Oxidation-induced Changes Research Articles

Phase stability, microstructure and high-temperature properties of NbSi2- and TaSi2-oxide conducting ceramic composites

NbSi2- and TaSi2-based electroconductive ceramic composites with the addition of 40–70 vol% Al2O3 and ZrO2 particles were fabricated by high-temperature sintering (1400–1600 °C) under argon. Their phase stability, microstructural evolution, oxidation kinetics and electrical properties were studied at high temperatures. The densification of the composites was improved by increasing the oxide phase content and sintering temperature. The interaction of the starting metal disilicides with residual oxygen sources resulted in the formation of the hexagonal-structured 5–3 metal silicide (Nb5Si3 and Ta5Si3) phases. The increasing sintering temperature and volume percentage of the oxide phase reduced the pest oxidation, particularly for the silicide–alumina composites, which exhibited lower oxidation-induced mass changes than their dense monolithic metal silicides. Depending on the silicide–oxide volume percentage, their electrical conductivities ranged from 5.3 to 111.3 S/cm at 900 °C. Their phase stability, reduced oxidation rates and high electrical conductivities at high temperatures show promise for future high-temperature applications in advanced sensing.

Probing Charge Delocalization in Solid State Polychromophoric Cation Radicals Using X-ray Crystallography and DFT Calculations

Assessing the charge delocalization in polychromophoric assemblies is a critical step toward designing novel charge transfer materials. Triptycene-based materials are particularly attractive, owing to their unique packing arrangement in the solid state. Here, we systematically probe, both experimentally (with X-ray crystallography) and theoretically (using Density Functional Theory, DFT), the extent of cationic charge (i.e., hole) delocalization in a set of triptycene derivatives with one, two, and three electron-rich 1,2-dimethoxybenzenoid (veratrole) rings. We demonstrate that the amount of charge at each veratrole can be deduced from experiment by analysis of the oxidation-induced bond length changes in comparison with a model compound containing one veratrole ring as a reference. In contrast, DFT calculations provide not only oxidation-induced structural reorganization, but also the charge distribution with the aid of natural population analysis. A comparative analysis shows that both experiment and t...

Oxidation-Induced Increase In Photoreactivity of Bovine Retinal Lipid Extract

The mammalian retina contains a high level of polyunsaturated fatty acids, including docosahexaenoic acid (22:6) (DHA), which are highly susceptible to oxidation. It has been shown that one of the products of DHA oxidation—carboxyethylpyrrole (CEP), generated in situ, causes modifications of retinal proteins and induces inflammation response in the outer retina. These contributing factors may play a role in the development of age-related macular degeneration (AMD). It is also possible that some of the lipid oxidation products are photoreactive, and upon irradiation with blue light may generate reactive oxygen species. Therefore, in this work we analysed oxidation-induced changes in photoreactivity of lipids extracted from bovine neural retinas. Lipid composition of bovine neural retinas closely resembles that of human retinas making the bovine tissue a convenient model for studying the photoreactivity and potential phototoxicity of oxidized human retinal lipids. Lipid composition of bovine neural retinas Folch’ extracts (BRex) was determined by gas chromatography (GC) and liquid chromatography coupled to an electrospray ionization source-mass spectrometer (LC-ESI-MS) analysis. Liposomes prepared from BRex, equilibrated with air, were oxidized in the dark at 37 °C for up to 400 h. The photoreactivity of BRex at different stages of oxidation was studied by EPR-oximetry and EPR-spin trapping. Photogeneration of singlet oxygen (1O2, 1Δg) by BRex was measured using time-resolved detection of the characteristic phosphorescence at 1270 nm. To establish contribution of lipid components to the analysed photoreactivity of Folch’ extract of bovine retinas, a mixture of selected synthetic lipids in percent by weight (w/w %) ratio resembling that of the BRex has been also studied. Folch’s extraction of bovine neural retinas was very susceptible to oxidation despite the presence of powerful endogenous antioxidants such as α-tocopherol and zeaxanthin. Non-oxidized and oxidized BRex photogenerated singlet oxygen with moderate quantum yield. Blue-light induced generation of superoxide anion by Folch’ extract of bovine neural retinas strongly depended on the oxidation time. The observed photoreactivity of the studied extract gradually increased during its in vitro oxidation.

PARAFAC Modeling of Irradiation- and Oxidation-Induced Changes in Fluorescent Dissolved Organic Matter Extracted from Poultry Litter.

Parallel factor analysis (PARAFAC) applied to fluorescence excitation emission matrices (EEMs) allows quantitative assessment of the composition of fluorescent dissolved organic matter (DOM). In this study, we fit a four-component EEM-PARAFAC model to characterize DOM extracted from poultry litter. The data set included fluorescence EEMs from 291 untreated, irradiated (253.7 nm, 310-410 nm), and oxidized (UV-H2O2, ozone) poultry litter extracts. The four components were identified as microbial humic-, terrestrial humic-, tyrosine-, and tryptophan-like fluorescent signatures. The Tucker's congruence coefficients for components from the global (i.e., aggregated sample set) model and local (i.e., single poultry litter source) models were greater than 0.99, suggesting that the global EEM-PARAFAC model may be suitable to study poultry litter DOM from individual sources. In general, the transformation trends of the four fluorescence components were comparable for all poultry litter sources tested. For irradiation at 253.7 nm, ozonation, and UV-H2O2 advanced oxidation, transformation of the humic-like components was slower than that of the tryptophan-like component. The opposite trend was observed for irradiation at 310-410 nm, due to differences in UV absorbance properties of components. Compared to the other EEM-PARAFAC components, the tyrosine-like component was fairly recalcitrant in irradiation and oxidation processes. This novel application of EEM-PARAFAC modeling provides insight into the composition and fate of agricultural DOM in natural and engineered systems.

Topical applied nutraceutical antioxidant formulation reduces ocular oxidative stress

Background: Oral nutraceutical antioxidants have shown disappointing clinical results in reducing oxidation-induced age-related cataract and other ocular diseases. Based on the hypothesis that nutraceuticals do not adequately reach the lens by oral administration, we have developed a unique topical antioxidant formulation whose active ingredients have the reported ability to reduce oxidative stress through free radical scavenging and chelating activity. This topical nutraceutical formulation was designed to mimic the in vivo activity of multifunctional antioxidants, compounds which are being developed in our laboratory to independently scavenge free radicals and selectively bind redox metals. A comparison of the efficacy of this topical nutraceutical to multifunctional antioxidants in laboratory animal models of oxidation-induced lens changes, retinal changes, and dry eye is reviewed. Although it is less potent than the small molecule multifunctional antioxidants that will require FDA approval, the topical nutraceutical formulation beneficially reduces ocular oxidative stress. These studies suggest that this topical antioxidant may fill an unmet therapeutic need by providing a nutraceutical that beneficially reduces the effects of oxidation on age-related ocular diseases. Keywords: oxidative stress, nutraceutical antioxidants, age-related ocular diseases, dry eye, cataracts, retinal degeneration

Predicting Oxidation-Limited Lifetime of Thin-Walled Components of NiCrW Alloy 230

Using alloy 230 as an example, a generalized oxidation lifetime model for chromia-forming Ni-base wrought alloys is proposed, which captures the most important damaging oxidation effects relevant for component design: wall thickness loss, scale spallation, and the occurrence of breakaway oxidation. For deriving input parameters and for verification of the model approach, alloy 230 specimens with different thicknesses were exposed for different times at temperatures in the range 950–1050 °C in static air. The studies focused on thin specimens (0.2–0.5 mm) to obtain data for critical subscale depletion processes resulting in breakaway oxidation within reasonably achievable test times up to 3000 h. The oxidation kinetics and oxidation-induced subscale microstructural changes were determined by combining gravimetric data with results from scanning electron microscopy with energy dispersive X-ray spectroscopy. The modeling of the scale spallation and re-formation was based on the NASA cyclic oxidation spallation program, while a new model was developed to describe accelerated oxidation occurring after longer exposure times in the thinnest specimens. The calculated oxidation data were combined with the reservoir model equation, by means of which the relation between the consumption and the remaining concentration of Cr in the alloy was established as a function of temperature and specimen thickness. Based on this approach, a generalized lifetime diagram is proposed, in which wall thickness loss is plotted as a function of time, initial specimen thickness, and temperature. The time to reach a critical Cr level at the scale/alloy interface of 10 wt% is also indicated in the diagrams.

Degradation of Redox-Sensitive Proteins including Peroxiredoxins and DJ-1 is Promoted by Oxidation-induced Conformational Changes and Ubiquitination.

Reactive oxygen species (ROS) are key molecules regulating various cellular processes. However, what the cellular targets of ROS are and how their functions are regulated is unclear. This study explored the cellular proteomic changes in response to oxidative stress using H2O2 in dose- and recovery time-dependent ways. We found discernible changes in 76 proteins appearing as 103 spots on 2D-PAGE. Of these, Prxs, DJ-1, UCH-L3 and Rla0 are readily oxidized in response to mild H2O2 stress, and then degraded and active proteins are newly synthesized during recovery. In studies designed to understand the degradation process, multiple cellular modifications of redox-sensitive proteins were identified by peptide sequencing with nanoUPLC-ESI-q-TOF tandem mass spectrometry and the oxidative structural changes of Prx2 explored employing hydrogen/deuterium exchange-mass spectrometry (HDX-MS). We found that hydrogen/deuterium exchange rate increased in C-terminal region of oxidized Prx2, suggesting the exposure of this region to solvent under oxidation. We also found that Lys191 residue in this exposed C-terminal region of oxidized Prx2 is polyubiquitinated and the ubiquitinated Prx2 is readily degraded in proteasome and autophagy. These findings suggest that oxidation-induced ubiquitination and degradation can be a quality control mechanism of oxidized redox-sensitive proteins including Prxs and DJ-1.

Thermal oxidation of amorphous Al0.44Zr0.56 alloys

The oxidation of amorphous Al0.44Zr0.56 alloys upon exposure to pure O2(g) at 500 and 560°C (and pO2=1×105Pa) was investigated by a combinatorial experimental approach using X-ray diffraction, spectroscopic ellipsometry, transmission electron microscopy and Auger electron spectroscopy. During the early stages of oxidation at 500 and 560°C, an amorphous (Zr,Al)-oxide layer of homogeneous composition and uniform thickness is formed, which is enriched in Zr with respect to the alloy substrate. At 500°C, both the alloy substrate and the oxide layer remain amorphous during continued oxidation, whereas at 560°C, a crystalline tetragonal ZrO2 (t-ZrO2) phase nucleates after prolonged oxidation, while the alloy remains amorphous. The nucleation and growth of t-ZrO2 at 560°C occurs exclusively close to the interface between the initially formed amorphous (Zr,Al)-oxide layer and the alloy, immediately underneath a region of Al enrichment in the substrate, as triggered by oxidation-induced compositional changes in the alloy below the reacting alloy/oxide interface and a favorable energy of the interface between t-ZrO2 crystallites and the amorphous alloy matrix. The growing t-ZrO2 oxide crystallites eventually laterally coalesce to form a continuous layer constituted of branches of dendrite-shaped t-ZrO2 phase crystallites surrounded by an Al-rich amorphous Al–Zr alloy matrix. The underlying mechanism of the oxidation process is discussed.

Anti Oxidative Effect of Black Tea Theaflavin on Erythrocytes Subjected to Oxidative Stress

Tea (Camellia sinensis) is one of the most popularly consumed beverage worldwide. It is consumed mostly as green tea, oolong, or black tea. Black tea, good source of flavan-3-ols the theaflavins: mixture of theaflavin (TF), theaflavin-3-gallates, theaflavin-3′-gallates and theaflavin-3,3′-digallates, possess numerous biological and therapeutic properties. However, the exact mechanisms underlying these properties of TFs remain speculative. In the present study, we investigated the in vitro protective effect of theaflavin on membrane protein carbonyl group, sulfhydryl group (–SH) and erythrocyte hemolysis in rat. TFs (at micromolar concentration) showed significant antioxidant effect in protecting erythrocytes from oxidation-induced changes.

Oxidation-induced conformational changes in calcineurin determined by covalent labeling and tandem mass spectrometry.

The Ca2+/calmodulin activated phosphatase, calcineurin, is inactivated by H2O2 or superoxide-induced oxidation, both in vivo and in vitro. However, the potential for global and/or local conformation changes occurring within calcineurin as a function of oxidative modification, that may play a role in the inactivation process, has not been examined. Here, the susceptibility of calcineurin methionine residues toward H2O2-induced oxidation were determined using a multienzyme digestion strategy coupled with capillary HPLC–electrospray ionization mass spectrometry and tandem mass spectrometry analysis. Then, regions within the protein complex that underwent significant conformational perturbation upon oxidative modification were identified by monitoring changes in the modification rates of accessible lysine residues between native and oxidized forms of calcineurin, using an amine-specific covalent labeling reagent, S,S′-dimethylthiobutanoylhydroxysuccinimide ester (DMBNHS), and tandem mass spectrometry. Importantly, methionine residues found to be highly susceptible toward oxidation, and the lysine residues exhibiting large increases in accessibility upon oxidation, were all located in calcineurin functional domains involved in Ca2+/CaM binding regulated calcineurin stimulation. These findings therefore provide initial support for the novel mechanistic hypothesis that oxidation-induced global and/or local conformational changes within calcineurin contribute to inactivation via (i) impairing the interaction between calcineurin A and calcineurin B, (ii) altering the low-affinity Ca2+ binding site in calcineurin B, (iii) inhibiting calmodulin binding to calcineurin A, and/or (iv) by altering the affinity between the calcineurin A autoinhibitory domain and the catalytic center.

Photooxidative damage in retinal pigment epithelial cells via GRP78 and the protective role of grape skin polyphenols

Blue light induced oxidative damage and ER stress are related to the pathogenesis of age-related macular degeneration (AMD). However, the mechanism of blue light-induced damage remained obscure. The objective of this work is to assess the photooxidative damage to retinal pigment epithelial cells (RPE) and oxidation-induced changes in expression of ER stress associated apoptotic proteins, and investigate the mechanism underlying the protective effects of grape skin extracts. To mimic lipofuscin-mediated photooxidation in vivo, ARPE-19 cells that accumulated A2E, one of lipofuscin fluorophores, were used as a model system to investigate the mechanism of photooxidative damage and the protective effects of grape skin polyphenols. Exposure of A2E containing ARPE-19 cells to blue light resulted in significant apoptosis and increases in levels of GRP78, CHOP, p-JNK, Bax, cleaved caspase-9, and cleaved caspase-3, indicating that photooxidative damage to RPE cells is mediated by the ER-stress-induced intrinsic apoptotic pathway. Cells in which GRP78 had been knocked down with shRNA were more vulnerable to photooxidative damage. Pre-treatment of blue-light-exposed A2E containing ARPE-19 cells, with grape skin extracts, inhibited apoptosis, in a dose dependent manner. Knockdown GRP78 blocked the protective effect of grape skin extracts.

Characterization of the aging behavior of polyethylene by photoluminescence spectroscopy

Abstract Two commercial polyethylene grades were oven-aged at 95 °C and 115 °C for more than 1000 h. Aging characterization was performed by laser-induced photoluminescence spectroscopy ( λ Ex = 375 nm), laser confocal microscopy, infrared (IR) spectroscopy, high performance liquid chromatography, differential scanning calorimetry and tensile testing. Photoluminescence increased significantly upon oven-aging, especially at 115 °C. The maximum of emission was around 450 nm. Decreasing oxidation onset temperatures (DSC) and stabilizer concentrations (HPLC) indicate oxidation-induced changes in the materials that are in agreement with increasing photoluminescence. IR spectroscopy and tensile testing results showed no global oxidative degradation and no premature failure. Hence, the materials were still in the induction period of oxidative degradation. The evolution of photoluminescence is presumably related to the formation of oxygenated groups like α,β-unsaturated carbonyl groups. The investigations clearly indicated that photoluminescence spectroscopy is a sensitive method to monitor aging-induced changes within the induction period.

Vibrational dynamics in dendridic oligoarylamines by Raman spectroscopy and incoherent inelastic neutron scattering.

Vibrational dynamics in triarylamine dendrimers was studied in a complementary way by Raman and infrared (IR) spectroscopies and incoherent inelastic neutron scattering (IINS). Three molecules were investigated, namely, unsubstituted triarylamine dendrimer of the first generation and two dendrimers of the first and second generation, substituted in the crown with butyl groups. To facilitate the assignment of the observed IR and Raman modes as well as the IINS peaks, vibrational models, based on the general valence force field method (GVFF), were calculated for all three compounds studied. A perfect consistency between the calculated and experimental results was found. Moreover, an important complementarity of the vibrational spectroscopies and IINS was established for the investigated dendrimers. The IINS peaks originating mainly from the C-H motions were not restricted by particular selection rules and only dependent on the IINS cross section. To the contrary, Raman and IR bands were imposed by the selection rules and the local geometry of the dendrimers yielding mainly C-C and C-N deformation modes with those of C-H nature of much lower intensity. Raman spectroscopy was also applied to the studies of the oxidation of dendrimers to their cationic forms. A strong Raman resonance effect was observed, since the spectra of the studied compounds, registered at different levels of their oxidation, strongly depended on the position of the excitation line with respect to their electronic spectrum. In particular, the blue (458 nm) excitation line turned out to be insensitive toward the cationic forms yielding very limited spectral information. To the contrary, the use of the red (647 nm) and infrared (1064 nm) excitation lines allowed for an unambiguous monitoring of the spectral changes in dendrimers oxidized to nominally monocationic and tricationic states. The analysis of oxidation-induced spectral changes in the tricationic state indicated that the charge storage configuration predominantly involved one spinless dication of the quinoid bond sequence and one radical cation. However, small numbers of dications were also found in a nominally monocationic state, where only radical cations should have been present. This finding was indicative of some inhomogeneity of the oxidation.

Oxidation-induced Structural Changes of Ceruloplasmin Foster NGR Motif Deamidation That Promotes Integrin Binding and Signaling

Asparagine deamidation occurs spontaneously in proteins during aging; deamidation of Asn-Gly-Arg (NGR) sites can lead to the formation of isoAsp-Gly-Arg (isoDGR), a motif that can recognize the RGD-binding site of integrins. Ceruloplasmin (Cp), a ferroxidase present in the cerebrospinal fluid (CSF), contains two NGR sites in its sequence: one exposed on the protein surface ((568)NGR) and the other buried in the tertiary structure ((962)NGR). Considering that Cp can undergo oxidative modifications in the CSF of neurodegenerative diseases, we investigated the effect of oxidation on the deamidation of both NGR motifs and, consequently, on the acquisition of integrin binding properties. We observed that the exposed (568)NGR site can deamidate under conditions mimicking accelerated Asn aging. In contrast, the hidden (962)NGR site can deamidate exclusively when aging occurs under oxidative conditions, suggesting that oxidation-induced structural changes foster deamidation at this site. NGR deamidation in Cp was associated with gain of integrin-binding function, intracellular signaling, and cell pro-adhesive activity. Finally, Cp aging in the CSF from Alzheimer disease patients, but not in control CSF, causes Cp deamidation with gain of integrin-binding function, suggesting that this transition might also occur in pathological conditions. In conclusion, both Cp NGR sites can deamidate during aging under oxidative conditions, likely as a consequence of oxidative-induced structural changes, thereby promoting a gain of function in integrin binding, signaling, and cell adhesion.

Structural Effects of Methionine Oxidation on Isolated Subdomains of Human Fibrin D and αC Regions

Oxidation of key methionine residues on fibrin leads to altered fibrin polymerization producing severely altered fibrin gel structure and function. This is important because fibrinogen and its modification by oxidative stress have been implicated as key contributors to both pathological thrombotic and hemorrhagic diseases ranging from cardiovascular thrombosis to the acute coagulopathy of trauma. However, how oxidation leads to altered fibrin polymerization remains poorly understood at the molecular level. We have applied a powerful and novel well-tempered ensemble parallel tempering (PT-WTE) technique along with conventional molecular dynamics (MD) simulation to investigate the molecular-level consequences of selective methionine oxidation of fibrinogen. We offer new insights into molecular mechanisms of oxidation-induced changes in fibrin polymerization, while focusing on the D region knob ‘B’ and hole ‘b’ interaction and αC-domain interactions, both of which are hypothesized to contribute to the lateral aggregation mechanism of fibrin fibrils. Methionine oxidation did not alter the native state or the stability of a bound knob ‘B’ surrogate when interacting with hole ‘b’ in the D region. However, applying PT-WTE simulation to a human homology model of the bovine N-terminal subdomain fragment from the αC-domain revealed that methionine oxidation altered the conformation of the hairpin-linking region to favor open rather than closed hairpin structures. We attribute this alteration to the disruption of the hairpin-linking region's conformation, with oxidation increasing the radius of gyration for this segment. This result is in agreement with experimental data demonstrating decreased fibrin protofibril lateral aggregation when methionine oxidation is present in the same αC-domain fragment. Therefore, single methionine oxidation within the αC-domain is a likely molecular mechanism.

Pulsed EPR Distance Measurements Resolve the Impact of Site-Specific Calmodulin Methionine Oxidation

We have examined the structural impact of oxidizing specific protein methionines (Met) in the C-ter lobe of calmodulin (CaM); these oxidation sites are known to abolish CaM regulation of the major calcium release channel, the ryanodine receptor complex (RyR). Protein oxidation by reactive oxygen species (ROS) is strongly associated with loss of strength in skeletal muscle and is proposed to play major roles in aging and degenerative muscle disease.We have linked oxidation-induced changes in RyR regulation to changes in CaM-RyR structure using (1) protein mutagenesis to mimic oxidation at specific sites and (2) spectroscopy to resolve oxidation-induced changes in protein structural dynamics. Pulsed EPR distance measurements across CaM's lobes (multiple pairs of labeling sites, one label on each lobe) were sensitive to large-scale conformational changes that accompany both calcium binding and RyR peptide binding. In the absence of calcium, CaM was highly disordered, populating a broad distribution of conformations. Calcium binding strongly stabilized the elongated conformation, while RyR peptide binding to calcium-loaded CaM strongly stabilized the compact conformation. CaM conformation, particularly the distribution over structural states, was sensitive to Met to Gln substitutions (M109Q and M124Q) designed to mimic CaM Met oxidation. Structural sensitivity to M-to-Q mutations was observed in both the presence and absence of calcium, and in complex with RyR peptide. We conclude that Met oxidation alters CaM's functional interaction with RyR through changes in the orientation and flexibility of CaM's lobes.This work is supported by a University of Wisconsin-La Crosse Faculty Research Grant to JC Klein, NIH grants to DD Thomas (R37AG026160 and P30AR057220), RJ Moen (F31AG037303), the Minnesota Biophysical Spectroscopy Center and the Minnesota Supercomputing Institute.

Computational Simulations Reveal How Calmodulin Methionine Oxidation Triggers Large-Scale Changes in Structural Dynamics

We have examined the structural consequences of methionine (Met) oxidation in the calcium-sensing muscle regulatory protein calmodulin (CaM) using molecular dynamics simulations. Protein oxidation by reactive oxygen species (ROS), and subsequent reduction by the antioxidant enzyme methionine sulfoxide reductase, has emerged as a crucial cell regulatory mechanism. In the context of oxidative stress, protein oxidation is implicated in disease progression and biological aging. Our goal is to bridge our understanding of muscle dysfunction and protein oxidation with atomic-level insights into site-specific methionine oxidation and calmodulin structural dynamics.We have carried out multiple 50 ns molecular dynamics simulations of explicitly solvated calmodulin, starting from the calcium-bound (1cll) and apo (1cfd) structures. Simulations were performed using NAMD (University of Illinois) and the CHARMM27 force-field. Simulations suggest that Met oxidation alters the flexibility of calcium binding sites, the conformation of the linker helix connecting the lobes, and the relative orientation of the lobes. This work is a component of a larger study in which spectroscopic distance measurements and NMR experiments have been used to resolve the structural impact of site-specific CaM Met oxidation. We expect that our in silico results will bring atomic-level insight to spectroscopic measurements, and will be integral to creating a more complete model for oxidation-induced changes in CaM structural dynamics.This work is supported by a University of Wisconsin-La Crosse Faculty Research Grant to JC Klein, NIH grants to DD Thomas (R37AG026160), and the Minnesota Supercomputing Institute.

Oxidation-induced microstructural changes of a polymer-derived Nextel™ 610 ceramic composite and impact on the mechanical performance

This study analyses the effects of heat treatments in oxidative atmosphere on the mechanical and microstructural properties of a fiber-reinforced weak interface composite (UMOX™) which is composed of a mullite-SiOC matrix and Nextel™ 610 fibers with fugitive coatings. Composites of different porosity grades, depending on the polymer infiltration and pyrolysis cycle, are exposed to 1000 and 1200 °C for 50 h. The exposure provokes the formation of silica, which leads to matrix densification and the formation of silica bridges at the fiber–matrix interface, resulting in an increased interfacial bonding strength. Consequently, the fracture toughness and the flexural strength are significantly reduced. The study confirms that SiOC-based materials are suitable for an application at high temperatures in oxygen-rich atmospheres up to 1000 °C. It is, however, important to consider the microstructural changes and thereby induced decrease of the overall mechanical performance during a high-temperature use.

Structural Impact of Site-Specific Calmodulin Methionine Oxidation

We have examined the structural consequences of methionine (Met) oxidation in the calcium-sensing muscle regulatory protein calmodulin (CaM) using molecular dynamics simulations. Protein oxidation by reactive oxygen species (ROS), and subsequent reduction by the antioxidant enzyme methionine sulfoxide reductase, has emerged as a crucial cell regulatory mechanism. In the context of oxidative stress, protein oxidation is implicated in disease progression and biological aging. Our goal is to bridge our understanding of muscle dysfunction and protein oxidation with atomic-level insights into site-specific methionine oxidation and calmodulin structural dynamics. We have carried out multiple 500 ns molecular dynamics simulations of explicitly solvated calmodulin, both the calcium-bound (1cll) and apo (1cfc) crystal structures. Results from preliminary simulations suggest that the structure of calcium bound CaM is structurally insensitive to methionine oxidation, while methionine oxidation in apo CaM causes considerable changes the relative orientation of the N-ter and C-ter lobes. Our work is a component of a larger study in which spectroscopic distance measurements and nuclear magnetic resonance experiments are being carried out for site-specifically oxidized CaM in both the calcium bound and apo biochemical states. We expect that our in silico results will bring atomic-level insight to spectroscopic measurements, and will be integral to creating a more complete model for oxidation-induced changes in calmodulin structural dynamics. Further, we anticipate that our results will be applicable to the many biological and pharmaceutical contexts in which a detailed understanding of protein oxidation, function and structure relationships is sought. This work is supported by an NIH grant to Dave Thomas (2R37AG026160-06) and the Minnesota Supercomputing Institute.

Heterogeneous OH Oxidation of Motor Oil Particles Causes Selective Depletion of Branched and Less Cyclic Hydrocarbons

Motor oil serves as a useful model system for atmospheric oxidation of hydrocarbon mixtures typical of anthropogenic atmospheric particulate matter, but its complexity often prevents comprehensive chemical speciation. In this work we fully characterize this formerly "unresolved complex mixture" at the molecular level using recently developed soft ionization gas chromatography techniques. Nucleated motor oil particles are oxidized in a flow tube reactor to investigate the relative reaction rates of observed hydrocarbon classes: alkanes, cycloalkanes, bicycloalkanes, tricycloalkanes, and steranes. Oxidation of hydrocarbons in a complex aerosol is found to be efficient, with approximately three-quarters (0.72 ± 0.06) of OH collisions yielding a reaction. Reaction rates of individual hydrocarbons are structurally dependent: compared to normal alkanes, reaction rates increased by 20-50% with branching, while rates decreased ∼20% per nonaromatic ring present. These differences in rates are expected to alter particle composition as a function of oxidation, with depletion of branched and enrichment of cyclic hydrocarbons. Due to this expected shift toward ring-opening reactions heterogeneous oxidation of the unreacted hydrocarbon mixture is less likely to proceed through fragmentation pathways in more oxidized particles. Based on the observed oxidation-induced changes in composition, isomer-resolved analysis has potential utility for determining the photochemical age of atmospheric particulate matter with respect to heterogeneous oxidation.