Unusual Reaction Research Articles

Perianal Pulse Granuloma Induced by Plant-Derived Baby Wipes.

Pulse granulomas are unusual foreign body reactions to exogenous plant material, featuring the presence of hyaline ring structures and granulomatous inflammation. Pulse granulomas have been reported to occur in the oral cavity, gastrointestinal tract, and respiratory tract. Cutaneous pulse granulomas are exceedingly rare. All reported cases have been closely associated with underlying pathology such as chronic inflammatory conditions, trauma, or surgical procedures which likely facilitated implantation of exogenous plant material. We report a novel case of a cutaneous pulse granuloma presenting in the perianal region of an otherwise healthy man. The authors propose that the source of the exogenous plant material is plant-derived baby wipes, which the patient had been using daily to the perianal region.

Hyperconjugation-Driven Isodesmic Reaction of Indoles and Anilines: Reaction Discovery, Mechanism Study, and Antitumor Application.

Isodesmic reactions, in which chemical bonds are redistributed between substrates and products, provide a general and powerful strategy for both biological and chemical synthesis. However, most isodesmic reactions involve either metathesis or functional-group transfer. Here, we serendipitously discovered a novel isodesmic reaction of indoles and anilines that proceeds intramolecularly under weakly acidic conditions. In this process, the five-membered ring of the indole motif is broken and a new indole motif is constructed on the aniline side, accompanied by the formation of a new aniline motif. Mechanistic studies revealed the pivotal role of σ→π* hyperconjugation on the nitrogen atom of the indole motif in driving this unusual isodesmic reaction. Furthermore, we successfully synthesized a diverse series of polycyclic indole derivatives; among quinolines, potential antitumor agents were identified using cellular and in vivo experiments, thereby demonstrating the synthetic utility of the developed methodology.

Interception of Alkynyl Tetracoordinate Borons with Sulfur Electrophiles beyond the Zweifel Pathway

Zweifel reaction is a powerful strategy to construct olefins from alkenyl tetracoordinate borons in organoboron chemistry, however, it usually only involves one functional group migration and then undergoes an elimination process affording alkenes or alkynes exclusively. Herein, we disclose several intriguing interception of alkynyl tetracoordinate borons with sulfur electrophiles. Wherein, the substituted benzothiophenes are accessed by consecutive 1,2‐migrations and intramolecular electrophilic substitution, meanwhile, the challenging and elusive five/four‐membered boracycles are easily assembled, and an approach to alkenyl sulfides with good stereoselectivity was developed as well. Moreover, by adding readily available deuterium sources, the tetrasubstituted deuterated alkenyl sulfides with high deuteration rates are constructed. These protocols not only improve atom economy by prohibiting the elimination of Zweifel intermediate, but also enriches the reaction modes of alkynyl tetracoordinate borons achieving versatile value‐added sulfur‐containing molecules. Mechanistic investigations illustrate that dichlorosulfoxide (SOCl2) and dialkylaminosulfur trifluoride‐type reagents (DAST‐type) as surfur sources could promote dual 1,2‐aryl migration of alkynyl tetracoordinate borons, which are distinct from traditional Zweifel reaction, and the regulation of steric hindrance could also make four‐membered boracycles and alkenyl sulfides feasible. And these transformations feature novel reaction modes and unusual reaction mechanisms with valuable products in high efficiency.

Interception of Alkynyl Tetracoordinate Borons with Sulfur Electrophiles beyond the Zweifel Pathway.

Zweifel reaction is a powerful strategy to construct olefins from alkenyl tetracoordinate borons in organoboron chemistry, however, it usually only involves one functional group migration and then undergoes an elimination process affording alkenes or alkynes exclusively. Herein, we disclose several intriguing interception of alkynyl tetracoordinate borons with sulfur electrophiles. Wherein, the substituted benzothiophenes are accessed by consecutive 1,2-migrations and intramolecular electrophilic substitution, meanwhile, the challenging and elusive five/four-membered boracycles are easily assembled, and an approach to alkenyl sulfides with good stereoselectivity was developed as well. Moreover, by adding readily available deuterium sources, the tetrasubstituted deuterated alkenyl sulfides with high deuteration rates are constructed. These protocols not only improve atom economy by prohibiting the elimination of Zweifel intermediate, but also enriches the reaction modes of alkynyl tetracoordinate borons achieving versatile value-added sulfur-containing molecules. Mechanistic investigations illustrate that dichlorosulfoxide (SOCl2) and dialkylaminosulfur trifluoride-type reagents (DAST-type) as surfur sources could promote dual 1,2-aryl migration of alkynyl tetracoordinate borons, which are distinct from traditional Zweifel reaction, and the regulation of steric hindrance could also make four-membered boracycles and alkenyl sulfides feasible. And these transformations feature novel reaction modes and unusual reaction mechanisms with valuable products in high efficiency.

Immediate allergies to chlorhexidine: A series of pediatric cases from the French pharmacovigilance database: Immediate allergies to chlorhexidine: series of pediatric cases from the French pharmacovigilance database

BackgroundImmediate allergic reactions to chlorhexidine have been clearly identified in numerous countries, generating governmental warnings worldwide. ObjectivesThe aim of our study was to characterize (i) these allergies, which are less reported in pediatric populations, and (ii) the patient-at-risk profile so as to suggest preventive measures. MethodsIn association with the allergy department and the regional pharmacovigilance center in Rennes University Hospital, France, a multicenter retrospective, descriptive, and observational study was conducted using data from the national pharmacovigilance database for the period of January 1, 2010 to June 30, 2020. Immediate allergies to chlorhexidine cases based on a clinical history compatible with an immunoglobulin E (IgE)-mediated reaction, along with positive allergic testing, were analyzed. ResultsOf the 478 cases identified, 17 pediatric cases of immediate allergic reaction to chlorhexidine (13 cases of grades II–IV anaphylaxis) were retained for the analysis. For 58.8 % of these cases, a history of a previous more moderate reaction to the substance was identified. The reactions occurred most frequently in cases of domestic misuse (88.2 %, n = 15/17) of chlorhexidine to dress a wound. Recurrence was reported for two cases, later leading to severe reactions at each new exposure to the allergen, suggesting an aggravation mechanism. ConclusionThe number of pediatric cases of immediate allergies to chlorhexidine has possibly been underestimated on account of insufficient knowledge of the allergy and in view of its common usage. Information on the method of caring for wounds among children and on the risk of allergic sensitization as well as exploring any unusual reaction to chlorhexidine application could reduce the number of allergic reactions.

Pd/Cu Dual Catalysis for the Oxidative Dearomatization of PyrroleDerivatives: Mechanistic Insights and Biological Studies

AbstractHerein we report dearomatization of pyrrole ring followed by rearomatization of cyclohexyl ring to obtain isoindolinone scaffold by a Pd/Cu dual catalysis approach in an atom economic way with moderate to high yield. The expected Pd/Cu catalyzed dual C(sp2)‐H activation via normal catalytic cycle can be override by unusual oxidative dearomatization reaction which has been established by DFT calculation. The biological importance of isoindolinone scaffold insists us to successfully investigate in vitro antileishmanial activity of L.Donovani.

Henkel‐like Decarboxylation Produces Mononuclear Arylalkalis, [4‐(CH3)3N(C6H4)M]+ which Hydrolyse and Undergo Surprising SN2 Reactions Between Alkali Hydroxides and (CH3)3NC6H5+

AbstractBenzoate substituted with a cationic quaternary ammonium group at the para‐position, [4‐(CH3)3N(C6H4)CO2], forms mononuclear alkali metal ion complexes, [4‐(CH3)3N(C6H4)CO2M]+ (M=Li, Na, K, Rb and Cs), which are observed by electrospray‐ionisation mass spectrometry. When mass selected and subjected to collision‐induced dissociation each of these complexes undergoes decarboxylation to produce the mononuclear arylalkali complex cations, [4‐(CH3)3N(C6H4)M]+, which subsequently react with water via hydrolysis to yield the quaternary ammonium cation, (CH3)3NC6H5+. The unexpected product ions, [M((CH3)2NC6H5)]+, [M(CH3OH)]+, and M+, which are associated with the hydrolysis pathway, suggest an unusual reaction occurring within the exit channel ion‐molecule complex, [(CH3)3NC6H5+MOH]+. DFT calculations were used to examine the: decarboxylation reaction of [4‐(CH3)3N(C6H4)CO2M]+, which readily proceeds via a four‐centred transition state; the hydrolysis and SN2 reactions accounting for formation of products in the exit channel, which are connected via a roaming mechanism in which the metal hydroxide moiety migrates from the para‐hydrogen of (CH3)3NC6H5+ to one of the methyl groups.

Detoxification Mechanism of Hinokitiol by Alternaria alternata and Its Application in Agricultural Antifungal Control.

Alternaria alternata is a common plant pathogen that can infect crops and reduce their production. In this work, an antagonism experiment between A. alternata and the essential oil of arborvitae (Platycladus orientalis) was performed, and it was proven that A. alternata had developed resistance to this plant-derived fungicide. A. alternata facilitated the biotransformation of hinokitiol (1), the main antifungal compound in the essential oil of arborvitae, into (R)-2-hydroxy-β-methylbenzeneethanol (2), which does not have antifungal activity against A. alternata. This biotransformation is an unusual ring-contraction reaction that was verified to be catalyzed by P450 enzyme hydroxylation and Baeyer-Villiger oxidation. In addition, the P450 enzyme inhibitors 1-aminobenzotriazole and piperonyl butoxide effectively prevented the destruction of the hinokitiol structure by A. alternata, and the combined use of these P450 enzyme inhibitors significantly increased the antifungal activity of hinokitiol. This work provides a theoretical reference for the further development of botanical fungicides.

Synthesis of Alkene Atropisomers with Multiple Stereogenic Elements via Catalytic Asymmetric Rearrangement of 3‐Indolylmethanols

AbstractCatalytic enantioselective preparation of alkene atropisomers with multiple stereogenic elements and discovery of their applications have become significant but challenging issues in the scientific community due to the unique structures of this class of atropisomers. We herein report the first catalytic atroposelective preparation of cyclopentenyl[b]indoles, a new kind of alkene atropisomers, with stereogenic point and axial chirality via an unusual rearrangement reaction of 3‐indolylmethanols under asymmetric organocatalysis. Notably, this novel type of alkene atropisomers have promising applications in developing chiral ligands or organocatalysts, discovering antitumor drug candidates and fluorescence imaging materials. Moreover, the theoretical calculations have elucidated the possible reaction mechanism and the non‐covalent interactions to control the enantioselectivity. This approach offers a new synthetic strategy for alkene atropisomers with multiple stereogenic elements, and represents the first catalytic enantioselective rearrangement reaction of 3‐indolylmethanols, which will advance the chemistry of atropisomers and chiral indole chemistry.

Synthesis of Alkene Atropisomers with Multiple Stereogenic Elements via Catalytic Asymmetric Rearrangement of 3-Indolylmethanols.

Catalytic enantioselective preparation of alkene atropisomers with multiple stereogenic elements and discovery of their applications have become significant but challenging issues in the scientific community due to the unique structures of this class of atropisomers. We herein report the first catalytic atroposelective preparation of cyclopentenyl[b]indoles, a new kind of alkene atropisomers, with stereogenic point and axial chirality via an unusual rearrangement reaction of 3-indolylmethanols under asymmetric organocatalysis. Notably, this novel type of alkene atropisomers have promising applications in developing chiral ligands or organocatalysts, discovering antitumor drug candidates and fluorescence imaging materials. Moreover, the theoretical calculations have elucidated the possible reaction mechanism and the non-covalent interactions to control the enantioselectivity. This approach offers a new synthetic strategy for alkene atropisomers with multiple stereogenic elements, and represents the first catalytic enantioselective rearrangement reaction of 3-indolylmethanols, which will advance the chemistry of atropisomers and chiral indole chemistry.

Pyridine-Catalyzed Chemoselective Four-Component Cascade Reaction of Aromatic Aldehydes, Malononitrile/Cyanoacetates, MBH Carbonates, and Alcohols.

An efficient pyridine-catalyzed chemoselective four-component cascade reaction of aromatic aldehydes, malononitrile/cyanoacetates, Morita-Baylis-Hillman (MBH) carbonates, and alcohols has been established. This one-pot reaction progressed in an unusual reaction with solvent participation via a Knoevenagel condensation/oxa-Michael addition/SN2' substitution sequence. This method allowed for facile access to an array of functionalized chain alkylbenzenes and dihydroquinolinones bearing one all-carbon quaternary center in moderate to excellent yields. It is worth noting that the configuration of the all-carbon quaternary center could be modulated by changing only the electron-withdrawing groups via a tandem reduction/cyclization reaction.

Nimesulide-induced Erythema Multiforme Major: A Case Report

Erythema Multiforme Major (EMM) is a rare hypersensitivity reaction that primarily affects the skin and mucosa, typically self-limiting. This case discusses a patient who developed severe EMM lesions after consuming nimesulide, a non-steroidal anti-inflammatory drug (NSAID), for abdominal discomfort. Patient was admitted to the hospital, the drug was discontinued, and supportive measures such as pain management and fluid replacement were initiated. This case, being the first to identify nimesulide as a possible trigger for EMM, aims to contribute to the growing body of knowledge on this topic. It emphasizes the need for vigilance and swift intervention for unusual drug reactions.

Novel fragrant aldehydes from (1R,5R)-sabinene: An experimental study supported by DFT calculations revealing an unusual hydroformylation mechanism

The fragrance industry continually searches for compounds that introduce new scent notes or improve existing ones. Herein, we report a methodology for obtaining two novel aldehydes, potentially interesting for application in fragrance formulations, via rhodium-catalyzed hydroformylation of (1R,5R)-sabinene, a biorenewable monoterpene available in many essential oils. One of the aldehydes, which retained the original sabinene skeleton, was derived from the hydroformylation of the exocyclic C-C double bond through the accepted hydroformylation mechanism. The other aldehyde arose from the interaction of rhodium with the cyclopropane ring through an unusual mechanism, which resulted in the cyclopropane ring cleavage, forming a product that shares structural similarities with established fragrant molecules. The selectivity was controlled by adjusting the reaction conditions (temperature, pressure, P-ligand, and P/Rh ratio). Each aldehyde was obtained in a 70–80 % yield, depending on the reaction conditions. Combining our experimental findings with DFT calculations allowed us to propose an unusual hydroformylation reaction mechanism involving cyclopropane moiety in vinylcyclopropanes.

Biochemical and structural elucidation of the L-carnitine degradation pathway of the human pathogen Acinetobacter baumannii.

Acinetobacter baumannii is an opportunistic human pathogen which can use host-derived L-carnitine as sole carbon and energy source. Recently, an L-carnitine transporter (Aci1347) and a specific monooxygense (CntA/CntB) for the intracellular cleavage of L-carnitine have been characterized. Subsequent conversion of the resulting malic semialdehyde into the central metabolite L-malate was hypothesized. Alternatively, L-carnitine degradation via D-malate with subsequent oxidation into pyruvate was proposed. Here we describe the in vitro and in vivo reconstitution of the entire pathway, starting from the as yet uncharacterized gene products of the carnitine degradation gene operon. Using recombinantly purified enzymes, enantiomer-specific formation of D-malate by the NAD(P)+-dependent malic semialdehyde dehydrogenase (MSA-DH) is demonstrated. The solved X-ray crystal structure of tetrameric MSA-DH reveals the key catalytic residues Cys290 and Glu256, accessible through opposing substrate and cofactor funnels. Specific substrate binding is enabled by Arg166, Arg284 and Ser447 while dual cofactor specificity for NAD+ and NADP+ is mediated by Asn184. The subsequent conversion of the unusual D-malate reaction product by an uncharacterized NAD+-dependent malate dehydrogenase (MDH) is shown. Tetrameric MDH is a β-decarboxylating dehydrogenase that synthesizes pyruvate. MDH experiments with alternative substrates showed a high degree of substrate specificity. Finally, the entire A. baumannni pathway was heterologously reconstituted, allowing E. coli to grow on L-carnitine as a carbon and energy source. Overall, the metabolic conversion of L-carnitine via malic semialdehyde and D-malate into pyruvate, CO2 and trimethylamine was demonstrated. Trimethylamine is also an important gut microbiota-dependent metabolite that is associated with an increased risk of cardiovascular disease. The pathway reconstitution experiments allowed us to assess the TMA forming capacity of gut microbes which is related to human cardiovascular health.

Elucidating the Mechanism of Solid-Electrolyte Interphase Formation in Hybrid Aqueous Zn-Ion Batteries

The formation of a favorable solid-electrolyte interphase (SEI) is essential to the reversible performance of zinc metal anodes in aqueous solutions. Thus far, it has been well agreed that the interphase layer should be passivating, ionically conductive, electronically insulating, and ideally self-repairable. When comprised of both organic and inorganic components, an SEI can effectively prevent hydrogen evolution reaction (HER) and corrosion on the metal surface, resulting in increased Coulombic efficiency and overall longevity. Here, we report the use of in-depth spectroscopic and electrochemical techniques to understand the unique solvation and decomposition of dimethyl carbonate (DMC) in high concentrated zinc water-in-salt electrolyte. Nuclear Magnetic Resonance (NMR) of both the liquid and solid states reveal an unusual dual reaction pathway that allows for the formation of a hybrid organic/inorganic SEI capable of achieving unprecedented capacity retention for zinc metal batteries.

A quantum mechanistic investigation into the unusual reactions of nitrilimine and nitrile oxide with 2,3,4,5-tetraphenylcyclopentadienone.

The theoretical study investigates the [3 + 2] cycloaddition (32CA) reactions between C, N-diphenyl nitrilimine with 2,3,4,5-tetraphenylcyclopentadienone and benzonitrile oxide with 2,3,4,5-tetraphenylcyclopentadienone. Nitrilimines and nitrile oxides are dipoles used in the synthesis of several heterocyclic compounds, including spiropyrazoline oxindoles and isoxazolines. The derivatives of these compounds are found with different biological activities, such as ion channel blockers, anti-inflammatory and anticancer agents as well as antimalarial. Conceptual density functional theory (CDFT) analysis, along with the activation energies of the 32CA reaction between C, N-diphenyl nitrilimine with 2,3,4,5-tetraphenylcyclopentadienone, demonstrates concordance with the empirical findings. The 32CA reaction is found to proceed through a very polar single-step asynchronous mechanism. While deductions from the activation energies of the 32CA reaction between benzonitrile oxide and 2,3,4,5-tetraphenylcyclopentadienone are found to lead to the experimental product, the parr function analysis could not explain the observed chemo- and regioselectivity. This 32CA reaction is also found to proceed through a one-step asynchronous mechanism, though with a non-polar character. The modulation of substituents positioned at the reactive sites of the reactants is found to influence the kinetics, thermodynamics, and CDFT parameters of the two 32CA reactions, consequently impacting the observed selectivities. The 32CA reactions between C, N-diphenyl nitrilimine with 2,3,4,5-tetraphenylcyclopentadienone and benzonitrile oxide with 2,3,4,5-tetraphenylcyclopentadienone have been explored theoretically using the density functional theory method at the hybrid ωB97X-D coupled with the split valence triple-ξ (TZ) basis set as implemented in the Gaussian 09. Solvent effects were taken into account by full optimization of the gas phase geometries through the polarizable continuum model developed within the self-consistent reaction field.

Case report of an unusual allergic reaction to a routine skin prick test performed in an outpatient clinic: Diagnosis, management, and knowledge gaps.

The skin prick test (SPT) is a standard procedure in allergy/immunology clinics, crucial for evaluating conditions like allergic rhinitis and food allergies. As a cornerstone in investigating immunoglobulin E-mediated allergy, it plays a vital role in diagnosing allergies, including those triggered by common dust mites like Dermatophagoides pteronyssinus, Dermatophagoides farinae, Euroglyphus maynei, and Blomia tropicalis. Despite its widespread use, adverse reactions to SPT are uncommon (15 per 100,000 patients), though the procedure is not entirely risk-free. This article presents a clinical case involving a 17-year-old female who experienced a moderately delayed allergic reaction 120 minutes post-SPT, managed effectively with subsequent symptom resolution. The patient, with a history of persistent rhinorrhea, itchy nose, eyes, and postnasal drip, sought consultation due to worsening symptoms. Diagnostic measures, including patient-reported outcomes and SPT with a standard aeroallergen panel, revealed sensitization to various allergens. Post-test, the patient reported ocular pruritus, left eyelid swelling, and moderate rhinorrhea, persisting for about 24 hours. On the subsequent medical visit, the patient received rupatadine and deflazacort, leading to symptom resolution within 3 hours. This article delves into a systemic allergic reaction post-SPT, emphasizing the 2 main stages of type I hypersensitivity reactions. While the acute phase involves mast cell-driven mediators within 15 minutes, the delayed phase (4-8 hours) includes de novo cytokine release. Vigilance regarding symptom onset and differentiation between mild and severe reactions is crucial. Notably, the absence of specific waiting time guidelines post-SPT underscores the need for reporting to enhance understanding and subsequent management. Performing these procedures in specialized centers with qualified professionals is essential for effectively managing potential anaphylactic reactions. Addressing these knowledge gaps will contribute to enhanced patient safety during diagnostic procedures.

Heavy Water Microdroplet Surface Enriches the Lighter Isotopologue Impurities.

Water microdroplets promote unusual chemical reactions at the air-water interface. However, the interfacial structure of water microdroplets and its potential influence on chemical processes are still enigmatic. Here, we present evidence of in-droplet fractionation of water isotopologues. Employing a sonic spray, we atomized the heavy water (D2O, 99.9 atom % D) solution of three classes of organic compounds (basic, acidic, and neutral). The analytes were predominantly desorbed from the resulting droplet surface in protonated form rather than deuterated form, as detected by mass spectrometry. This result remained unaltered upon adding formic acid-d2 (DCOOD) to the droplet. Monitoring Dakin oxidation of benzaldehyde at the surface of binary microdroplets composed of 1:1 (v/v) D2O/H218O revealed the preferred formation of phenolate-16O over phenolate-18O. Atmospheric pressure chemical ionization mass spectrometric analysis of the vapor composition in the sprayed aerosol revealed the preferential evaporation of lighter water isotopologue impurities from the surface of heavy water microdroplets. These results indicate the enrichment of lighter water isotopologue impurities (HOD/H2O) on the surface of heavy water microdroplets, implying possible future developments for water isotopologue fractionation using microdroplets.

Studying the Intrinsic Reactivity of Chromanes by Gas-Phase Infrared Spectroscopy.

Tandem mass spectrometry is routinely used for the structural analysis of organic molecules, but many fragmentation reactions are not well understood. Because several potential structures can correspond to a measured mass, the assignment of product ions is ambiguous using mass spectrometry alone. Here, we combine mass spectrometry with high-resolution gas-phase infrared spectroscopy and computational chemistry tools to identify product ion structures and derive collision-induced fragmentation mechanisms of the chromane derivatives Trolox and Methyltrolox. We find that protonated Trolox and Methyltrolox fragment identically via dehydration and decarbonylation, while deprotonated ions display substantially diverging reactivities. For deprotonated Methyltrolox, we observe unusual radical fragmentation reactions and suggest a [1,2]-Wittig rearrangement involving aryl migration in the gas phase. Overall, the combined experimental and theoretical approach presented here revealed complex proton dynamics and intramolecular rearrangement reactions, which expand our understanding on structure-reactivity relationships of isolated molecules in different protonation states.

Chemo-, regio- and stereoselective access to polysubstituted 1,3-dienes via Nickel-catalyzed four-component reactions

1,2-Difunctionalization of alkynes offers a straightforward approach to access polysubstituted alkenes. However, simultaneous multi-component cascade transformations including difunctionalization of two alkynes with both syn- and anti-selectivity in one catalyst system is undeveloped and proves to be a significant challenge. Herein, we report a Nickel-catalyzed four-component reaction to access polysubstituted 1,3-dienes using two terminal alkynes, aryl boroxines, and perfluoroalkyl iodides, wherein the reaction forms three new C-C bonds in a single vessel and serve as a modular strategy to access polysubstituted 1,3-dienes with excellent chemoselectivity, good regioselectivity and exclusive stereoselectivity. Control experiments reveal the plausible reaction mechanism and DFT calculations explain the cause for the formation of this unusual four-component reaction. Furthermore, we successfully incorporate two biologically active units into 1,2,3,4-tetrasubstituted 1,3-dienes, which greatly increases the diversity of molecular scaffolds and brings more potential values to medicinal chemistry, the synthetic utility of our protocol is further demonstrated by the late-stage transformations.