Tandem MS Elucidation of the Late-Stage Degradation Mechanism of Nitroplasticizer.

Understanding the degradation behavior of nitroplasticizer (NP) and the subsequent production of nitro-organics is crucial for both environmental monitoring and material development. A nontargeted approach via LC-QTOF-MS was employed to thoroughly study the degradation mechanism of NP in its late aging stage. Both positive and negative modes of ESI were performed to increase the compound coverage. To shed light on the fragmentation behavior of NP degradants (e.g., compounds containing a high density of NO2 moieties and oxygen sites) in the positive mode, which is rarely reported, the high-resolution tandem MS information on precursor ions at m/z 251(+), 254(+), 266(+), and 270(+) and a pair of isomeric ions at m/z 284(+) was investigated to extract their common diagnostic ions and dissociation channels, including the neutral loss of 2,2-dinitropropanol, nitro-nitrite rearrangement, homolytic cleavage of NO2, and simple inductive cleavage. Additionally, leveraging the sensitivity for nitroaromatics in the negative polarity, negative ions m/z 182(-) and 233(-) are identified as dinitroaniline and dinitronaphthol, respectively, which confirm the secondary hydrolysis pathway of the antioxidant (e.g., N-phenyl-2-naphthylamine) postulated in our previous work. In addition to earlier findings, the detection of these eight degradants further supports the evidence of increased acid concentration and aging temperatures in the late-stage NP environment, which contribute to intricate degradation behaviors in different aging environments.

The developments of C-N bond formation via electrochemical Ritter-type reactions.

With the development of organic electrochemical synthesis, a series of notable achievements have been made in electrochemical Ritter amination reactions, which have enriched the methods available for constructing C-N bonds. In this review, electrochemical Ritter amination reactions are introduced based on the classification of reaction substrates, including olefins, aromatics, alkylbenzenes, and the less reported carboxylic acids, ketones, sulfides, and alkanes. The application of electrochemical technology to Ritter reactions has improved the harsh conditions of the traditional reactions, and extended the substrate scope and the structural diversity of the products. The application value of Ritter reactions in organic synthesis has also been further expanded.

Electrocatalytic reductive deuteration of arenes and heteroarenes.

The incorporation of deuterium to organic molecules has widespread applications in medicinal chemistry and material science1,2. For example, deuterated drugs e.g. Austedo3, Donafenib4 and Sotyktu5 were recently approved. There are various methods for the synthesis of deuterated compounds with high deuterium incorporation6. However, the reductive deuteration of aromatic hydrocarbons, ubiquitous chemical feedstocks, to saturated cyclic compounds has rarely been achieved. Here, we describe a scalable and general electrocatalytic method for the reductive deuteration and deuterodefluorination of (hetero)arenes using a prepared nitrogen doped electrode and D2O, giving perdeuterated and saturated deuterocarbon products. This protocol has been successfully applied to the synthesis of 13 highly deuterated drug molecules. Mechanistic investigations suggest that the Ru-D species, generated by electrolysis of D2O in the presence of nitrogen-doped Ru electrode, are key intermediates that directly reduce aromatic compounds. This quick and cost-effective methodology for the preparation of highly D-labeled saturated (hetero)cycles compounds could be applied in the drug development and metabolism studies.

Multiscale Anion-Hybrid in Atomic Ni Sites for High-Rate Water Electrolysis: Insights into the Charge Accumulation Mechanism.

Single-atom catalysts, characterized by transition metal-(N/O)4 units on nanocarbon (M-(N/O)4-C), have emerged as efficient performers in water electrolysis. However, there are few guiding principles for accurately controlling the ligand fields of single atoms to further stimulate the catalyst activities. Herein, using the Ni-(N/O)4-C unit as a model, we develop a further modification of the P anion on the outer shells to modulate the morphology of the ligand. The catalyst thus prepared possesses high activity and excellent long-term durability, surpassing commercial Pt/C, RuO2, and currently reported single-atom catalysts. Notably, mechanistic studies demonstrated that the pseudocapacitive feature of multiscale anion-hybrid nanocarbon is considerable at accumulating enough positive charge [Q], contributing to the high oxygen evolution reaction (OER) order (ß) through the rate formula. DFT calculations also indicate that the catalytic activity is decided by the suitable barrier energy of the intermediates due to charge accumulation. This work reveals the activity origin of single atoms on multihybrid nanocarbon, providing a clear experiential formula for designing the electronic configuration of single-atom catalysts to boost electrocatalytic performance.

Catalytic conversion of mixed polyolefins under mild atmospheric pressure.

The chemical recycling of polyolefin presents a considerable challenge, especially as upcycling methods struggle with the reality that plastic wastes typically consist of mixtures of polyethylene (PE), polystyrene (PS), and polypropylene (PP). We report a catalytic aerobic oxidative approach for polyolefins upcycling with the corresponding carboxylic acids as the product. This method encompasses three key innovations. First, it operates under atmospheric pressure and mild conditions, using O2 or air as the oxidant. Second, it is compatible with high-density polyethylene, low-density polyethylene, PS, PP, and their blends. Third, it uses an economical and recoverable metal catalyst. It has been demonstrated that this approach can efficiently degrade mixed wastes of plastic bags, bottles, masks, and foam boxes.

Valve turning towards on-cycle in cobalt-catalyzed Negishi-type cross-coupling.

Ligands and additives are often utilized to stabilize low-valent catalytic metal species experimentally, while their role in suppressing metal deposition has been less studied. Herein, an on-cycle mechanism is reported for CoCl2bpy2 catalyzed Negishi-type cross-coupling. A full catalytic cycle of this kind of reaction was elucidated by multiple spectroscopic studies. The solvent and ligand were found to be essential for the generation of catalytic active Co(I) species, among which acetonitrile and bipyridine ligand are resistant to the disproportionation events of Co(I). Investigations, based on Quick-X-Ray Absorption Fine Structure (Q-XAFS) spectroscopy, Electron Paramagnetic Resonance (EPR), IR allied with DFT calculations, allow comprehensive mechanistic insights that establish the structural information of the catalytic active cobalt species along with the whole catalytic Co(I)/Co(III) cycle. Moreover, the acetonitrile and bipyridine system can be further extended to the acylation, allylation, and benzylation of aryl zinc reagents, which present a broad substrate scope with a catalytic amount of Co salt. Overall, this work provides a basic mechanistic perspective for designing cobalt-catalyzed cross-coupling reactions.

Roles of HNO x and Carboxylic Acids in the Thermal Stability of Nitroplasticizer.

In the thermal aging of nitroplasticizer (NP), the produced nitrous acid (HONO) can decompose into reactive nitro-oxide species and nitric acid (HNO3). These volatile species are prone to cause cascaded deterioration of NP and give rise to various acidic constituents. To gain insight on the early stage of NP degradation, an adequate method for measuring changes in the concentrations of HONO, HNO3, and related acidic species is imperative. The typical assessment of acidity in nonaqueous solutions (i.e., acid number) cannot differentiate acidic species and thus presents difficulty in the measurement of HONO and HNO3 at a micromolar concentration level. Using liquid-liquid extraction and ion chromatography (IC), we developed a fast and unambiguous analytical method to accurately determine the concentration of HONO, HNO3, acetic/formic acids, and oxalic acid in aged NP samples. Given by the overlay analysis results of liquid chromatography coupled with quadrupole time-of-flight mass spectrometry and IC, the prominent increase of produced HONO after the depletion of antioxidants is the primary cause of HNO3 formation in the late stage of NP degradation, which results in the acid-catalyzed hydrolysis of NP into 2,2-dinitropropanol and acetic/formic acids. Our study has demonstrated that the aging temperature plays a crucial role in accelerating the formation and decomposition of HONO, which consequently increases the acidity of aged NP samples and hence accelerates the hydrolyzation of NP. Therefore, to prevent NP from undergoing rapid degradation, we suggest that the concentration of HNO3 should be maintained below 1.35 mM and the temperature under 38 °C.

Unraveling the Structure and Reactivity Patterns of the Indole Radical Cation in Regioselective Electrochemical Oxidative Annulations.

Oxidation-induced strategy for inert chemical bond activation through highly active radical cation intermediate has exhibited unique reactivity. Understanding the structure and reactivity patterns of radical cation intermediates is crucial in the mechanistic study and will be beneficial for developing new reactions. In this work, the structure and properties of indole radical cations have been revealed using time-resolved transient absorption spectroscopy, in situ electrochemical UV-vis, and in situ electrochemical electron paramagnetic resonance (EPR) technique. Density functional theory (DFT) calculations were used to explain and predict the regioselectivity of several electrochemical oxidative indole annulations. Based on the understanding of the inherent properties of several indole radical cations, two different regioselective annulations of indoles have been successfully developed under electrochemical oxidation conditions. Varieties of furo[2,3-b]indolines and furo[3,2-b]indolines were synthesized in good yields with high regioselectivities. Our mechanistic insights into indole radical cations will promote the further development of oxidation-induced indole functionalizations.

Liquid Chromatography Quadrupole Time-of-Flight Mass Spectrometry Analysis of Eutectic Bis(2,2-dinitropropyl) Acetal/Formal Degradation Profile: Nontargeted Identification of Antioxidant Derivatives.

In the eutectic mixture of bis(2,2-dinitropropyl) acetal (BDNPA) and bis(2,2-dinitropropyl) formal (BDNPF), also known as nitroplasticizer (NP), n-phenyl-ß-naphthylamine (PBNA), an antioxidant, is used to improve the long-term storage of NP. PBNA scavenges nitrogen oxides (e.g., NO x radicals) that are evolved from NP decomposition, hence slowing down the degradation of NP. Yet, little is known about the associated chemical reaction between NP and PBNA. Herein, using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF), we thoroughly characterize nitrated PBNA derivatives with up to five NO2 moieties in terms of retention time, mass verification, fragmentation pattern, and correlation with NP degradation. The propagation of PBNA nitration is found to depend on the temperature and acidity of the NP system and can be utilized as an indirect, yet reliable, means of determining the extent of NP degradation. At low temperatures (<55 °C), we find that the scavenging efficiency of PBNA is nullified when three NO2 moieties are added to PBNA. Hence, the dinitro derivative can be used as a reliable indicator for the onset of hydrolytic NP degradation. At elevated temperatures (≥55 °C) and especially in the dry environment, the trace amount of water in the condensed NP (<700 ppm) is essentially removed, which accelerates the production of reactive species (e.g., HONO, HNO3 and NO x ). In return, the increased acidity due to HNO3 formation catalyzes the hydrolysis of NP and PBNA nitro derivatives into 2,2-dinitropropanol (DNPOH) and nitrophenol/dinitrophenol, respectively.

Liquid Chromatography Quadrupole Time-of-Flight Mass Spectrometry: A Strategy for Optimization, Characterization, and Quantification of Antioxidant Nitro Derivatives.

As an antioxidant, N-phenyl-ß-naphthylamine (PBNA) inhibits the activity of oxidants, such as NO x , to prevent the degradation of energetic materials. In the presence of NO x , nitrated products can be generated in the process potentially. To characterize nitrated PBNA in a nontargeted analysis of complex samples as such, liquid chromatography tandem quadrupole time-of-flight (LC-QTOF), as an excellent analytic technique, is used due to its high resolution and sensitivity. However, a systematic approach of instrumentation optimization, data interpretation, and quantitative determination of products is needed. Through a step-by-step evaluation of the instrumental parameters used in the Q0, Q1, and Q2 compartments of LC-QTOF, optimal ion yields of precursor ions and high-resolution MS2 fragmentation spectra at low mass defects were obtained in both negative and positive electrospray ionization modes. Through rationalization of the fragmentation pathways and verification using theoretical masses, the mononitro derivative of PBNA was accurately identified as N-(4-nitrophenyl)-naphthalen-2-amine and further confirmed using a reference standard. Using strict criteria provided by the analytical guidelines (e.g., SANTE), limit of quantitation, limit of detection, and calibration were established for the quantitation of PBNA and nitrated PBNA. From optimization to characterization and subsequent quantification of the mononitro-PBNA derivative, for the first time, the applicability of this strategy is demonstrated in the aged energetic binders.

Electrophotochemical Ce-Catalyzed Ring-Opening Functionalization of Cycloalkanols under Redox-Neutral Conditions: Scope and Mechanism.

Selective cleavage and functionalization of C-C bonds in alcohols is gaining increasing interest in organic synthesis and biomass conversion. In particular, the development of redox-neutral catalytic methods with cheap catalysts and clean energy is of utmost interest. In this work, we report a versatile redox-neutral method for the ring-opening functionalization of cycloalkanols by electrophotochemical (EPC) cerium (Ce) catalysis. The EPC-Ce-enabled catalysis allows for cycloalkanols with different ring sizes to be cleaved while tolerating a broad range of functional groups. Notably, in the presence of chloride as a counteranion and electrolyte, this protocol selectively leads to the formation of C-CN, C-C, C-S, or C-oxime bonds instead of a C-halide bond after ß-scission. A preliminary mechanistic investigation indicates that the redox-active Ce catalyst can be tuned by electro-oxidation and photo-reduction, thus avoiding the use of an external oxidant. Spectroscopic characterizations (cyclic voltammetry, UV-vis, electron paramagnetic resonance, and X-ray absorption fine structure) suggest a Ce(III)/Ce(IV) catalytic pathway for this transformation, in which a Ce(IV)-alkoxide is involved.

Pfizer and Palbociclib in China: Analyzing an Oncology Pay-for-Performance Plan.

OBJECTIVES: China is poised to become the world's second-largest oncology drug market. Its ability to continue broadening health coverage is in question. Institutional innovations such as performance-based risk-sharing agreements (PBRSAs) have been developed to promote access to novel therapeutics beyond that provided by public health insurance and central procurement systems. We examine in depth the financial implications of a PBRSA developed in China for the breast cancer drug palbociclib. METHODS: We generated a 2-state Markov model from PBRSA information made publicly available. Model inputs included breast cancer outcomes data from the published literature. The primary analysis estimates the percentage reduction in overall drug expenditures due to the PBRSA. Sensitivity analyses explored the financial impact of varied computed tomography scan utilization, rebate rate, and rebate duration. RESULTS: Estimated palbociclib expenditures for the PBRSA cohort totaled $36 278 000. Based on the publicly available information for the PBRSA, an effective discount of 1.3% was estimated. The effective discount was insensitive to changes in computed tomography scan utilization. CONCLUSIONS: The palbociclib PBRSA likely had negligible impact on patient access to therapy and limited downstream financial impact to patients and payers. The short duration of the rebate window, small rebate, and disease indolence contributed to the low expected rebate percentage.

Scalable and selective deuteration of (hetero)arenes.

Isotope labelling, particularly deuteration, is an important tool for the development of new drugs, specifically for identification and quantification of metabolites. For this purpose, many efficient methodologies have been developed that allow for the small-scale synthesis of selectively deuterated compounds. Due to the development of deuterated compounds as active drug ingredients, there is a growing interest in scalable methods for deuteration. The development of methodologies for large-scale deuterium labelling in industrial settings requires technologies that are reliable, robust and scalable. Here we show that a nanostructured iron catalyst, prepared by combining cellulose with abundant iron salts, permits the selective deuteration of (hetero)arenes including anilines, phenols, indoles and other heterocycles, using inexpensive D2O under hydrogen pressure. This methodology represents an easily scalable deuteration (demonstrated by the synthesis of deuterium-containing products on the kilogram scale) and the air- and water-stable catalyst enables efficient labelling in a straightforward manner with high quality control.

In Situ Synthesis of CuN4 /Mesoporous N-Doped Carbon for Selective Oxidative Crosscoupling of Terminal Alkynes under Mild Conditions.

The 1,3-conjugated diynes are an important class of chemical intermediates, and the selective crosscoupling of terminal alkynes is an efficient chemical process for manufacturing asymmetrical 1,3-conjugated diynes. However, it often occurs in homogenous conditions and costs a lot for reaction treatment. Herein, a copper catalyzed strategy is used to synthesize highly ordered mesoporous nitrogen-doped carbon material (OMNC), and the copper species is in situ transformed into the copper single-atom site with four nitrogen coordination (CuN4 ). These features make the CuN4 /OMNC catalyst efficient for selective oxidative crosscoupling of terminal alkynes, and a wide range of asymmetrical and symmetrical 1,3-diynes (26 examples) under mild conditions (40 °C) and low substrates ratio (1.3). Density functional theory (DFT) calculations reveal that the aryl-alkyl crosscoupling has the lowest energy barrier on the CuN4 site, which can explain the high selectivity. In addition, the catalyst can be separated and reused by simply centrifugation or filtration. This work can open a facile avenue for constructing single-atom loaded mesoporous materials to bridge homogeneous and heterogeneous catalysis.

Electrochemical Oxidation Enables Regioselective and Scalable α-C(sp3)-H Acyloxylation of Sulfides.

A highly selective, environmentally friendly, and scalable electrochemical protocol for the construction of α-acyloxy sulfides, through the synergistic effect of self-assembly-induced C(sp3)-H/O-H cross-coupling, is reported. It features exceptionally broad substrate scope, high regioselectivity, gram-scale synthesis, construction of complex molecules, and applicability to a variety of nucleophiles. Moreover, the soft X-ray absorption technique and a series of control experiments have been utilized to demonstrate the pivotal role of the self-assembly of the substrates, which indeed is responsible for the excellent compatibility and precise control of high regioselectivity in our electrochemical protocol.

Revealing the reduction process of Cu(ii) by sodium bis(trimethylsilyl)amide.

The mechanistic investigation of copper-catalysed transformations has been an important and fundamental task. Herein, we report via XAS and EPR spectroscopy that the sodium bis(trimethylsilyl)amide could reduce Cu(ii) to a Cu(i) species serving as an electron donor. XAS spectroscopy demonstrates that the newly formed Cu(i) species is the Cu[N(TMS)2]2Na ate complex, in which the nitrogen atoms coordinate with copper linearly.

Low-Pressure Flow Chemistry of CuAAC Click Reaction Catalyzed by Nanoporous AuCu Membrane.

Click chemistry has been widely used in bioconjugation, polymer synthesis, and the development of new anticancer drugs. Here, we report a nanoporous membrane made of AuCu alloy nanowires, which can effectively catalyze copper(I)-catalyzed 1,3-dipolar cycloaddition between azide and terminal alkyne (CuAAC) in flow condition with pressure less than one bar. Comparison studies of the nanowires before and after the reaction using X-ray photoelectron spectroscopy reveal Cu(0) and Cu(I) are main species that promote the reaction. This simple strategy can be used to synthesize a variety of compounds with triazole linkage and extended to gram level chemical production.

Binary Transition-Metal Oxide Hollow Nanoparticles for Oxygen Evolution Reaction.

Low-cost transition metal oxides are actively explored as alternative materials to precious metal-based electrocatalysts for the challenging multistep oxygen evolution reaction (OER). We utilized the Kirkendall effect allowing the formation of hollow polycrystalline, highly disordered nanoparticles (NPs) to synthesize highly active binary metal oxide OER electrocatalysts in alkali media. Two synthetic strategies were applied to achieve compositional control in binary transition metal oxide hollow NPs. The first strategy is capitalized on the oxidation of transition-metal NP seeds in the presence of other transition-metal cations. Oxidation of Fe NPs treated with Ni (+2) cations allowed the synthesis of hollow oxide NPs with a 1-4.7 Ni-to-Fe ratio via an oxidation-induced doping mechanism. Hollow Fe-Ni oxide NPs also reached a current density of 10 mA/cm2 at 0.30 V overpotential. The second strategy is based on the direct oxidation of iron-cobalt alloy NPs which allows the synthesis of hollow Fe xCo100- x-oxide NPs where x can be tuned in the range between 36 and 100. Hollow Fe36Co64-oxide NPs also revealed the current density of 10 mA/cm2 at 0.30 V overpotential in 0.1 M KOH.

Copper-catalyzed selective radical-radical cross-coupling for C-S bond formation: an access to α-alkylthionitriles.

A new protocol for C-S bond formation was developed by selective cross-coupling between a thiyl radical and an isobutyronitrile radical. Using this strategy, a series of valuable α-alkylthionitrile derivatives were synthesized from basic starting materials. Preliminary mechanistic investigation was performed by EPR and XAFS, revealing that the transient thiyl radical could be stabilized by a copper catalyst to a persistent one. Therefore, on the basis of the persistent radical effect, selective radical-radical cross-coupling between the thiyl radical and the isobutyronitrile radical was achieved successfully in this work.

Chemoselective Hydrogenation with Supported Organoplatinum(IV) Catalyst on Zn(II)-Modified Silica.

Well-defined organoplatinum(IV) sites were grafted on a Zn(II)-modified SiO2 support via surface organometallic chemistry in toluene at room temperature. Solid-state spectroscopies including XAS, DRIFTS, DRUV-vis, and solid-state (SS) NMR enhanced by dynamic nuclear polarization (DNP), as well as TPR-H2 and TEM techniques revealed highly dispersed (methylcyclopentadienyl)methylplatinum(IV) sites on the surface ((MeCp)PtMe/Zn/SiO2, 1). In addition, computational modeling suggests that the surface reaction of (MeCp)PtMe3 with Zn(II)-modified SiO2 support is thermodynamically favorable (Δ G = -12.4 kcal/mol), likely due to the increased acidity of the hydroxyl group, as indicated by NH3-TPD and DNP-enhanced 17O{1H} SSNMR. In situ DRIFTS and XAS hydrogenation experiments reveal the probable formation of a surface Pt(IV)-H upon hydrogenolysis of Pt-Me groups. The heterogenized organoplatinum(IV)-hydride sites catalyze the selective partial hydrogenation of 1,3-butadiene to butenes (up to 95%) and the reduction of nitrobenzene derivatives to anilines (up to 99%) with excellent tolerance of reduction-sensitive functional groups (olefin, carbonyl, nitrile, halogens) under mild reaction conditions.