Reductive Doping Inhibits the Formation of Isomerization-Derived Structural Defects in N-doped Poly(benzodifurandione) (n-PBDF).

Recently, solution-processable n-doped poly(benzodifurandione) (n-PBDF) has been made through in-situ oxidative polymerization and reductive doping, which exhibited exceptionally high electrical conductivities and optical transparency. The discovery of n-PBDF is considered a breakthrough in the field of organic semiconductors. In the initial report, the possibility of structural defect formation in n-PBDF was proposed, based on the observation of structural isomerization from (E)-2H,2'H-[3,3'-bibenzofuranylidene]-2,2'-dione (isoxindigo) to chromeno[4,3-c]chromene-5,11-dione (dibenzonaphthyrone) in the dimer model reactions. In this study, we present clear evidence that structural isomerization is inhibited during polymerization. We reveal that the dimer (BFD1) and the trimer (BFD2) can be reductively doped by several mechanisms, including hydride transfer, forming charge transfer complexes (CTC) or undergoing an integer charge transfer (ICT) with reactants available during polymerization. Once the hydride transfer adducts, the CTC, or the ICT product forms, structural isomerization can be effectively prevented even at elevated temperatures. Our findings provide a mechanistic understanding of why isomerization-derived structural defects are absent in n-PBDF backbone. It lays a solid foundation for the future development of n-PBDF as a benchmark polymer for organic electronics and beyond.

Gas Phase Reactivity of [Mo6X14]2- Dianions (X = Cl - I).

We investigate collision-induced dissociation (CID) of [Mo6X14]2- (X = Cl, Br, I) and the reactivity of fragment ions of these precursors with background gases. Ion mobility measurements and theoretical calculations provide structural information for some of the observed ions. Sequential losses of MoX2 units dominate the dissociation pathways of [Mo6Cl14]2-. Meanwhile, loss of X radicals is the main channel for X = Br and I. Ion mobility measurements and computational investigations indicate minor structural changes in the octahedral Mo6 unit for [Mo6Im]- (m = 6-13) fragments. We observe that mass spectra obtained using CID substantially vary among mass spectrometers: Specifically, ions with molecular formula [Mo6Xm(O2)n]- (X = Br and I) are observed as dominant species produced through reactions with O2 in several mass spectrometers, but also adduct free fragment ions were observed in other instruments, depending on the background conditions. Ion-trap fragmentation combined with theoretical investigations indicates that spontaneous losses of X radicals occur upon binding of O2 to [Mo6Im]- fragments (m ≤ 12). Theoretical investigations indicate that both oxygen atoms are bound to the vacant sites of the Mo6 units. This study opens up a new vista to generate and study a large variety of hexanuclear Mo6Xm(O2)n anions.

Multiplexing of Electrospray Ionization Sources Using Orthogonal Injection into an Electrodynamic Ion Funnel.

In this contribution, we report an efficient approach to multiplex electrospray ionization (ESI) sources for applications in analytical and preparative mass spectrometry. This is achieved using up to four orthogonal injection inlets implemented on the opposite sides of an electrodynamic ion funnel interface. We demonstrate that both the total ion current transmitted through the mass spectrometer and the signal-to-noise ratio increase by 3.8-fold using four inlets compared to one inlet. The performance of the new multiplexing approach was examined using different classes of analytes covering a broad range of mass and ionic charge. A deposition rate of >10 µg of mass-selected ions per day may be achieved by using the multiplexed sources coupled to preparative mass spectrometry. The almost proportional increase in the ion current with the number of ESI inlets observed experimentally is confirmed using gas flow and ion trajectory simulations. The simulations demonstrate a pronounced effect of gas dynamics on the ion trajectories in the ion funnel, indicating that the efficiency of multiplexing strongly depends on gas velocity field. The study presented herein opens up exciting opportunities for the development of bright ion sources, which will advance both analytical and preparative mass spectrometry applications.

Assessment of Serum Concentrations of 12 Aldehydes in the U.S. Population from the 2013-2014 National Health and Nutrition Examination Survey.

Aldehydes are known carcinogens and irritants that can negatively impact health. They are present in tobacco smoke, the environment, and food. The prevalence of aldehyde exposure and potential health impact warrants a population-wide study of serum aldehydes as exposure biomarkers. We analyzed 12 aldehydes in sera collected from 1843 participants aged 12 years or older in the 2013-2014 National Health and Nutrition Examination Survey. Several aldehydes were detected at high rates, such as isopentanaldehyde (99.2%) and propanaldehyde (88.3%). We used multiple linear regression models to examine the impact of tobacco smoke and dietary variables on serum concentrations of isopentanaldehyde and propanaldehyde. Although 12 serum aldehydes were analyzed and compared to tobacco smoke exposure, only isopentanaldehyde and propanaldehyde showed any significant association with tobacco smoke exposure. Survey participants who smoked 1-10 cigarettes per day (CPD) had 168% higher serum isopentanaldehyde and 28% higher propanaldehyde compared with nonusers. Study participants who smoked 11-20 CPD had higher serum isopentanaldehyde (323%) and propanaldehyde (70%). Similarly, study participants who smoked >20 CPD had 399% higher serum isopentanaldehyde and 110% higher serum propanaldehyde than nonexposed nonusers. The method could not, however, differentiate between nonexposed nonusers and nonusers exposed to secondhand smoke for either of these two aldehydes. No dietary variables were consistently predictive of serum isopentanaldehyde and propanaldehyde concentrations. This report defines baseline concentrations of serum aldehydes in the U.S. population and provides a foundation for future research into the potential health effects of aldehydes. In addition, this study suggests that tobacco smoke is a significant source of exposure to some aldehydes such as isopentanaldehyde and propanaldehyde.

Quantification of Seven Terpenes in Human Serum by Headspace Solid-Phase Microextraction-Gas Chromatography-Tandem Mass Spectrometry.

Terpenes are a class of volatile organic hydrocarbons commonly produced by vegetation and released into the atmosphere. These compounds are responsible for the scents of pine forests, citrus fruits, and some flowers. Human terpene exposure can come from inhalation, diet, smoking, and more recently, using e-cigarettes. Terpenes are present in tobacco smoke and are used as flavor chemicals in e-liquids. The health effects of terpenes are not widely known, though several studies have suggested that they may prove useful in future medical applications. We have developed a novel, high-throughput method of quantifying seven terpenes (α-pinene, ß-pinene, ß-myrcene, 3-carene, limonene, ß-caryophyllene, and α-humulene) in human serum to aid human-exposure investigations. This method employs headspace sampling using solid-phase microextraction (SPME) coupled to gas chromatography-tandem mass spectrometry to detect and quantify five monoterpenes and two sesquiterpenes in the low parts-per-trillion to low parts-per-billion range. The intraday and interday variability (percent error) of the method are ≤2 and ≤11%, respectively. In addition, this method showed excellent recovery in human serum (between 80 and 120% for all analytes). The assay precision ranges between 4.0 and 11%. Limits of detection ranged between 0.032 and 0.162 µg/L. Using serum cotinine values to classify tobacco use showed that smokers have higher serum concentrations of six terpenes compared to nonusers. Terpene concentrations were 14-78% higher in smokers than nonusers. Our method can provide essential biomonitoring data to establish baseline exposure levels for terpenes in humans.

Principles of Operation of a Rotating Wall Mass Analyzer for Preparative Mass Spectrometry.

In this contribution, we describe the principles of operation of a rotating wall mass analyzer (RWMA), a mass-dispersive device for preparative mass spectrometry. Ions of different m/z are spatially separated by RWMA and deposited onto ring-shaped areas of distinct radii on a surface. We use a combination of an analytical equation for predicting the radius of the deposition ring and SIMION simulations to understand how to optimize the experimental conditions for the separation of multicomponent mixtures. The results of these simulations are compared with the experimental data. We introduce a universal mass calibration procedure, based on a series of polyacrylamide ions, which is subsequently used to predict the deposition radii of unknown analytes. The calibration is independent of the polarity, kinetic energy, and charge state of the ion as demonstrated by assigning m/z values of different analytes including multiply charged ubiquitin ions. We demonstrate that mass resolution of the RWMA is affected by the width and kinetic energy distribution of the ion beam. The best mass resolution obtained in this study is m/Δm = ∼20. Preparative mass spectrometry using RWMA provides the advantages of simplicity, compactness, and low fabrication cost, which are particularly promising for the development of miniaturized instrumentation. The results presented in this work can be readily adapted to preparative separation of a variety of charged species of interest to the broad scientific community.

Methyl Tertiary-Butyl Ether Exposure from Gasoline in the U.S. Population, NHANES 2001-2012.

BACKGROUND: Methyl tertiary-butyl ether (MTBE) was used as a gasoline additive in the United States during 1995-2006. Because of concerns about potential exposure and health effects, some U.S. states began banning MTBE use in 2002, leading to a nationwide phaseout in 2006. OBJECTIVES: We investigated the change in blood MTBE that occurred during the years in which MTBE was being phased out of gasoline. METHODS: We used data from the National Health and Nutrition Examination Survey (NHANES) from 2001-2012 to assess the change in blood MTBE over this period. We fit sample-weighted multivariate linear regression models to 12,597 human blood MTBE concentrations from the NHANES 2001-2002 to 2011-2012 survey cycles. RESULTS: The unweighted proportion of the individuals with MTBE blood levels above the limit of detection (LOD) of 1.4 ng/L was 93.9% for 2001-2002. This portion dropped to 25.4% for the period 2011-2012. Weighted blood MTBE median levels (ng/L) (25th and 75th percentiles) decreased from 25.8 (6.08, 68.1) ng/L for the period from 2001-2002 to 4.57 (1.44, 19.1) ng/L for the period from 2005-2006. For the entire postban period (2007-2012), MTBE median levels were below the detection limit of 1.4 ng/L. DISCUSSION: These decreases in blood MTBE coincided with multiple statewide bans that began in 2002 and a nationwide ban in 2006. The multivariate log-linear regression model for the NHANES 2003-2004 data showed significantly higher blood MTBE concentrations in the group who pumped gasoline less than 7 h before questionnaire administration compared to those who pumped gasoline more than 12 h before questionnaire administration (p=0.032). This study is the first large-scale, national-level confirmation of substantial decrease in blood MTBE levels in the general population following the phaseout of the use of MTBE as a fuel additive. https://doi.org/10.1289/EHP5572.

Nitromethane Exposure from Tobacco Smoke and Diet in the U.S. Population: NHANES, 2007-2012.

Nitromethane is a known toxicant and suspected human carcinogen. Exposure to nitromethane in a representative sample of the civilian, noninstitutionalized population in the United States ≥12 years old was assessed using 2007-2012 National Health and Nutritional Examination Survey (NHANES) data. Nitromethane was detected in all 8000 human blood samples collected, of which 6730 were used for analyses reported here. Sample-weighted median blood nitromethane was higher among exclusive combusted tobacco users (exclusive smokers; 774 ng/L) than nonusers of tobacco products (625 ng/L). In stratified sample-weighted regression analysis, smoking 0.5 pack of cigarettes per day was associated with a statistically significant increase in blood nitromethane by 150 ng/L, and secondhand smoke exposure (serum cotinine >0.05 ng/mL and <10 ng/mL) was statistically significant with a 31.1 ng/L increase in blood nitromethane. Certain dietary sources were associated with small but statistically significant increases in blood nitromethane. At median consumption levels, blood nitromethane was associated with an increase of 7.55 ng/L (meat/poultry), 9.32 ng/L (grain products), and 14.5 ng/L (vegetables). This is the first assessment of the magnitude and relative source apportionment of nitromethane exposure in the U.S. population.

Quantification of 19 Aldehydes in Human Serum by Headspace SPME/GC/High-Resolution Mass Spectrometry.

Sources of human aldehyde exposure include food additives, combustion of organic matter (tobacco smoke), water disinfection byproducts via ozonation, and endogenous processes. Aldehydes are potentially carcinogenic and mutagenic, and chronic human aldehyde exposure has raised concerns about potential deleterious health effects. To aid investigations of human aldehyde exposure, we developed a novel method to measure 19 aldehydes released from Schiff base protein adducts in serum using controlled acid hydrolysis, solid-phase microextraction (SPME), gas chromatography (GC), and high-resolution mass spectrometry (HRMS). Aldehydes are released from Schiff base protein adducts through acid hydrolysis, and are quantified in trace amounts (µg/L) using stable isotope dilution. Detection limits range from 0.1 to 50 µg/L, with calibration curves spanning 3 orders of magnitude. The analysis of fortified quality control material over a three-month period showed excellent precision and long-term stability (3-22% CV) for samples stored at -70 °C. The intraday precision is also excellent (CV, 1-10%). The method accuracy ranges from 89 to 108% for all measured aldehydes, except acrolein and crotonaldehyde, two aldehydes present in tobacco smoke; their analysis by this method is not considered robust due in part to their reactivity in vivo. However, results strongly suggest that propanal, butanal, isobutanal, and isopentanal levels in smokers are higher than levels in nonsmokers, and thus may be useful as biomarkers of tobacco smoke exposure. This method will facilitate large epidemiological studies involving aldehyde biomonitoring to examine nonoccupational environmental exposures.