Oxidation Of C1 Research Articles

Chemical Synthesis of a Densely Functionalized Aminodisaccharide from Fusobacterium nucleatum ATCC 23726 O-Antigen.

Fusobacterium nucleatum, a colorectal-cancer-associated oncomicrobe, can trigger or accelerate numerous pathologies. We report the first synthesis of a conjugation-ready disaccharide containing six amino groups from F. nucleatum ATCC 23726 O-antigen. Rare 2,3-diamido-d-glucuronic acid amide and 2-acetamido-4-amino-d-fucose were synthesized from d-glucosamine through configuration inversion, nucleophilic substitution, C6 oxidation, and C6 deoxygenation. A judicious choice of protecting groups and reaction conditions enabled the selective installation of N-acetyl, N-propanoyl, N-formyl, and carboxamido groups.

Diversely regio-oxidative degradation of konjac glucomannan by lytic polysaccharide monooxygenase AA10 and generating antibacterial hydrolysate

Konjac glucomannan (KGM) hydrolysate exhibit various biological activities and health-promoting effects. Lytic polysaccharide monooxygenases (LPMOs) play an important role on enzymatic degradation of recalcitrant polysaccharides to obtain fermentable sugars. It is generally accepted that LPMOs exhibits high substrate specificity and oxidation regioselectivity. Here, a bacteria-derived SmAA10A, with chitin-active with strict C1 oxidation, was used to catalyse KGM degradation. Through ethanol precipitation, two hydrolysed KGM components (4 kDa (KGM-1) and 5 kDa (KGM-2)) were obtained that exhibited antibacterial activity against Staphylococcus aureus. In natural KGM, KGM-1, and KGM-2, the molar ratios of mannose to glucose were 1:2.19, 1:3.05, and 1:2.87, respectively, indicating that SmAA10A preferentially degrades mannose in KGM. Fourier-transform infrared spectroscopy and scanning electron microscopy imaging revealed the breakage of glycosylic bonds during enzymatic catalysis. The regioselectivity of SmAA10A for KGM degradation was determined based on the fragmentation behaviour of the KGM-1 and KGM-2 oligosaccharides and their NaBD4-reduced forms. SmAA10A exhibited diverse oxidation degradation of KGM and generated single C1-, single C4-, and C1/C4-double oxidised oligosaccharide forms. This study provides an alternative method for obtaining KGM degradation components with antibacterial functions and expands the substrate specificity and oxidation regioselectivity of bacterial LPMOs.

A designed Copper Histidine-brace enzyme for oxidative depolymerization of polysaccharides as a model of lytic polysaccharide monooxygenase

The "Histidine-brace" (His-brace) copper-binding site, composed of Cu(His)2 with a backbone amine, is found in metalloproteins with diverse functions. A primary example is lytic polysaccharide monooxygenase (LPMO), a class of enzymes that catalyze the oxidative depolymerization of polysaccharides, providing not only an energy source for native microorganisms but also a route to more effective industrial biomass conversion. Despite its importance, how the Cu His-brace site performs this unique and challenging oxidative depolymerization reaction remains to be understood. To answer this question, we have designed a biosynthetic model of LPMO by incorporating the Cu His-brace motif into azurin, an electron transfer protein. Spectroscopic studies, including ultraviolet-visible (UV-Vis) absorption and electron paramagnetic resonance, confirm copper binding at the designed His-brace site. Moreover, the designed protein is catalytically active towards both cellulose and starch, the native substrates of LPMO, generating degraded oligosaccharides with multiturnovers by C1 oxidation. It also performs oxidative cleavage of the model substrate 4-nitrophenyl-D-glucopyranoside, achieving a turnover number ~9% of that of a native LPMO assayed under identical conditions. This work presents a rationally designed artificial metalloenzyme that acts as a structural and functional mimic of LPMO, which provides a promising system for understanding the role of the Cu His-brace site in LPMO activity and potential application in polysaccharide degradation.

Identification, Formation, and Occurrence of Perlolyrine: A β-Carboline Alkaloid with a Furan Moiety in Foods.

β-Carbolines are naturally occurring bioactive alkaloids found in foods and in vivo. This research reports the identification, characterization, mechanism of formation, and occurrence of perlolyrine (1-(5-(hydroxymethyl)furan-2-yl)-9H-pyrido[3,4-b]indole), a β-carboline with a furan moiety. Perlolyrine did not arise from l-tryptophan and hydroxymethylfurfural but from the reaction of l-tryptophan with 3-deoxyglucosone, an intermediate of carbohydrate degradation. The mechanism of formation occurs through 3,4-dihydro-β-carboline-3-carboxylic acid intermediates (imines), followed by the oxidation of C1'-OH to ketoimine and oxidative decarboxylation at C-3, along with dehydration and cyclization to afford the β-carboline with a furan moiety. The formation of perlolyrine was favored in acidic conditions and temperatures in the range of 70-110 °C. Perlolyrine occurred in the reactions of tryptophan with carbohydrates. The formation rate from fructose was much higher than from glucose. Sucrose also gave perlolyrine under acidic conditions and heating. Perlolyrine was identified in many foods by HPLC-MS and analyzed by HPLC-fluorescence. It occurred in many processed foods such as tomato products including tomato puree, fried tomato, ketchups, tomato juices, and jams but also in soy sauce, beer, balsamic vinegar, fruit juices, dried fruits, fried onion, and honey. The concentrations ranged from an undetected amount to 3.5 μg/g with the highest average levels found in tomato concentrate (1.9 μg/g) and soy sauce (1.5 μg/mL). The results show that perlolyrine formed during the heating process of foods. It is concluded that perlolyrine is widely present in foods and it is daily ingested in the diet.

Characterization of a unique polysaccharide monooxygenase from the plant pathogen Magnaporthe oryzae

Blast disease in cereal plants is caused by the fungus Magnaporthe oryzae and accounts for a significant loss in food crops. At the outset of infection, expression of a putative polysaccharide monooxygenase (MoPMO9A) is increased. MoPMO9A contains a catalytic domain predicted to act on cellulose and a carbohydrate-binding domain that binds chitin. A sequence similarity network of the MoPMO9A family AA9 showed that 220 of the 223 sequences in the MoPMO9A-containing cluster of sequences have a conserved unannotated region with no assigned function. Expression and purification of the full length and two MoPMO9A truncations, one containing the catalytic domain and the domain of unknown function (DUF) and one with only the catalytic domain, were carried out. In contrast to other AA9 polysaccharide monooxygenases (PMOs), MoPMO9A is not active on cellulose but showed activity on cereal-derived mixed (1→3, 1→4)-β-D-glucans (MBG). Moreover, the DUF is required for activity. MoPMO9A exhibits activity consistent with C4 oxidation of the polysaccharide and can utilize either oxygen or hydrogen peroxide as a cosubstrate. It contains a predicted 3-dimensional fold characteristic of other PMOs. The DUF is predicted to form a coiled-coil with six absolutely conserved cysteines acting as a zipper between the two α-helices. MoPMO9A substrate specificity and domain architecture are different from previously characterized AA9 PMOs. The results, including a gene ontology analysis, support a role for MoPMO9A in MBG degradation during plant infection. Consistent with this analysis, deletion of MoPMO9A results in reduced pathogenicity.

Analysis of lytic polysaccharide monooxygenase activity in thermophilic fungi by high-performance liquid chromatography-refractive index detector.

Most current methods for analysing the activity of LPMO are based on the quantification of H2O2, a side product of LPMO; however, these methods cannot assay the LPMO activity of thermophilic fungi because of the low thermostability of H2O2. Therefore, we present a high-performance liquid chromatography-refractive index detector (HPLC-RID) method to assay the LPMO activity of the thermophilic fungus Thermoascus aurantiacus. According to the established method, the specific activities of nTaAA9A C1 and C4 oxidation were successfully analysed and were 0.646 and 0.574 U/mg, respectively. By using these methods, we analyzed the C1 and C4 oxidation activities of the recombinant TaAA9A (rTaAA9A) and mutated rTaAA9A (Y24A, F43A, and Y212A) expressed in Pichia pastoris. The specific activities of rTaAA9A C1 and C4 oxidation were 0.155 and 0.153 U/mg, respectively. The specific activities of Y24A, F43A, and Y212A C1 and C4 oxidation were 0.128 and 0.125 U/mg, 0.194 and 0.192 U/mg, and 0.097 and 0.146 U/mg, respectively. In conclusion, the method can assay the LPMO activity of thermophilic fungi and directly target C1 and C4 oxidation, which provides an effective activity assay method for LPMOs of thermophilic fungi.

Reaction Mechanism and Three-Dimensional Structure of GDP-d-glycero-α-d-manno-heptose 4,6-Dehydratase from Campylobacter jejuni.

Campylobacter jejuni is a human pathogen and a leading cause of food poisoning in the United States and Europe. Surrounding the outside of the bacterium is a carbohydrate coat known as the capsular polysaccharide. Various strains of C. jejuni have different sequences of unusual sugars and an assortment of decorations. Many of the serotypes have heptoses with differing stereochemical arrangements at C2 through C6. One of the many common modifications is a 6-deoxy-heptose that is formed by dehydration of GDP-d-glycero-α-d-manno-heptose to GDP-6-deoxy-4-keto-d-lyxo-heptose via the action of the enzyme GDP-d-glycero-α-d-manno-heptose 4,6-dehydratase. Herein, we report the biochemical and structural characterization of this enzyme from C. jejuni 81-176 (serotype HS:23/36). The enzyme was purified to homogeneity, and its three-dimensional structure was determined to a resolution of 2.1 Å. Kinetic analyses suggest that the reaction mechanism proceeds through the formation of a 4-keto intermediate followed by the loss of water from C5/C6. Based on the three-dimensional structure, it is proposed that oxidation of C4 is assisted by proton transfer from the hydroxyl group to the phenolate of Tyr-159 and hydride transfer to the tightly bound NAD+ in the active site. Elimination of water at C5/C6 is most likely assisted by abstraction of the proton at C5 by Glu-136 and subsequent proton transfer to the hydroxyl at C6 via Ser-134 and Tyr-159. A bioinformatic analysis identified 19 additional 4,6-dehydratases from serotyped strains of C. jejuni that are 89-98% identical in the amino acid sequence, indicating that each of these strains should contain a 6-deoxy-heptose within their capsular polysaccharides.

Chemical synthesis of a synthetically useful L-galactosaminuronic acid building block.

Most bacterial cell surface glycans are structurally unique, and have been considered as ideal target molecules for the developments of detection and diagnosis techniques, as well as vaccines. Chemical synthesis has been a promising approach to prepare well-defined oligosaccharides, facilitating the structure-activity relationship exploration and biomedical applications of bacterial glycans. L-Galactosaminuronic acid is a rare sugar that has been only found in cell surface glycans of gram-negative bacteria. Here, an orthogonally protected L-galactosaminuronic acid building block was designed and chemically synthesized. A synthetic strategy based on glycal addition and TEMPO/BAIB-mediated C6 oxidation served well for the transformation of commercial L-galactose to the corresponding L-galactosaminuronic acid. Notably, the C6 oxidation of the allyl glycoside was more efficient than that of the selenoglycoside. In addition, a balance between the formation of allyl glycoside and the recovery of selenoglycoside was essential to improve efficiency of the NIS/TfOH-catalyzed allylation. This synthetically useful L-galactosaminuronic acid building block will provide a basis for the syntheses of complex bacterial glycans.

Evolution of OH reactivity in NO-free volatile organic compound photooxidation investigated by the fully explicit GECKO-A model

Abstract. OH reactivity (OHR) is an important control on the oxidative capacity in the atmosphere but remains poorly constrained in many environments, such as remote, rural, and urban atmospheres, as well as laboratory experiment setups under low-NO conditions. For an improved understanding of OHR, its evolution during oxidation of volatile organic compounds (VOCs) is a major aspect requiring better quantification. We use the fully explicit Generator of Explicit Chemistry and Kinetics of Organics in the Atmosphere (GECKO-A) model to study the OHR evolution in the NO-free photooxidation of several VOCs, including decane (an alkane), m-xylene (an aromatic), and isoprene (an alkene). Oxidation progressively produces more saturated and functionalized species. Total organic OHR (including precursor and products, OHRVOC) first increases for decane (as functionalization increases OH rate coefficients) and m-xylene (as much more reactive oxygenated alkenes are formed). For isoprene, C=C bond consumption leads to a rapid drop in OHRVOC before significant production of the first main saturated multifunctional product, i.e., isoprene epoxydiol. The saturated multifunctional species in the oxidation of different precursors have similar average OHRVOC per C atom. The latter oxidation follows a similar course for different precursors, involving fragmentation of multifunctional species to eventual oxidation of C1 and C2 fragments to CO2, leading to a similar evolution of OHRVOC per C atom. An upper limit of the total OH consumption during complete oxidation to CO2 is roughly three per C atom. We also explore the trends in radical recycling ratios. We show that differences in the evolution of OHRVOC between the atmosphere and an environmental chamber, and between the atmosphere and an oxidation flow reactor (OFR), can be substantial, with the former being even larger, but these differences are often smaller than between precursors. The Teflon wall losses of oxygenated VOCs in chambers result in large deviations of OHRVOC from atmospheric conditions, especially for the oxidation of larger precursors, where multifunctional species may suffer substantial wall losses, resulting in significant underestimation of OHRVOC. For OFR, the deviations of OHRVOC evolution from the atmospheric case are mainly due to significant OHR contribution from RO2 and lack of efficient organic photolysis. The former can be avoided by lowering the UV lamp setting in OFR, while the latter is shown to be very difficult to avoid. However, the former may significantly offset the slowdown in fragmentation of multifunctional species due to lack of efficient organic photolysis.

An Expeditious Modular Hybrid Strategy for the Diversity-Oriented Synthesis of Lamellarins/Azalamellarins with Anticancer Cytotoxicity.

A modular hybrid strategy has been developed for the diversity-oriented synthesis of lamellarins/azalamellarins. The common pentacyclic pyrrolodihydroisoquinoline lactone/lactam core was formed via the Michael addition/ring closure (Mi-RC) and the copper(I) thiophene-2-carboxylate (CuTC)-catalyzed C-O/C-N Ullmann coupling. Subsequent direct functionalization at C1, DDQ-mediated C5═C6 oxidation, and global deprotection of all benzyl-type O- and N-protecting groups furnished the desired lamellarins/azalamellarins. The late-stage functionalization at C1 provided a handle to accommodate a wider scope of functional groups as they need to tolerate only the DDQ oxidation and global deprotection. Moreover, with the C1-H pyrrole as the late-stage common intermediate, it was also possible to divergently exploit not only its nucleophilic nature to react with some electrophilic species but also some transition-metal-catalyzed cross-coupling reactions (via the intermediacy of the C1-iodopyrrole) to incorporate diversity at this position. Overall, this strategy simplifies the preparation of lamellarins/azalamellarins; including the Mi-RC, these C1-structurally diverse analogues could be prepared efficiently in 6-7 steps from the easily accessed 1-acetoxymethyldihydroisoquinoline and β-nitrocinnamate. Some selected azalamellarins were evaluated for their inhibitory effect against HeLa cervical cancer cells. An acute induction of intrinsic apoptosis was detected and may lead to growth suppression of or cytotoxicity against cancer cells.

Iron Tetrasulfonatophthalocyanine-Catalyzed Starch Oxidation Using H2O2: Interplay between Catalyst Activity, Selectivity, and Stability.

Oxidized starch can be efficiently prepared using H2O2 as an oxidant and iron(III) tetrasulfophthalocyanine (FePcS) as a catalyst, with properties in the same range as those for commercial oxidized starches prepared using NaOCl. Herein, we performed an in-depth study on the oxidation of potato starch focusing on the mode of operation of this green catalytic system and its fate as the reaction progresses. At optimum batch reaction conditions (H2O2/FePcS molar ratio of 6000, 50 °C, and pH 10), a high product yield (91 wt %) was obtained with substantial degrees of substitution (DSCOOH of 1.4 and DSCO of 4.1 per 100 AGU) and significantly reduced viscosity (197 mPa·s) by dosing H2O2. Model compound studies showed limited activity of the catalyst for C6 oxidation, indicating that carboxylic acid incorporation likely results from C–C bond cleavage events. The influence of the process conditions on the stability of the FePcS catalyst was studied using UV–vis and Raman spectroscopic techniques, revealing that both increased H2O2 concentration and temperature promote the irreversible degradation of the FePcS catalyst at high pH. The rate and extent of FePcS degradation were found to strongly depend on the initial H2O2 concentration where also the rapid decomposition of H2O2 by FePcS occurs. These results explain why the slow addition of H2O2 in combination with low FePcS catalyst concentration is beneficial for the efficient application in starch oxidation.

Current efficiency and mass transfer effects in electrochemical oxidation of C1 and C2 carboxylic acids on boron doped diamond electrodes

The oxidation of acetic, glycolic, glyoxylic, oxalic and formic acid has been studied on boron doped diamond electrodes. Our voltammetry study on rotating disk electrodes highlights clear differences between the carboxylic acids (formic, oxalic, glyoxylic and glycolic acid) that can be oxidized via a direct electron transfer (DET) and acetic acid which can presumably solely be oxidized by •OH radicals formed in the region where water oxidation takes place. In glycolic and glyoxylic oxidation oxalic acid is the main intermediate formed. Surprisingly, glyoxylic acid could not be detected as an intermediate in the glycolic acid oxidation. Chronoamperometric experiments confirm that all compounds except acetic acid react further to CO2, which could be deduced from the electron balances. It was shown that formic, oxalic, glyoxylic and glycolic acid can be selectively oxidized at 2.3 V vs. Ag/AgCl with high current efficiencies, below or close to mass transfer limiting rates. At higher potentials (2.4 V and 2.5 V) simultaneous water electrolysis results in lower current efficiencies. At these potentials the conversion rates can exceed the limiting rates, which might be attributed to effects related to water oxidation (i.e. O2 evolution and •OH radical formation).

Synthesis, characterization and activity of Pd/CaWO4 catalyst in the complete oxidation of C1–C6 alkanes and toluene

Synthesis, characterization and activity of Pd/CaWO4 catalyst in the complete oxidation of C1–C6 alkanes and toluene

Functional characterization of a novel copper-dependent lytic polysaccharide monooxygenase TgAA11 from Trichoderma guizhouense NJAU 4742 in the oxidative degradation of chitin

Lytic polysaccharide monooxygenases (LPMOs) are attracting much attention for their potential application in biodegradation. However, there are limited studies on the characterization of the AA11 family. Here, a novel AA11 family protein, TgAA11, from Trichoderma guizhouense NJAU 4742 was characterized, and the isothermal titration calorimetry (ITC) analysis results showed that it exhibited tight binding capacity for copper ions with a Kd value of 4.83 ± 0.79 μM. The MALDI-TOF-MS analysis results indicated that TgAA11 could act on β-chitin to form C1 oxidation products, and some deacetylated chitooligosaccharides. In addition, the degradation of α-chitin and β-chitin by a chitinolytic enzyme Sg-chi was substantially increased in the presence of TgAA11 by 39.9 % and 288.2 %, respectively. Furthermore, the active site residues predicted showed that His61 and Tyr142 might be critical for the active site residues of the TgAA11 protein. This study will contribute to the understanding of the function of AA11 LPMOs in the degradation of chitin.

An electrochemical method for detecting the biomarker 4-HPA by allosteric activation of Acinetobacterbaumannii reductase C1 subunit

The C1 (reductase) subunit of 4-hydroxy-phenylacetate (4-HPA) 3-hydroxylase (HPAH) from the soil-based bacterium Acinetobacterbaumannii catalyzes NADH oxidation by molecular oxygen, with hydrogen peroxide as a by-product. 4-HPA is a potent allosteric modulator of C1, but also a known urinary biomarker for intestinal bacterial imbalance and for some cancers and brain defects. We thus envisioned that C1 could be used to facilitate 4-HPA detection. The proposed test protocol is simple and in situ and involves addition of NADH to C1 in solution, with or without 4-HPA, and direct acquisition of the H2O2 current with an immersed Prussian Blue–coated screen-printed electrode (PB-SPE) assembly. We confirmed that cathodic H2O2 amperometry at PB-SPEs is a reliable electrochemical assay for intrinsic and allosterically modulated redox enzyme activity. We further validated this approach for quantitative NADH electroanalysis and used it to evaluate the activation of NADH oxidation of C1 by 4-HPA and four other phenols. Using 4-HPA, the most potent effector, allosteric activation of C1 was related to effector concentration by a simple saturation function. The use of C1 for cathodic biosensor analysis of 4-HPA is the basis of the development of a simple and affordable clinical routine for assaying 4-HPA in the urine of patients with a related disease risk. Extension of this principle to work with other allosteric redox enzymes and their effectors is feasible.

Analysis of Four Chitin-Active Lytic Polysaccharide Monooxygenases from Streptomyces griseus Reveals Functional Variation.

Lytic polysaccharide monooxygenases (LPMOs) are redox-active enzymes that cleave insoluble polysaccharides by an oxidative reaction. In the present study, we have characterized four recombinant putative chitin-active LPMOs from Streptomyces griseus (SgLPMO10B, -C, -D, and -F) and evaluated their potential in enhancing hydrolysis of α- and β-chitin by three families of 18 chitinases of Serratia marcescens, SmChiA, -B, and -C. All four recombinant SgLPMO10s showed oxidative activity toward both α- and β-chitin but exhibited different abilities to promote the release of chitobiose from chitin by chitinases depending on both the chitinase and the chitin type. These effects were observed under conditions where the amount of LPMO in the reaction was not rate-limiting, showing that the observed functional differences relate to different abilities of the LPMOs to interact with and act on the substrate. These results show that four seemingly similar LPMOs carrying out the same reaction, cleavage of chitin by C1 oxidation, may have different roles in natural chitin conversion, which provides a rationale for the multiplicity of these enzymes within the same organism. The ability of the LPMOs to act on more natural substrates was demonstrated by showing that SgLPMO10B improved chitin solubilization in dried powdered shrimp shells.

On the oxidation mechanism of C1-C2 organic molecules on platinum. A comparative analysis

The rational design of better electrocatalysts for the oxidation of C1–C2 organic molecules requires the detailed knowledge of their oxidation mechanism. Pt single crystals are powerful tools to study, in a simple way, the surface structure effect on the different reaction pathways. Here, the oxidation mechanism of these molecules is compared so that the knowledge gained with the simpler mechanism is transferred in the analysis of the more complex ones. The goal is to design strategies so that the platinum electrodes improve their performance in their oxidation by the appropriate modification with other elements by attacking the bottlenecks in the reaction mechanism. • Similarities and differences between the oxidation mechanisms of C1–C2 molecules are highlighted. • The active pathway of formic acid oxidation through CO 2 requires the adsorption of monodentate formate. • A surface covered by adsorbed OH is required for methanol and ethanol oxidation reactions. • Greater reactivity towards the C–C cleavage by partially oxidizing the α carbon of ethanol molecule.

Near-infrared in vitro measurements of photosystem I cofactors and electron-transfer partners with a recently developed spectrophotometer.

A kinetic-LED-array-spectrophotometer (Klas) was recently developed for measuring in vivo redox changes of P700, plastocyanin (PCy), and ferredoxin (Fd) in the near-infrared (NIR). This spectrophotometer is used in the present work for in vitro light-induced measurements with various combinations of photosystem I (PSI) from tobacco and two different cyanobacteria, spinach plastocyanin, cyanobacterial cytochrome c6 (cyt. c6), and Fd. It is shown that cyt. c6 oxidation contributes to the NIR absorption changes. The reduction of (FAFB), the terminal electron acceptor of PSI, was also observed and the shape of the (FAFB) NIR difference spectrum is similar to that of Fd. The NIR difference spectra of the electron-transfer cofactors were compared between different organisms and to those previously measured in vivo, whereas the relative absorption coefficients of all cofactors were determined by using single PSI turnover conditions. Thus, the (840nm minus 965nm) extinction coefficients of the light-induced species (oxidized minus reduced for PC and cyt. c6, reduced minus oxidized for (FAFB), and Fd) were determined with values of 0.207 ± 0.004, - 0.033 ± 0.006, - 0.036 ± 0.008, and - 0.021 ± 0.005 for PCy, cyt. c6, (FAFB) (single reduction), and Fd, respectively, by taking a reference value of + 1 for P700+. The fact that the NIR P700 coefficient is larger than that of PCy and much larger than that of other contributing species, combined with the observed variability in the NIR P700 spectral shape, emphasizes that deconvolution of NIR signals into different components requires a very precise determination of the P700 spectrum.

Theoretical study on the mechanism of N- and α-carbon oxidation of lapatinib catalyzed by cytochrome P450 monooxygenase.

Lapatinib, an orally active dual tyrosine kinase inhibitor, is efficacious in combination therapy with capecitabine for advanced metastatic breast cancer. Despite its importance, it has been associated with hepatotoxicity observed in clinical trials and postmarketing surveillance. The mechanisms of hepatotoxicity at the chemical and cellular levels may link to drug metabolism. In this study, the N- and α-carbon oxidation processes of lapatinib catalyzed by CYP3A4 were explored by density functional theory method. The calculation results show that oxidation of C6 is the primary metabolic process and carboxylic acid is the main metabolic product. Both hydroxylation of C8 and subsequent formation of primary amines are feasible. However, it is not easy for the primary amines to form active metabolites nitroso, which indicates that there are other paths for the production of nitroso. Carboxylic acid is not the main metabolite of N7 oxidation because of higher hydrolysis energy barrier of intermediate nitrone. It is worthy to study subsequent N-hydroxylation and its downstream reaction, which may be the main pathway for the formation of nitroso. These results lay the foundation for drug design and optimization.

On the stabilization of the oxidized state of palladium by CuWO4 for application as catalyst in abatement of C1–C4 hydrocarbons emissions

In this work for the first time we demonstrate a stabilization of Pd in its oxidation state within Pd-modified CuWO4 for application as reliable active phase in catalytic converters for abatement of exhaust gases from liquefied petroleum gas motor engines. The effect of Pd on the catalytic properties in reaction of complete oxidation of C1–C4 hydrocarbons, the crystal structure and the chemical state have been investigated in details. The presence of supported palladium influences the system properties in respect to oxidation of organic compounds in two ways: (i) increases the reactive oxygen storage capacity of the catalyst; (ii) lowers the temperature of oxidation of the organics by enhancing the reducibility of the supporting metal oxide. The catalytic performance of Pd-modified CuWO4 is explained by partial reduction of surface Cu2+ to Cu1+ state, thus the copper from CuWO4 aids to avoid the reduction of PdO species during the catalytic reaction, i.e. the interaction between Pd and Cu stabilizes the oxidized Pd nanoparticles.