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The electrochemical reduction of a series of nitro-substituted benzenesulfonyl chlorides is investigated. The results of the electrochemical study are analysed with the assistance of theoretical calculations. The study shows that the electron transfer mechanism depends on the position of the nitro substituent on the phenyl ring. The 3-nitrobenzenesulfonyl chloride follows a stepwise mechanism where the reduction leads to an intermediate radical anion. For the 4-nitrobenzenesulfonyl chloride, 2-nitrobenzenesulfonyl chloride, and 2,4-nitrobenzenesulfonyl chloride, the reduction follows a "sticky" dissociative mechanism, where the electron transfer and S–Cl bond cleavage are concerted. The dissociation products (arylsulfinyl radical and chloride anion) show strong interactions. The difference in behaviour is associated with the overlap of the π* orbital and the S–Cl σ* orbital for the latter three compounds. The through resonance stability of the arylsulfinyl radicals for the para and ortho nitro-substituted compounds facilitates the dissociation of the reduced structures. Upon reduction, the 3-nitrobenzenesulfonyl chloride and 4-nitrobenzenesulfonyl chloride, also produce the corresponding diaryl disulfones, which are easier to reduce that the parent molecules and hence induce an interesting autocatalytic mechanism. Such a mechanism, which depends on the concentration and the scan rate, does not take place with the 2-nitrobenzenesulfonyl chloride and 2,4-dinitrobenzenesulfonyl chloride due to the sterical hindrance of the nitro substituent at the ortho position, as it prevents the formation of the disulfones. [ABSTRACT FROM AUTHOR]

We report a synthesis of the trans and cis isomers of 1,4‐di‐tert‐butyl‐2,2,3,3,5,5,6,6‐octamethyl‐1,4‐diphenylcyclohexasilane (3), together with the solid‐state structure of cis‐3. Both isomers were characterized using multinuclear NMR and UV spectroscopies and were compared based on these data, together with DFT calculations. Remarkably, we found that both isomers of 3 showcase redshifted UV maxima when compared with other known cyclosilanes. To explain this, the theoretical calculations show that the transitions involved in the excited states of trans‐3 and cis‐3 have, in addition to the expected σ conjugation component of the Si6 ring, significant π contributions of phenyl substituents. The results presented herein show the effect of the substituent's electronic properties regarding reactivity of intermediates, reaction yield, identity, and electronic properties of novel silicon‐containing molecules. [ABSTRACT FROM AUTHOR]

Photosystem II (PSII) is a multi‐subunit protein‐pigment complex with diverse redox‐active cofactors, which enabled the biological availability of O2 on Earth. The substrate specificity and the underlying redox chemistry of the Mn4CaO5 catalytic center are investigated using alternate substrates such as small molecules (ammonia and methanol) and halides (Cl‐, Br‐, I‐) instead of the natural substrate water. Changes in the kinetic profiles of steady‐state O2 evolution and of dichlorophenolindophenol (DCIP) photochemical reduction by PSII as well as the detection of modified sites by proteomic analysis implied the possibility of alternate substrate photooxidation. Of particular interest is the role of two chlorides bound close to the putative water channels in the native system. The mutation of D2‐K317 to alanine is believed to impair the binding of a catalytically relevant chloride, eliminating the chloride requirement for water oxidation catalysis. The efficiency of small molecule photooxidation by the OEC is enhanced by the mutated D2‐K317A PSII complex without the competition from chloride. These results provide insight into the role of bound chloride in native PSII as a filter for enhancing the selectivity of water oxidation. The design principles for PSII may be extended to new strategies for developing highly selective catalysts. [ABSTRACT FROM AUTHOR]

The combination of continuous wave electron paramagnetic resonance (cw‐EPR) with electrochemistry is highly attractive as it allows a clean in‐situ generation and the subsequent spectroscopic characterisation of radical ions, which are important intermediates in many photocatalytic cycles as well as light‐induced processes occurring in biological systems or optoelectronic devices. Although commercial setups for spectroelectrochemical EPR are available, they are often expensive and tailored to a particular spectroscopic setup. Here we present a design for a low‐cost electrochemical EPR cell that can be used in combination with any commercial cw‐EPR instrumentation. The cell design is compared to existing setups and the performance of the cell is evaluated by comparison of EPR spectra obtained by chemical and electrochemical oxidation of a graphene fragment. [ABSTRACT FROM AUTHOR]

Trimethyl phosphate (TMP), an organophosphorus compound (OPC), is a promising fire‐retardant candidate for lithium‐ion battery (LIB) electrolytes to mitigate fire spread. This study aims to understand the mechanism of TMP unimolecular thermal decomposition to support the integration of a TMP chemical kinetic model into a LIB electrolyte surrogate model. Reactive intermediates and products of TMP thermal decomposition were experimentally detected using vacuum ultraviolet (VUV) synchrotron radiation and double imaging photoelectron photoion coincidence (i2PEPICO) spectroscopy. Phosphorus‐containing intermediates such as PO, HPO and HPO2 were identified. Sampling effects could successfully be obviated thanks to photoion imaging, which also showed evidence for isomerization reactions upon wall collisions in the ionization chamber. Quantum chemical calculations performed for the unimolecular decomposition of TMP revealed for the first time that isomerization channels via hydrogen and methyl transfer (barrier heights of 65.9 and 72.6 kcal/mol, respectively) are the lowest‐energy primary steps of TMP decomposition followed by CH3OH/CH3/CH2O or dimethyl ether (DME) production, respectively. We found an analogous DME production channel in the unimolecular decomposition of dimethyl methylphosphonate (DMMP), another important OPC fire‐retardant additive with a similar molecular structure to TMP, which are not included in currently available chemical kinetic models. [ABSTRACT FROM AUTHOR]

Non-thermal plasma is a promising alternative to be utilized for the synthesis of hydroxytoluenes through one-pot hydroxylation of toluene. Direct preparation of hydroxytoluenes from vaporized toluene was conducted in air at room temperature and atmospheric pressure using a dielectric-barrier discharge (DBD) reactor. The preliminary results obtained from this study showed that cresols were formed along with benzaldehyde, benzyl alcohol, and phenol. O atoms generated by air plasma in collision with toluene produced OH and benzyl radicals, which led to further reactions. The mechanism of the reaction of reactive oxygen species (ROS) with toluene and toluene-derived radicals to yield the observed oxidation products was discussed. [ABSTRACT FROM AUTHOR]

Vibrational circular dichroism (VCD) spectra of chiral high‐spin organic radicals are expected to show a strong intensity enhancement and are thought to be difficult to predict using state‐of‐the‐art theoretical methods. Herein we show that the chiral triplet nitrene obtained from photochemical cleavage of N2 from enantiopure 2‐azido‐9H‐fluorenol does not feature extraordinarily strong intensities and that the experimental spectra match nicely with calculated ones. Thereby, this study demonstrates the general feasibility of studies on chiral high‐spin organics by matrix‐isolation VCD. [ABSTRACT FROM AUTHOR]

Probing quantum mechanical tunneling (QMT) in chemical reactions is crucial to understanding and developing new transformations. Primary H/D kinetic isotopic effects (KIEs) beyond the semiclassical maximum values of 7–10 (room temperature) are commonly used to assess substantial QMT contributions in one‐step hydrogen transfer reactions, because of the much greater QMT probability of protium vs. deuterium. Nevertheless, we report here the discovery of a reaction model occurring exclusively by H‐atom QMT with residual primary H/D KIEs. 2‐Hydroxyphenylnitrene, generated in N2 matrix, was found to isomerize to an imino‐ketone via sequential (domino) QMT involving anti to syn OH‐rotamerization (rate determining step) and [1,4]‐H shift reactions. These sequential QMT transformations were also observed in the OD‐deuterated sample, and unexpected primary H/D KIEs between 3 and 4 were measured at 3 to 20 K. Analogous residual primary H/D KIEs were found in the anti to syn OH‐rotamerization QMT of 2‐cyanophenol in a N2 matrix. Evidence strongly indicates that these intriguing isotope‐insensitive QMT reactivities arise due to the solvation effects of the N2 matrix medium, putatively through coupling with the moving H/D tunneling particle. Should a similar scenario be extrapolated to conventional solution conditions, then QMT may have been overlooked in many chemical reactions. [ABSTRACT FROM AUTHOR]

This article explores the potential of using volatile organic compounds (VOCs) in environmentally friendly industrial processes. It discusses the challenges associated with working with VOCs and presents a study on their reaction with organolithium species in a flow microreactor system. The study demonstrates successful molecular transformations with high yields and purity, suggesting that this approach could lead to the development of novel, environmentally friendly industrial processes. Additionally, the article discusses the development of a flow microreactor system for selective formylation of organolithium species, which significantly improves yield compared to a batch reaction system and allows for safe and precise handling of VOCs. This approach has the potential to contribute to the sustainable development of organic synthesis using VOCs. [Extracted from the article]

Abstract Straw returning is an important strategy for effectively using straw resources to improve soil fertility and quality, but the effects of this process on reactive intermediates (RIs) formation in paddy water are not fully explored. In this study, we conducted a field experiment to explore the effects of straw returning on RIs formation including triplet chromophoric dissolved organic matter (3CDOM*), hydroxyl radicals (•OH), and singlet oxygen (1O2) in paddy water. It was found that straw returning considerably increased the steady-state concentration of RIs, and the application of rice straw with 25% and 75% organic replacement ratio increased RIs concentration by 2.52 and 2.25 times, respectively. The optical spectroscopy, Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) analysis and structural equation model showed that straw returning produces abundant humified and aromatic DOM containing fulvic acid, lignin and protein-like substances, which could induce more RIs under irradiation. In addition, straw returning significantly accelerated imidacloprid (IMD) degradation, yielding degradation products that were highly toxic to aquatic animals (i.e., fish and daphnia) but less toxic to aquatic plants (i.e., green algae). This study would offer an innovative viewpoint on the effects of straw returning on the photochemistry of paddy water and the naturally occurring abiotic degradation pathway of organic contaminants.

A novel class of diazonium salts is introduced for the photochemical aryl‐aryl coupling to produce (substituted) biphenyls. As common diazonium tetrafluoroborate salts fail, soluble and safe aryl diazonium trifluoroacetates are applied. In this mild synthesis route no catalysts are required to generate an aryl‐radical by irradiation with UV‐A light (365 nm). This reactive species undergoes direct C−H arylation at an arene, forming the product in reasonable reaction times. With the implementation of a continuous flow setup in a capillary photoreactor 13 different biphenyl derivatives are successfully synthesized. By integrating an inline 19F‐NMR benchtop spectrometer, samples are reliably quantified as the fluorine‐substituents act as a probe. Here, real‐time NMR spectroscopy is a perfect tool to monitor the continuously operated system, which produces fine chemicals of industrial relevance even in a multigram scale. [ABSTRACT FROM AUTHOR]

The diatomic molecule PH is very reactive, and it serves as the parent compound for phosphinidenes featuring a monovalent phosphorus atom. Herein, we report the characterization and reactivity of a rare hydrogen‐bonded complex of PH. Specifically, the molecular complex between PH and HCl has been generated by photolysis of chlorophosphine (H2PCl) at 254 nm in a solid Ar‐matrix at 10 K. The IR spectrum of the complex HP⋅⋅⋅HCl and quantum chemical calculations at the UCCSD(T)‐F12a/haTZ level consistently prove that the phosphorus atom acts as a hydrogen bond acceptor with a binding energy (D0) of −0.6 kcal mol−1. In line with the observed absorption at 341 nm for the binary complex, the triplet phosphinidene PH undergoes prototype H−Cl bond insertion by reformation of H2PCl upon photoexcitation at 365 nm. However, this hydrogen‐bonded complex is unstable in the presence of N2 and HCl, as both molecules prefers stronger interactions with HCl than PH in the observed complexes HP⋅⋅⋅HCl⋅⋅⋅N2 and HP⋅⋅⋅2HCl. [ABSTRACT FROM AUTHOR]

A series of chemically and biologically relevant N‐(arylthio)phthalimides is synthesized and its electrochemical reduction investigated. The results of the electrochemical study are analysed through application of Savéant's dissociative electron transfer theory and with the assistance of theoretical calculations. Reduction of all investigated N‐(arylthio)phthalimides leads to the corresponding radical anions, followed by the ejection of the phthalimide anion resulting from the dissociation of the N−S chemical bond. This stepwise electron transfer mechanism is evidenced by the electrochemical data which allow determination of the standard reduction potentials of all compounds. In the formation of the N‐(arylthio)phthalimide radical anions, the theoretical calculations show that the incoming electron, is hosted by the phthalimidyl group indicating a homolytic dissociation mechanism. The dissociation rate constants of the radical anions are deduced and show that upon changing the substituent from the MeO, to Me, H, F, Cl and Br the dissociation becomes faster. A good correlation with the Hammett substituent constants is also obtained. Application of Savéant's theory through determination of the associated driving force and the intrinsic barrier energies help rationalize the observed results and show that the change in the dissociation rate constant depends mainly on the standard reduction potential of the parent compounds. [ABSTRACT FROM AUTHOR]

Acrolein is a commonly encountered pollutant of health concern, yet the processes that decompose acrolein are poorly understood. Frequently used in industrial synthesis, it is also a byproduct of combustion and other high temperature processes, especially those involving biological substances, e.g., forest fires, deep frying, or cigarette smoke. Despite the need for investigation of the chemical behavior of acrolein at high temperatures, little experimental work exists on decomposition of acrolein using apparatus capable of observing reactive species. Here, the pyrolysis of acrolein was studied at temperatures of up to 1700 K. We identified radicals and other unstable species produced in the early reaction stages, including vinyl radical, methyl radical, and methyl ketene. Detection of these reactive intermediates, and indirect evidence on the formation of others, reveals reaction pathways to stable species, including carbon monoxide, ethylene, and acetylene. [ABSTRACT FROM AUTHOR]

Straw returning is an important strategy for effectively using straw resources to improve soil fertility and quality, but the effects of this process on reactive intermediates (RIs) formation in paddy water are not fully explored. In this study, we conducted a field experiment to explore the effects of straw returning on RIs formation including triplet chromophoric dissolved organic matter (3CDOM*), hydroxyl radicals (•OH), and singlet oxygen (1O2) in paddy water. It was found that straw returning considerably increased the steady-state concentration of RIs, and the application of rice straw with 25% and 75% organic replacement ratio increased RIs concentration by 2.52 and 2.25 times, respectively. The optical spectroscopy, Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) analysis and structural equation model showed that straw returning produces abundant humified and aromatic DOM containing fulvic acid, lignin and protein-like substances, which could induce more RIs under irradiation. In addition, straw returning significantly accelerated imidacloprid (IMD) degradation, yielding degradation products that were highly toxic to aquatic animals (i.e., fish and daphnia) but less toxic to aquatic plants (i.e., green algae). This study would offer an innovative viewpoint on the effects of straw returning on the photochemistry of paddy water and the naturally occurring abiotic degradation pathway of organic contaminants. Highlights: • Straw returning produces abundant humified and aromatic DOM as a key photosensitizer. • Straw returning increased the steady-state concentration of RIs in paddy water. • Straw returning significantly accelerated IMD degradation and 3DOM* was the dominant RI for IMD degradation in paddy water. [ABSTRACT FROM AUTHOR]

While smaller polyhedral oligomeric silsesquioxanes TnRn (POSS) are readily accessible or even commercially available, unambiguously authenticated larger systems (n>12) have barely been reported. Synthesis and isolation procedures are lengthy, and yields are often very low. Herein, we present the surprisingly straightforward and high‐yielding access to the phenyl‐substituted derivative of a so far only postulated second D3h‐symmetric T14 isomer and with that the largest crystallographically characterized POSS cage with organic substituents. Treatment of the commercially available incompletely condensed T7Ph7(OH)3 silsesquioxane with catalytic amounts of trifluoromethanesulfonic acid results in high yields of the T14Ph14 framework, which is isolated in crystalline form by a simple work‐up. D3h‐T14Ph14 was analyzed by single crystal X‐ray diffraction, multinuclear NMR spectroscopy and thermal analysis. The relative energies of all four theoretically possible T14Ph14 isomers were determined by optimization of the corresponding structure using DFT methods. [ABSTRACT FROM AUTHOR]

While smaller polyhedral oligomeric silsesquioxanes TnRn (POSS) are readily accessible or even commercially available, unambiguously authenticated larger systems (n>12) have barely been reported. Synthesis and isolation procedures are lengthy, and yields are often very low. Herein, we present the surprisingly straightforward and high‐yielding access to the phenyl‐substituted derivative of a so far only postulated second D3h‐symmetric T14 isomer and with that the largest crystallographically characterized POSS cage with organic substituents. Treatment of the commercially available incompletely condensed T7Ph7(OH)3 silsesquioxane with catalytic amounts of trifluoromethanesulfonic acid results in high yields of the T14Ph14 framework, which is isolated in crystalline form by a simple work‐up. D3h‐T14Ph14 was analyzed by single crystal X‐ray diffraction, multinuclear NMR spectroscopy and thermal analysis. The relative energies of all four theoretically possible T14Ph14 isomers were determined by optimization of the corresponding structure using DFT methods. [ABSTRACT FROM AUTHOR]

Phosphinidenes are heavy congeners of nitrenes that have been broadly used as in situ reagents in synthetic phosphorus chemistry and also serve as versatile ligands in coordination with transition metals. However, the detection of free phosphinidenes is largely challenged by their high reactivity and also the lack of suitable synthetic methods, rendering the knowledge about the fundamental properties of this class of low‐valent phosphorus compounds limited. Recently, an increasing number of free phosphinidenes bearing prototype structural and bonding properties have been prepared for the first time, thus enabling the exploration of their distinct reactivity from the nitrene analogues. This Concept article will discuss the experimental approaches for the generation of the highly unstable phosphinidenes and highlight their distinct reactivity from the nitrogen analogues so as to stimuate future studies about their potential applications in phosphorus chemistry. [ABSTRACT FROM AUTHOR]

The participation of both ligand and the metal center in the redox events has been recognized as one of the ways to attain the formal high valent complexes for the late 3d metals, such as Ni and Cu. Such an approach has been employed successfully to stabilize a Ni(III) bisphenoxyl diradical species in which there exist an equilibrium between the ligand and the Ni localized resultant spin. The present work, however, broadens the scope of the previously reported three oxidized equivalent species by conveying the approaches that tend to affect the reported equilibrium in CH3CN at 233 K. Various spectroscopic characterization revealed that employing exogenous N‐donor ligands like 1‐methyl imidazole and pyridine favors the formation of the Ni centered localized spin though axial binding. In contrast, due to its steric hinderance, quinoline favors an exclusive ligand localized radical species. DFT studies shed light on the novel intermediates′ complex electronic structure. Further, the three oxidized equivalent species with the Ni centered spin was examined for its hydrogen atom abstraction ability stressing their key role in alike reactions. [ABSTRACT FROM AUTHOR]

Abstract A series of chemically and biologically relevant N‐(arylthio)phthalimides is synthesized and its electrochemical reduction investigated. The results of the electrochemical study are analysed through application of Savéant's dissociative electron transfer theory and with the assistance of theoretical calculations. Reduction of all investigated N‐(arylthio)phthalimides leads to the corresponding radical anions, followed by the ejection of the phthalimide anion resulting from the dissociation of the N−S chemical bond. This stepwise electron transfer mechanism is evidenced by the electrochemical data which allow determination of the standard reduction potentials of all compounds. In the formation of the N‐(arylthio)phthalimide radical anions, the theoretical calculations show that the incoming electron, is hosted by the phthalimidyl group indicating a homolytic dissociation mechanism. The dissociation rate constants of the radical anions are deduced and show that upon changing the substituent from the MeO, to Me, H, F, Cl and Br the dissociation becomes faster. A good correlation with the Hammett substituent constants is also obtained. Application of Savéant's theory through determination of the associated driving force and the intrinsic barrier energies help rationalize the observed results and show that the change in the dissociation rate constant depends mainly on the standard reduction potential of the parent compounds.

Benzophenones (BPs) frequently occur in water environments, and they are able to both screen UV light and to sensitize reactive intermediate (RI) production. However, BPs have largely been overlooked as a background water component when studying photodegradation of co-existing organic micropollutants (OMPs). Therefore, in this study, we investigated the influence of BP and its derivative oxybenzone (BP3) on the degradation of the co-existing model OMP sulfamethoxazole (SMX). A series of photodegradation experiments were conducted covering a range of BPs concentrations in μg/L levels, and the degradation of 1.00 μM of SMX was studied. The addition of BP at 0.10 μM, 0.25 μM, and 0.30 μM, and BP3 at 0.10 μM and 0.25 μM, significantly increased the first order degradation rate constant of 1.00 μM of SMX (kobs(BP)) by 36.2%, 50.0%, 7.3%, 31.5%, and 36.2% respectively, compared to that in the absence of any BPs. The maximum indirect photodegradation induced by BP and BP3 reached 33.8% and 27.7%, respectively, as a percentage of the observed SMX degradation rate at the [BPs]/[SMX] ratio of 0.25. In general, triplet excited dissolved organic matter (3SMX*, 3BP*, and 3BP3*) played the major role in the photosensitizing ability of BPs. The results further implied that the increase of SMX degradation at the molar ratio of 0.25 was possibly due to 3BP* for the mixture of SMX and BP. Overall, this study revealed the sensitizing ability of BP and BP3 on the co-existing OMP, SMX, in water for the first time. Our findings can be applied to other BP type UV filters which are similar to BP and PB3 in molecular structure.

Phycocolloids have aroused research interest due to their remarkable functional properties, including immunostimulatory and antioxidant activities. In this study, the yield of Centroceras clavulatum sulfated polysaccharides (CCSP) was 4.36% and had a sulfate content of 9.42%. The main monosaccharide units of CCSP were galactose (25.23 ± 0.81 mg/l) and glucose (4.32 ± 0.31 mg/l). Specifically, FT-IR spectrum of CCSP revealed a peak at 843 cm−1 which indicates the occurrence of sulfate groups on C-4 of galactose. CCSP stimulated Carp Leukocyte Culture (CLC) cell line to generate reactive oxygen species (ROS) and nitric oxide (NO) in a dose-dependent manner. Remarkably, exposure of CLC cells to CCSP at a dose of 12.5 µg/ml significantly increased superoxide dismutase activity and reduced malondialdehyde level. These results suggest that CCSP could stimulate CLC cells without compromising the intracellular antioxidant system, hence, may have potential applications as nutraceuticals.

Comprehensive Summary: Knowledge of asymmetric catalytic reaction mechanism is very important for rational design and synthesis of new chiral catalysts or catalytic systems with high catalytic activity and stereoselectivity. The studies of nonlinear effect have attracted wide attentions as a simple and practical mechanistic tool to probe complex asymmetric catalytic reactions. This review documents the application of the study of nonlinear effects on how to reveal the mechanism in asymmetric catalytic reactions that were catalyzed by the first‐row transition‐metals in the last decade and gives a brief discussion on the different models of nonlinear effect. [ABSTRACT FROM AUTHOR]

On‐surface synthesis is at the verge of emerging as the method of choice for the generation and visualization of unstable or unconventional molecules, which could not be obtained via traditional synthetic methods. A case in point is the on‐surface synthesis of the structurally elusive cyclotriphosphazene (P3N3), an inorganic aromatic analogue of benzene. Here, we report the preparation of this fleetingly existing species on Cu(111) and Au(111) surfaces at 5.2 K through molecular manipulation with unprecedented precision, i.e. voltage pulse‐induced sextuple dechlorination of an ultra‐small (about 6 Å) hexachlorophosphazene P3N3Cl6 precursor by the tip of a scanning probe microscope. Real‐space atomic‐level imaging of cyclotriphosphazene reveals its planar D3h‐symmetric ring structure. Furthermore, this demasking strategy has been expanded to generate cyclotriphosphazene from a hexaazide precursor P3N21 via a different stimulation method (photolysis) for complementary measurements by matrix isolation infrared and ultraviolet spectroscopy. [ABSTRACT FROM AUTHOR]

On‐surface synthesis is at the verge of emerging as the method of choice for the generation and visualization of unstable or unconventional molecules, which could not be obtained via traditional synthetic methods. A case in point is the on‐surface synthesis of the structurally elusive cyclotriphosphazene (P3N3), an inorganic aromatic analogue of benzene. Here, we report the preparation of this fleetingly existing species on Cu(111) and Au(111) surfaces at 5.2 K through molecular manipulation with unprecedented precision, i.e. voltage pulse‐induced sextuple dechlorination of an ultra‐small (about 6 Å) hexachlorophosphazene P3N3Cl6 precursor by the tip of a scanning probe microscope. Real‐space atomic‐level imaging of cyclotriphosphazene reveals its planar D3h‐symmetric ring structure. Furthermore, this demasking strategy has been expanded to generate cyclotriphosphazene from a hexaazide precursor P3N21 via a different stimulation method (photolysis) for complementary measurements by matrix isolation infrared and ultraviolet spectroscopy. [ABSTRACT FROM AUTHOR]

The synthesis of [n]cycloparaphenylenes ([n]CPPs) and similar nanohoops is usually based on combining building blocks to a macrocyclic precursor, which is then aromatized in the final step. Access to those building blocks in large amounts will simplify the synthesis and studies of CPPs as novel functional materials for applications. Herein, we report a continuous‐flow synthesis of key CPP building blocks by using versatile synthesis techniques such as electrochemical oxidation, lithiations and Suzuki cross‐couplings in self‐built reactors on up‐to kilogram scale. [ABSTRACT FROM AUTHOR]

On‐surface synthesis is at the verge of emerging as the method of choice for the generation and visualization of unstable or unconventional molecules, which could not be obtained via traditional synthetic methods. A case in point is the on‐surface synthesis of the structurally elusive cyclotriphosphazene (P3N3), an inorganic aromatic analogue of benzene. Here, we report the preparation of this fleetingly existing species on Cu(111) and Au(111) surfaces at 5.2 K through molecular manipulation with unprecedented precision, i.e. voltage pulse‐induced sextuple dechlorination of an ultra‐small (about 6 Å) hexachlorophosphazene P3N3Cl6 precursor by the tip of a scanning probe microscope. Real‐space atomic‐level imaging of cyclotriphosphazene reveals its planar D3h‐symmetric ring structure. Furthermore, this demasking strategy has been expanded to generate cyclotriphosphazene from a hexaazide precursor P3N21 via a different stimulation method (photolysis) for complementary measurements by matrix isolation infrared and ultraviolet spectroscopy. [ABSTRACT FROM AUTHOR]

On‐surface synthesis is at the verge of emerging as the method of choice for the generation and visualization of unstable or unconventional molecules, which could not be obtained via traditional synthetic methods. A case in point is the on‐surface synthesis of the structurally elusive cyclotriphosphazene (P3N3), an inorganic aromatic analogue of benzene. Here, we report the preparation of this fleetingly existing species on Cu(111) and Au(111) surfaces at 5.2 K through molecular manipulation with unprecedented precision, i.e. voltage pulse‐induced sextuple dechlorination of an ultra‐small (about 6 Å) hexachlorophosphazene P3N3Cl6 precursor by the tip of a scanning probe microscope. Real‐space atomic‐level imaging of cyclotriphosphazene reveals its planar D3h‐symmetric ring structure. Furthermore, this demasking strategy has been expanded to generate cyclotriphosphazene from a hexaazide precursor P3N21 via a different stimulation method (photolysis) for complementary measurements by matrix isolation infrared and ultraviolet spectroscopy. [ABSTRACT FROM AUTHOR]

Herein, we report a minimalistic protocol for the solvent‐free, mechanochemical difluoromethylation of (thio)phenols and N‐heteroarenes using non‐ozone depleting chlorodifluoromethyl phenyl sulfone as a difluorocarbene source. This mechanochemical difluoromethylation features a short reaction time, excellent functional group tolerance, and compatibility with complex biologically active scaffolds. [ABSTRACT FROM AUTHOR]

Alternating current (AC) electrolysis is an emerging field in synthetic chemistry, however its mechanistic studies are challenged by the effective characterization of the elusive intermediate processes. Herein, we develop an operando electrochemical mass spectrometry platform that allows time‐resolved mapping of stepwise electrosynthetic reactive intermediates in both direct current and alternating current modes. By dissecting the key intermediate processes of electrochemical functionalization of arylamines, the unique reactivities of AC electrosynthesis, including minimizing the over‐oxidation/reduction through the inverse process, and enabling effective reaction of short‐lived intermediates generated by oxidation and reduction in paired electrolysis, were evidenced and verified. Notably, the controlled kinetics of reactive N‐centered radical intermediates in multistep sequential AC electrosynthesis to minimize the competing reactions was discovered. Overall, this work provides direct evidence for the mechanism of AC electrolysis, and clarifies the underlying reasons for its high efficiency, which will benefit the rational design of AC electrosynthetic reactions. [ABSTRACT FROM AUTHOR]

Over decades diazoalkenes (R2C=C=N2) were postulated as reactive intermediates in organic chemistry even though their direct spectroscopic detection proved very challenging. In the 1970/80ies several groups probed their existence mainly indirectly by trapping experiments or directly by matrix‐isolation studies. In 2021, our group and the Severin group reported independently the synthesis and characterization of the first room‐temperature stable diazoalkenes, which initiated a rapidly expanding research field. Up to now four different classes of N‐heterocyclic substituted room‐temperature stable diazoalkenes have been reported. Their properties and unique reactivity, such as N2/CO exchange or utilization as vinylidene precursors in organic and transition metal chemistry are presented. This review summarizes the early discoveries of diazoalkenes from their initial postulation as transient, elusive species up to the recent findings of the room‐temperature stable derivatives. [ABSTRACT FROM AUTHOR]

Glutathione transferases (GSTs) are a class of phase II detoxifying enzymes catalysing the conjugation of glutathione (GSH) to endogenous and exogenous electrophilic molecules, with microsomal glutathione transferase 1 (MGST1) being one of its key members. MGST1 forms a homotrimer displaying third‐of‐the‐sites‐reactivity and up to 30‐fold activation through modification of its Cys‐49 residue. It has been shown that the steady‐state behaviour of the enzyme at 5 °C can be accounted for by its pre‐steady‐state behaviour if the presence of a natively activated subpopulation (~ 10%) is assumed. Low temperature was used as the ligand‐free enzyme is unstable at higher temperatures. Here, we overcame enzyme lability through stop‐flow limited turnover analysis, whereby kinetic parameters at 30 °C were obtained. The acquired data are more physiologically relevant and enable confirmation of the previously established enzyme mechanism (at 5 °C), yielding parameters relevant for in vivo modelling. Interestingly, the kinetic parameter defining toxicant metabolism, kcat/KM, is strongly dependent on substrate reactivity (Hammett value 4.2), underscoring that glutathione transferases function as efficient and responsive interception catalysts. The temperature behaviour of the enzyme was also analysed. Both the KM and KD values decreased with increasing temperature, while the chemical step k3 displayed modest temperature dependence (Q10: 1.1–1.2), mirrored in that of the nonenzymatic reaction (Q10: 1.1–1.7). Unusually high Q10 values for GSH thiolate anion formation (k2: 3.9), kcat (2.7–5.6) and kcat/KM (3.4–5.9) support that large structural transitions govern GSH binding and deprotonation, which limits steady‐state catalysis. [ABSTRACT FROM AUTHOR]

A small-molecule cysteine sulfenic acid (Cys–SOH) was synthesized and isolated as stable crystals, for the first time, by utilizing a nanosized molecular cavity as a protective cradle. The cradled Cys–SOH was synthesized by direct oxidation of the corresponding cysteine thiol with H2O2 under basic conditions and its structure was established by X-ray crystallographic analysis. In the reaction of the cradled Cys–SOH with a thiol to produce the disulfide, a remarkable acceleration was observed upon the addition of an amine base. This suggests the important role of base in the reaction of Cys–SOH with thiols in biological systems. The cradled Cys–SOH was reduced to the cysteine thiol by dithiothreitol or triphenylphosphine. The high stability and sufficient reactivity of the cradled Cys–SOH indicate its usefulness as a small-molecule model compound for better understanding the chemical behavior of Cys–SOH in biological systems. [ABSTRACT FROM AUTHOR]

Benzophenones (BPs) frequently occur in water environments, and they are able to both screen UV light and to sensitize reactive intermediate (RI) production. However, BPs have largely been overlooked as a background water component when studying photodegradation of co-existing organic micropollutants (OMPs). Therefore, in this study, we investigated the influence of BP and its derivative oxybenzone (BP3) on the degradation of the co-existing model OMP sulfamethoxazole (SMX). A series of photodegradation experiments were conducted covering a range of BPs concentrations in μg/L levels, and the degradation of 1.00 μM of SMX was studied. The addition of BP at 0.10 μM, 0.25 μM, and 0.30 μM, and BP3 at 0.10 μM and 0.25 μM, significantly increased the first order degradation rate constant of 1.00 μM of SMX (kobs(BP)) by 36.2%, 50.0%, 7.3%, 31.5%, and 36.2% respectively, compared to that in the absence of any BPs. The maximum indirect photodegradation induced by BP and BP3 reached 33.8% and 27.7%, respectively, as a percentage of the observed SMX degradation rate at the [BPs]/[SMX] ratio of 0.25. In general, triplet excited dissolved organic matter (3SMX*, 3BP*, and 3BP3*) played the major role in the photosensitizing ability of BPs. The results further implied that the increase of SMX degradation at the molar ratio of 0.25 was possibly due to 3BP* for the mixture of SMX and BP. Overall, this study revealed the sensitizing ability of BP and BP3 on the co-existing OMP, SMX, in water for the first time. Our findings can be applied to other BP type UV filters which are similar to BP and PB3 in molecular structure. [ABSTRACT FROM AUTHOR]

Fenebrutinib is an orally available Bruton tyrosine kinase inhibitor. It is currently in multiple phase III clinical trials for the management of B-cell tumors and autoimmune disorders. Elementary in-silico studies were first performed to predict susceptible sites of metabolism and structural alerts for toxicities by StarDrop WhichP450™ module and DEREK software; respectively. Fenebrutinib metabolites and adducts were characterized in-vitro in rat liver microsomes (RLM) using MS3 method in Ion Trap LC-MS/MS. Formation of reactive and unstable intermediates was explored using potassium cyanide (KCN), glutathione (GSH) and methoxylamine as trapping nucleophiles to capture the transient and unstable iminium, 6-iminopyridin-3(6H)-one and aldehyde intermediates, respectively, to generate a stable adducts that can be investigated and analyzed using mass spectrometry. Ten phase I metabolites, four cyanide adducts, five GSH adducts and six methoxylamine adducts of fenebrutinib were identified. The proposed metabolic reactions involved in formation of these metabolites are hydroxylation, oxidation of primary alcohol to aldehyde, n-oxidation, and n-dealkylation. The mechanism of reactive intermediate formation of fenebrutinib can provide a justification of the cause of its adverse effects. Formation of iminium, iminoquinone and aldehyde intermediates of fenebrutinib was characterized. N-dealkylation followed by hydroxylation of the piperazine ring is proposed to cause the bioactivation to iminium intermediates captured by cyanide. Oxidation of the hydroxymethyl group on the pyridine moiety is proposed to cause the generation of reactive aldehyde intermediates captures by methoxylamine. N-dealkylation and hydroxylation of the pyridine ring is proposed to cause formation of iminoquinone reactive intermediates captured by glutathione. FBB and several phase I metabolites are bioactivated to fifteen reactive intermediates which might be the cause of adverse effects. In the future, drug discovery experiments utilizing this information could be performed, permitting the synthesis of new drugs with better safety profile. Overall, in silico software and in vitro metabolic incubation experiments were able to characterize the FBB metabolites and reactive intermediates using the multistep fragmentation capability of ion trap mass spectrometry. [ABSTRACT FROM AUTHOR]

Recently, stable diazoalkenes have received significant attention as a new substance class in organic chemistry. While their previous synthetic access was exclusively limited to the activation of nitrous oxide, we here establish a much more general synthetic approach utilizing a Regitz‐type diazo transfer with azides. Importantly, this approach is also applicable to weakly polarized olefins such as 2‐pyridine olefins. The new pyridine diazoalkenes are not accessible by the activation of nitrous oxide, allowing for a considerable extension of the scope of this only recently accessed functional group. The new diazoalkene class has properties distinct from the previously reported classes, such as photochemically triggered loss of dinitrogen affording cumulenes and not C−H insertion products. Pyridine‐derived diazoalkenes represent the so far least polarized stable diazoalkene class reported. [ABSTRACT FROM AUTHOR]

Native reactive electrophilic species (RES) are long‐recognized regulators of pathophysiology; yet, knowledge surrounding how RES regulate context‐specific biology remains limited. The latest technological advances in profiling and precision decoding of RES sensing and signaling have begun to bring about improved understanding of localized RES regulatory paradigms. However, studies in purified systems — prerequisites for gaining structure/function insights — prove challenging. We here introduce emerging chemical biology tools available to probe RES signaling, and the new knowledge that these tools have brought to the field. We next discuss existing structural data of RES‐sensor proteins complexed with electrophilic metabolites or small molecule drugs (limited to <300 Da), including challenges faced in acquiring homogenous RES‐bound proteins. We further offer considerations that could promote enhanced understanding of RES regulation derived from three‐dimensional structures of RES‐modified proteins. [ABSTRACT FROM AUTHOR]

Visible‐light photocatalysis provides numerous useful methodologies for synthetic organic chemistry. However, the mechanisms of these reactions are often not fully understood. Common mechanistic experiments mainly aim to characterize excited state properties of photocatalysts and their interaction with other species. Recently, in situ reaction monitoring using dedicated techniques was shown to be well‐suited for the identification of intermediates and to obtain kinetic insights, thereby providing more holistic pictures of the reactions of interest. This minireview surveys these technologies and discusses selected examples where reaction monitoring was used to elucidate the mechanism of photocatalytic reactions. [ABSTRACT FROM AUTHOR]

Electrochemically reducing CO2 to valuable fuels or feedstocks is recognized as a promising strategy to simultaneously tackle the crises of fossil fuel shortage and carbon emission. Sn‐based catalysts have been widely studied for electrochemical CO2 reduction reaction (CO2RR) to make formic acid/formate, which unfortunately still suffer from low activity, selectivity and stability. In this work, halogen (F, Cl, Br or I) was introduced into the Sn catalyst by a facile hydrolysis method. The presence of halogen was confirmed by a collection of ex situ and in situ characterizations, which rendered a more positive valence state of Sn in halogen‐incorporated Sn catalyst as compared to unmodified Sn under cathodic potentials in CO2RR and therefore tuned the adsorption strength of the key intermediate (*OCHO) toward formate formation. As a result, the halogen‐incorporated Sn catalyst exhibited greatly enhanced catalytic performance in electrochemical CO2RR to produce formate. [ABSTRACT FROM AUTHOR]

Electrochemically reducing CO2 to valuable fuels or feedstocks is recognized as a promising strategy to simultaneously tackle the crises of fossil fuel shortage and carbon emission. Sn‐based catalysts have been widely studied for electrochemical CO2 reduction reaction (CO2RR) to make formic acid/formate, which unfortunately still suffer from low activity, selectivity and stability. In this work, halogen (F, Cl, Br or I) was introduced into the Sn catalyst by a facile hydrolysis method. The presence of halogen was confirmed by a collection of ex situ and in situ characterizations, which rendered a more positive valence state of Sn in halogen‐incorporated Sn catalyst as compared to unmodified Sn under cathodic potentials in CO2RR and therefore tuned the adsorption strength of the key intermediate (*OCHO) toward formate formation. As a result, the halogen‐incorporated Sn catalyst exhibited greatly enhanced catalytic performance in electrochemical CO2RR to produce formate. [ABSTRACT FROM AUTHOR]

Anionic polymerizations are of exceptional practical importance, but difficult to analyze due to the high reactivity of the growing polymer chains. Here, we demonstrate that electrospray‐ionization mass spectrometry (ESI‐MS) permits direct observation of the active carbanionic intermediates formed in the anionic ring‐opening polymerization of 1‐cyanocyclopropanecarboxylate in tetrahydrofuran. This includes the identification of a side product, as well as real‐time analysis of the polymerization reaction. From the mass spectra obtained, we can derive not only the mean molar mass and the polydispersity, but also the rate constants for the initiation and the individual propagation steps. The initiation proceeds significantly faster than the propagation steps. Accordingly, the examined reaction corresponds to a living polymerization, as we also confirmed by additional control experiments. Besides giving detailed insight into the reaction system probed here, we also expect the presented methodology to make possible the in‐situ analysis of further anionic polymerizations. [ABSTRACT FROM AUTHOR]

Two-dimensional black phosphorus (BP) has emerged as a perspective material for various micro- and opto-electronic, energy, catalytic, and biomedical applications. Chemical functionalization of black phosphorus nanosheets (BPNS) is an important pathway for the preparation of materials with improved ambient stability and enhanced physical properties. Currently, the covalent functionalization of BPNS with highly reactive intermediates, such as carbon-free radicals or nitrenes, has been widely implemented to modify the material's surface. However, it should be noted that this field requires more in-depth research and new developments. Herein, we report for the first time the covalent carbene functionalization of BPNS using dichlorocarbene as a functionalizing agent. The P–C bond formation in the obtained material (BP–CCl2) has been confirmed by Raman, solid-state 31P NMR, IR, and X-ray photoelectron spectroscopy methods. The BP–CCl2 nanosheets exhibit an enhanced electrocatalytic hydrogen evolution reaction (HER) performance with an overpotential of 442 mV at −1 mA cm−2 and a Tafel slope of 120 mV dec−1, outperforming the pristine BPNS. [ABSTRACT FROM AUTHOR]

Spebrutinib is a new Bruton tyrosine kinase inhibitor developed by Avila Therapeutics and Celgene. Spebrutinib (SPB) is currently in phase Ib clinical trials for the treatment of lymphoma in the United States. Preliminary in-silico studies were first performed to predict susceptible sites of metabolism, reactivity pathways and structural alerts for toxicities by StarDrop WhichP450™ module, Xenosite web predictor tool and DEREK software; respectively. SPB metabolites and adducts were characterized in vitro from rat liver microsomes (RLM) using LC-MS/MS. Formation of reactive intermediates was investigated using potassium cyanide (KCN), glutathione (GSH) and methoxylamine as trapping nucleophiles for the unstable and reactive iminium, iminoquinone and aldehyde intermediates, respectively, with the aim to produce stable adducts that can be detected and characterized using mass spectrometry. Fourteen phase I metabolites, four cyanide adducts, six GSH adducts and three methoxylamine adducts of SPB were identified and characterized. The proposed metabolic pathways involved in generation of phase I metabolites of SPB are oxidation, hydroxylation, o-dealkylation, epoxidation, defluorination and reduction. Several in vitro reactive intermediates were identified and characterized, the formation of which can aid in explaining the adverse drug reactions of SPB. Several iminium, 2-iminopyrimidin-5(2H)-one and aldehyde intermediates of SPB were revealed. Acrylamide is identified as a structural alert for toxicity by DEREK report and was found to be involved in the formation of several glycidamide and aldehyde reactive intermediates.

β-Hydrazonophosphine oxides are precursors of useful organophosphorus compounds, including phosphorylated N-heterocycles, α-aminophosphonates, and vinylphosphonates. In this work, a general transition metal-free synthesis of β-hydrazonophosphine oxides was developed. The method relies on the Michael addition of phosphine oxides R2P(O)H to reactive azoalkenes (1,2-diaza-1,3-butadienes), which are generated in situ from α-halohydrazones and Hunig’s base. The reaction stereoselectively leads to Z-isomers of β-hydrazonophosphine oxides that are stabilized by intramolecular hydrogen bonding. The conversion of the products thus obtained into potential chelating ligands was showcased.

Comprehensive Summary: The discovery of Kahne glycosylation forwards a big step in the carbohydrate chemistry. Despite an extensive series of studies, the precise mechanism of this powerful glycosylation is still not fully understood. To address these 30‐year puzzles, the far side of Kahne glycosylation is explored in this study. After a series of control and tracking experiments, a number of important intermediates including glycosyl oxo‐sulfonium ion and sulfenic anhydride (Crich's intermediate) are suggested to be responsible for the complex reaction pathway. It also reveals that in addition to the conventional ionic glycosylation pathway, a novel free radical pathway is very likely to contribute to the various side‐and co‐products. This study provides further understanding of Kahne glycosylation, and it also sheds light on how to improve the efficiency of sulfoxide‐based glycosylation reactions. [ABSTRACT FROM AUTHOR]

In many metalloenzymes, sulfur‐containing ligands participate in catalytic processes, mainly via the involvement in electron transfer reactions. In a biomimetic approach, we now demonstrate the implication of S‐ligation in cobalt mediated oxygen reduction reactions (ORR). A comparative study between the catalytic ORR capabilities of the four‐nitrogen bound [Co(cyclam)]2+ (1; cyclam=1,5,8,11‐tetraaza‐cyclotetradecane) and the S‐containing analog [Co(S2N2‐cyclam)]2+ (2; S2N2‐cyclam=1,8‐dithia‐5,11‐diaza‐cyclotetradecane) reveals improved catalytic performance once the chalcogen is introduced in the Co coordination sphere. Trapping and characterization of the intermediates formed upon dioxygen activation at the CoII centers in 1 and 2 point to the involvement of sulfur in the O2 reduction process as the key for the improved catalytic ORR capabilities of 2. [ABSTRACT FROM AUTHOR]

Thiourea S‐oxides can be viewed as formal analogs of the currently unknown diamino‐substituted Criegee intermediates (urea O‐oxides). However, the preparation of such S‐oxides is rather challenging, and the direct oxidation of thioureas typically only leads to formation of desulfurized products. Employing the accurate revDSD‐PBEP86‐D4 double hybrid density functional, it was found that the peracid mediated oxidation of thiourea S‐oxides exhibits a lower reaction barrier than the oxidation of the corresponding thiourea itself in contrast to most other ordinary thioketones. The undesired overoxidation reactivity, which is associated with strong π‐donation from the thiourea's nitrogen atoms, can be partially suppressed by introduction of bulky substituents and the utilization of protic solvents. In this regard, we managed to prepare two sterically encumbered thiourea S‐oxides in isolated yields of 35–40 %. The S‐oxides are stable in the solid state and in alcoholic solutions at room temperature for extended periods of time, but swiftly decompose in aprotic solvents by disproportionation. A dimesityl‐substituted thiourea S‐oxide complexed with residual mCBA could be characterized by means of X‐ray crystallography, confirming the importance of hydrogen bonding in the stabilization of the amino‐substituted C=S+−O− moiety. [ABSTRACT FROM AUTHOR]