Reactive Carbonyl Groups Research Articles

ChemInform Abstract: Metal Organic Framework as Solid Catalysts in Condensation Reactions of Carbonyl Groups

AbstractReview: 100 refs.

Control of Transient Aluminum–Aminals for Masking and Unmasking Reactive Carbonyl Groups

A new reagent, the dimethylaluminum N,O-dimethylhydroxylamine complex, is effective at masking reactive carbonyl groups in situ from nucleophilic addition. This reagent allows chemoselective addition of reducing reagents, Grignard reagents, organolithiums, Wittig reagents, and enolates into substrates with multiple carbonyl groups. Moreover, the trapped carbonyl group, a stable aminal, can be unmasked in situ for additional synthetic manipulations.

Preparation and Characteristics of Chitin-Gelatin Composite Film

Using hydrogen peroxide as oxidant, the chitin has been oxidized under a certain conditions. And then the IR and SEM of product has been tested, and the results show that hydroxyl group can be transform carbonyl group. What’s more, the oxidation reaction occurred not only in the surface of chitin, but also in its interior. Owing to the reaction of carbonyl group in the oxidation product, this chitin derivatives was applied to cross link with gelatin material, and the properties of modified gelatin film then has been tested. The results of Differential Scanning Calorimeter (DSC) show that the denaturation temperature of composite gelatin film has been enhanced to 109.8°C, and its swelling rate also has been slow, which ensure the stability as a kind of biomaterials, such as microcapsule and microspheres. And the time of native gelatin film achieving equilibrium swelling state is 9 minutes, and the time is 14 minutes for composite film, which means the oxidized chitin can delay the complete swelling rate. And the equilibrium swelling ratio of native gelatin film is larger than that of composite film. Therefore, the composite film will have a good prospects as a kind of potential biomedical.

Novel regulatory system nemRA–gloA for electrophile reduction in Escherichia coli K‐12

Electrophilic compounds such as glyoxals, which are toxic due to their reactive carbonyl group, are generated in vivo through various pathways. In this study, we obtained evidence indicating that the nemRA operon, previously reported to encode a repressor and the N-ethylmaleimide reductase, respectively, is co-transcribed with the 3'-proximal gloA gene encoding glyoxalase I. The operon is not only involved in cytosolic detoxification but is also regulated by electrophiles such as quinones and glyoxals. A gel mobility shift assay revealed that purified NemR repressor bound to DNA was dissociated upon interaction with quinones and glyoxals, while their reduced forms were ineffective. The cysteines of NemR at 21 and 116 were essential in sensing electrophiles in vivo and in vitro. Reversible intermolecular disulphide bonds were observed with a reducing agent as well as with electrophiles. DNA binding affinity reduced by glyoxal was also increased with a reducing agent. The NemA reductase, an FMN-containing enzyme, exhibited catalytic activity toward various electrophiles including quinones, while GloA played a major role in glyoxal detoxification. Therefore, we propose that cells have a cytosolic system consisting of the nemRA-gloA operon for the reduction of electrophiles, especially quinones and glyoxals, to maintain an appropriate intracellular redox balance.

Potential of Nanocrystalline Cellulose–Fibrin Nanocomposites for Artificial Vascular Graft Applications

The potential of synthesizing new nanocomposites from nanocrystalline cellulose (NCC) and fibrin for small-diameter replacement vascular graft (SDRVG) application was demonstrated. Periodate oxidation of NCC can augment reactive carbonyl groups on NCC and facilitate its cross-linking with fibrin. NCC-fibrin nanocomposites were synthesized, composed of homogeneously dispersed oxidized NCC (ONCC) in a fibrin matrix, with fibrin providing elasticity and ONCC providing strength. The maximum strength and elongation of the nanocomposites were determined by Atomic Force Microscopy (AFM) and compared with a native blood vessel. The manipulation of degree of oxidation of NCC and the NCC-to-fibrin ratio resulted in the variation of strength and elongation of the nanocomposites, indicating that the nanocomposites can be tailored to conform to the diverse mechanical properties of native blood vessels. A mechanistic understanding of the molecular interactions of ONCC and fibrin was illustrated. This study established fundamental information to utilizing NCC for SDRVG applications.

Metal Organic Frameworks as Solid Catalysts in Condensation Reactions of Carbonyl Groups

AbstractThis review summarizes the use of metal organic frameworks (MOFs) as solid catalysts for condensation reactions. After an introductory section, in which condensation reactions are generally presented, a list of the MOFs employed as condensation catalyst is given. The main part of the present review is organized according to the use of MOFs as solid acids, solid bases or as bi‐functional solids containing both acid and basic sites. Throughout the review, the emphasis has been made on discussing the stability of the MOFs, their reusability and in providing a comparison of the performance of MOFs with respect to other homogeneous and heterogeneous catalysts. Finally, we summarize the current state‐of‐the‐art and provide our view on future trends and developments in this field.

Qualitative and quantitative evaluation of derivatization reagents for different types of protein-bound carbonyl groups

Mass spectrometry (MS) of 'carbonylated proteins' often involves derivatization of reactive carbonyl groups to facilitate their enrichment, identification and quantification. Among the many reported reagents, 2,4-dinitrophenylhydrazine (DNPH), biotin hydrazide (BHZ) and O-(biotinylcarbazoylmethyl) hydroxylamine (ARP) are the most frequently used. Despite their common use in carbonylation research, their reactivity towards protein-bound carbonyls has not been quantitatively evaluated in detail, to the best of our knowledge. Thus we studied the reactivity and specificity of these reagents towards different classes of reactive carbonyl groups (e.g. aldehydes, ketones and lactams), each being represented by a synthetic peptide carrying an accordingly modified residue. All three tagging reagents were selective for aliphatic aldehydes and ketones. Lactams and carbonyl-containing tryptophan oxidation products, however, were labelled only at low levels or not at all. Whereas DNPH derivatization was efficient under the published standard conditions, the derivatization conditions for BHZ and ARP had to be altered. Acidic conditions provided quantitative labelling yields for ARP. Peptides derivatized with DNPH, BHZ and ARP fragmented efficiently in tandem mass spectrometry, when the experimental conditions were chosen carefully for each reagent. Importantly, the tested carbonylated peptides did not cross-react with amino groups in other proteins present during sample preparations or enzymatic digestion. Thus, it appears favourable to digest proteins first and then derivatise the reactive carbonyl groups more efficiently at the peptide level under acidic conditions. The carbonylated model peptides used in this study might be valid internal standards for carbonylation proteomics.

A Pictet-Spengler ligation for protein chemical modification

Aldehyde- and ketone-functionalized proteins are appealing substrates for the development of chemically modified biotherapeutics and protein-based materials. Their reactive carbonyl groups are typically conjugated with α-effect nucleophiles, such as substituted hydrazines and alkoxyamines, to generate hydrazones and oximes, respectively. However, the resulting C=N linkages are susceptible to hydrolysis under physiologically relevant conditions, which limits the utility of such conjugates in biological systems. Here we introduce a Pictet-Spengler ligation that is based on the classic Pictet-Spengler reaction of aldehydes and tryptamine nucleophiles. The ligation exploits the bioorthogonal reaction of aldehydes and alkoxyamines to form an intermediate oxyiminium ion; this intermediate undergoes intramolecular C–C bond formation with an indole nucleophile to form an oxacarboline product that is hydrolytically stable. We used the reaction for site-specific chemical modification of glyoxyl- and formylglycine-functionalized proteins, including an aldehyde-tagged variant of the therapeutic monoclonal antibody Herceptin. In conjunction with techniques for site-specific introduction of aldehydes into proteins, the Pictet-Spengler ligation offers a means to generate stable bioconjugates for medical and materials applications.

Optimization of Lysozyme – Inulin Conjugation and Investigation on its Functional Properties

In recent years, several oconjugation protocols have been developed to improve the functional properties of the enzyme lysozyme. In this study, the optimum conditions of lysozyme – oxidized inulin conjugation and functional properties of the modified lysozyme were investigated. Initially, inulin (MW about 25 kDa) was oxidized by periodate to provide the reactive carbonyl groups to attach to amino groups of lysozyme for Maillard reaction and was then conjugated to the enzyme at a molar ratio of oxidized inulin to enzyme of 5:1. A number of studies were conducted to investigate the optimization of lysozyme – Inulin conjugation consisting of different pH levels (3, 7, and 9), different temperatures (40, 60, and 80°C), and different reaction times. The degree of modification was determined by SDS-PAGE and sugar analysis of the product. The best condition for conjugation was determined to be 60°C at pH 7.0 for one week. The results showed that under these conditions, the inulin-lysozyme conjugate had 58% of the lytic activity of the native enzyme and had better emulsifying properties and heat stability than native lysozyme. Moreover, there was significantly higher protein solubility at pH 7.0 and 9.0 at different temperatures than heated lysozyme. Taken together, the results of this study indicated that lysozyme modification by oxidized inulin results in a new product with improved functional properties which may be employed for different industrial purposes.

Investigation of thermal degradation characteristics of polyamide-6 containing melamine or melamine cyanurate via direct pyrolysis mass spectrometry

In this work the changes in thermal degradation characteristics of polyamide 6 (PA6) in the presence of melamine (Me) or melamine cyanurate (MC) were investigated systematically via direct pyrolysis mass spectrometry. Though thermal stability of PA6 was not affected by the presence of flame retardants, the changes in the products and in their distributions were detected. The reaction of carbonyl groups of PA6 with amine groups of melamine was the main cause for the changes in the product distribution. In the presence of melamine cyanurate, new products due to the reaction of cyanic acid generated by the decomposition of cyanurate, with the amine groups of PA6 were detected. Significant increases in the evolution temperatures of melamine and melamine cyanurate in the presence of PA6 were attributed to intermolecular interactions, most probably by H-bonding, with PA6.

Differential effect of UV-B radiation on growth, oxidative stress and ascorbate–glutathione cycle in two cyanobacteria under copper toxicity

Effects of low (UV-B(L); 0.1 μmol m(-2) s(-1)) and high (UV-B(H); 1.0 μmol m(-2) s(-1)) fluence rates of UV-B radiation on growth, oxidative stress and ascorbate-glutathione cycle (AsA-GSH cycle) were investigated in two cyanobacteria viz. Phormidium foveolarum and Nostoc muscorum under copper (2 and 5 μM) toxicity after 24 and 72 h of experiments. Cu at 2 and 5 μM and UV-B(H) irradiation decreased growth in both the organisms and the effect was more pronounced in N. muscorum. Superoxide radical (SOR) and hydrogen peroxide (H(2)O(2)) productions were significantly enhanced by Cu and UV-B(H) which was accompanied by accelerated lipid peroxidation (malondialdehyde; MDA) and protein oxidation (reactive carbonyl groups; RCG). The components of AsA-GSH cycle, i.e. ascorbate peroxidase (APX), glutathione reductase (GR), monodehydroascobate reductase (MDHAR) and dehydroascorbate reductase (DHAR) activities as well as total ascorbate and glutathione contents and their reduced/oxidized ratios were decreased considerably by Cu and UV-B(H). Further, combined treatments of Cu and UV-B(H) exacerbated damaging effects in both the cyanobacteria. Unlike UV-B(H), UV-B(L) irradiation rather than damaging cyanobacteria caused alleviation in Cu-induced toxicity by down-regulating the levels of SOR, H(2)O(2), MDA and RCG due to enhanced activity of APX, GR, MDHAR and DHAR, and contents of ascorbate and glutathione. Results revealed that UV-B radiation at low fluence rate (UV-B(L)) stimulated protective responses in both the organisms under Cu toxicity while UV-B(H) irradiation caused damage alone as well as together with Cu, and the components of AsA-GSH cycle play significant role in these responses.

Mass spectrometry analysis of modified bee venom phospholipase A2 in correlation with increased activity

Oxidative stress and inflammatory conditions result in the formation of carbonyl-containing lipid derivatives. These reactive carbonyl groups can interact with amine groups on proteins via the formation of Schiff base adducts, modifications that can lead to changes to the proteins structure and influence overall activity. Phospholipase A2 (PLA2) modified with 1-palmitoyl-2-(9'oxononanoyl)-sn-glycero-3-phosphocholine (PoxnoPC) forms Schiff bases that trigger an increase in protein activity, possibly through changes in enzyme conformation, protein-protein interaction, or peptide-protein heteroligomerisation (Code et al., 2010). However, the site of carbonyl modification that is responsible for the change in PLA2 activity remains unknown, so further studies were required to address this question. In this study, PLA2 from Apis mellifera modified with physiological concentrations of PoxnoPC (15μM) was analysed by mass spectrometry. Fragmentation data was used to identify the nature and sites of modification in the modified PLA2. No modifications containing PoxnoPC were found in the protein; however, modifications containing 9-oxononanoic acid (ON) were found on a number of lysine residues including Lys14 and Lys66. These residues are located in the vicinity of the catalytic site, the calcium binding site, and the carboxyl terminal end loop of the PLA2 structure, suggesting that PLA2 catalysed the breakdown of PoxnoPC to ON, although it is not known whether this occurred before or after adduct formation. The modifications of lysine residues found could account for the generation of highly reactive protofibril intermediates that increase the enzyme's overall activity (Code et al., 2010) which supports the need for detailed quantitative mass spectrometry and 3D mapping studies to complement these findings.

Nonenzymic carotenoid oxidation and photooxidative stress signalling in plants

Carotenoids play a crucial protective role in photosynthetic organisms as quenchers of singlet oxygen ((1)O(2)). This function occurs either via a physical mechanism involving thermal energy dissipation or via a chemical mechanism involving direct oxidation of the carotenoid molecule. The latter mechanism can produce a variety of aldehydic or ketonic cleavage products containing a reactive carbonyl group. One such molecule, the volatile β-carotene derivative β-cyclocitral, triggers changes in the expression of (1)O(2)-responsive genes and leads to an enhancement of photooxidative stress tolerance. Thus, besides their well-known functions in light harvesting and photoprotection, carotenoids can also play a role through their nonenzymic oxidation in the sensing and signalling of reactive oxygen species and photooxidative stress in photosynthetic organisms. Enzymic carotenoid oxidation does not seem to play a significant role in this phenomenon. Elucidation of the carotenoid-mediated (1)O(2) signalling pathway could provide new targets for improving photooxidative stress tolerance of plants.

One-pot method for α-phenylation of ketones using isoxazolidine and triphenylaluminum

The efficient one-pot umpolung α-phenylation of ketones via N-alkenylisoxazolidine is described. When the various ketones are treated with triphenylaluminum prepared from phenylmagnesium chloride and AlCl3 in the presence of isoxazolidine, the desired products are obtained in good to moderate yield. This method is equivalent to a direct α-arylation reaction of carbonyl groups.

Impact of low and high fluence rates of UV-B radiation on growth and oxidative stress in Phormidium foveolarum and Nostoc muscorum under copper toxicity: differential display of antioxidants system

In the present study, impact of low (UV-BL) and high (UV-BH) fluence rates of UV-B on growth, oxidative stress and antioxidant system was studied in two cyanobacteria i.e. Phormidium foveolarum and Nostoc muscorum under Cu (2 and 5 μM) toxicity after 24 and 72 h of experiments. UV-BH and Cu treatment decreased growth of both the cyanobacteria and Cu induced decrease in growth was accompanied by a significant increase in Cu accumulation. Levels of reactive oxygen species (ROS), i.e. superoxide radicals (SOR; \( \text O_{2}^{\cdot\,-} \)) and hydrogen peroxide (H2O2) were significantly increased by Cu and UV-BH exposure which in turn accelerated lipid peroxidation (malondialdehyde: MDA) and protein oxidation (reactive carbonyl groups: RCG). Activities of enzymatic antioxidants, such as superoxide dismutase (SOD), peroxidase (POD) and glutathione-S-transferase (GST) were increased by both doses of Cu as well as UV-B. Conversely, Cu and UV-BH drastically decreased catalase (CAT) activity. After the commencement of 24 h of treatment with Cu alone and together with UV-BH, non-protein thiols (NP-SH) contents were decreased while after 72 h, a reverse trend was noticed. Unlike NP-SH, cysteine content decreased appreciably during the treatments. In contrast to this, low dose (UV-BL) of UV-B did not influence growth, SOR, H2O2, MDA and RCG contents. An improvement in CAT activity and NP-SH content was observed under Cu and UV-BL treatment; hence, UV-BL treatment resulted into certain degree of protection against Cu toxicity in both the organisms. Thus, the results showed that UV-BH and UV-BL exerted differential effects on both the organisms under Cu toxicity, and compared to N. muscorum, P. foveolarum was less affected by Cu and UV-BH.

Covalent immobilization of β‐galactosidase onto electrospun nanofibers of poly (AN‐co‐MMA) copolymer

AbstractImmobilization of β‐galactosidase in poly (acrylonitrile‐co‐methyl methacrylate) poly (AN‐co‐MMA) Nanofibers was studied by electrospinning, and a spacer‐arm i.e., (Polyethyleneimine (PEI)) was covalently attached by the reaction of carbonyl groups of Poly (AN‐co‐MMA) nanofibers. β‐galactosidase was then covalently immobilized through the spacer‐arm of the Poly (AN‐co‐MMA) nanofibers by using glutaraldehyde (GA) as a coupling agent. Nanofibers mode of interaction was proven by FTIR and thermal gravimetric analysis and supported by morphological changes recognized through SEM examination. Factors affecting the modification process such as PEI concentration, reaction time, and reaction temperature have been studied. Its influence on the amount of coupled PEI was consequently correlated to the changes of the catalytic activity and the retained activity of immobilized enzyme, the main parameters judging the success of the immobilization process. Evidences of Poly (AN‐co‐MMA) nanofibers modification were extracted from morphological changes recognized through SEM examination. The maximum activity (Vmax) and michaelis constant (Km) of immobilized enzyme were found to be 8.8 μmole/min mg protein and 236.7 mM, respectively. Stabilities of the immobilized β‐galactosidase were obviously improved. The optimum temperature for β‐galactosidase immobilized on the spacer‐arm attached nanofiber was 5°C higher than that of the free enzyme and was also significantly broader. The immobilized β‐galactosidase had better resistance to temperature inactivation than did the free form. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013

Characterization of oxidation products from 1-palmitoyl-2-linoleoyl-sn-glycerophosphatidylcholine in aqueous solutions and their reactions with cysteine, histidine and lysine residues

This report focuses on studies of lipid peroxidation products reactivity towards the side chains of cysteine, histidine, and lysine residues in structurally unordered peptides. Thus we have analyzed linoleic acid peroxidation products (LaPP) obtained by incubating 1-palmitoyl-2-linoleoyl-sn-glycerophosphatidylcholine (PLPC) overnight with or without H2O2 in the presence or absence of CuCl. In total, 55 different LaPP were identified with 26 containing reactive carbonyl groups. The strongest oxidation conditions (H2O2 and Cu(I), i.e. a Fenton-like reagent) yielded 51 LaPP, whereas air oxidation produced only 12 LaPP. Independent of the oxidation conditions, around half of all LaPP were short-chain (oxidative cleavage) and the others long-chain (oxygen addition) PLPC oxidation products. The stronger oxidation conditions increased the number of LaPP, but also oxidized the added peptide Ac-PAAPAAPAPAEXTPV-OH (X=Cys, His or Lys) very quickly, especially under Fenton conditions. Thus, PLPC was oxidized by milder conditions (air or Cu(I)), incubated with the peptide and the peptide modifications were then analyzed by nano-RPC-ESI-Orbitrap-MS. Ten LaPP-derived peptide modifications were identified at lysine, whereas nine products were identified for cysteine and only three for histidine. Three high molecular weight LaPP still esterified to the GPC backbone were detected on Lys-containing peptide. Furthermore, three LaPP-derived mass shifts were obtained at cysteine, which have not previously been reported.

Impact of silicon-based quantum dots on the antioxidative system in white muscle of Carassius auratus gibelio

Silicon-based quantum dots were intraperitoneally injected in individuals of Carassius auratus gibelio. Their effects on white muscle were investigated by following their distribution and impact on the antioxidative system. The GSH level significantly increased after 1 and 3days of exposure by, respectively, 85.3 and 25.4%. Seven days later, GSH levels were similar to control concentrations. MDA concentration rose after three days by 46.9% and remained at the same level after 7days. Protein thiol levels significantly decreased by 6.7 and 8.1% after 3 and 7days, whereas advanced oxidation protein products increased by 12.7, respectively, 28.1% in the same time intervals. The protein reactive carbonyl groups were raised only after the first day of exposure and returned to the control level later on. SOD specific activity increased up to 48% after 7days, while CAT activity increased by 328, 176, and 26% after 1, 3, and 7days of treatment. GST specific activity was up-regulated by 87, 18, and 9%, while GR activity increased by 68, 34, and 9%. G6PD activity was up-regulated by 12, 22, and 50%, whereas GPx activity raised by 75 and 109% compared to control after, respectively, 1, 3, and 7days. Our results suggest that oxidative stress induced by silicon-based quantum dots was not strong enough to cause permanent damage in the white muscle of crucian carp.

Identification of carbonylated peptides by tandem mass spectrometry using a precursor ion-like scan in negative ion mode

Reactive oxygen species (ROS) can oxidize proteins at almost any amino acid residue. Whereas some modifications are reversible within the cells, the higher oxidation states are especially irreversible. These irreversible post translational modifications are widely used as biomarkers of oxidative stress, such as protein carbonylation, which refers to aldehydes, ketones and lactams as 'reactive carbonyl groups'. This study relied on a set of synthetic peptides containing a C-terminal aldehyde (arginal) or modification with pyruvic acid (ketone) or 4-hydroxynonenal (aldehyde) at lysine or histidine residues, as well as peptides containing pyroglutamic acid (oxidation product of proline) and 2-amino-3-butyric acid (oxidation product of threonine). The carbonylation sites were specifically derivatized with 2,4-dinitrophenylhydrazine (DNPH) and the fragmentation behavior of the products investigated in electrospray ionization (ESI-) MS. Importantly, the DNPH-labeled carbonylated peptides showed favorable ionization behaviors in negative ion mode ESI, providing a sensitive detection method. Regular peptides were mostly discriminated under these conditions. Among the fragmentation techniques tested for the negatively charged ions, pulsed Q dissociation provided three diagnostic ions at m/z values 152.0, 163.1 and 179.0, specific for DNPH-modified peptides. These marker ions were successfully applied to detect the carbonylated model peptides in a spiked tryptic digest of bovine serum albumin and a complex protein mixture obtained from HeLa cells.

Efficient carbonyl hydrosilylation reaction: Toward EVA copolymer crosslinking

AbstractIn this article, the hydrosilylation reaction of carbonyl groups of acetate derivatives and SiH groups of hydride‐terminated polydimethylsiloxane at high temperature (100–130 °C) are described. Triruthenium dodecacarbonyl, Ru3(CO)12, was used as effective catalyst for hydrosilylation reaction. The hydrosilylation reactions with octyl acetate and 4‐heptyl acetate were investigated by multinuclear NMR spectroscopy (1H, 13C, and 29Si). This work provides evidence of the addition reaction of SiH groups onto carbonyl groups. The influence of the nature of the acetate structure on the reaction kinetics was shown and the slight contribution of side reactions at high temperature highlighted. Hydrosilylation reaction was extent to the crosslinking of ethylene‐vinyl acetate (EVA) copolymer in the same range of temperature. The formation of EVA chemical network was demonstrated by HR‐MAS NMR spectroscopy and by measuring the gel fraction of EVA chains in hot toluene. From Flory theory, the crosslinking density of elastic strand was calculated to be 80 mol m−3 in agreement with the measurements from swelling ratio (VA/SiH molar ratio: 11.8). © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011