Comprehensive Association Analyses of Extraintestinal Manifestations in Inflammatory Bowel Disease.

BACKGROUND & AIMS: Patients with inflammatory bowel disease (IBD) frequently develop extraintestinal manifestations (EIMs) that contribute substantially to morbidity. We assembled the largest multicohort data set to date to investigate the clinical, serologic, and genetic factors associated with EIM complications in IBD. METHODS: Data were available in 12,083 unrelated European ancestry IBD cases with presence or absence of EIMs (eg, ankylosing spondylitis [ankylosing spondylitis and sacroiliitis], primary sclerosing cholangitis [PSC], peripheral arthritis, and skin and ocular manifestations) across 4 cohorts (Cedars-Sinai Medical Center, National Institute for Diabetes and Digestive and Kidney Diseases IBD Genetics Consortium, Sinai Helmsley Alliance for Research Excellence Consortium, and Risk Stratification and Identification of Immunogenetic and Microbial Markers of Rapid Disease Progression in Children with Crohn's Disease cohort). Clinical and serologic parameters were analyzed by means of univariable and multivariable regression analyses using a mixed-effects model. Within-case logistic regression was performed to assess genetic associations. RESULTS: Most EIMs occurred more commonly in female subjects (overall EIM: P = 9.0E-05, odds ratio [OR], 1.2; 95% CI, 1.1-1.4), with CD (especially colonic disease location; P = 9.8E-09, OR, 1.7; 95% CI, 1.4-2.0), and in subjects who required surgery (both CD and UC; P = 3.6E-19, OR, 1.7; 95% CI, 1.5-1.9). Smoking increased risk of EIMs except for PSC, where there was a "protective" effect. Multiple serologic associations were observed, including with PSC (anti-nuclear cytoplasmic antibody; IgG and IgA, anti-Saccharomyces cerevisiae antibodies; and anti-flagellin) and any EIM (anti-nuclear cytoplasmic antibody; IgG and IgA, anti-Saccharomyces cerevisiae antibodies; and anti-Pseudomonas fluorescens-associated sequence). We identified genome-wide significant associations within major histocompatibility complex (ankylosing spondylitis and sacroiliitis, P = 1.4E-15; OR, 2.5; 95% CI, 2.0-3.1; PSC, P = 2.7E-10; OR, 2.8; 95% CI, 2.0-3.8; ocular, P = 2E-08, OR, 3.6; 95% CI, 2.3-5.6; and overall EIM, P = 8.4E-09; OR, 2.2; 95% CI, 1.7-2.9) and CPEB4 (skin, P = 2.7E-08; OR, 1.5; 95% CI, 1.3-1.8). Genetic associations implicated tumor necrosis factor, JAK-STAT, and IL6 as potential targets for EIMs. Contrary to previous reports, only 2% of our subjects had multiple EIMs and most co-occurrences were negatively correlated. CONCLUSIONS: We have identified demographic, clinical, and genetic associations with EIMs that revealed underlying mechanisms and implicated novel and existing drug targets-important steps toward a more personalized approach to IBD management.

Progression of Pediatric Crohn's Disease Is Associated With Anti-Tumor Necrosis Factor Timing and Body Mass Index Z-Score Normalization.

BACKGROUND & AIMS: The evolution of complicated pediatric Crohn's disease (CD) in the era of anti-tumor necrosis factor (aTNF) therapy continues to be described. Because CD progresses from inflammatory to stricturing (B2) and penetrating (B3) disease behaviors in a subset of patients, we aimed to understand the risk of developing complicated disease behavior or undergoing surgery in relation to aTNF timing and body mass index z-score (BMIz) normalization. METHODS: Multicenter, 5-year longitudinal data from 1075 newly diagnosed CD patients were analyzed. Descriptive statistics, univariate and stepwise multivariate Cox proportional hazard regression (CPHR), and log-rank analyses were performed for risk of surgery and complicated disease behaviors. Differential gene expression from ileal bulk RNA sequencing was correlated with outcomes. RESULTS: Stricturing complications had the largest increase: from 2.98% to 10.60% over 5 years. Multivariate CPHR showed aTNF exposure within 3 months from diagnosis (hazard ratio [HR], 0.33; 95% CI, 0.15-0.71) and baseline L2 disease (HR, 0.29; 95% CI, 0.09-0.92) to be associated with reduced B1 to B2 progression. For children with a low BMIz at diagnosis (n = 294), multivariate CPHR showed BMIz normalization within 6 months of diagnosis (HR, 0.47; 95% CI, 0.26-0.85) and 5-aminosalicyclic acid exposure (HR, 0.32; 95% CI, 0.13-0.81) were associated with a decreased risk for surgery while B2 (HR, 4.20; 95% CI, 1.66-10.65) and B2+B3 (HR, 8.24; 95% CI, 1.08-62.83) at diagnosis increased surgery risk. Patients without BMIz normalization were enriched for genes in cytokine production and inflammation. CONCLUSIONS: aTNF exposure up to 3 months from diagnosis may reduce B2 progression. In addition, lack of BMIz normalization within 6 months of diagnosis is associated with increased surgery risk and a proinflammatory transcriptomic profile.

Microstructure characterization and mechanistic insight into polyether polyols and their associated polyurethanes.

This article reviews the analytical tool chest used for characterizing alkoxylates and their associated copolymer mixtures. Specific emphasis will be placed upon the use of mass spectrometry-based techniques as rapid characterization tools for optimizing reaction processes in an industrial R&D setting. An initial tutorial will cover the use of matrix-assisted laser desorption/ionization-mass spectrometry and tandem mass spectrometry fragmentation for detailed component analysis (e.g., polyol and isocyanate) of a model polyurethane-based foam. Next, this critical feedback information will be used with the guidance of mass spectrometry to initiate the development of a new, more efficient, tris(pentafluorophenyl)borane (FAB) catalyst-based alkoxylation process for generating the next generation of glycerin-initiated poly(propylene oxide)-co-poly(ethylene oxide) copolymers. Examples will be provided for each step in the FAB-based optimization process that were required to generate the final product. Following this example, two-dimensional liquid chromatography, supercritical fluid chromatography, and ion mobility separations, along with their coupling to mass spectrometry, will be reviewed for their efficiency in characterizing and quantitating the components within these complex polyether polyol mixtures.

Mass spectrometry and ion mobility study of poly(ethylene glycol)-based polyurethane oligomers.

RATIONALE: Commercial-grade polymer synthesis is performed via melt polymerization, which leads to polydispersion. The work reported herein provides a synthetic strategy to produce mono-dispersive polyurethane oligomers and an analytical strategy to distinguish these oligomers, providing chemists with the tools necessary to synthesize and identify specific polymer structures that exhibit a desired property. METHODS: Three isomeric poly(ethylene glycol)-polyurethane (PEG-PUR) oligomers were synthesized and analyzed via flow-injection ion mobility mass spectrometry (IM-MS). Each polymer oligomer was injected and run independently via flow injection at 100 µL•min-1 and analyzed in positive ion mode on a drift tube quadrupole time-of-flight (QTOF) instrument. Mobility measurements were determined using a single-field approach. For tandem mass spectrometry (MS/MS) experiments, the sodium-adducted singly charged precursor ion was isolated in the quadrupole and subjected to a range of collision energies. RESULTS: In MS experiments, both +1 and +2 sodium-adducted species were observed for each oligomer at m/z 837.4 and 430.2, respectively. When isolated and fragmented via MS/MS, the +1 precursor yielded distinct product ions for each of the three isomeric oligomers. Fragmentation generally occurred at urethane linkages via 1,3- and 1,5-H shift mechanisms. IM was also used to distinguish the three isomers, with greater IM separation observed for the +2 versus the +1 species. CONCLUSIONS: Mono-disperse PEG-PUR oligomers were synthesized and analyzed. Although the polymeric oligomers analyzed in this study are quite small and structurally simple, this work serves as a model system for the synthesis and structural characterization of larger, more complex block copolymers.

Alkali Metal Cation Adduct Effect on Polybutylene Adipate Oligomers: Ion Mobility-Mass Spectrometry.

Polyurethane (PU) di-block copolymers are one of the most versatile polymeric materials, comprised of hard and soft segments that contribute to PU's broad range of applications. Polybutylene adipate (PBA) is a commonly used soft segment in PU systems. Characterizing the structure of PBA polymers is essential to understanding complex heterogeneity within a PU sample. In this study, ion mobility-mass spectrometry (IM-MS) and tandem mass spectrometry (MS/MS) are used to structurally characterize a PBA standard (Mn = 2250) adducted with a combination of monovalent alkali cations (Li, Na, K, Rb, and Cs). IM-MS profiles show unique trends associated with each cation-adducted PBA sample. Charge state trends: +1, +2, and +3 were extracted for cation-adducted PBA oligomers, and investigated to study gas-phase transitional folding. To quantitatively assess the gas-phase structural similarities and differences, a statistical test (ANOVA) was used to compare PBA oligomer-cation collisional cross sections (CCS). Fragmentation studies (MS/MS) identified the unique behavior of Li and Na for promoting 1,5 H-shift and 1,3 H-shift fragmentation, whereas the PBA precursor preferentially loses the larger K, Rb, and Cs cations as the ion activation energy is increased. The combination of adducted alkali cations, IM-MS, and MS/MS allow for unique structural characterization of this important PBA system.

Mass Spectrometry of Polyurethanes.

This review covers the applications of mass spectrometry (MS) and its hyphenated techniques to characterize polyurethane (PU) synthetic polymers and their respective hard and soft segments. PUs are commonly composed of hard segments including methylene bisphenyl diisocyanate (MDI) and toluene diisocyanate (TDI), and soft segments including polyester and polyether polyols. This literature review highlights MS techniques such as electrospray ionization (ESI), matrix assisted laser/desorption ionization (MALDI), ion mobility-mass spectrometry (IM-MS), and computational methods that have been used for the characterization of this polymer system. Here we review specific case studies where MS techniques have elucidated unique features pertaining to the makeup and structural integrity of complex PU materials and PU precursors.

Structural Characterization of Methylenedianiline Regioisomers by Ion Mobility-Mass Spectrometry and Tandem Mass Spectrometry. 4. 3-Ring and 4-Ring Isomers.

Matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS) is used to characterize methylenedianiline (MDA) 3-ring and 4-ring species. Building on our previous MALDI-MS 2-ring MDA isomer study, here we compare 3-ring and 4-ring electrospray ionization (ESI) and MALDI results. In ESI, 3-ring and 4-ring MDAs each form a single [M + H]+ parent ion. However, in MALDI, each MDA multimer forms three unique precursor ions: [M + H]+, [M•]+, and [M - H]+. In this study, 3-ring and 4-ring MDA precursors are characterized to identify the unique fragment ions formed and their respective fragmentation pathways. In addition to the three possible precursors, the 3-ring and 4-ring species are higher-order oligomer precursors in polyurethane (PUR) production and thus provide additional insight into the polymeric behavior of these PUR hard block precursors. The combination of ion mobility-mass spectrometry (IM - MS) and tandem mass spectrometry (MS/MS) allow the structural characterization of these larger MDA multimers.

Structural Characterization of Methylenedianiline Regioisomers by Ion Mobility-Mass Spectrometry, Tandem Mass Spectrometry, and Computational Strategies. 3. MALDI Spectra of 2-Ring Isomers.

Characterization of methylenedianiline (MDA) 2-ring isomers (2,2'-, 2,4'-, and 4,4'-MDA) is reported using matrix assisted laser desorption/ionization-mass spectrometry (MALDI-MS), a common technique used for characterizing synthetic polymers. MDA is a precursor to methylene diphenyl diisocyanate (MDI), a hard block component in polyurethane (PUR) synthesis. This work focuses on comparing MALDI results to those of our previous electrospray ionization-mass spectrometry (ESI-MS) studies. In ESI, 2-ring MDA isomers formed single unique [M + H]+ (199 Da) parent ions, whereas in MALDI each isomer shows significant formation of three precursor ions: [M - H]+ = 197 Da, [M•]+ = 198 Da, and [M + H]+ = 199 Da. Structures and schemes are proposed for the MALDI fragment ions associated with each precursor ion. Ion mobility-mass spectrometry (IM-MS), tandem mass spectrometry (MS/MS), and computational methods were all critical in determining the structures for both precursor and fragment ions as well as the fragmentation mechanisms. The present study indicates that the [M - H]+ and [M•]+ ions are formed by the MALDI process, explaining why they were not observed with ESI.

Novel behavior of the chromatographic separation of linear and cyclic polymers.

In various polymerization processes, the formation of a wide variety of chains, not only in length but also in chemical composition, broadly complicates comprehensive polymer characterization. In this communication, we compare different stationary and mobile phases for the analysis of complex polymer mixtures via size-exclusion chromatography-mass spectrometry (SEC-MS). To the best of our knowledge, we report novel chromatographic effects for the separation of linear and cyclic oligomers for polyesters (PE) and polyurethanes (PUR). A complete separation for the different structures was achieved for both polymer types with a single-solvent system (acetonitrile, ACN) and without extensive optimization. Additionally, cyclic species were found to show an inverse elution profile compared to their linear counterparts, suggesting distinct physical properties between species.

Structural Characterization of Methylenedianiline Regioisomers by Ion Mobility-Mass Spectrometry, Tandem Mass Spectrometry, and Computational Strategies. 2. Electrospray Spectra of 3-Ring and 4-Ring Isomers.

Building on results from our previous study of 2-ring methylenedianiline (MDA), a combined mass spectrometry approach utilizing ion mobility-mass spectrometry (IM-MS) and tandem mass spectrometry (MS/MS) coupled with computational methods enables the structural characterization of purified 3-ring and 4-ring MDA regioisomers in this current study. The preferred site of protonation for the 3-ring and 4-ring MDA was determined to be on the amino groups. Additionally, the location of the protonated amine along the MDA multimer was found to influence the gas phase stability of these molecules. Fragmentation mechanisms similar to the 2-ring MDA species were observed for both the 3-ring and 4-ring MDA. The structural characterization of 3-ring and 4-ring MDA isomers using modern MS techniques may aid polyurethane synthesis by the characterization of industrial grade MDA, multimeric MDA species, and methylene diphenyl diisocyanate (MDI) mixtures.

MALDI-TOF/TOF CID Study of Poly(1,4-dihydroxybenzene terephthalate) Fragmentation Reactions.

MALDI-TOF/TOF collision-induced dissociation (CID) experiments were conducted on model aromatic polyester oligomers. CID fragmentation studies identified initial fracture of the ester bond and subsequent CO loss as a major pathway, consistent with the general fragmentation mechanism used to explain the origin of poly(p-phenylenediamine terephthalamide) (PPD-T) fragment ions. Specifically, both charge-remote and charge-site fragmentation were observed. Different parent-ion species were observed, the major ones being carboxyl-hydroxyl, di-carboxyl, di-hydroxyl, and phenyl-carboxyl terminated. One species observed was hydroxyl-diethylamine terminated caused by reaction of carboxyl groups with triethylamine added to the synthesis reaction mixture. Fragment ions reflected the end groups of the parent oligomers. Some MALDI fragment-ion spectra were obtained for species showing exchange between Li and H at the carboxyl end group. Bond energy calculations provide further insight into suggested fragmentation mechanisms.

Structural characterization of methylenedianiline regioisomers by ion mobility-mass spectrometry, tandem mass spectrometry, and computational strategies: I. Electrospray spectra of 2-ring isomers.

Purified methylenedianiline (MDA) regioisomers were structurally characterized and differentiated using tandem mass spectrometry (MS/MS), ion mobility-mass spectrometry (IM-MS), and IM-MS/MS in conjunction with computational methods. It was determined that protonation sites on the isomers can vary depending on the position of amino groups, and the resulting protonation sites play a role in the gas-phase stability of the isomer. We also observed differences in the relative distributions of protonated conformations depending on experimental conditions and instrumentation, which is consistent with previous studies on aniline in the gas phase. This work demonstrates the utility of a multifaceted approach for the study of isobaric species and elucidates why previous MDA studies may have been unable to detect and/or differentiate certain isomers. Such analysis may prove useful in the characterization of larger MDA multimeric species, industrial MDA mixtures, and methylene diphenyl diisocyanate (MDI) mixtures used in polyurethane synthesis.

The nuclear receptor LRH-1 discriminates between ligands using distinct allosteric signaling circuits.

Nuclear receptors (NRs) are transcription factors that regulate essential biological processes in response to cognate ligands. An important part of NR function involves ligand-induced conformational changes that recruit coregulator proteins to the activation function surface (AFS), ~15 Å away from the ligand binding pocket. Ligands must communicate with the AFS to recruit appropriate coregulators and elicit different transcriptional outcomes, but this communication is poorly understood. These studies illuminate allosteric communication networks underlying activation of liver receptor homolog-1 (LRH-1), a NR that regulates development, metabolism, cancer progression and intestinal inflammation. Using >100 microseconds of all-atom molecular dynamics simulations involving 69 LRH-1 complexes, we identify distinct signaling circuits used by active and inactive ligands for AFS communication. Inactive ligands communicate via strong, coordinated motions along paths through the receptor to the AFS. Activating ligands disrupt the "inactive" circuit by inducing connectivity elsewhere. Ligand-contacting residues in helix 7 help mediate the switch between circuits, suggesting new avenues for developing LRH-1-targeted therapeutics. We also elucidate aspects of coregulator signaling, showing that localized, destabilizing fluctuations are induced by inappropriate ligand-coregulator pairings. These studies have uncovered novel features of LRH-1 allostery, and the quantitative approach used to analyze many simulations provides a framework to study allosteric signaling in other receptors.

The nuclear receptor LRH-1 discriminates between ligands using distinct allosteric signaling circuits.

Nuclear receptors (NRs) are transcription factors that regulate essential biological processes in response to cognate ligands. An important part of NR function involves ligand-induced conformational changes that recruit coregulator proteins to the activation function surface (AFS), ~15 Å away from the ligand-binding pocket. Ligands must communicate with the AFS to recruit appropriate coregulators and elicit different transcriptional outcomes, but this communication is poorly understood. These studies illuminate allosteric communication networks underlying activation of liver receptor homolog-1 (LRH-1), a NR that regulates development, metabolism, cancer progression, and intestinal inflammation. Using >100 µs of all-atom molecular dynamics simulations involving 74 LRH-1 complexes, we identify distinct signaling circuits used by active and inactive ligands for AFS communication. Inactive ligands communicate via strong, coordinated motions along paths through the receptor to the AFS. Activating ligands disrupt the "inactive" circuit and induce connectivity with a second allosteric site. Ligand-contacting residues in helix 7 help mediate the switch between circuits, suggesting new avenues for developing LRH-1-targeted therapeutics. We also elucidate aspects of coregulator signaling, showing that localized, destabilizing fluctuations are induced by inappropriate ligand-coregulator pairings. These studies have uncovered novel features of LRH-1 allostery, and the quantitative approach used to analyze many simulations provides a framework to study allosteric signaling in other receptors.

Association of Baseline Luminal Narrowing With Ileal Microbial Shifts and Gene Expression Programs and Subsequent Transmural Healing in Pediatric Crohn Disease.

BACKGROUND: Transmural healing (TH) is associated with better long-term outcomes in Crohn disease (CD), whereas pretreatment ileal gene signatures encoding myeloid inflammatory responses and extracellular matrix production are associated with stricturing. We aimed to develop a predictive model for ileal TH and to identify ileal genes and microbes associated with baseline luminal narrowing (LN), a precursor to strictures. MATERIALS AND METHODS: Baseline small bowel imaging obtained in the RISK pediatric CD cohort study was graded for LN. Ileal gene expression was determined by RNASeq, and the ileal microbial community composition was characterized using 16S rRNA amplicon sequencing. Clinical, demographic, radiologic, and genomic variables were tested for association with baseline LN and future TH. RESULTS: After controlling for ileal location, baseline ileal LN (odds ratio [OR], 0.3; 95% confidence interval [CI], 0.1-0.8), increasing serum albumin (OR, 4; 95% CI, 1.3-12.3), and anti-Saccharomyces cerevisiae antibodies IgG serology (OR, 0.97; 95% CI, 0.95-1) were associated with subsequent TH. A multivariable regression model including these factors had excellent discriminant power for TH (area under the curve, 0.86; positive predictive value, 80%; negative predictive value, 87%). Patients with baseline LN exhibited increased Enterobacteriaceae and inflammatory and extracellular matrix gene signatures, coupled with reduced levels of butyrate-producing commensals and a respiratory electron transport gene signature. Taxa including Lachnospiraceae and the genus Roseburia were associated with increased respiratory and decreased inflammatory gene signatures, and Aggregatibacter and Blautia bacteria were associated with reduced extracellular matrix gene expression. CONCLUSIONS: Pediatric patients with CD with LN at diagnosis are less likely to achieve TH. The association between specific microbiota, wound healing gene programs, and LN may suggest future therapeutic targets.

MALDI-TOF MS stability study of model poly(p-phenylene terephthalamide)s.

In the present study, we address the possibility of matrix-assisted laser desorption/ionization (MALDI)-time-of-flight MS analysis-induced chain fragmentation in poly(p-phenylene terephthalamide) (PPD-T) by considering two possible sources: (1) grinding-induced fragmentation resulting from the evaporation-grinding MALDI sample preparation method (E-G method) and (2) in-source/metastable fragmentation induced by the MALDI laser. An analysis of variance (ANOVA) statistical study found, with a high probability, that obtaining MALDI spectra with the effective laser area as large as possible (the "fanned-out" setting) did not cause any chain fragmentation due to the E-G MALDI sample preparation method, even when three additional grinding steps were used. However, the effect of laser fluence was less clear. A significant effect of laser fluence was observed for lower mass oligomers (<1,400 Da), but there was essentially no effect for higher mass species up to our limit of ANOVA measurement (approximately 2,300 Da). Plausible explanations are presented to explain these observations. The most likely scenario is that "unexpected" end-group modifications occur during PPD-T synthesis, producing small quantities of low mass species, which are amplified by the MALDI-EG extraction procedure.

Rewiring Ancient Residue Interaction Networks Drove the Evolution of Specificity in Steroid Receptors.

Understanding how changes in amino acid sequence alter protein dynamics and allosteric signaling would illuminate strategies for protein design. To gain insight into this process, we have combined molecular dynamics simulations with ancestral sequence reconstruction to explore conformational dynamics in two ancient steroid receptors (SRs) to determine how allosteric signaling pathways were altered over evolution to generate hormone specificity. In a broad panel of aromatized and non-aromatized hormones, we investigate inter-residue contacts that facilitate allosteric signaling. This work reveals interhelical interactions that act as ligand sensors and explain the structural and dynamical basis for ligand discrimination in SRs. These sensors are part of a conserved SR allosteric network and persist over long simulation time scales, indicating that evolutionary substitutions rewire ancient SR networks to achieve functional evolution. This powerful combination of computation, ancestral reconstruction, and biochemistry may illuminate allosteric mechanisms and functional evolution in other protein families.

MALDI-TOF/TOF CID study of 4-alkyl-substituted polystyrene fragmentation reactions.

MALDI-TOF/TOF CID experiments were conducted on a variety of hydrogen-terminated poly(4-methylstyrene), hydroxylated poly(t-butylstyrene), and polystyrene precursor ions: n = 10, 15, 20, 25, and 30, where the number of repeat units n corresponds to the oligomer mass number. The influences of structure, molecular weight, and effective collision kinetic energy on degradation mechanisms were examined to test the generality of our multi-chain fragmentation model developed for polystyrene. Each depolymerization mechanism is presented in detail with experimental and computational data to justify/rationalize its occurrence and effective kinetic energy dependence. These processes show the complex interrelationship between the various pathways along with preferred production of secondary radicals, which suppresses the appearance of primary radicals. Additionally, Py-GC/MS experimental data are presented, for comparison of the multimolecular free radical reactions in pyrolysis with the unimolecular fragmentation reactions of MS/MS.

MALDI-TOF/TOF CID study of poly(alpha-methylstyrene) fragmentation reactions.

MALDI-TOF/TOF CID experiments are reported for hydroxylated poly(alpha-methylstyrene) precursor ions (PAMS: m/z 1,445.9 (n = 10), 2,036.3 (n = 15), 2,626.7 (n = 20), 3,217.1 (n = 25), and 3,807.5 (n = 30), where the number of repeat units n corresponds to the oligomer mass numbers). The influences of structure, molecular weight, and kinetic energy on degradation mechanisms were examined to test the generality of our multi-chain fragmentation model developed for polystyrene. Our results indicate that poly(alpha-methylstyrene) free radicals are formed initially through multiple chain breaks and subsequently undergo a variety of depolymerization reactions to yield predominantly monomer and dimer species; the intensity of each species depends on the effective kinetic energy selected for the CID process. Each depolymerization mechanism is presented in detail with experimental and computational data to justify/rationalize the process and its kinetic energy dependence. These processes show the complex interrelationships between the various pathways along with preferred production of tertiary radicals, which suppresses the appearance of primary radicals. Additionally, Py-GC/MS experimental data are presented to allow a comparison of the multimolecular free radical reactions in pyrolysis with the unimolecular fragmentation reactions of MS/MS.

Preparation of Pt-Re/Vulcan carbon nanocomposites using a single-source molecular precursor and relative performance as a direct methanol fuel cell electrooxidation catalyst.

Pt-Re/Vulcan carbon powder nanocomposites have been prepared with total metal loadings of 18 wt.% and 40 wt.% using a new non-cluster (1:1)-PtRe bimetallic precursor as the source of metal. Pt-Re nanoparticles having an average diameter of ca. 6 nm and atomic stoichiometry near 1:1 are formed. TEM, on-particle HR-EDS, and powder XRD data are consistent with the formation of Pt-Re alloy nanoparticles having a hexagonal unit cell with cell constants of a = 2.77 A and c = 4.47 A. A nanocomposite prepared at higher total metal loading under more rigorous thermal treatment also contains Pt-Re alloy nanoparticles having a fcc unit cell structure (a = 3.95 A). The precise dependence of Pt-Re nanocrystal structure on the thermal history of the nanocomposite specimen has not been investigated in detail. While these Pt-Re/carbon nanocomposites are active as anode catalysts in operating direct methanol fuel cells, the measured performance is less than that of commercial Pt-Ru/carbon catalysts and has marginal practical importance.