ARC Insights and Resources

Structure elucidation and quantitation of leachable impurities in pharmaceutical and medical products are crucial because unidentified and potentially toxic leachable impurities can pose health hazards to patients. Therefore, extractables and leachables (E&L) investigations have received significantly increased emphasis from regulatory agencies in recent years. Owing to the diverse chemical structures and properties of E&L compounds, various analytical challenges are encountered during their identification and quantification process. This review provides an overview of analytical challenges encountered during E&L analysis by LC-MS and GC-MS from an industrial standpoint along with the most recent advances in this field. Some of these challenges including Analytical Evaluation Threshold (AET), sample preparation, complex identification processes, and quantitation are discussed. Furthermore, the recent regulations have made analysis of E&L compounds more stringent in terms of lower AET, higher level of identification confidence and method validation requirements, necessitating the use of advanced analytical instrumentation and novel analytical approaches.

With the increasing demand for net-zero sustainable aviation fuels (SAF), new conversion technologies are needed to process waste feedstocks and meet carbon reduction and cost targets. Wet waste is a low-cost, prevalent feedstock with the energy potential to displace over 20% of US jet fuel consumption; however, its complexity and high moisture typically relegates its use to methane production from anaerobic digestion. To overcome this, methanogenesis can be arrested during fermentation to instead produce C2 to C8 volatile fatty acids (VFA) for catalytic upgrading to SAF. Here, we evaluate the catalytic conversion of food waste–derived VFAs to produce n-paraffin SAF for near-term use as a 10 vol% blend for ASTM “Fast Track” qualification and produce a highly branched, isoparaffin VFA-SAF to increase the renewable blend limit. VFA ketonization models assessed the carbon chain length distributions suitable for each VFA-SAF conversion pathway, and food waste–derived VFA ketonization was demonstrated for >100 h of time on stream at approximately theoretical yield. Fuel property blending models and experimental testing determined normal paraffin VFA-SAF meets 10 vol% fuel specifications for “Fast Track.” Synergistic blending with isoparaffin VFA-SAF increased the blend limit to 70 vol% by addressing flashpoint and viscosity constraints, with sooting 34% lower than fossil jet. Techno-economic analysis evaluated the major catalytic process cost-drivers, determining the minimum fuel selling price as a function of VFA production costs. Life cycle analysis determined that if food waste is diverted from landfills to avoid methane emissions, VFA-SAF could enable up to 165% reduction in greenhouse gas emissions relative to fossil jet.

A hydrothermal pre-treatment has been developed to improve sewage sludge quality or to produce low nitrogen biocrude via hydrothermal liquefaction (HTL) in a subsequent step. The mild hydrothermal pre-treatment (150 °C) step was performed with deionized water, sulfuric acid (0.5 M), or citric acid (0.5 M) to solubilize nitrogen containing compounds in the aqueous supernatant. Downstream, the residual solid material was liquefied with the addition of sodium carbonate via hydrothermal liquefaction (350 °C). The pre-treatment with citric acid transferred up to 66.7 wt. % of nitrogen into the aqueous supernatant, while 62.0 wt. % of carbon was recovered in the solid. Due to the pre-treatment lipids retained in the sewage sludge solid, which increased the favored biocrude yield up to 42.9 wt. % and the quality evaluating value H/Ceff ratio significantly to 1.48. Multi-method characterization of the resulted biocrude samples showed a lower concentration of N-heterocycles, while long-chain aliphatics and free fatty acid are increased.

Formaldehyde (HCHO), formed in situ by transfer dehydrogenation of methanol in methanol-to-hydrocarbon (MTH) conversion, reacts with other organic species including olefins, dienes, and aromatics to cause deactivation. The propensity of these formaldehyde-mediated pathways to cause deactivation during MTH catalysis is evaluated using site-loss selectivity and yield as numerical assessors of catalyst deactivation. The site-loss selectivity of HCHO with 0.2 kPa HCHO and 12 kPa CH3OH at 673 K decreases by 80% when co-feeding 1 kPa propylene, increases by 2× when co-feeding toluene, and increases by 150× when co-feeding 1,3-butadiene, suggesting that olefins react with HCHO in nondeactivating pathways, while aromatics and dienes react with HCHO in pathways that lead to deactivation. Further, dienes have a much higher propensity than aromatics to cause deactivation via HCHO-mediated reactions when compared on a molar basis, suggesting that dienes may be critical intermediates in HCHO-mediated deactivation pathways. This is corroborated by evidence that the site-loss selectivity of HCHO increases with increasing HCHO co-feed pressure, implying that prevalent deactivation pathways are higher order in HCHO than predominant competing nondeactivation pathways. Plausibly this occurs because HCHO reacts with itself or with a HCHO-derived species en route to deactivation, such as a diene or an aromatic, which are known products of HCHO-mediated pathways during MTH catalysis. Therefore, dienes along with HCHO should be considered as critical intermediates in fomenting deactivation in MTH catalysis and strategies to eliminate polyunsaturated species and/or intercept reaction sequences of these intermediates with HCHO will likely enhance catalyst lifetime during MTH catalysis.

A kinetic investigation of the vapor phase Hofmann elimination of tert-butylamine over H-ZSM-5 reveals a carbocation mediated E1-like mechanism, where isobutene and ammonia are exclusively produced over Brønsted acid sites. Hofmann elimination kinetics are found to be insensitive to Al content or siting, varying only with alkylamine carbocation stability (rtertiary > rsecondary > rprimary). Under conditions of complete tert-butylamine surface coverage, experimentally measurable apparent kinetics are directly equivalent to the intrinsic kinetics of the rate determining unimolecular surface elimination. The direct measurement of elementary step kinetics served as a water-free reactive probe, providing a direct measurement of the impact of water on solid Brønsted acid catalyzed chemistries at a microscopic level. Over a range of temperatures (453‒513 K) and tert-butylamine partial pressures (6.8×10-2‒6.8 kPa), water reversibly inhibits the rate of Hofmann elimination. Despite expected changes in aluminosilicate hydrophobicity, the water-induced inhibition is found to be insensitive to Al content, demonstrated to be due to one water molecule per Brønsted acid site. Regardless of the significant reduction in the rate of Hofmann elimination, kinetic interrogations and operando spectroscopic measurements reveal that the coverage of TBA adsorbed on H-ZSM-5 is unaltered in the presence of water. Cooperative adsorption between the tert-butylammonium surface reactant and water adsorbed on a neighboring framework oxygen is proposed to be responsible for the observed rate inhibition, the surface dynamics of which is quantitatively captured through kinetic modeling of experimental rate measurements.

The overall goal of this research was to study the effects of temperature and pine-to-HDPE ratios on the pyrolysis products. Catalytic co-pyrolysis of pine and HDPE was carried out in a double-column staged reactor, wherein the temperature was varied as 450 °C, 500 °C, and 550 °C for each pine/HDPE ratio of 0/100, 25/75, 50/50, 75/25, and 100/0. Thermal cracking of the feedstock is initiated at the first column, and the zeolitic-based ZSM-5 catalyst offered secondary cracking at a catalyst-to-feedstock ratio of 1:1 in the second column of the reactor. Catalytic pyrolysis of HDPE produced 31 wt% pyrolysis oil (40 MJ/kg calorific value) with a selectivity of above 90% toward gasoline-range hydrocarbons at 500 °C. Comparatively, pine offered 26.3% wt.% pyrolysis liquid yield with 7.9% dark pyrolysis oil (30 MJ/kg calorific value) that has a gasoline selectivity of 69.3%. Thus, the addition of HDPE increased the gasoline selectivity by increasing the hydrogen/carbon effective (H/Ceff) ratio. At pine/HDPE ratio of 25/75, the pyrolysis oil content was 22.5% at 500 °C, which is 3 times more than that of pine pyrolysis. The optimum yield and higher gasoline selectivity were observed at 500 °C for 0/100 and 25/75 pine to HDPE ratios.

Plastic buildup and accumulation in the environment are an increasingly large problem facing civilization. Petroleum-based plastics can exist for hundreds to thousands of years in the environment, destroying habitats and polluting water. Environmentally conscious replacements for plastics are urgently needed. In this publication, we present a biobased alternative to petroleum-based polycarbonates. Using a diol monomer derived from glycerol and glycerol products, we have synthesized aliphatic polycarbonates with comparable physical properties to petroleum-based incumbents. The polymer can be quantitatively depolymerized using warm methanol to recover the monomer which can be repolymerized multiple times, or alternatively, the monomer, which is inherently nontoxic, can slowly break apart to the original components. This provides two end-of-life options for this material recycle or decomposition under environmental conditions to benign building blocks, thus providing a potential pathway to avoid environmental and bioaccumulation of plastics. We also demonstrate the ability to selectively recover the monomer from a simulated mixed-plastic waste environment; the monomer recovered this way functions identically to the virgin monomer after purification. This work represents an important step in the progress toward environmentally conscious polymer design with multiple end-of-life options.

The rapid development of additive technologies in recent years is accompanied by their intensive introduction into various fields of science and related technologies, including analytical chemistry. The use of 3D printing in analytical instrumentation, in particular, for making prototypes of new equipment and manufacturing parts having complex internal spatial configuration, has been proved as exceptionally effective. Additional opportunities for the widespread introduction of 3D printing technologies are associated with the development of new optically transparent, current- and thermo-conductive materials, various composite materials with desired properties, as well as possibilities for printing with the simultaneous combination of several materials in one product. This review will focus on the application of 3D printing for production of new advanced analytical devices, such as compact chromatographic columns for high performance liquid chromatography, flow reactors and flow cells for detectors, devices for passive concentration of toxic compounds and various integrated devices that allow significant improvements in chemical analysis. A special attention is paid to the complexity and functionality of 3D-printed devices.

We introduce a comprehensive conceptual framework for selecting solvents for reactive extraction in biphasic organic-water systems and demonstrate it for the separation of HMF (5-hydroxylmethylfurfural), a platform chemical produced in the acid-catalyzed dehydration of hexoses. We first perform in silico screening of ∼2500 solvents, from the ADFCRS-2018 database using the ADF COSMO-RS implementation, and classification, based on the solvent partition coefficient. We then determine experimentally the partition coefficients for HMF, fructose, and products of HMF rehydration (levulinic acid (LA), and formic acid (FA)), the mutual water-organic solvent solubilities, and the separation factors in >50 select solvents spanning multiple homologous series at room temperature and a typical reaction temperature with in situ sampling. We find that COSMO-RS is excellent for screening purposes (typical error in most cases within a factor of ∼2). Increased temperatures lead to significant reduction in partitioning, and room temperature measurements are clearly inadequate for solvent selection. Upon down selecting classes of solvents based on separation performance, we perform experimental thermal stability and reaction compatibility studies of a small set of solvents at relevant reactive-extraction temperatures. We discover that many substituted phenols exhibit an order-of-magnitude increase in partitioning compared to conventional solvents due chiefly to hydrogen bond interactions and show the necessary stability but retain a significant fraction of water and LA, factors that need to be considered in technoeconomic analysis. In contrast, anilines, aldehydes, and acids are good to excellent regarding separation but incompatible with this specific reaction medium. This multifaceted framework can be extended to other biomass-derived products and processes

Defect engineering is an effective strategy to enhance the activity of catalysts for various applications. Herein, it was demonstrated that in addition to enhancing surface properties via doping, the influence of dopants on the surface–intermediate interaction is a critical parameter that impacts the catalytic activity of doped catalysts for low-temperature formaldehyde (HCHO) oxidation. The incorporation of Co into the lattice structure of δ-MnO₂ led to the generation of oxygen vacancies, which promoted the formation of surface active oxygen species, reduced activation energy, and enhanced catalytic activity for low-temperature oxidation of HCHO. On the contrary, Cu doping led to a drastic suppression of the catalytic activity of δ-MnO₂, despite its enhanced redox properties and slight increase in the surface concentration of active oxygen species, compared to pristine δ-MnO₂. Diffuse reflectance infrared Fourier transform analysis revealed that in the presence of Cu, carbonate intermediate species accumulate on the surface of the catalysts, leading to partial blockage of active sites and suppression of catalytic activity.

The advent of Comprehensive Two-dimensional Gas Chromatography (GC × GC) as a practical and accessible analytical tool had a considerable impact on analytical procedures associated to the so-called “omics” sciences. Specially when GC × GC is hyphenated to mass spectrometers or other multichannel detectors, in a single run it is possible to separate, detect and identify up to thousands of metabolites. However, the resulting data sets are exceedingly complex, and retrieving proper biochemical information from them demands powerful statistical tools to deal effectively with the massive amount of information generated by GC × GC. Nevertheless, the obtention of results valid on a chemical and biological standpoint depends on a deep understanding by the analyst of the fundamentals both of GC × GC and chemometrics. This review focuses on the basics of contemporary, fundamental chemometric tools applied to proccessing of GC × GC obtained from metabolomic, petroleomic and foodomic analyses. Here, we described the fundamentals of pattern recognition methods applied to GC × GC. Also, we explore how different detectors affect data structure and approaches for better data handling. Limitations regarding data structure and deviations from linearity are stressed for each algorithm, as well as their typical applications and expected output.

Manganese oxide catalysts with self-modulating K⁺ content and tunable concentration of lattice oxygen and Mn⁴⁺ were synthesized and investigated for HCHO oxidation. The preparation method affects the physicochemical properties and catalytic activity of the catalysts. Herein, the role of K⁺ in enhancing the lattice oxygen mobility of manganese oxide catalysts for enhanced formaldehyde (HCHO) is presented. The presence of K⁺ enhances the redox properties of Mn and promotes catalytic activity by enhancing the mobility of the lattice oxygen and sustaining the availability of surface active oxygen to sustain the reaction. Catalytic activity was observed to improve with increasing K⁺ content and the surface concentration of lattice oxygen and Mn⁴⁺. A drastic reduction in catalytic activity was observed in the acid-treated samples, with low K⁺ concentration. Characterization results indicate that the presence of K⁺ enhances activity and mobility of the lattice oxygen by the weakening the Mn-O bond in manganese oxide and promotes the redox properties of the catalyst. The absence of K⁺ impacted the mobility of the lattice oxygen and the ability of the catalyst to supplement the consumed oxygen species, resulting into reduced catalytic activity and deactivation in the room-temperature (30 °C) activity and stability test.

Atomically precise metallic clusters offer total structural information lacking in metal oxide and nanoparticle catalysts. However, their use as heterogeneous catalysts requires accessible and robust catalytic sites, yet directing clusters into ordered and porous assemblies through functional control remains elusive. Herein, we report a supramolecular strategy to induce permanent porosity within assemblies of two cerium oxide clusters through the capping ligands used. Single-crystal X-ray crystallography and density functional theory calculations revealed cluster assemblies with accessible channels, while adsorption isotherms showed permanent porosity. The clusters exhibited a bulk modulus >5 GPa in variable pressure diffraction studies. X-ray photoelectron spectroscopy, electron paramagnetic resonance spectroscopy, and Raman spectroscopy demonstrated mixed valency (Ce³⁺/Ce⁴⁺) and oxygen vacancies in the clusters. We benchmarked catalytic activities through the photooxidation of 2-propanol.

We describe a two-step catalytic process for the selective and rapid conversion of biomass-derived acetylfurans into vinylfurans. This is accomplished by nearly quantitatively reducing acetylfurans into furyl alcohols using a copper chromite catalyst and exploiting the promoter-like properties of ethanol, the solvent. Subsequently, the furyl alcohol is dehydrated using solid-acid catalysts. Catalyst deactivation due to oligomeric species is a major issue, but the activity can be partially recovered by calcination. Optimization of reaction conditions showed that the selectivity could be increased by using nitrobenzene, a polar aprotic solvent. The high-boiling point solvent allows the formation of vinylfurans with a selectivity of up to 85%; the product can be isolated in high purity by distillation.

Multisubstituted pyrroles are commonly found in many bioactive small molecule scaffolds,yet thesynthesis of highly-substituted pyrrole cores remains challenging. Herein, we report an efficient catalytic synthesis of 2-heteroatom-substituted (9-BBN or SnR₃) pyrroles via Ti-catalyzed [2+2+1] heterocoupling of heteroatom-substituted alkynes. In particular, the 9-BBN-alkyne coupling reactions were found to be very sensitive to Lewis basic ligands in the reaction:exchange ofpyridine ligands from Ti to B inhibited catalysis, as evidenced by in situ ¹¹B NMR studies. The resulting 2-borylsubstituted pyrroles can then be used in Suzuki reactions in a 1-pot sequential fashion, resulting in pentasubstituted 2-aryl pyrroles that are inaccessible via previous [2+2+1] heterocoupling strategies. This reaction provides a complementary approach to previous [2+2+1] heterocouplings of TMS-substituted alkynes, which could be further functionalized via electrophilic aromatic substitution.

Fast pyrolysis is traditionally defined as the rapid decomposition of organic material in the absence of oxygen to produce primarily a liquid product known as bio-oil. However, the introduction of small amounts of oxygen to the process holds prospects of internally generating the energy needed for pyrolysis. The present study investigates the partial oxidation of lignin-derived compounds during pyrolysis, which generates both carbon oxides and aromatic carbonyl compounds. Analysis of lignin derived phenolic compounds was performed to determine if the composition had changed under oxidative conditions. NMR analyses indicates aromatic carbonyls increased under oxidative conditions, with a corresponding decrease in phenolic hydroxyl groups. Model phenolic compounds were pyrolyzed to help understand the role of partial oxidation during autothermal pyrolysis of lignocellulosic biomass.

Characterization of Extractables and Leachables (E&Ls) is an important aspect of product quality in important fields such as pharmaceuticals, medical devices and food contact materials. The main goal of an E&L study is identification and quantification of those species which may leach from packaging materials used to contain pharmaceuticals or which may leach directly out of a medical device or food contact material and thus may result in patient exposure. It is common practice to perform relative quantitation of extractables and leachables using surrogate standards due to the large diversity of species observed and the lack of available reference standards. A key problem in obtaining accurate E&L results arises due to response factor (RF) variation. Different compounds at the same concentration give different signal intensities and thus have different RF values. Two key aspects of study quality are affected by this problem. First, the evaluation of the number of compounds which are above the toxicologically relevant threshold (analytical evaluation threshold, (AET)) can be affected (RF Problem 1: AET Underreporting). Second, quantitative accuracy is affected which can reduce the reliability of the margin of safety (MOS) calculations which serves as the basis of the toxicological evaluation (RF Problem 2: Quantitative Error). RF databases have been the main solution proposed for solving these problems but do not reduce the underlying RF variation and lack the scope required to address quantitative error for compounds not contained in the database. In the absence of other solutions, large uncertainty factors (UF) have been applied in the AET calculations to account for RF Problem 1: AET Underreporting. These UF factors have been assigned values of 4 for GCMS and up to 10 for LCMS. Large uncertainty factors have a number of unintended negative consequences including the need for large amounts of sample concentration (>10X) prior to analysis resulting in potential compound loss or degradation and increased matrix effects. To overcome these problems, this publication demonstrates a multidetector approach using an HPLC system coupled with a Quadrupole Time of Flight Liquid Chromatography Mass Spectrometer (QTOF-LCMS), Charged Aerosol Detector (CAD) and an Ultraviolet-Visible Detector (UV) and a dual detection Gas Chromatography Mass Spectrometry (GCMS) system using a Polyarc Reactor system with Flame Ionization Detection (FID). Herein, it is demonstrated that this combination of methods (the multidetector approach) allowed detection and accurate surrogate standard quantitation of 217 unique extractables spanning a wide range of chemical properties (Mw, logP, pKa and boiling point). The combination of optimized detector selection with appropriate standard selection was verified to provide positive detection for 94% of the compounds at the AET level and a high level of quantitative accuracy (± 20% for 85% of the compounds and ±40% for 91% of the compounds) while using only a UF of 2. Unlike the RF database approach, the multidetector approach is not limited to only those compounds contained in the database but is applicable to the majority of extractables.

Recently, the photocatalytic conversion of glucose appeared as an environmentally friendly route to produce valuable molecules. However, the potential of this new route in comparison with the usual hydrothermal catalytic process remained questionable. In this paper, we compared the two routes using three commercial TiO2 as catalysts in the same reactor. The TiO2 superficial acidity and basicity were determined by calorimetry and FTIR of CO2, NH3 and pyridine adsorption. Relationships between the acid-base properties, the TiO2 glucose adsorption capacities measured in water and their photocatalytic or hydrothermal performances were proposed: while the photocatalytic performances could be linked to the catalysts’ Lewis acid sites density and their glucose adsorption capacities, the hydrothermal performances were dependent of the catalysts’ basic/acid sites balance. We highlighted that the conversion of glucose over TiO2 was as efficient with the photocatalytic process at ambient temperature as with the hydrothermal process at 120 °C. This underlines the potential of the photocatalytic route at the lab scale as regards to the milder experimental conditions involved.

The mechanism by which humans absorb therapeutic light in winter seasonal and nonseasonal depression is unknown. Bright-light-induced release and generation of blood-borne gasotransmitters such as carbon monoxide (CO) may be one mechanism. Here, 24 healthy female volunteers had peripheral blood samples drawn. Samples were collected in a dimly lit room and protected from light exposure. Samples were analyzed for CO concentrations by gas chromatography after 2 h of continuous exposure to darkness vs. bright white light. In a similar confirmatory study, 11 additional volunteers had samples analyzed for CO concentrations after 2 h of continuous exposure to gentle rocking in darkness vs. in bright white light. In the first study, light-unexposed peripheral blood had a mean CO concentration of 1.8 ± 0.4 SD ppm/g. Identically treated samples with 2 h of rocking and exposure to bright white light at illuminance 10,000 lux had a mean CO of 3.6 ± 1.2 ppm/g (p < 0.0001). Post hoc analysis of that study showed that time of day was significantly inversely associated with increase in CO concentration under bright light vs. dark (p < 0.04). In a smaller confirmatory study of 11 healthy female volunteers, after 2 h of rocking, light-unexposed peripheral blood had a mean CO of 1.4 ± 0.5 SD ppm/g. Identically treated blood samples with 2 h of exposure to bright white light at illuminance 10,000 lux had a mean CO of 2.8 ± 1.7 ppm/g (p < 0.02). In conclusion, bright-light exposure robustly increases human blood CO in vitro. This supports the putative role of CO as a physiological regulator of circadian rhythms and light’s antidepressant effects. This human evidence replicates earlier data from a preclinical in vivo model. This effect may be stronger in the morning than in the afternoon.

Economic viability of biofuels and bioproducts depends on system-level optimization including biomass production and conversion. Hydrothermal liquefaction (HTL) can convert wet biomass such as microalgae into biofuel intermediate (BFI) under elevated temperatures and pressure. Understanding the impacts of biomass composition on BFI yield and quality can inform genetic engineering strategies to improve biochemical composition for biofuel production. In this work, wild type cyanobacterium Synechocystis sp. PCC 6803 biomass was doped with various common cellular storage compounds in lab-scale HTL experiments. Doping with glycogen or polyhydroxybutyrate (PHB) significantly reduced BFI yields, while doping with triglycerides (TAG) or medium chain-length polyhydroxyalkanoate (mcl-PHA) increased BFI yield and quality. In light of these observations, a genetically engineered Synechocystis strain deficient in glycogen biosynthesis was cultivated to produce biomass for HTL, leading to a 17% increase in BFI yield. In addition, we have built a multiphase component additivity (MCA) model that can predict BFI yield and quality with PHAs in the biomass. This work demonstrates an effective strategy to integrate strain development with downstream biomass conversion to maximize biofuel yield, with lessons applicable to microalgae as well as other biomass.

Simple Ti imido halide complexes such as [Br2Ti(NtBu)py2]2 are competent catalysts for the synthesis of unsymmetrical carbodiimides via Ti-catalyzed nitrene transfer from diazenes or azides to isocyanides. This is the only example of catalytic nitrene transfer to isocyanides where diazenes have been employed as the nitrene source. Both alkyl and aryl isocyanides are compatible with the reaction conditions, although product inhibition with sterically unencumbered substrates sometimes limits the yield when diazenes are employed as the oxi-dant. The reaction mechanism has been investigated both experimentally and computationally, wherein a key feature is that product release is triggered by electron transfer from an η2-carbodiimide to a Ti-bound azobenzene. This ligand-to-ligand redox buffering obviates the need for high-energy formally TiII intermediates, and provides further evidence that substrate and product “redox noninnocence” can promote unusual Ti redox catalytic transformations.

Fast gas chromatography that leverages the high chromatographic efficiency of narrow bore capillary column technology and temperature programming was successfully integrated with a third-generation low void-volume, 3D-printed two-stage microreactor. Effective management of extra-column effect and the capability to perform post-column backflushing were achieved with the incorporation of a recently commercialized, electronically controlled pneumatic switching device and a deactivated metal three-way microdevice. With this configuration, narrow bore capillary columns having internal diameters between 100 µm to 150 µm can be employed to produce chromatographic peaks in the domain of fast gas chromatography, with peak widths at half-height ranging from 0.42 s to 0.92 s for probe compounds having k’ over a range from 1.7 for toluene to 60 with the last analyte (nC44) eluted in less than 12 min. The carbon independent response capability of the 3D-printed microreactor affords unique and advantaged differentiators, for instance, conducting measurement of the target analytes using one single carbon-containing compound for calibration with an acceptable accuracy of ±10%, achieving a higher degree of accuracy by eliminating the need for multi-level and multi-compound calibration, and improving sensitivity for compounds that are not efficiently ionized by flame ionization detection. Using this platform, repeatability of retention times for 14 probe compounds was less than 0.1 % RSD (n = 10), and less than 1.0 % RSD (n = 10) for area counts. The utility of the analytical approach was illustrated with relevant, challenging applications.

A 3D-printed microreactor for post-column reaction was successfully integrated with comprehensive two-dimensional gas chromatography. A two-stage post-column reaction provided carbon independent response, it enhanced flame ionization detection uniformity, and it improved detector sensitivity. These enhancements are critical to overcome challenges in analyses using comprehensive two-dimensional gas chromatography and flame ionization detection, which aim to separate and quantify multiple components. Post-column reaction flame ionization detection eliminated the requirement of multi-level and multi-compound calibration, it enabled determination of target analytes with a single carbon-containing calibration compound with an accuracy of ±10%, and it improved sensitivity for compounds that were not efficiently ionized by flame ionization detection. Extra column band-broadening caused by the incorporation of the 3D-printed microreactor was minimized using optimized reactor operating parame-ters and inter-column connectivity. Chromatographic fidelity was in the practical domain of comprehensive two-dimensional gas chromatography. Typical peak widths at half-height using the described approach ranged from 165 ms to 235 ms for probe com-pounds with retention factors spanning 5 < k < 40.

Despite the ubiquity of reports describing titanium (Ti)-catalyzed [2 + 2 + 2] cyclotrimerization of alkynes, the incorporation of arynes into this potent manifold has never been reported. The in situ generation of arynes often requires fluoride, which instead will react with the highly fluorophilic Ti center, suppressing productive catalysis. Herein, we describe the use of group 4 diarylmetallocenes, CpR2MAr2 (CpR = C5H5, C5Me5; M = Ti, Zr), as aryne precursors for the Ti-catalyzed synthesis of substituted naphthalenes via coupling with 2 equiv of an alkyne. Fair-to-good yields of the desired naphthalene products could be obtained with 1% catalyst loadings, which is roughly an order of magnitude lower than similar reactions catalyzed by palladium or nickel. Additionally, naphthalenes find broad applications in the electronics, photovoltaics, and pharmaceutical industries, urging the discovery of more economic syntheses. These results indicate that aryne transfer from a CpR2M(η2-aryne) complex to another metal is a viable route for the introduction of aryne fragments into organometallic catalytic processes.

Specifying effective analytical techniques and methods can be very challenging when a large number of sample streams need to be analyzed with high frequency. Combining those requirements with the need to monitor multiple components over a wide range of concentrations makes at-line analytical approaches preferred by many analytical scientists. Traditionally, at-line analytical support requires sample preparation and operator time. Recently developed technologies enabled automated sample preparation tools coupled with gas chromatography; thus, eliminating sample preparation steps and increasing productivity. Recently a commercial micro-reactor was introduced that can be combined with a flame ionization detector, providing the ability to quantify components without the need to perform a standard calibration, which saves significant time and materials. In this manuscript, we describe a unique analytical capability that combines automated sample preparation and gas chromatography with flame ionization detection and universal carbon response to provide high flexibility and accuracy when there is minimal information about the unknowns or reference materials are not available. Some of the challenges and performance monitoring techniques for this technology are also discussed in this manuscript.

The copolymerization of vinyl benzyl alcohol (VBA) and carbon monoxide (CO) to give a new polyester poly(VBA-CO) has been achieved via palladium-catalyzed hydroesterification. Reaction conditions involve moderate temperatures, moderate to low CO pressures, and low catalyst loadings to give a low molar mass (Mn ∼ 3–4 kg/mol) polymer as a ∼2:1 mixture of linear to branched repeat units. The polymer molar mass increase is consistent with a step-growth polymerization mechanism, and ester yields of >97% are achieved within 24 h. However, increases in Mn cease beyond 16 h. Control experiments indicate that the degree of polymerization is limited due to a combination of side reactions such as alcoholic end-group oxidation, hydroxycarbonylation, and alcohol acetylation, which lead to the degradation of monomeric and polymeric end groups. When a less promiscuous substrate is used such as 10-undecenol, higher molar masses (Mn ∼ 16 kg/mol) are achieved. This method has the potential to be a mild route to new polyester architectures with appropriate mitigation of side reactions.

Metal oxide-filled reactors constructed with ceramic tubes or fused silica capillary are widely used for combustion in gas chromatography combustion isotope ratio mass spectrometry (GCC-IRMS). However, they tend to be easily cracked or broken and prone to leaks at operating temperatures of ∼950 °C. Here we introduce a modified commercially available catalytic combustion/reduction methanizer to quantitatively convert organics to CO2 for δ13C analysis while retaining chromatographic resolution. These modified “ARC” reactors operate with a transition-metal catalyst that requires a flowing O2 gas to enable complete conversion to CO2 at lower temperature (620 °C) with acceptable reactor life, reduced complexity, and improved robustness. Performance of two versions of the ARC reactors with different combustion volumes was characterized by analysis of steroid and alkane isotopic standard materials. Linearity of steroid isotopic standards ranged from 0.02 to 0.60 ‰/V in the range of 25 to 200 ng of each steroid injected. Precisions and accuracies of measurements for steroids and alkanes had average standard deviations of SD(δ13C) less than ±0.18 ‰ and average accuracy of better than 0.19 ‰ δ13CVPDB. Peak width expansion within both devices were similar to that in traditionally used metal oxide reactors. These data demonstrate for the first time that novel combustion schemes enable operation at lower temperatures as an alternative approach comparable to high temperature techniques to yield high precision δ13C data with GCC-IRMS.

The first part of this chapter presents the main objectives for performing derivatization of a sample to be analyzed by gas chromatography (GC) or gas chromatography/mass spectrometry (GC/MS). The derivatization is typically done to change the analyte properties for a better separation and also for enhancing the method sensitivity. In GC/MS, derivatization may improve the capability of compound identification. Examples illustrating such improvements are included. The second part describes several types of derivatization that are more frequently used in analytical practice. These include alkylation (e.g., methylation), formation of aryl derivatives, silylation (e.g., formation of trimethylsilyl derivatives), acylation (e.g., reactions with acyl chlorides or with chloroformates), and several other types of derivatizations. The chapter also presents typical derivatizations for analytes with specific functional groups and discusses artifact formation in certain derivatization reactions.

A reliable and practical approach for the direct measurement of volatile oxygenated compounds in high pressure liquefied light hydrocarbons has been successfully developed. The approach incorporates the use of a pressurized liquid injection device for sample introduction, a highly selective and polar ionic sorbent column technology to achieve separation of the targeted oxygenated compounds, and the augmentation of a recently commercialized dual-stage post column microreactor to convert carbon compounds; first to carbon dioxide by combustion and subsequently to methane by methanation. This two-stage conversion strategy is highly advantageous as it enables carbon compound independent response as well as sensitivity improvements, particularly for short-chain oxygenated compounds. Oxygenated compounds such as acetaldehyde, propionaldehyde, methanol, ethanol, iso-propanol, n-propanol, and acetone in light hydrocarbons were found to have respectable linear ranges from 0.1 ppm (v/v) to 3,000 ppm (v/v) with R2 greater than 0.997 and a relative precision of less than 10% RSD (n = 7). With the incorporation of carbon compound independent response capability, one single carbon-containing compound can be used for calibration to measure any of the target analytes with a respectable accuracy of less than ±10% error. The unique feature of carbon equimolar response also enables the possibility of determining a “total” concentration for the known volatile oxygenated compounds. As well, the need for multi-level calibration was eliminated over the range of interest. This novel concept enables new measurement capability and flexibility, enhances analytical throughput, and substantially decreases the overall cost of ownership. The utility of the methodology was demonstrated with practical industrial applications.

Methylbenzenes entrained within the cavities of silicoaluminophosphate zeotype HSAPO-34 react with methanol in H+-mediated dealkylation to give ethylene and propylene in methanol-to-olefins catalysis. Methylbenzenes dealkylation on solid acids is proposed to occur either via the side-chain mechanism, where an exocyclic CC undergoes successive methylation prior to CC cleavage for olefin elimination, or the paring mechanism, where ring contraction to a bicyclohexenyl cation precedes CC cleavage for olefin elimination. Distinct dealkylation mechanisms prescribe distinct combinations of C atoms—from aromatic methyl, aromatic ring, and methanol/dimethyl ether—to comprise the olefin product. Site-specific isotope tracing that distinguishes between isotope labels in aromatic methyl and aromatic ring positions for each methylbenzene shows that tetramethylbenzene gives ethylene via the side-chain mechanism and penta- and hexamethylbenzene give propylene via the paring mechanism. The ratio of propylene selectivity to ethylene selectivity increases in methanol reactions on HSAPO-34 entrained with a distribution of methylbenzenes deliberately manipulated towards increasing fractions of penta- and hexamethylbenzene, corroborating the conclusion that aromatic precursors and dealkylation mechanisms for ethylene diverge from those for propylene.

A gas chromatographic strategy to advance the direct detection and quantification of volatile aliphatic aldehydes such as formal-dehyde and acetaldehyde in gas phase matrices without the need for sample pre-treatment or concentration has been successfully developed. The catalytic hydrogenolysis of aldehydes to alkanes is conducted in-situ within the 3D printed steel jet assembly of the flame ionization detector and without any additional hardware required. Reliable conversion efficiencies of greater than 90% with respectable peak symmetries for the analytes were attained at 400 °C. Quantification of formaldehyde and acetaldehyde at parts-per-million level over a range of 0.5-300 ppm (v/v) for formaldehyde and 0.2-430 ppm (v/v) for acetaldehyde with a respect-able precision of less than 5% RSD (n = 10) was achieved. Total analysis time is less than 10 min. Linearity with a correlation coef-ficient of R2 greater than 0.9997 and measured recoveries of >99% for spike tests under the specified conditions were achieved. The 3D printed steel jet assembly was found to be reliable and resilient to matrices such as air, water, hydrocarbons, and aromatics. An additional benefit realized with this analytical strategy is that the slight restriction induced by the presence of the catalyst in the 3D printed jet assembly enables backflush via the inlet split vent without the need for additional pressure control and inter-column connection devices. The utility of this technique was demonstrated with important aldehyde applications from various segments.

Medium chain-length linear α-olefins (mcl-LAO) are versatile precursors to commodity products such as synthetic lubricants and biodegradable detergents, and have been traditionally produced from ethylene oligomerization and Fischer–Tropsch synthesis. Medium chain-length polyhydroxyalkanoic acid (mcl-PHA) can be produced by some microorganisms as an energy storage. In this study, Pseudomonas putida biomass that contained mcl-PHA was used in HTL at 300 °C for 30 min, and up to 65 mol% of mcl-PHA was converted into mcl-LAO. The yield and quality of the bio-oil co-produced in the HTL was remarkably improved with the biomass rich in mcl-PHA. Experiments with extracted mcl-PHA revealed the degradation mechanism of mcl-PHA in HTL. Overall, this work demonstrates a novel process to co-produce mcl-LAO and bio-oil from renewable biomass.

In the current study, low-density polyethylene and polystyrene were co-pyrolyzed with dealkaline lignin in a micro-reactor at 500°C with and without low-cost red clay catalyst. The products were analyzed with GC-MS/FID to quantify phenolic compounds, alkanes and alkenes. The synergistic effect between plastics and lignin was studied by comparing the carbon yield of compounds from co-pyrolysis with that from individual pyrolysis. The co-pyrolysis of lignin and polystyrene was also performed at 600, 700 and 800°C to examine the effect of pyrolysis temperature. The study explores a novel approach to enhance lignin depolymerization with red clay catalyst while utilizing waste plastics.

Quantification of complex carbon‐containing mixtures are typically very time‐intensive tasks with regards to the calibration process. A gas chromatograph with a flame ionization detector yields strong responses to organic compounds and provides a wide linear range over many orders of magnitude; however, responses for highly functionalized and heteroatom containing compounds can be variable. Here, a commercial Polyarc microreactor unit, placed before the flame ionization detector, was investigated as a means of normalizing carbon response across all compounds. The device includes two catalytic reaction chambers, ultimately evenly converting all carbon atoms to methane for flame ionization detection. Three groups of different complex mixtures from n‐alkane to terpene and polymer mixtures were analyzed to evaluate the potential for calibration‐free quantitation of the new detector arrangement. We have obtained accurate quantification results without time‐consuming calibration processes. The quantification of a terpene mixture and a polymer mixture confirm the ability of the detector for analyzing samples that either have complex physical or structural properties or wide concentration range. In summary, compared to other detectors, this methanizer – flame ionization detection system provides a simplified workflow, which can eliminate calibration steps and increase throughput.

Comprehensive two-dimensional gas chromatography (GC×GC) has impacted the workflow of GC-based methods used in petroleum industry. Application of GC×GC to petroleomic investigations have guided sample preparation to faster, cleaner, and more reliable formats. For instance, solvent consumption has been drastically reduced when using miniaturized devices in routine applications. Furthermore, flow-modulation has enabled cost-effective analysis and powerful separations of gases, fuels, and crude oils. Hyphenation of GC×GC to conventional and high resolution mass spectrometry has enabled the detection and identification of hundreds of compounds in a single analysis. Pixel-based methods enabled efficient handling of big data generated by GC×GC in forensic and geochemical investigations. This review has highlighted an ever-growing demand for modern and powerful analytical methods for oil & gas industry. Here, we described the most recent advances to sample preparation, GC×GC instrumentation, and multivariate data analysis in petroleum industry, including microextractions, high temperature GC×GC, and pixel-based data analysis.

An analytical technique that employs in-situ methanation with flame ionization detection for the measurement of carbon dioxide in various matrices has been developed and implemented. The methanation of carbon dioxide to methane is conducted in-situ within the 3D printed jet of the flame ionization detector without any additional hardware required. Quantification of carbon dioxide at the parts-per-million level over a range of 1-10,000 ppm (v/v) with respectable precision of less than 5% RSD (n = 10) was achieved. Total analysis time is less than 6 min. Linearity with a correlation coefficient of R2 = 0.9995 and a measured recovery of >99% under the specified conditions were achieved. Leveraging the additional back pressure generated by the modified jet assembly, a novel strategy of post-column backflushing with the detector fuel gas was successfully innovated to provide advantaged synergy in enhanced reliability and throughput of the analytical system. This backflushing approach had no known negative impact on conversion efficiency or performance of the jet assembly.The utility of this technique was demonstrated with relevant carbon dioxide applications in various sectors including carbonated beverage, environmental, and chemical industries.

The flame ionization detector (FID) is a robust tool in gas chromatography (GC) due to its sensitivity and linear response in the detection of common organic compounds. However, FID response to oxygenated or highly functionalized organic molecules is low, or in some cases non-existent, making it difficult or impossible to detect and quantify some organic compounds. In this work, the combination of a GC/FID system with a catalytic microreactor, which performs post-column combustion–methanation to convert organic compounds to methane, is shown to be an effective approach for quantifying low-response organic compounds. Molecules that were previously undetectable by conventional FID, including carbon monoxide and carbon dioxide, respond with the same high response of methane in the FID. Low-response molecules, including formaldehyde, formic acid, formamide, and ten other oxygenates also demonstrated enhanced detector response equivalent to that of methane in the FID. The linear response of the FID to these molecules and the equivalent sensitivity to methane indicate that accurate quantification is possible without the usual calibration-corrections (e.g., response factors or correction factors) to the FID response.

Scope of Review. Analysis of volatile and semi-volatile analytes by gas chromatography (GC) methods is an indispensable tool in the analytical chemist’s tool box. A myriad of fields of study rely upon the application of GC methods to address an ever growing demand to provide useful chemical information from GC data. As the realm of GC application has expanded, there has been an evolution to develop more powerful instrumental and data analysis approaches to keep pace with the wealth of complex samples that require analysis. To address this challenge, advances in GC instrumentation having evolved from one-dimensional gas chromatography (1D-GC) and heart cutting approaches such as (GC-GC), to instrumentation referred to broadly as multidimensional gas chromatography (MDGC), which can take on many forms. The principle form of MDGC that has gained wide implementation is comprehensive two-dimensional (2D) gas chromatography (GC × GC) as shown in Figure 1A, pioneered nearly 26 years ago by Liu and Phillips.1 When comparing 1D-GC (Figure 1B) relative to GC × GC (Figure 1C), the benefits of a secondary separation become evident. Blumberg and co-workers have theoretically determined that the 2D peak capacity provided by GC × GC compared to the peak capacity of 1D-GC is approximately an order of magnitude higher when the run times are held constant.2 This benefit is illustrated using a relatively complex sample of coffee. By adding a multivariate detector such as a time-of-flight mass spectrometry (TOFMS), another selective dimension of data is provided which may allow identification of analytes (Figure 1D). This review will focus essentially on GC × GC, with selected developments of other forms of MDGC also covered. In this regard, we focus primarily on research published since the last Fundamental Review published by Seeley and Seeley in 2013,3 with older publications covered as deemed necessary to provide additional insight into addressing the current challenges, and to put the more recent developments into historical context.

The Brønsted acid site densities of ZSM-5, BEA and single unit cell self-pillared pentasil (SPP) zeolites of varying Si/Al ratios were measured using a new technique, reactive gas chromatography (RGC), which utilizes alkylamine decomposition to selectively count Brønsted acid sites. Reactive gas chromatography condenses the conventional temperature-programmed desorption mass spectrometer (TPD-MS) setup into a single, fully-automated gas chromatograph (GC). Alkylamine decomposition reactions were conducted in a microcatalytic reactor placed within a temperature-controlled GC inlet liner. Products were then separated in a GC column and quantified with a flame ionization detector. A comparison between reactive gas chromatography measurements and conventional temperature programmed desorption methods showed agreement; RGC acid site density measurements were further confirmed by comparison with in situ pyridine titration of isopropanol dehydration. Reactive gas chromatography measurements performed using multiple alkylamines, were found to yield identical Brønsted acid site densities. The method of reactive gas chromatography was found to be highly sensitive, where siliceous materials with Brønsted acid site densities as low as ~1.0 μmol gcat-1 could be reliably measured.

While laboratories utilize many approaches to calibrate analytical assays, they always involve the analysis of one or more calibrators that have known levels of the analyte of interest. The response of the analyte of interest in test samples is directly or indirectly compared to the response of the same analyte in the calibrators to determine the concentration of the analyte in the test sample. Analyte calibration is burdened with limitations and potential bias: Calibrator preparation inherently contains a level of inaccuracy, which propagates to the quantitation of any unknown based on that calibration. Even small biases in the calibration will impact the quantitative accuracy of samples.

Quantitative analysis of complex mixtures containing hundreds-to-thousands of organic compounds rich in heteroatoms, including oxygen, sulfur, and nitrogen, is a major challenge in the fuel, food, and chemical industries. In this work, a two-stage (oxidation and methanation) catalytic process in a 3D-printed metal microreactor was evaluated for its capability to convert sulfur-containing organic compounds to methane. The microreactor was inserted into a gas chromatograph between the capillary column and flame ionization detector. Catalytic conversion of all sulfur-containing analytes to methane enabled carbon quantification without calibration, by the method identified as “quantitative carbon detection” or QCD. Quantification of tetrahydrothiophene, dimethyl sulfoxide, diethyl sulfide, and thiophene indicated complete conversion to methane at 450°C. Long-term performance of a commercial microreactor was evaluated for 2,000 consecutive injections of sulfur-containing organic analytes. The sulfur processing capacity of the microreactor was identified experimentally, after which reduced conversion to methane was observed.

Catalytic ring-opening dehydration of tetrahydrofuran (THF), itself a product of decarbonylation and reduction of biomass-derived furfural, yields 1,3-butadiene, an important monomer in rubbers and elastomers. It is demonstrated that dehydra-decyclization of THF with phosphorus-containing siliceous self-pillared pentasil (SPP) or MFI structure exhibits high selectivity to butadiene (85–99%) at both low (9%) and high (89%) conversion of THF. High selectivity to pentadiene and hexadiene was also obtained from 2-methyl-tetrahydrofuran and 2,5-dimethyl-tetrahydrofuran, respectively, with phosphorus-containing, all-silica zeolites.

Catalytic hydrogenation of itaconic acid (obtained from glucose fermentation) yields 3-methyl-tetrahydrofuran (3-MTHF), which then undergoes catalytic dehydra-decyclization to isoprene. It is demonstrated that a one-pot cascade reaction converts itaconic acid to 3-MTHF at ∼80% yield with Pd–Re/C catalyst and 1000 psig H2. Subsequent gas-phase catalytic ring opening and dehydration of 3-MTHF with phosphorus-containing zeolites including P-BEA, P-MFI, and P-SPP (self-pillared pentasil) exhibits 90% selectivity to dienes (70% isoprene, 20% pentadienes) at 20–25% conversion.

Analysis of trace compounds, such as pesticides and other contaminants, within consumer products, fuels, and the environment requires quantification of increasingly complex mixtures of difficult-to-quantify compounds. Many compounds of interest are non-volatile and exhibit poor response in current gas chromatography and flame ionization systems. Here we show the reaction of trimethylsilylated chemical analytes to methane using a quantitative carbon detector (QCD; the Polyarc reactor) within a gas chromatograph (GC), thereby enabling enhanced detection (up to 10×) of highly functionalized compounds including carbohydrates, acids, drugs, flavorants, and pesticides. Analysis of a complex mixture of compounds shows that the GC-QCD method exhibitsfaster and more accurate analysis of complex mixtures commonly encountered in everyday products and the environment.