Recycled Excavation Soils as Sustainable Supplementary Cementitious Materials: Kaolinite Content and Performance Implications.

In response to the environmental implications of the massive quantities of excavation soil generated by global urbanization and infrastructure development, recent research efforts have explored the repurposing of calcined excavation soils as sustainable supplementary cementitious materials (SCMs). As it is still at an early stage, current research lacks systematic analysis across diverse soil deposits regarding their reactivity and mechanical properties within cementitious binders, despite recognized geographical variability in kaolinite content. Through comprehensive experimentation with soils sourced from four major southern Chinese cities, this study presents a pioneering assessment of the compressive strength, pozzolanic reactivity (X-ray diffraction, Fourier-transform infrared spectroscopy, solid-state nuclear magnetic resonance), and microstructural development (mercury intrusion porosimetry, scanning electron microscopy) of mortars modified by various calcined excavation soils (up to 28 days curing). The experimental data suggest that soils with a kaolinite content above 53.39% produce mortars of equal or superior quality to plain cement mixes, primarily due to their refined pore structures, microstructural densification, and enhanced hydration reactions. The findings highlight kaolinite-specifically, aluminum content-as the principal indicator of excavation soil viability for SCM application, suggesting a promising avenue for sustainable construction practices.

Preparation and Application of Nano-Calcined Excavation Soil as Substitute for Cement.

Rapid urbanization in many cities has produced massive amounts of problematic excavation soil. The direct disposal of untreated excavation soil often leads to significant land use and severe environmental concerns. A sustainable solution is to transform the soil waste into high-quality nano-calcined excavation soil (NCES) for application as a substitute for cement in construction. However, research in this area is very limited. This study presents a systematic investigation of the nano-sized calcined soil materials from preparation to application in cementitious material. The influence of milling parameters, including the rotational speed, milling duration, ball diameter, and milling strategy, was investigated to produce NCES with various specific surface areas. The effect of NCES substitution (15 wt% of Portland cement) in cementitious materials was then examined for mechanical performance, hydration dynamics, hydration products, and microstructure. A cement mix with very fine NCES (specific surface area of 108.76 m2/g) showed a 29.7% enhancement in mechanical strength and refined pore structure while a cement mix with un-grounded calcined soil showed a mechanical loss in comparison to the Control specimen. Delayed and reduced heat release at an early age was observed in a cement paste mixed with NCES. The underlying mechanism was investigated. The results of this work will contribute to the high-quality application of excavation soil waste.

Hydroxylamine-Mediated C(sp2)-H Trifluoromethylation of Terminal Alkenes.

Introduction of the trifluoromethyl (CF3) group into organic compounds has garnered substantial interest because of its significant role in pharmaceuticals and agrochemicals. Here, we report a hydroxylamine-mediated radical process for C(sp2)-H trifluoromethylation of terminal alkenes. The reaction shows good reactivity, impressive E/Z selectivity (up to >20 : 1), and broad functional group compatibility. Expansion of this approach to perfluoroalkylation and late-stage trifluoromethylation of bioactive molecules demonstrates its promising application potential. Mechanistic studies suggest that the reaction follows a radical addition and subsequent elimination pathway.

Phosphonium-Catalyzed Monoreduction of Bisphosphine Dioxides: Origin of Selectivity and Synthetic Applications.

Controlling product selectivity in successive reactions of the same type is challenging owing to the comparable thermodynamic and kinetic properties of the reactions involved. Here, the synergistic interaction of the two phosphoryl groups in bisphosphine dioxides (BPDOs) with a bromo-phosphonium cation was studied experimentally to provide a practical tool for substrate-catalyst recognition. As the eventual result, we have developed a phosphonium-catalyzed monoreduction of chiral BPDOs to access an array of synthetically useful bisphosphine monoxides (BPMOs) with axial, spiro, and planar chirality, which are otherwise challenging to synthesize before. The reaction features excellent selectivity and impressive reactivity. It proceeds under mild conditions, avoiding the use of superstoichiometric amounts of additives and metal catalysts to simplify the synthetic procedure. The accessibility and scalability of the reaction allowed for the rapid construction of a ligand library for optimization of asymmetric Heck-type cyclization, laying the foundation for a broad range of applications of chiral BPMOs in catalysis.

Deoxygenation of Phosphine Oxides by PIII/PV═O Redox Catalysis via Successive Isodesmic Reactions.

Deoxygenation of phosphine oxides is of great significance to synthesis of phosphorus ligands and relevant catalysts, as well as to the sustainability of phosphorus chemistry. However, the thermodynamic inertness of P═O bonds poses a severe challenge to their reduction. Previous approaches in this regard rely primarily on a type of P═O bond activation with either Lewis/Brønsted acids or stoichiometric halogenating reagents under harsh conditions. Here, we wish to report a novel catalytic strategy for facile and efficient deoxygenation of phosphine oxides via successive isodesmic reactions, whose thermodynamic driving force for breaking the strong P═O bond was compensated by a synchronous formation of another P═O bond. The reaction was enabled by PIII/P═O redox sequences with the cyclic organophosphorus catalyst and terminal reductant PhSiH3. This catalytic reaction avoids the use of the stoichiometric activator as in other cases and features a broad substrate scope, excellent reactivities, and mild reaction conditions. Preliminary thermodynamic and mechanistic investigations disclosed a dual synergistic role of the catalyst.

Revisiting the Electrochemistry of TEMPOH Analogues in Acetonitrile.

Hydroxylamines, represented by 1-hydroxy-2,2,6,6-tetramethylpiperidine (TEMPOH), are widely involved as active species in various chemical and electrochemical oxidations. The electrochemical behavior of TEMPOH is crucial to understanding the mechanisms of TEMPO-mediated redox sequences. However, compared to abundant studies on TEMPOH electrochemistry in aqueous solutions, the sole value of its oxidation potential Eox(TEMPOH) in organic solutions was reported to be 0.7 V (vs Fc in acetonitrile), seemingly conflicting with experimentally observed facile oxidation of TEMPOH. Herein, the electrochemistry of TEMPOH derivatives in acetonitrile was revisited, featuring much smaller oxidation potentials (about 0 V) than literature ones. Acid/base effects and kinetic studies lent credibility to these new values. Such a 0.7 V energy discrepancy impelled us to review the thermodynamic properties and oxidation mechanisms of TEMPOH deduced from the old value.

Catalytic Vilsmeier-Haack Reactions for C1-Deuterated Formylation of Indoles.

The Vilsmeier-Haack reaction is a powerful tool to introduce formyl groups into electron-rich arenes, but its wide application is significantly restricted by stoichiometric employment of caustic POCl3. Herein, we reported a catalytic version of the Vilsmeier-Haack reaction enabled by a P(III)/P(V)═O cycle. This catalytic reaction provides a facile and efficient route for the direct construction of C1-deuterated indol-3-carboxaldehyde under mild conditions with stoichiometric DMF-d7 as the deuterium source. The products feature a remarkably higher deuteration level (>99%) than previously reported ones and are not contaminated by the likely unselective deuteration at other sites. The present transformation can also be used to transfer other carbonyl groups. Further downstream derivatizations of these deuterated products manifested their potential applications in the synthesis of deuterated bioactive molecules. Mechanistic insight was disclosed from studies of kinetics and intermediates.

Discovery of ABBV-3373, an Anti-TNF Glucocorticoid Receptor Modulator Immunology Antibody Drug Conjugate.

Using a convergent synthetic route to enable multiple points of diversity, a series of glucocorticoid receptor modulators (GRM) were profiled for potency, selectivity, and drug-like properties in vitro. Despite covering a large range of diversity, profiling the nonconjugated small molecule was suboptimal and they were conjugated to a mouse antitumor necrosis factor (TNF) antibody using the MP-Ala-Ala linker. Screening of the resulting antibody drug conjugates (ADCs) provided a better assessment of efficacy and physical properties, reinforcing the need to conduct structure-activity relationship studies on the complete ADC. DAR4 ADCs were screened in an acute mouse contact hypersensitivity model measuring biomarkers to ensure a sufficient therapeutic window. In a chronic mouse arthritis model, mouse anti-TNF GRM ADCs were efficacious after a single dose of 10 mg/kg i.p. for over 30 days. Data on the unconjugated payloads and mouse surrogate anti-TNF ADCs identified payload 17 which was conjugated to a human anti-TNF antibody and advanced to the clinic as ABBV-3373.

Synthetic applications of NHPs: from the hydride pathway to a radical mechanism.

The unique heterocyclic skeletons of N-heterocyclic phosphines (NHPs) endow them with excellent hydridic reactivity, which has enabled NHPs to be applied in a great array of catalytic hydrogenations of unsaturated substrates in the past few decades. Recently, applications of NHPs in radical reductions, especially in a catalytic fashion, have emerged as a promising forefront area. This new reaction pattern, distinctive from but complementary to the well-established hydride pathway, can greatly expand the reaction scope to σ-bond scission. Herein, we briefly summarized some representative examples of synthetic applications of NHPs in both hydridic and radical reductions with an emphasis on their radical reactivity, including the structural and property studies of NHP radicals and their precursors as well as their applications in radical processes.

LncRNA TUG1 Promoted Stabilization of BAG5 by Binding DDX3X to Exacerbate Ketamine-Induced Neurotoxicity.

As a clinically widely used anesthetic, ketamine (KET) has been reported to cause neurotoxicity in patients. Our work aimed to probe the function of long-chain non-coding RNA taurine-upregulated gene 1 (lncRNA TUG1) in KET-induced neurotoxicity. HT22 cells were subjected to KET to build the cell model. 3-(4, 5-Dimethylthiazolyl2)-2, 5-diphenyltetrazolium bromide (MTT) assay was employed to determine cell viability. Additionally, cell apoptosis was evaluated by flow cytometry. The binding relationships among TUG1, DEAD-box RNA helicase 3X (DDX3X), and Bcl-2-associated athanogene 5 (BAG5) were verified by RIP and RNA pull-down assays. Cell viability was impaired and cell apoptosis was increased in KET-treated HT22 cells accompanied by increased TUG1, DDX3X, and BAG5 expressions. TUG1 knockdown dramatically enhanced cell viability and repressed the of KET-induced apoptosis in HT22 cells, while TUG1 overexpression presented the opposite effects. In addition, we found that TUG1 promoted DDX3X expression via directly binding with DDX3X. As expected, DDX3X overexpression abolished the palliative effect of TUG1 knockdown on KET-induced neurotoxicity. Further research proved that TUG1 increased the stability of BAG5 through interacting with DDX3X. Finally, as expected, the moderating effect of TUG1 knockdown on KET-induced neuron injury was abolished by BAG5 overexpression. Taken together, TUG1 promoted BAG5 expression by binding DDX3X to exacerbate KET-induced neurotoxicity.

Diazaphospholene-Catalyzed Hydrodefluorination of Polyfluoroarenes with Phenylsilane via Concerted Nucleophilic Aromatic Substitution.

The metal-free catalytic C-F bond activation of polyfluoroarenes was achieved with diazaphospholene as the catalyst and phenylsilane as the terminal reductant. Density functional theory calculations suggested a concerted nucleophilic aromatic substitution mechanism.

Recent progress in reactivity study and synthetic application of N-heterocyclic phosphorus hydrides.

N-heterocyclic phosphines (NHPs) have recently emerged as a new group of promising catalysts for metal-free reductions, owing to their unique hydridic reactivity. The excellent hydricity of NHPs, which rivals or even exceeds those of many metal-based hydrides, is the result of hyperconjugative interactions between the lone-pair electrons on N atoms and the adjacent σ*(P-H) orbital. Compared with the conventional protic reactivity of phosphines, this umpolung P-H reactivity leads to hydridic selectivity in NHP-mediated reductions. This reactivity has therefore found many applications in the catalytic reduction of polar unsaturated bonds and in the hydroboration of pyridines. This review summarizes recent progress in studies of the reactivity and synthetic applications of these phosphorus-based hydrides, with the aim of providing practical information to enable exploitation of their synthetically useful chemistry.

Chemoselective catalytic hydrodefluorination of trifluoromethylalkenes towards mono-/gem-di-fluoroalkenes under metal-free conditions.

Fluorine-containing moieties show significant effects in improving the properties of functional molecules. Consequently, efficient methods for installing them into target compounds are in great demand, especially those enabled by metal-free catalysis. Here we show a diazaphospholene-catalyzed hydrodefluorination of trifluoromethylalkenes to chemoselectively construct gem-difluoroalkenes and terminal monofluoroalkenes by simple adjustment of the reactant stoichiometry. This metal-free hydrodefluorination features mild reaction conditions, good group compatibility, and almost quantitative yields for both product types. Stoichiometric experiments indicated a stepwise mechanism: hydridic addition to fluoroalkenes and subsequent ß-F elimination from hydrophosphination intermediates. Density functional theory calculations disclosed the origin of chemoselectivity, regioselectivity and stereoselectivity, suggesting an electron-donating effect of the alkene-terminal fluorine atom.

Novel Fe4-based metal-organic cluster-derived iron oxides/S,N dual-doped carbon hybrids for high-performance lithium storage.

Metal-organic frameworks (MOFs) have been extensively used in the fabrication of new advanced electrode materials for lithium ion batteries (LIBs). However, low-productivity and high-cost are some of the main challenges of MOF-derived electrodes. Herein, we report a simple solvothermal procedure to fabricate novel Fe4-based metal-organic clusters (Fe-MOCs) with their subsequent conversion to an S,N dual-doped carbon framework incorporating iron oxides under a N2 atmosphere (namely Fe2O3@Fe3O4-SNC). The as-prepared Fe2O3@Fe3O4-SNC composite, owing to the strong interaction between the dual-doped carbon and iron oxides, shows excellent lithium storage performance as an anode with high pseudocapacitance. Furthermore, DFT computational analyses confirm that the hybrid shows excellent adsorption ability with a low energy barrier due to strong electronic interactions between the iron oxides and S,N-doped carbon matrix. In addition, Fe2O3@Fe3O4-SNC-based LIB shows high energy and power densities at the full-cell level, confirming this synthesis strategy to be a promising approach towards MOC-derived electrode materials for their application in LIBs and beyond-lithium batteries.

Defect Engineering Enhances the Charge Separation of CeO2 Nanorods toward Photocatalytic Methyl Blue Oxidation.

Defect-rich photocatalytic materials with excellent charge transfer properties are very popular. Herein, Sm-doped CeO2 nanorods were annealed in a N2 atmosphere to obtain the defective Sm-doped CeO2 photocatalysts (Vo-Sm-CeO2). The morphology and structure of Vo-Sm-CeO2 were systematically characterized. The Vo-Sm-CeO2 nanorods demonstrated an excellent photodegradation performance of methyl blue under visible light irradiation compared to CeO2 nanorods and Sm-CeO2. Reactive oxygen species including OH, ·O2-, and h+ were confirmed to play a pivotal role in the removal of pollutants via electron spin resonance spectroscopy. Doping Sm enhances the conductivity of CeO2 nanorods, benefiting photogenerated electrons being removed from the surface reactive sites, resulting in the superior performance.

Bonding Energetics of Palladium Amido/Aryloxide Complexes in DMSO: Implications for Palladium-Mediated Aniline Activation.

Thermodynamic knowledge of the metal-ligand (M-L) σ-bond strength is crucial to understanding metal-mediated transformations. Here, we developed a method for determining the Pd-X (X=OR and NHAr) bond heterolysis energies (ΔGhet (Pd-X)) in DMSO taking [(tmeda)PdArX] (tmeda=N,N,N',N'-tetramethylethylenediamine) as the model complexes. The ΔGhet (Pd-X) scales span a range of 2.6-9.0 kcal mol-1 for ΔGhet (Pd-O) values and of 14.5-19.5 kcal mol-1 for ΔGhet (Pd-N) values, respectively, implying a facile heterolytic detachment of the Pd ligands. Structure-reactivity analyses of a modeling Pd-mediated X-H bond activation reveal that the M-X bond metathesis is dominated by differences of the X-H and Pd-X bond strengths, the former being more influential. The ΔGhet (Pd-X) and pKa (X-H) parameters enable regulation of reaction thermodynamics and chemoselectivity and diagnosing the probability of aniline activation with Pd-X complexes.

Holistic Prediction of the pKa in Diverse Solvents Based on a Machine-Learning Approach.

While many approaches to predict aqueous pKa values exist, the fast and accurate prediction of non-aqueous pKa values is still challenging. Based on the iBonD experimental pKa database (39 solvents), a holistic pKa prediction model was established using machine learning. Structural and physical-organic-parameter-based descriptors (SPOC) were introduced to represent the electronic and structural features of the molecules. The models trained with a neural network or the XGBoost algorithm showed the best prediction performance with a low MAE value of 0.87 pKa units. The approach allows a comprehensive mapping of all possible pKa correlations between different solvents and it was validated by predicting the aqueous pKa and micro-pKa of pharmaceutical molecules and pKa values of organocatalysts in DMSO and MeCN with high accuracy. An online prediction platform was constructed based on the current model, which can provide pKa prediction for different types of X-H acidity in the most commonly used solvents.

Predicting Absolute Rate Constants for Huisgen Reactions of Unsaturated Iminium Ions with Diazoalkanes.

The kinetics and stereochemistry of the reactions of iminium ions derived from cinnamaldehydes and MacMillan's imidazolidinones with diphenyldiazomethane and aryldiazomethanes were investigated experimentally and with DFT calculations. The reactions of diphenyldiazomethane with iminium ions derived from MacMillan's second-generation catalysts gave 3-aryl-2,2-diphenylcyclopropanecarbaldehydes with yields >90 % and enantiomeric ratios of ≥90:10. Predominantly 2:1 products were obtained from the corresponding reactions with monoaryldiazomethanes. The measured rate constants are in good agreement with the rate constants derived from the one-center nucleophilicity parameters N and sN of diazomethanes and the one-center electrophilicity parameters E of iminium ions as well as with quantum chemically calculated activation energies.

Toward Rational Understandings of α-C-H Functionalization: Energetic Studies of Representative Tertiary Amines.

Functionalization of α-C-H bonds of tertiary amines to build various α-C-X bonds has become a mainstream in synthetic chemistry nowadays. However, due to lack of fundamental knowledge on α-C-H bond strength as an energetic guideline, rational exploration of new synthetic methodologies remains a far-reaching anticipation. Herein, we report a unique hydricity-based approach to establish the first integrated energetic scale covering both the homolytic and heterolytic energies of α-C-H bonds for 45 representative tertiary amines and their radical cations. As showcased from the studies on tetrahydroisoquinolines (THIQs) by virtue of their thermodynamic criteria, the feasibility and mechanisms of THIQ oxidation were deduced, which, indeed, were found to correspond well with experimental observations. This integrated scale provides a good example to relate bond energetics with mechanisms and thermodynamic reactivity of amine α-C-H functionalization and hence, may be referenced for analyzing similar structure-property problems for various substrates.