Chain Cleavage Reaction Research Articles

Biotransformation of hydrocortisone succinate with whole cell cultures of Monascus purpureus and Cunninghamella echinulata

Hydrocortisone succinate (1) is a synthetic anti-inflammatory drug and key intermediate in the synthesis of other steroidal drugs. This work is based on the fungal biotransformation of 1, using Monascus purpureus and Cunninghamella echinulata strains. Comopound 1 was transformed into four metabolites, identified as hydrocortisone (2), 11β-hydroxyandrost-4-en-3,17-dione (3), Δ1-cortienic acid (4), and hydrocortisone-17-succinate (5), obtained through side chain cleavage, hydrolysis, dehydrogenation, and oxidation reactions. These compounds have previously been synthesized either chemically or enzymatically from different precursors. Though this is not the first report on the biotransformation of 1, but it obviously is a first, where the biotransformed products of compound 1 have been characterized structurally with the help of modern spectroscopic techniques. It is noteworthy that these products have already shown biological potential, however a more thorough investigation of the anti-inflammatory properties of these metabolites would be of high value. These results not only emphasize upon the immense potential of biotransformation in catalysis of reactions, otherwise not-achievable chemically, but also holds promise for the development of novel anti-inflammatory compounds.

Catalytic valorization of Kraft lignin into feedstock chemicals with methyltrioxorhenium (MTO) catalyst in microbial electrochemical cell

In this study, the authors investigate a novel approach to valorize Kraft lignin using the catalyst Methyltrioxorhenium (MTO) in tandem with in-situ produced H2O2 in a Microbial Electrochemical Cell (MEC). This study demonstrates the in-situ oxidation of Kraft lignin using different concentrations of MTO catalyst (2 mM to 8 mM) and H2O2 (5.24 ± 0.40 mM to 8.91 ± 0.70 mM) in three MECs. The depolymerized Kraft lignin samples were characterized using FTIR, CHNS/O, and 1H NMR analysis. The MTO/H2O2 combination showed high selectivity towards the oxidation of Kraft lignin, resulting in both aromatic ring and side chain cleavage reactions and the production of valuable feedstock chemicals. The oxidation also led to a reduction of 68.42 % to 78.18 % in Chemical Oxygen Demand (COD) of lignin. The selective oxidation favored the recovery of Guaiacyl (G) unit-derived feedstock chemicals, with Guaiacol being the most abundant compound (45.04 mg/mL) among the quantified products by HPLC. Additionally, the system demonstrated high efficiency in anodic wastewater treatment, achieving BOD and COD removal rates ranging from 67.68 % to 72.55 %. This method showcases the use of a sustainable system in combination with a selective catalyst to produce valuable products from usually discarded Kraft lignin while simultaneously treating wastewater.

Low-Temperature Oxidation of Heavy Oil Asphaltene with and without Catalyst.

In this study, the asphaltene extracted from Luntai heavy oil was oxidized by a mixture of propionic anhydride and hydrogen peroxide without and with a catalyst. Elemental analysis and infrared spectroscopy results indicated the occurrence of oxygen addition, condensation, and side chain cleavage reactions in the oxidation process. Oxidation products were divided into methanol solubles and methanol insolubles. The H/C and O/C atomic ratios of the MeOHS in the oxidation products without a catalyst were higher than those of the Luntai asphaltene. MeOHS had fewer aromatic rings than Luntai asphaltene. Compared with the oxidative reaction without a catalyst, the total mass of oxidation products and the proportion of MeOHS in oxidation products both increased after catalytic oxidation. This low-temperature oxidation technology can be used to upgrade asphaltenes, and thus can promote the exploitation and processing of heavy oil.

Programed Thermoresponsive Polymers with Cleavage-Induced Phase Transition.

A new programed upper critical solution temperature-type thermoresponsive polymer was developed using water-soluble anionic polymer conjugates derived from polyallylamine and phthalic acid with cleavage-induced phase transition property. Intrinsic charge inversion from anion to cation of the polymer side chain is induced through a side chain cleavage reaction in acidic aqueous media. With the progress of side chain cleavage under fixed external conditions, the polymer conjugates express a thermoresponsive property, followed by shifting a phase boundary due to the change in polymer composition. When the phase transition boundary eventually reached the examined temperature, phase transition occurs under fixed external conditions. Such new insight obtained in this study opens up the new concept of time-programed stimuli-responsive polymer possessing a cleavage-induced phase transition.

Rheological Properties and Melt Spinning Application of Controlled-Rheology Polypropylenes via Pilot-Scale Reactive Extrusion.

Based on pilot-scale twin-screw reactive extrusion, the structural and rheological properties of controlled-rheology polypropylenes (CR-PPs) are investigated, where the effects of peroxide content and extrusion conditions such as screw configuration, extrusion temperature, and screw speed are prioritized. The active chain cleavage reaction by a small peroxide content of less than 600 ppm inside the extruder gradually increases the melt index and narrows the molecular weight distribution of CR-PPs, thereby affording favorable properties that are applicable to the fiber spinning process. The mechanical properties of CR-PPs are slightly degraded owing to the generation of unsaturated chain ends during the reactive extrusion, which suppresses crystal growth. Under all extrusion conditions, the chain scission and thermal degradation of polypropylene samples occur actively in the harsh twin-screw extruder compared with those in the mild twin-screw extruder. Finally, it is confirmed that CR-PPs can be suitably applied to the melt-spinning process for staple fiber production, thereby guaranteeing a more stable spinning process window against draw resonance instability.

Detection of Unprecedented CYP74 Enzyme in Mammal: Hydroperoxide Lyase CYP74C44 of the Bat Sturnira hondurensis.

The genome of the neotropical fruit bat Sturnira hondurensis was recently sequenced, revealing an unexpected gene encoding a plant-like protein, CYP74C44, which shares ca. 90% sequence identity with the putative CYP74C of Populus trichocarpa. The preparation and properties of the recombinant CYP74C44 are described in the present work. The CYP74C44 enzyme was found to be active against the 13- and 9-hydroperoxides of linoleic and α-linolenic acids (13-HPOD, 13-HPOT, 9-HPOD, and 9-HPOT, respectively), as well as the 15-hydroperoxide of eicosapentaenoic acid (15-HPEPE). All substrates studied were specifically transformed into chain cleavage products that are typical for hydroperoxide lyases (HPLs). The HPL chain cleavage reaction was validated by the identification of NaBH4-reduced products (Me/TMS) of 15-HPEPE and 13- and 9-hydroperoxides as (all-Z)-14-hydroxy-5,8,11-tetradecatrienoic, (9Z)-12-hydroxy-9-dodecenoic, and 9-hydroxynonanoic acids (Me/TMS), respectively. Thus, CYP74C44 possessed the HPL activity that is typical for the CYP74C subfamily proteins.

Preliminary Study on the Simulation of a Radiation Damage Analysis of Biodegradable Polymers.

In this study, biodegradable poly(L-lactide-co-ε-caprolactone) (PLCL) and poly(L-co-d,l lactide) (PLDLA) were evaluated using Geant4 (G4EmStandardPhysics_option4) for damage simulation, in order to predict the safety of these biodegradable polymers against gamma ray sterilization. In the PLCL damage model, both chain scission and crosslinking reactions appear to occur at a radiation dose in the range 0–200 kGy, but the chain cleavage reaction is expected to be relatively dominant at high irradiation doses above 500 kGy. On the other hand, the PLDLA damage model predicted that the chain cleavage reaction would prevail at the total irradiation dose (25–500 kGy). To verify the simulation results, the physicochemical changes in the irradiated PLCL and PLDLA films were characterized by GPC (gel permeation chromatography), ATR-FTIR (attenuated total reflection Fourier transform infrared), and DSC (difference scanning calorimetry) analyses. The Geant4 simulation curve for the radiation-induced damage to the molecular weight was consistent with the experimentally obtained results. These results imply that the pre-simulation study can be useful for predicting the optimal irradiation dose and ensuring material safety, particularly for implanted biodegradable materials in radiation processing.

Photo-induced fragmentation of tyrosine side chains in IgG4-Fc: Effect of protein sequence, conformation and glycan structure

This account summarizes recent work on photo-induced side chain cleavage reactions of Tyr in IgG4-Fc. These processes are initiated via photo-ionization of Trp to a Trp radical cation, followed by one-electron oxidation of Tyr to a Tyr radical cation, where fragmentation of the Cα-Cβ bond leads to an intermediary glycyl radical. The latter converts into Gly via hydrogen atom transfer, or into various backbone cleavage products subsequent to the addition of oxygen. Site-directed mutation of Trp381 to Phe381 significantly reduces the yields of Tyr side chain cleavage products, underlining a critical role of Trp for these reactions. Likewise, conformational changes of IgG4-Fc induced by increasing contents of 1-propanol in the solution diminishes the yields of Tyr side chain cleavage products. Variations of the glycan structure at Asn297 had an effect on Tyr side chain cleavage, where larger glycan structures led to lower yields. This result is in interesting contrast to Trp side chain cleavage in IgG1-Fc, where larger glycan structures led to higher yields. The opposite trends for Trp and Tyr side chain cleavage as a function of glycan structure are consistent with a connection between the precursors for both reactions, radical cations of Trp and Tyr, related by electron transfer. The potential significance of these reactions for protein integrity in formulations of pharmaceutical proteins will be discussed.

Silver nanoparticles/polyvinyl alcohol film: studies of thermal characterization, AFM and corrosion protection by electrodeposition on 304L stainless steel

A composite polymeric system consisting of silver nanoparticles and polyvinyl alcohol (nAg/PVA) was characterized by thermal analysis and compared to the two basic components, namely the silver nanoparticles (nAg) and polyvinyl alcohol (PVA). The main stage of decomposition of PVA and nAg/PVA takes place in temperature range between 210 and 325 °C, when the thermal processes consist of dehydroxylation reaction and polyene formation, macromolecular chain cleavage and oxidation reactions. The finalization of the PVA decomposition reaction takes place around 420 °C. At temperature values higher than 325 °C, the composite degradation follows another trend compared to PVA, indicating the presence of silver nanoparticles inserted into polymer matrix. Due to its adsorption and inhibitory properties and relatively good thermal stability at temperature lower than 200 °C, the nAg/PVA composite was applied as protective coating against corrosion of 304L stainless steel. Over a prolonged time, the coating can deteriorate affecting the surface characteristics. To evaluate the stainless steel surface morphology and nAg/PVA electrochemical stability over time, the atomic force microscopy (AFM) and electrochemical impedance spectroscopy (EIS) were used. AFM and EIS confirmed that on the stainless steel surface, a relatively uniform and smooth composite film with a good electrochemical stability were formed, ensuring a corrosion protection performance (P%) of 81.7%.

Investigation of thermo-chemical properties of mechanochemically generated glucose–histidine Maillard reaction mixtures

Mechanochemistry is gaining increasing interest as an efficient tool for solvent-free organic transformations. Recently, it was applied to perform the Maillard reaction of glucose with various amino acids that lead to the selective formation of Schiff bases and their Amadori rearrangement products. In this study, we report the thermal properties of the mechanochemically generated glucose–histidine reaction mixtures. Direct video recordings of their melting behavior show that the browning of the ball-milled mixtures starts at lower temperatures and proceed more slowly compared to the non-milled mixtures. Furthermore, pyrolysis of ball-milled mixtures generated more pyrazines and fewer furan derivatives compared to the non-milled mixtures. The chemical composition of the ball-milled glucose–histidine was also investigated in depth by high-resolution mass spectrometry. The decarboxylation and C2–C3 sugar chain cleavage reactions were identified as the most important transformations during ball milling. These findings further support the utility of mechanochemically generated mixtures as potential Maillard flavor and browning precursors.

Nanocrystalline ferrihydrite activated peroxymonosulfate for butyl-4-hydroxybenzoate oxidation: Performance and mechanism.

Heterogeneous catalysts activated peroxymonosulfate (PMS) for degradation of refractory organic contaminants has been recognized as a promising removal technology for the environmental remediation. In this study, nanocrystalline ferrihydrite (NFH) was prepared to activate PMS for the degradation of butyl-4-hydroxybenzoate (BHB). XPS analysis indicates that calcination process played a key role in regulating the surface oxygen species of NFH, thus control its activation ability toward PMS. NFH exhibits excellent stability (the released concentration of Fe ions < 0.13 mg/L) and desirable reusability. Increasing solution temperature and NFH dosage exerted a positive role in PMS activation for BHB removal, while such positive correlation was not found in the case of increasing initial pH. Increasing the static solution dissolved oxygen remarkably enhanced BHB oxidation kinetics. However, continuous N2 and air blowing caused a significant decline in BHB removal. Reaction mechanism study showed that SO4‒, OH, O2‒, and 1O2 were the main reactive oxygen species for degrading BHB by NFH/PMS. LC/MS analysis indicated BHB was degraded by the pathways of hydroxylation, carboxylation, decarboxylation, dehydrogenation, ring cleavage and chain cleavage reaction. This work suggests the ferrihydrite might be a promising catalyst to activate PMS to destroy refractory organic pollutants in the environmental remediation.

Photoinduced Tyrosine Side Chain Fragmentation in IgG4-Fc: Mechanisms and Solvent Isotope Effects.

Immunoglobulin gamma (IgG) monoclonal antibodies (mAbs) are glycoproteins that have emerged as powerful and promising protein therapeutics. During the process of production, storage and transportation, exposure to ambient light is inevitable, which can cause protein physical and chemical degradation. For mechanistic studies of photodegradation, we have exposed IgG4-Fc to UV light. The photoirradiation of IgG4-Fc with monochromatic UVC light at λ = 254 nm and UVB light with λmax = 305 nm in air-saturated solutions revealed multiple photoproducts originating from tyrosine side chain fragmentation at Tyr300, Tyr373, and Tyr436. Tyr side chain fragmentation yielded either Gly or various backbone cleavage products, including glyoxal amide derivatives. A mechanism is proposed involving intermediate Tyr radical cation formation, either through direct light absorption of Tyr or through electron transfer to an initial Trp radical cation, followed by elimination of quinone methide. Product formation showed either no (cleavage of Tyr373) or significant (cleavage of Tyr436) inverse product solvent isotope effects (SIEs), indicating a role for proton transfer in the cleavage mechanism of Tyr436. The role of electron transfer in the cleavage of Tyr436 was further investigated through mutation of an adjacent Trp381. This is the first observation of a photoinduced Tyr side chain cleavage reactions in a protein.

Influence of ultrasonic assisted ionic liquid on heavy oil structure

The effect of ionic liquid concentration on the content of four components and structural composition of heavy oil was studied by using ultrasonic-assisted nickel based ionic liquid. The results reveals that compared with crude oil and individual ultrasonic crude oil, the combination of ultrasonic wave and ionic liquid can achieve synergistic effect. Saturate increased and aromatic decreased gradually as the increase of the concentration of ionic liquid. The structure of resin and asphaltene has been characterized by infrared and nuclear magnetic resonance spectroscopy. It has been indicated that the structure of polyaromatic compounds can be obviously changed and mainly occurrence in alkyl side chain cleavage and cycloalkanes ring-opening reaction.

The thermo-oxidation of chlorinated and brominated isobutylene-co-isoprene polymers: Activation energies and reactions from room temperature to 100 °C

The activation energies of Chlorinated isobutylene-co-isoprene (CIIR) and Brominated isobutylene-co-isoprene (BIIR) were determined after thermo-oxidation in the 23–100 °C temperature range. Fourier Transform Infrared (FTIR) spectroscopy was used to follow carbonyl growth and aid in the identification of oxidative species along with 1H Nuclear Magnetic Resonance (NMR). Two thermo-oxidative processes at high (100–80 °C) and at low temperatures (60–23 °C) including a transition zone at 70 °C were identified. Halobutyl oxidation is occurring at the exomethylene microstructure and residual isoprene units during low temperature aging while the isobutylene sequences undergo oxidation at higher temperatures. Loss of bromine radical is quicker than chlorine, which is in line with their inherent bond strengths and agrees with the lower activation energy for BIIR (22 kJ/mol) compared to CIIR (52 kJ/mol) at low temperatures. Chain cleavage reactions dominate at low temperatures and a reaction pathway showing loss of halogen and the formation of macroradicals which undergo oxidation has been proposed. At higher temperatures (80–100 °C), chain crosslinking reactions become more numerous causing a substantial increase in activation energies for halobutyl in comparison to butyl rubber.

Preparation of Hydroxyl-Terminated Polybutadiene with High Cis-1,4 Content

Hydroxyl-terminated polybutadiene (HTPB) with high cis-1,4 content (>95.0%) has been prepared via a two-step method by taking commercial butadiene rubber (BR9000) as a starting material, including the one-pot synthesis of aldehyde-group-terminated polybutadiene (ATPB) in high efficiency and the subsequent reduction reaction. The double bonds distributed in linear polybutadiene were first epoxidized and then cleaved at the exact epoxidized sites. The epoxidation reaction by 3-chloroperbenzoic acid and chain-cleavage reaction by periodic acid are controllable, highly efficient, selective, and quantitative. Along with an epoxy percent increase, the molecular weight of ATPB prepared via a one-pot method decreased with a relatively narrow polydispersity index. The aldehyde groups in the chain ends were reduced by NaBH4 to produce HTPB, in which the high cis-1,4 content of BR was retained.

Downregulation of cytochrome P450scc as an initial adverse effect of adult exposure to diethylstilbestrol on testicular steroidogenesis

Reproductive toxicities and endocrine disruptions caused by chemicals in adult males are still poorly understood. It is our objectives to understand further details of the initial adverse effects leading severe testicular toxicities of a pharmaceutical endocrine disruptor, diethylstilbestrol (DES). Downregulations of both testicular regulatory proteins, such as the steroidogenic acute regulatory protein (StAR) and the peripheral benzodiazepine receptor (PBR), which play important roles in the transport of cholesterol into the mitochondria, and cytochrome P450 mediating the cholesterol side chain cleavage reaction (P450scc), were observed in the rat orally administered DES (340 μg/kg/2 days) for 2 weeks. We found that after only 1 week treatment with DES, the blood and testicular testosterone (TS) levels were drastically decreased without abnormalities of the StAR and PBR; however, the protein and mRNA levels of P450scc were diminished. Decrease in the conversion rate of cholesterol to pregnenolone was delayed in the in vitro assay using the testicular mitochondrial fraction from the rat treated with DES for 1 week. When the precursors in TS biosynthesis containing the testis were identified and determined by liquid chromatography-mass spectrometry analysis, decreased levels of all precursors except cholesterol were observed. In conclusion, suppressed cytochrome P450scc expression in adult male rat was identified as an initial target of DES in testicular steroidogenesis disorder leading reproductive toxicities.

Presolvated Low Energy Electron Attachment to Peptide Methyl Esters in Aqueous Solution: C–O Bond Cleavage at 77 K

In this study, the reactions of presolvated electrons with glycine methyl ester and N-acetylalanylalanine methyl ester (N-aAAMe) are investigated by electron spin resonance (ESR) spectroscopy and DFT calculations. Electrons were produced by γ-irradiation in neutral 7.5 M LiCl-D2O aqueous glasses at low temperatures. For glycine methyl ester, electron addition at 77 K results in both N-terminal deamination to form a glycyl radical and C-O ester bond cleavage to form methyl radicals. For samples of N-acetylalanylalanine methyl ester, electrons are found to add to the peptide bonds at 77 K and cleave the carboxyl ester groups to produce methyl radicals. On annealing to 160 K, electron adducts at the peptide links undergo chain scission to produce alanyl radicals and on further annealing to 170 K α-carbon peptide backbone radicals are produced by hydrogen abstraction. DFT calculations for electron addition to the methyl ester portion of N-aAAMe show the cleavage reaction is highly favorable (free energy equals to -30.7 kcal/mol) with the kinetic barrier of only 9.9 kcal/mol. A substantial electron affinity of the ester link (38.0 kcal/mol) provides more than sufficient energy to overcome this small barrier. Protonated peptide bond electron adducts also show favorable N-C chain cleavage reactions of -12.7 to -15.5 kcal/mol with a barrier from 7.4 to 10.0 kcal/mol. The substantial adiabatic electron affinity (AEA) of the peptide bond and ester groups provides sufficient energy for the bond dissociation.

The effect of microwave irradiation on poly(vinyl alcohol) dissolved in ethylene glycol

AbstractPoly(vinyl alcohol) (PVA) dissolved in ethylene glycol is subjected to microwave (MW) irradiation for 1 h to determine possible degradation. Fourier transform infrared spectroscopy results show that MW treatment produces a minor effect on the solutions. Ultraviolet–visible spectroscopy suggests that PVA could undergoes loss of hydroxyl groups followed by formation of unsaturated conjugated bonds although the extent of degradation is limited, whereas size exclusion chromatography indicates that MW irradiation do not cause significant changes in PVA molar mass and neither chain cleavage nor crosslinking reactions are observed. Hence, polymer degradation induced by MWs in solution can be considered as negligible for prospective applications. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013

Ring-opening polymerization of ethylene carbonate using ionic liquids as catalysts

AbstractThe ring-opening polymerization of ethylene carbonate was examined using ionic liquids, 1-butyl-3-methylimidazolium tetrafluoroborate ([bmim]BF4) and 1-butyl-3-methylimidazolium chlorozincate ([bmim]Cl-(ZnCl2)x), as polymerization catalysts. It was shown that the polymerization was accompanied with decarboxylation and chain cleavage reaction. As the reaction time increased, the monomer conversion increased and the content of ethylene carbonate units in the resultant polymer decreased, while the polymer molecular weight increased at first, reached a maximum and then decreased. It was also found that not only the polymerizing activity of the [bmim]Cl-(ZnCl2)x but also its performance for suppressing the decarboxylation and chain cleavage increased with the molar fraction of ZnCl2. It was deduced that the catalytic performance of ionic liquids mainly depended on their inorganic anions and that the larger the amount of these anions in the reaction system, the better the catalytic performance. The polymerizing activity of ionic liquids was much higher than conventional catalysts often used for the polymerization of ethylene carbonate.

Synthesis of dihydroperoxides of linoleic and linolenic acids and studies on their transformation to 4‐hydroperoxynonenal

The cytotoxic aldehydes 4-hydroxynonenal, 4-hydroperoxynonenal (4-HPNE), and 4-oxononenal are formed during lipid peroxidation via oxidative transformation of the hydroxy or hydroperoxy precursor fatty acids, respectively. The mechanism of the carbon chain cleavage reaction leading to the aldehyde fragments is not known, but Hock-cleavage of a suitable dihydroperoxide derivative was implicated to account for the fragmentation [Schneider, C., Tallman, K.A., Porter, N.A., and Brash, A.R. (2001) Two Distinct Pathways of Formation of 4-Hydroxynonenal. Mechanisms of Nonenzymatic Transformation of the 9- and 13-Hydroperoxides of Linoleic Acid to 4-Hydroxyalkenals, J. Biol. Chem. 275, 20831-20838]. Both 8,13- and 10,13-dihydroperoxyoctadecadienoic acids (diHPODE) could serve as precursors in a Hock-cleavage leading to 4-HPNE via two different pathways. Here, we synthesized diastereomeric 9,12-, 10,12-, and 10,13-diHPODE using singlet oxidation of linoleic acid. 8,13-Dihydroperoxyoctadecatrienoic acid was synthesized by vitamin E-controlled autoxidation of gamma-linolenic acid followed by reaction with soybean lipoxygenase. The transformation of these potential precursors to 4-HPNE was studied under conditions of autoxidation, hematin-, and acid-catalysis. In contrast to 9- or 13-HPODE, neither of the dihydroperoxides formed 4-HPNE on autoxidation (lipid film, 37 degrees C), regardless of whether the free acid or the methyl ester derivative was used. Acid treatment of 10,13-diHPODE led to the expected formation of 4-HPNE as a significant product, in accord with a Hock-type cleavage reaction. We conclude that, although the suppression of 4-H(P)NE formation from monohydroperoxides by alpha-tocopherol indicates peroxyl radical reactions in the major route of carbon chain cleavage, the dihydroperoxides previously implicated are not intermediates in the autoxidative transformation of monohydroperoxy fatty acids to 4-HPNE and related aldehydes.