Catalytic Hydroxylation Research Articles

CYP4F3B Expression Is Associated with Differentiation of HepaRG Human Hepatocytes and Unaffected by Fatty Acid Overload

Fatty acid microsomal ω-oxidation involves cytochrome P450 enzymes. Some of them belonging to the CYP4F3 family are mainly expressed in the liver, making this organ a major player in energy homeostasis and lipid metabolism. To study this important regulation pathway, we used HepaRG cells, which gradually undergo a complete differentiation process. Even at the early stage of the differentiation process, CYP4F3B generated by alternative splicing of the CYP4F3 gene represented the prevalent isoform in HepaRG cells as in the liver. Its increasing expression associated with hepatocyte differentiation status suggested a hepatic-specific control of this isoform. As in liver microsomes, the catalytic hydroxylation of the CYP4F3B substrate [1-¹⁴C]Z9(10)-epoxystearic acid led to major production of 18-hydroxy-9(10)-epoxystearic acid. When treated with saturated, monounsaturated, or polyunsaturated fatty acids, CYP4F3B and CYP4A11 expression remained unchanged whereas CYP4F2 and CYP4F12 expression was transiently up-regulated. A 24-h exposure of differentiated HepaRG cells to various polyunsaturated fatty acids and derivatives induced microvesicular steatosis; down-regulation of lipid metabolism gene regulators such as sterol regulatory element-binding protein-1c, fatty acid synthase, peroxisome proliferator-activated receptor γ (PPARγ), PPARα, and decreased expression of glucose-dependent metabolism genes, which could limit de novo lipogenesis. Docosahexaenoic acid seemed to be the most effective compound. These results suggest that a PPARα-independent pathway could participate to limit lipogenesis and emphasize the role of hepatocytes in the fatty acid ω-hydroxylation pathway. They also give insights on the use of HepaRG hepatocytes to open new avenues of investigations on factors mediating the lipid metabolic pathway and finding new hypolipidemic molecules.

Catalytic hydroxylation of [Closo-B12H12]2−—adaptation of the Periana reaction to a polyhedral borane

Per-B-hydroxylation of a polyhedral borane anion has been demonstrated by the catalytic hydroxylation of icosahedral [closo-B(12)H(12)](2-) using soft electrophiles such as platinum group metal catalysts or iodine cation. A new route to [closo-B(12)(OH)(12)](2-) from [closo-B(12)H(12)](2-) without the use of H(2)O(2) oxidant provides an alternative hydroxylation process.

ChemInform Abstract: Catalytic Hydroxylation of Benzoic Acid with Hydrogen Peroxide.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: Hydroxylation of Aliphatic Hydrocarbons with m-Chloroperbenzoic Acid Catalyzed by Electron-Deficient Iron(III) Porphyrin Complexes.

The catalytic hydroxylation of aliphatic hydrocarbons by m-chloroperbenzoic acid (MCPBA) has been studied in the presence of elecrtron-deficient iron(III) porphyrin complexes. High yields of alcohol products were obtained with small amounts of ketone formation under mild reaction conditions. The stereospecificity and regioselectivity of the iron porphyrin complexes have been investigated in hydroxylation reactions as well. The hydroxylation of alkanes has been performed in the presence of isotopically 18O-labeled water, H218O, in order to understand the effects of the electronic nature of iron porphyrin complexes, the concentration of H218O, the C–H bond strength of alkanes, and the reaction temperature on the 18O-incorporation from the labeled water into alcohols. We found that the amounts of 18O incorporated into the alcohol products varied in the reactions; these results were interpreted with that the reaction of oxygen atom transfer from a high-valent iron oxoporphyrin complex to alkanes competes with...

Stable Bulky Particles Formed by TS‐1 Zeolite Nanocrystals in the Presence of H2O2

AbstractBulky particles of TS‐1 zeolite (larger than 20 μm) are successfully collected by simple filtration after crystallization of TS‐1 zeolite in the presence of H2O2. Bulky TS‐1 (B‐TS‐1) has good stability under both ultrasonic conditions and in recycling of the catalyst. Nitrogen isotherms show that B‐TS‐1 has a larger mesopore volume (0.55 cm3 g−1) than conventional TS‐1 nanocrystals (N‐TS‐1; less than 300 nm) obtained from high‐speed centrifugation (0.28 cm3 g−1). In catalytic hydroxylation of phenol with H2O2, both fresh (25 %) and recycled B‐TS‐1 (24 %) show similar high activities to N‐TS‐1 (28 %). B‐TS‐1 was further characterized by X‐ray diffraction, scanning electron microscopy, transmission electron microscopy, UV/Vis spectroscopy, and other techniques. The results suggest that bulky particles of B‐TS‐1 were formed by strong interactions of the nanocrystals with each other in the synthesis of TS‐1 zeolite. Such unique structural features might be responsible for the high stability of the bulky particles, large mesopore volume, and high catalytic activities in phenol hydroxylation, as well as the collection of B‐TS‐1 from a simple filtration route.

Anchoring of Fe(III)salicylamide onto MCM-41 for Catalytic Hydroxylation of Phenol in Aqueous Medium Using Hydrogen Peroxide as Oxidant

Fe(III)salicylamide immobilized on MCM-41 has been developed for hydroxylation of phenol in water medium using hydrogen peroxide as the oxidant. In the first step, the amine group containing 3-aminopropyltrimethoxy silane has been immobilized on the surface of MCM-41 via co-condensation. The amine group upon condensed with methyl salicylate afford a bidentate ligand in the mesoporous matrix for anchoring Fe(III) ions in the second step. Small angle XRD, N2 adsorption–desorption isotherms, 13C and 29Si cross-polarization magic angle spinning NMR spectroscopy, Fourier transform infrared spectroscopy (FT-IR) and diffuse reflectance UV–vis spectra were employed for the characterization of the catalysts. The heterogeneous iron salicylamide complex shows excellent catalytic activity in phenol hydroxylation using hydrogen peroxide as the oxidant and water as the solvent. Notably, phenol shows high conversion (64.6%) with very high selectivity for dihydroxybenzene compounds. The heterogeneous catalyst shows a successive slight decrease in catalytic activity when reused for three more times. Fe(III)salicylamide–MCM-41 has been synthesized successfully through an easy co-condensation route. XRD and N2 adsorption–desorption showed mesoporosity is retained even after complexation and FT-IR and diffuse reflectance UV–vis spectra confirmed the formation of complex. The heterogeneous catalyst exhibit excellent catalytic performance and stability in phenol hydroxylation reaction for the formation of dihydroxybenzene derivatives using H2O2.

Preparation and characterization of Mesopoous VO x/SBA-16 and their application for the direct catalytic hydroxylation of benzene to phenol

Vanadium oxide supported on mesoporous SBA-16 (VO x /SBA-16) catalysts have been prepared by the impregnation method and characterized by small-angle XRD, wide-angle XRD, TEM, N 2-physisorption, DRUV–vis, Raman spectrum and H 2-TPR. The VO x /SBA-16 catalysts retained the cubic cage-like pore structure of SBA-16. The dispersion and the nature of the vanadium species depend strongly on the V amount. At V loading of less than 3.6 wt%, isolated tetrahedral VO 4 is the main existence species that is highly dispersed in the pores of the support SBA-16. With the increase in V loading, the aggregation of isolated tetrahedral VO 4 species occurred to form polymerized VO 4 units. When the V loading was above 5.5 wt%, nanostructured V 2O 5 crystallites were formed besides aggregation of polymerized VO 4 units. VO x /SBA-16 with 7.3 wt% V showed excellent activity for the hydroxylation of benzene. The effect of reaction time, temperature and the amount of catalyst was investigated over VO x /SBA-16 (7.3 wt%) catalyst. The highest phenol yield and turnover number were 13.8% and 32.4, respectively, which were attributed to the formation of highly dispersed VO 4 species and polymerized VO 4 units. The TON and yield of phenol also increase in the presence of the V 2O 5 crystallites but its selectivity decreases.

PPIB Mutations Cause Severe Osteogenesis Imperfecta

Deficiency of cartilage-associated protein (CRTAP) or prolyl 3-hydroxylase 1(P3H1) has been reported in autosomal-recessive lethal or severe osteogenesis imperfecta (OI). CRTAP, P3H1, and cyclophilin B (CyPB) form an intracellular collagen-modifying complex that 3-hydroxylates proline at position 986 (P986) in the alpha1 chains of collagen type I. This 3-prolyl hydroxylation is decreased in patients with CRTAP and P3H1 deficiency. It was suspected that mutations in the PPIB gene encoding CyPB would also cause OI with decreased collagen 3-prolyl hydroxylation. To our knowledge we present the first two families with recessive OI caused by PPIB gene mutations. The clinical phenotype is compatible with OI Sillence type II-B/III as seen with COL1A1/2, CRTAP, and LEPRE1 mutations. The percentage of 3-hydroxylated P986 residues in patients with PPIB mutations is decreased in comparison to normal, but it is higher than in patients with CRTAP and LEPRE1 mutations. This result and the fact that CyPB is demonstrable independent of CRTAP and P3H1, along with reported decreased 3-prolyl hydroxylation due to deficiency of CRTAP lacking the catalytic hydroxylation domain and the known function of CyPB as a cis-trans isomerase, suggest that recessive OI is caused by a dysfunctional P3H1/CRTAP/CyPB complex rather than by the lack of 3-prolyl hydroxylation of a single proline residue in the alpha1 chains of collagen type I.

Synthesis and Characterization of V-HMS Employed for Catalytic Hydroxylation of Benzene

V-HMS catalysts with different vanadium content have been prepared by co-synthesis method using dodecylamine as template. The isolated VO4 species are successfully incorporated into the framework of HMS for the samples with low vanadium content. The effect of various reaction conditions on the hydroxylation of benzene to phenol with H2O2 as oxidant in aqueous acetic acid solvent was investigated where the yield of phenol achieves 11.1% under the optimized condition.

Characteristics and modifying factors of asbestos‐induced oxidative DNA damage

Respiratory exposure to asbestos has been linked with mesothelioma in humans. However, its carcinogenic mechanism is still unclear. Here we studied the ability of chrysotile, crocidolite and amosite fibers to induce oxidative DNA damage and the modifying factors using four distinct approaches. Electron spin resonance analyses revealed that crocidolite and amosite containing high amounts of iron, but not chrysotile, catalyzed hydroxyl radical generation in the presence of H(2)O(2), which was enhanced by an iron chelator, nitrilotriacetic acid, and suppressed by desferal. Natural iron chelators, such as citrate, adenosine 5'-triphosphate and guanosine 5'-triphosphate, did not inhibit this reaction. Second, we used time-lapse video microscopy to evaluate how cells cope with asbestos fibers. RAW264.7 cells, MeT-5 A and HeLa cells engulfed asbestos fibers, which reached not only cytoplasm but also the nucleus. Third, we utilized supercoiled plasmid DNA to evaluate the ability of each asbestos to induce DNA double strand breaks (DSB). Crocidolite and amosite, but not chrysotile, induced DNA DSB in the presence of iron chelators. We cloned the fragments to identify break sites. DSB occurred preferentially within repeat sequences and between two G:C sequences. Finally, i.p. administration of each asbestos to rats induced not only formation of nuclear 8-hydroxy-2'-deoxyguanosine in the mesothelia, spleen, liver and kidney but also significant iron deposits in the spleen. Together with the established carcinogenicity of i.p. chrysotile, our data suggest that asbestos-associated catalytic iron, whether constitutional or induced by other mechanisms, plays an important role in asbestos-induced carcinogenesis and that chemoprevention may be possible through targeting the catalytic iron.

A facile direct route to synthesize large-pore mesoporous silica incorporating high CuO loading with special catalytic property

CuO-loaded large-pore mesoporous SBA-15 silica was synthesized by a simple and efficient direct route in an acid media. Owing to a mesophase transformation behavior induced by inorganic salts, cubic mesostructued silica was also obtained in this system. Characterization of these mesostructured materials by the XRD, TEM, BET, FT–IR, UV–VIS, XPS, CV and ICP–AES showed that ∼37 wt.% or ∼45 wt.% copper oxide was directly introduced into hexagonal or cubic large-pore mesoporous silica, respectively. The mechanism study revealed that in-situ formation of a large amount of copper oxalate was the key step in this synthesis. The catalytic hydroxylation of benzene to phenol reveals that the direct-synthesized mesoporous CuO/silica showed the special catalytic property in comparison to the post-impregnated samples.

“Chelatable iron pool”: inositol 1,2,3-trisphosphate fulfils the conditions required to be a safe cellular iron ligand

Mammalian cells contain a pool of iron that is not strongly bound to proteins, which can be detected with fluorescent chelating probes. The cellular ligands of this biologically important "chelatable", "labile" or "transit" iron are not known. Proposed ligands are problematic, because they are saturated by magnesium under cellular conditions and/or because they are not "safe", i.e. they allow iron to catalyse hydroxyl radical formation. Among small cellular molecules, certain inositol phosphates (InsPs) excel at complexing Fe(3+) in such a "safe" manner in vitro. However, we previously calculated that the most abundant InsP, inositol hexakisphosphate, cannot interact with Fe(3+) in the presence of cellular concentrations of Mg(2+). In this work, we study the metal complexation behaviour of inositol 1,2,3-trisphosphate [Ins(1,2,3)P(3)], a cellular constituent of unknown function and the simplest InsP to display high-affinity, "safe", iron complexation. We report thermodynamic constants for the interaction of Ins(1,2,3)P(3) with Na(+), K(+), Mg(2+), Ca(2+), Cu(2+), Fe(2+) and Fe(3+). Our calculations indicate that Ins(1,2,3)P(3) can be expected to complex all available Fe(3+) in a quantitative, 1:1 reaction, both in cytosol/nucleus and in acidic compartments, in which an important labile iron subpool is thought to exist. In addition, we calculate that the fluorescent iron probe calcein would strip Fe(3+) from Ins(1,2,3)P(3) under cellular conditions, and hence labile iron detected using this probe may include iron bound to Ins(1,2,3)P(3). Therefore Ins(1,2,3)P(3) is the first viable proposal for a transit iron ligand.

Catalytic Asymmetric Phase-Transfer Hydroxylation of Oxindoles

Catalytic Asymmetric Phase-Transfer Hydroxylation of Oxindoles

Catalytic Asymmetric Hydroxylation of Oxindoles by Molecular Oxygen Using a Phase-Transfer Catalyst

The highly enantioselective catalytic hydroxylation of 3-substituted oxindoles was achieved by using a phase-transfer catalyst with molecular oxygen as an oxidant. The product then was converted to an optically active compound 8, which was a synthetic precursor of alkaloid CPC-1.

Photocatalytic Hydroxylation of Phenol over Ti-Containing Zeolites (TS-1, Ti-MCM-41)

The photo-catalytic hydroxylation of phenol with hydrogen peroxide was carried out over TS-1 and Ti-MCM-41 catalysts. For comparison, the dark (thermal)-catalytic hydroxylation of phenol was also performed. The difference in catalytic behaviors of TS-1 and Ti-MCM-41 and product distribution in both the reactions were investigated. The TS-1 and Ti-MCM-41 catalysts having the Si/Ti ratio of 50 were prepared by in-situ crystallization and characterized using XRD, UV-DRS. In the all reactions, the main products were catechol (CAT), hydroquinone (HQ) and benzoquinone (BQ). In dark (thermal)-reaction, TS-1 showed a higher catalytic activity than Ti- MCM-41. In photo-reaction, however, the activity of Ti-MCM-41 was comparable to that of TS-1. The conversion of phenol and the selectivity to CAT in the photo-catalytic reaction were higher than those in dark (thermal)-reaction. In the all reactions, the selectivity to CAT increased remarkably when the selectivities to HQ and BQ decreased with reaction time.

The Synthesis of Copper(II) Salicylaldiminato Complexes and their Catalytic Activity in the Hydroxylation of Phenol

The synthesis of copper(II) salicylaldiminato complexes and their application in the catalytic hydroxylation of phenol is reported. Tetracoordinated copper complexes (Cu(Ln)2) were obtained by reacting the N-phenylsalicylaldimine ligands (HL1 -HL7) with copper acetate in a 2 : 1 mole ratio. The reaction of N-(2,6-diisopropyl)phenyl-3,5-di-tert-butylsalicylaldimine (HL7) with copper acetate in a 1 : 1 mole ratio afforded a dinuclear complex, which was not obtained with the other ligand systems. All complexes were characterized using FT-IR and elemental analysis. X-Ray crystal structures of complexes 2, 5 and 8 have also been obtained. The catalytic activity of these complexes was evaluated in the hydroxylation of phenol using oxygen and hydrogen peroxide as co-oxidants in aqueous media in the pH range 3 - 6. All complexes studied were found to be active for the hydroxylation process over the pH range studied with higher selectivity for catechol formation.

Preferential inhibition of xanthine oxidase by 2-amino-6-hydroxy-8-mercaptopurine and 2-amino-6-purine thiol

BackgroundThe anticancer drug, 6-mercaptopurine (6MP) is subjected to metabolic clearance through xanthine oxidase (XOD) mediated hydroxylation, producing 6-thiouric acid (6TUA), which is excreted in urine. This reduces the effective amount of drug available for therapeutic efficacy. Co-administration of allopurinol, a suicide inhibitor of XOD, which blocks the hydroxylation of 6MP inadvertently enhances the 6MP blood level, counters this reduction. However, allopurinol also blocks the hydroxylation of hypoxanthine, xanthine (released from dead cancer cells) leading to their accumulation in the body causing biochemical complications such as xanthine nephropathy. This necessitates the use of a preferential XOD inhibitor that selectively inhibits 6MP transformation, but leaves xanthine metabolism unaffected.ResultsHere, we have characterized two such unique inhibitors namely, 2-amino-6-hydroxy-8-mercaptopurine (AHMP) and 2-amino-6-purinethiol (APT) on the basis of IC50 values, residual activity in bi-substrate simulative reaction and the kinetic parameters like Km, Ki, kcat. The IC50 values of AHMP for xanthine and 6MP as substrate are 17.71 ± 0.29 μM and 0.54 ± 0.01 μM, respectively and the IC50 values of APT for xanthine and 6MP as substrates are 16.38 ± 0.21 μM and 2.57 ± 0.08 μM, respectively. The Ki values of XOD using AHMP as inhibitor with xanthine and 6MP as substrate are 5.78 ± 0.48 μM and 0.96 ± 0.01 μM, respectively. The Ki values of XOD using APT as inhibitor with xanthine and 6MP as substrate are 6.61 ± 0.28 μM and 1.30 ± 0.09 μM. The corresponding Km values of XOD using xanthine and 6MP as substrate are 2.65 ± 0.02 μM and 6.01 ± 0.03 μM, respectively. The results suggest that the efficiency of substrate binding to XOD and its subsequent catalytic hydroxylation is much superior for xanthine in comparison to 6MP. In addition, the efficiency of the inhibitor binding to XOD is much more superior when 6MP is the substrate instead of xanthine. We further undertook the toxicological evaluation of these inhibitors in a single dose acute toxicity study in mice and our preliminary experimental results suggested that the inhibitors were equally non-toxic in the tested doses.ConclusionWe conclude that administration of either APT or AHMP along with the major anti-leukemic drug 6MP might serve as a good combination cancer chemotherapy regimen.

Catalytic hydroxylation of phenol using immobilized late transition metal salicylaldimine complexes

Immobilized late transition metal complexes based on salicylaldimine ligands were used as catalysts in the wet air hydroxylation of phenol in the presence of hydrogen peroxide. Three metals, viz. cobalt, nickel and copper, and two different kinds of supports, namely, amorphous silica and mesoporous MCM-41, were employed. The effect of pH on the hydroxylation process was also investigated. It was observed that the regioselectivity of the hydroxylation process strongly depends on the kind of support employed.

Preparation of Cu 2+/+–VSB-5 and their catalytic properties on hydroxylation of phenol

The Cu 2+–VSB-5 samples were prepared by a simple ion-exchanged reaction of Cu 2+ with the H + in the channel of VSB-5. The as-synthesized Cu 2+–VSB-5 and calcined Cu 2+/+–VSB-5 samples were characterized in detail by XRD, ICP, UV–vis and XPS spectra. Liquid phase catalytic hydroxylation of phenol was carried out over the calcined Cu 2+/+–VSB-5 samples, which exhibited high activity for the phenol oxidation. High TOF (69.1) and Cat/HQ ratio (1.6) were achieved over the 0.01Cu–VSB-5 catalyst. The studies on the mechanism of phenol hydroxylation show that the hydroxy radicals participated in the processes.

Fast Catalytic Hydroxylation of Hydrocarbons with Ruthenium Porphyrins

Ruthenium porphyrin complexes such as carbonylruthenium(II) tetrakispentafluorophenylporphyrin [Ru(II)(TPFPP)(CO)] were found to be efficient catalysts for the hydroxylation of alkanes in the presence of 2,6-dichloropyridine N-oxide as the oxidant under mild, nonacidic conditions. Up to 14 800 turnovers (TO) and rates of 800 TO/min were obtained for the hydroxylation of adamantane. The hydroxylation of cis-decalin afforded cis-9-decalol and cis-decalin-9,10-diol, exclusively, thus, excluding a long-lived radicals mechanism. The kinetics of product evolution in a typical catalytic oxygenation showed an initial induction period followed by a fast, apparently zero-order phase with maximum rates and high efficiencies. Deuterium isotope effects (kH/kD) in the range of 4.2-6.4 were found for the hydroxylation of alkanes. A Hammett treatment of the data for the oxidation of para-substituted toluene derivatives showed a linear correlation with a highly negative rho+ value of -2.0. On the basis of kinetic and spectroscopic evidence, Ru(VI)(TPFPP)(O)2, Ru(II)(TPFPP)(CO), and Ru(IV)(TPFPP)Cl2 observed during catalysis were ruled out as candidates for the active catalyst responsible for the high efficiencies and turnover rates in the oxidation reactions. The fastest rates of adamantane hydroxylation with 2,6-dichloropyridine N-oxide were achieved by the reductive activation of Ru(IV)(TPFPP)Cl2 with a zinc amalgam. This redox activation is consistent with the formation of an active Ru(III) intermediate in situ by a one-electron reduction of the Ru(IV) porphyrin. EPR spectra characteristic of Ru(III) have been observed upon the reduction of Ru(IV)(TPFPP)Cl2 with a zinc amalgam. In the adamantane oxidation mediated with Ru(III)(TPFPP)(OEt), it was found that, during this process, the Ru(III) porphyrin was gradually converted to a dioxoRu(VI) porphyrin. Concomitant with this conversion, the reaction rates decreased. Catalyst activation was also stimulated by autoxidation of the solvent CH2Cl2. On the basis of these data, a mechanism is proposed that incorporates a "fast" cycle involving metastable Ru(III) and oxoRu(V) intermediates and a "slow" oxidation cycle, mediated by oxoRu(IV) and trans-dioxoRu(VI) porphyrin complexes.