pressure, type of catalyst, etc. In this work, copper-based solids were obtained from hydrotalcites, which were characterized through various techniques and evaluated within the WGS reaction at different temperatures. Hydrotalcite-type precursors displayed thermal behaviors that depend on their composition, whereby higher temperatures become necessary for the collapse of the HTLc structure in the solids with higher zinc and aluminum content. The calcination of precursors led to the formation of CuO particles in all the materials, which were more resistant to the reduction processes as the aluminum content augmented. The catalysts were active in the reaction under study with C0.50Z0.25A0.25 being the most active material due to the higher content of metallic copper on the surface. The most effective material in terms of metallic copper content present on the surface was C0.33Z0.33A0.33, in which the occurrence of CuO was not evinced after its use, in addition to displaying the smallest particle size of Cu0 as well as, possibly, the existence of Cu–Zn interactions on the surface.

Catalytic hydroxylation of 2,3,6-trimethylphenol with hydrogen peroxide over copper hydroxyphosphate (Cu 2(OH)PO 4)

Catalytic hydroxylation of 2,3,6-trimethylphenol with hydrogen peroxide over copper hydroxyphospate Cu 2(OH)PO 4 was studied. Catalytic data shows that the Cu 2(OH)PO 4 catalyst is active, giving the theoretical conversion at 40.2%. The main products in this reaction are trimethylhydroquinone and trimethylbenzoquinone; there is particularly high selectivity for trimethylhydroquinone. When the reaction is carried out in air, the selectivity for trimethylhydroquinone is at 72.2% and when the reaction is carried out under N 2, the selectivity is at 94.7%. The other important factors associated with the catalytic properties have been investigated extensively.

Catalytic hydroxylation using chloroplatinum compounds

Using “PtCl 4” as the Pt(IV) component in the mixture of aqueous chloroPt(II)/chloroPt(IV) compounds makes the “Shilov” functionalization of alkyl groups considerably faster and more chemoselective to alcohols, and adding hydrogen peroxide re-oxidizes the Pt(II) reduction product to Pt(IV). Run in this manner, the reaction system is long-lived and catalytic in platinum.

Molecular and cellular mechanisms of iron homeostasis and toxicity in mammalian cells

Iron is an essential metal for almost all living organisms due to its involvement in a large number of iron-containing enzymes and proteins, yet it is also toxic. The mechanisms involved in iron absorption across the intestinal tract, its transport in serum and delivery to cells and iron storage within cells is briefly reviewed. Current views on cellular iron homeostasis involving the iron regulatory proteins IRP1 and IRP2 and their interactions with the iron regulatory elements, affecting either mRNA translation (ferritin and erythroid cell δ-aminolaevulinate synthase) or mRNA stability (transferrin receptor) are discussed. The potential of Fe(II) to catalyse hydroxyl radical formation via the Fenton reaction means that iron is potentially toxic. The toxicity of iron in specific tissues and cell types (liver, macrophages and brain) is illustrated by studies with appropriate cellular and animal models. In liver, the high levels of cyoprotective enzymes and antioxidants, means that to observe toxic effects substantial levels of iron loading are required. In reticuloendothelial cells, such as macrophages, relatively small increases in cellular iron (2–3-fold) can affect cellular signalling, as measured by NO production and activation of the nuclear transcription factor NFκB, as well as cellular function, as measured by the capacity of the cells to produce reactive oxygen species when stimulated. The situation in brain, where anti-oxidative defences are relatively low, is highly regionally specific, where iron accumulation in specific brain regions is associated with a number of neurodegenerative diseases. In the brains of animals treated with either trimethylhexanoylferrocene or aluminium gluconate, iron and aluminium accumulate, respectively. With the latter compound, iron also increases, which may reflect an effect of aluminium on the IRP2 protein. Chelation therapy can reduce brain aluminium levels significantly, while iron can also be removed, but with greater difficulty. The prospects for chelation therapy in the treatment and possible prevention of neurodegenerative diseases is reviewed.

Catalytic hydroxylation of phenol over ternary hydrotalcites containing Cu, Ni and Al

Liquid phase catalytic hydroxylation of phenol was carried out over ternary hydrotalcites containing copper, nickel and aluminum using hydrogen peroxide as oxidant. The influence of various reaction parameters, namely, substrate:catalyst ratio, substrate:oxidant ratio, nature of oxidant, solvent, pH, time-on-stream, reaction temperature and calcination temperature on the activity and selectivity for the “sought for” reaction, were studied. The catalysts were synthesized by the coprecipitation technique using metal nitrates and a NaOH/Na 2CO 3 mixture. Hydroxylation of phenol over these catalysts resulted mainly in the formation of catechol and hydroquinone. Among the catalysts studied, CuNiAl3-5 (( Cu+ Ni)/Al=3.0; Cu/Ni=5.0) and CuNiAl2-1 (( Cu+ Ni)/Al=2.0; Cu/Ni=1.0) showed maximum activity with a catechol:hydroquinone ratio close to 1.6. An increase in the substrate:catalyst ratio enhanced the conversion of phenol over these catalysts. With respect to the influence of reaction temperature, the conversion increased up to 65 °C and decreased when the temperature was further increased. Oxidants other than H 2O 2 and solvents other than water have not showed measurable conversion of phenol. Time-on-stream studies indicated that around 90% of conversion of phenol was achieved in 10 min and longer reaction time did not significantly enhance the conversion. Among the calcined samples studied, that calcined at 800 °C showed a maximum activity for phenol hydroxylation; however, the activities of calcined catalysts were lower than those of fresh hydrotalcites. The observed variation in the activity may be attributed to the copper concentration, especially those present on the surface. A reaction pathway involving hydroxy radical is proposed for the formation of dihydroxybenzenes.

Disease mechanisms revealed by transcription profiling in SOD1-G93A transgenic mouse spinal cord.

Mutations of copper,zinc-superoxide dismutase (cu,zn SOD) are found in patients with a familial form of amyotrophic lateral sclerosis. When expressed in transgenic mice, mutant human cu,zn SOD causes progressive loss of motor neurons with consequent paralysis and death. Expression profiling of gene expression in SOD1-G93A transgenic mouse spinal cords indicates extensive glial activation coincident with the onset of paralysis at 3 months of age. This is followed by activation of genes involved in metal ion regulation (metallothionein-I, metallothionein-III, ferritin-H, and ferritin-L) at 4 months of age just prior to end-stage disease, perhaps as an adaptive response to the mitochondrial destruction caused by the mutant protein. Induction of ferritin-H and -L gene expression may also limit iron catalyzed hydroxyl radical formation and consequent oxidative damage to lipids, proteins, and nucleic acids. Thus, glial activation and adaptive responses to metal ion dysregulation are features of disease in this transgenic model of familial amyotrophic lateral sclerosis.

Catalytic hydroxylation of steroids by cytochrome P-450 mimics. Hydroxylation at C-9 with novel catalysts and steroid substrates

Double binding of a steroid substrate to our previously described mimic of the cytochrome P-450 enzymes hydroxylates carbon 9 of the steroid, but with a second significant product. The geometry has been adjusted with new catalysts that show high selectivity and excellent turnover for the C-9 hydroxylation.

Synthesis, characterization and catalytic hydroxylation of phenol over CuCoAl ternary hydrotalcites

Copper–cobalt–aluminium hydrotalcites with (Cu + Co)/Al atomic ratio of 3.0 and Cu/Co atomic ratios 80:20, 75:25, 50:50, 33:67, 25:75 and 20:80 were synthesized by coprecipitation under low supersaturation and characterized by various physicochemical techniques. Powder X-ray diffraction (PXRD) showed a single phase with a resemblance to hydrotalcite, whose crystallinity increased with increasing copper concentration. A continuous blue shift of the νOH band with a concomitant red shift in the ν2 vibration of the carbonate was observed with increasing cobalt content. Thermal analysis of these samples showed a significant variation depending on the nature of the atmosphere, more marked at higher temperatures, owing to the possibility of oxidation of cobalt. UV–vis spectroscopy showed absorption maxima close to 750 and 530 nm with the former becoming stronger and the latter weaker as the copper content is increased. TPR of fresh samples substantiated the lack of oxidation of cobalt, as evidenced by an M/H2 (M = Cu + Co) ratio for these samples close to 1.0. N2 adsorption measurements showed type II isotherms with a hysteresis loop closing at P/P0 = 0.45. The total pore volume, the specific surface area and the area of the hysteresis loop increased with cobalt content. Thermal calcination of these samples at 500°C showed a diffuse pattern exhibiting both a tenorite and a spinel phase, whose peak intensities varied with Cu/Co atomic ratio. TPR for these samples showed higher M/H2 values, suggesting partial oxidation of Co2+. Liquid phase hydroxylation of phenol was carried out over these catalysts using H2O2 as oxidant. Among the catalysts studied, that with a Cu:Co atomic ratio of 3:1 showed the maximum activity with a catechol: hydroquinone ratio close to 3.4. An increase in substrate:catalyst ratio enhanced the conversion of phenol. Oxidants other than H2O2 and solvents other than water did not show measurable conversion of phenol. Time-on-stream studies indicated that 80% conversion of phenol was achieved in 10 min. The normalized activity of these catalysts indicated the influence of cobalt, probably together with surface properties, on the intrinsic activity of copper in controlling the course of reaction. A reaction pathway involving hydroxyl radical is proposed.

Assessment of Structural Features of the Pseudomonas Siderophore Pyochelin Required for Its Ability to Promote Oxidant-Mediated Endothelial Cell Injury

We previously showed that iron chelated to the Pseudomonas aeruginosa siderophore pyochelin enhances oxidant-mediated injury to pulmonary artery endothelial cells by catalyzing hydroxyl radical (HO•) formation. Therefore, we examined pyochelin structural/chemical features that may be important in this process. Five pyochelin analogues were examined for (i) capacity to accentuate oxidant-mediated endothelial cell injury, (ii) HO• catalytic ability, (iii) iron transfer to endothelial cells, and (iv) hydrophobicity. All compounds catalyzed similar HO• production, but only the hydrophobic ones containing a thiazolidine ring enhanced cell injury. Transfer of iron to endothelial cells did not correlate with cytotoxicity. Finally, binding of Fe3+ by pyochelin led to Fe2+ formation, perhaps explaining how Fe3+–pyochelin augments H2O2-mediated cell injury via HO• formation. The ability to bind iron in a catalytic form and the molecule's thiazolidine ring, which increases its hydrophobicity, are key to pyochelin's cytotoxicity. Reduction of Fe3+ to Fe2+ may also be important.

Generation of hydroxyl radicals by the antiviral compound phosphonoformic acid (foscarnet).

Phosphonoformic acid (foscarnet) is an antiviral agent that is used to treat severe cytomegalovirus infections in AIDS patients. We demonstrate by using the ferrous iron indicator Ferrozine and ascorbic acid (vitamin C) that foscarnet can chelate ferric iron and form a redox-active iron complex. By using the hydroxyl radical indicator coumarin-3-carboxylic acid we found that the foscarnet-Fe3 complex formed can readily catalyze hydroxyl radical (.OH) generation by the Fenton reaction: (Fe2+ + H2O2-4Fe3+ + .OH + -OH) if hydrogen peroxide and ascorbic acid are present. Hydroxylation of coumarin-3-carboxylic acid could be blocked by addition of known hydroxyl radical scavengers such as mannitol, sucrose, glucose and dimethyl sulfoxide. Moreover, by using a DNA nicking assay, we found that foscarnet catalyzed hydroxyl radicals can induce single strand brakes in DNA. The potency of the hydroxyl radicals formed to induce damage could also be demonstrated in a phosphate-free buffer where the hydroxyl radicals formed attacked and liberated phosphate from the foscarnet molecule. Our results indicate that foscarnet catalyzed hydroxyl radical formation might take place during conditions where a peroxide generating system(s), vitamin C and transitions metals are present.

Generation of Hydroxyl Radicals by the Antiviral Compound Phosphonoformic Acid (Foscarnet)

Abstract: Phosphonoformic acid (foscarnet) is an antiviral agent that is used to treat severe cytomegalovirus infections in AIDS patients. We demonstrate by using the ferrous iron indicator Ferrozine and ascorbic acid (vitamin C) that foscarnet can chelate ferric iron and form a redox‐active iron complex. By using the hydroxyl radical indicator coumarin‐3‐carboxylic acid we found that the foscarnet‐Fe3 complex formed can readily catalyze hydroxyl radical (˙OH) generation by the Fenton reaction: (Fe2++ H2O2→Fe3++˙OH +−OH) if hydrogen peroxide and ascorbic acid are present. Hydroxylation of coumarin‐3‐carboxylic acid could be blocked by addition of known hydroxyl radical scavengers such as mannitol, sucrose, glucose and dimethyl sulfoxide. Moreover, by using a DNA nicking assay, we found that foscarnet catalyzed hydroxyl radicals can induce single strand brakes in DNA. The potency of the hydroxyl radicals formed to induce damage could also be demonstrated in a phosphate‐free buffer where the hydroxyl radicals formed attacked and liberated phosphate from the foscarnet molecule. Our results indicate that foscarnet catalyzed hydroxyl radical formation might take place during conditions where a peroxide generating system(s), vitamin C and transitions metals are present.

Studies on 24-Membered Macrocyclic Mononuclear and Dinuclear Iron Complexes: Stability and Catalytic Hydroxylation of Adamantane by Divalent Iron Complexes.

Studies on 24-Membered Macrocyclic Mononuclear and Dinuclear Iron Complexes: Stability and Catalytic Hydroxylation of Adamantane by Divalent Iron Complexes.