Asymmetric Paired Electrolysis: Enantioselective Alkylation of Sulfonylimines via C(sp3)-H Functionalization.

Enantioselective transformation of ubiquitous C(sp3)-H bonds into three-dimensional chiral scaffolds is of longstanding interest to synthetic chemists. Herein, an asymmetric paired electrolysis enables a highly efficient and sustainable approach to the enantioselective alkylation of sulfonylimines via C(sp3)-H functionalization. In this protocol, anodic oxidation for benzylic radical formation and Lewis acid-catalyzed sulfonylimine reduction on the cathode were seamlessly cross-coupled (up to 88% yield). Enantioenriched chiral amines containing a tetrasubstituted carbon stereocenter are accessed with high enantioselectivity (up to 96% ee). Mechanistic studies suggest that the amine generated in situ could serve as a base to deprotonate phenols and decrease the oxidation potential of the reaction, allowing phenols with lower potentials to be preferentially oxidized.

Efficient C(sp3)-H bond oxidation on perovskite quantum dots based on Ce-oxygen affinity.

Perovskite quantum dots (QDs) have shown attractive prospects in the field of visible photocatalysis, especially in the synthesis of high value-added chemicals. However, under aerobic conditions, the stable operation of QD catalysts has been limited by the reactive oxygen species (ROS) generated by photoexcitation, especially superoxide species. Here, we propose a strategy of Ce3+ doping in perovskite QDs to guide superoxide species for photocatalytic oxidation reactions. In C(sp3)-H bond oxidation of hydrocarbons, superoxide species were rapidly generated and efficiently utilized on the surface of perovskite QDs, which achieves the stable operation of the catalytic system and obtains a high product conversion rate (15.3 mmol/g/h for benzaldehydes). The mechanism studies show that the strong Ce-oxygen affinity accelerates the relaxation process of photoinduced exciton transfer to superoxide species and inhibits the radiative recombination pathway. This work provides a new idea of utilizing oxygen species on perovskite surface and broadens the design strategy of high-performance QD photocatalysts.

Asymmetric Coordination of Single-Atom Ru Sites Achieves Efficient N(sp3)-H Dehydrogenation Catalysis for Ammonia Oxidation.

Ruthenium single-atom catalysts have great potential in ammonia-selective catalytic oxidation (NH3-SCO); however, the stable sp3 hybrid orbital of NH3 molecules makes N(sp3)-H dissociation a challenge for conventional symmetrical metallic oxide catalysts. Herein, we propose a heterogeneous interface reverse atom capture strategy to construct Ru with unique asymmetric Ru1N2O1 coordination. Ru1N2O1/CeO2 exhibits intrinsic low-temperature conversion (T100 at 160 °C) compared to symmetric coordinated Ru-based (280 °C), Ir-based (220 °C), and Pt-based (200 °C) catalysts, and the TOF is 65.4 times that of Ag-based catalysts. The experimental and theoretical studies show that there is a strong d-p orbital interaction between Ru and N atoms, which not only enhances the adsorption of ammonia at the Ru1N2O1 position but also optimizes the electronic configuration of Ru. Furthermore, the affinity of Ru1N2O1/CeO2 to water is significantly weaker than that of conventional catalysts (the binding energy of the Pd3Au1 catalyst is -1.19 eV, but it is -0.39 eV for our material), so it has excellent water resistance. Finally, the N(sp3)-H activation of NH3 requires the assistance of surface reactive oxygen species, but we found that asymmetric Ru1N2O1 can directly activate the N(sp3)-H bond without the involvement of surface reactive oxygen species. This study provides a novel principle for the rational design of the proximal coordination of active sites to achieve its optimal catalytic activity in single-atom catalysis.

Strong Bases and beyond: The Prominent Contribution of Neutral Push-Pull Organic Molecules towards Superbases in the Gas Phase.

In this review, the principles of gas-phase proton basicity measurements and theoretical calculations are recalled as a reminder of how the basicity PA/GB scale, based on Brønsted-Lowry theory, was constructed in the gas-phase (PA-proton affinity and/or GB-gas-phase basicity in the enthalpy and Gibbs energy scale, respectively). The origins of exceptionally strong gas-phase basicity of some organic nitrogen bases containing N-sp3 (amines), N-sp2 (imines, amidines, guanidines, polyguanides, phosphazenes), and N-sp (nitriles) are rationalized. In particular, the role of push-pull nitrogen bases in the development of the gas-phase basicity in the superbasicity region is emphasized. Some reasons for the difficulties in measurements for poly-functional nitrogen bases are highlighted. Various structural phenomena being in relation with gas-phase acid-base equilibria that should be considered in quantum-chemical calculations of PA/GB parameters are discussed. The preparation methods for strong organic push-pull bases containing a N-sp2 site of protonation are briefly reviewed. Finally, recent trends in research on neutral organic superbases, leaning toward catalytic and other remarkable applications, are underlined.

Synergistic Copper-Aminocatalysis for Direct Tertiary α-Alkylation of Ketones with Electron-Deficient Alkanes.

In this study, a novel approach for the tertiary α-alkylation of ketones using alkanes with electron-deficient C─H bonds is presented, employing a synergistic catalytic system combining inexpensive copper salts with aminocatalysis. This methodology addresses the limitations of traditional alkylation methods, such as the need for strong metallic bases, regioselectivity issues, and the risk of over alkylation, by providing a high reactivity and chemoselectivity without the necessity for pre-functionalized substrates. The dual catalytic strategy enables the direct functionalization of C(sp3)─H bonds, demonstrating remarkable selectivity in the presence of conventional C(sp3)─H bonds that are adjacent to heteroatoms or π systems, which are typically susceptible to single-electron transfer processes. The findings contribute to the advancement of alkylation techniques, offering a practical and efficient route for the construction of C(sp3)─C(sp3) bonds, and paving the way for further developments in the synthesis of complex organic molecules.

Streamlining Protein Fractional Synthesis Rates Using SP3 Beads and Stable Isotope Mass Spectrometry: A Case Study on the Plant Ribosome.

Ribosomes are an archetypal ribonucleoprotein assembly. Due to ribosomal evolution and function, r-proteins share specific physicochemical similarities, making the riboproteome particularly suited for tailored proteome profiling methods. Moreover, the structural proteome of ribonucleoprotein assemblies reflects context-dependent functional features. Thus, characterizing the state of riboproteomes provides insights to uncover the context-dependent functionality of r-protein rearrangements, as they relate to what has been termed the ribosomal code, a concept that parallels that of the histone code, in which chromatin rearrangements influence gene expression. Compared to high-resolution ribosomal structures, omics methods lag when it comes to offering customized solutions to close the knowledge gap between structure and function that currently exists in riboproteomes. Purifying the riboproteome and subsequent shot-gun proteomics typically involves protein denaturation and digestion with proteases. The results are relative abundances of r-proteins at the ribosome population level. We have previously shown that, to gain insight into the stoichiometry of individual proteins, it is necessary to measure by proteomics bound r-proteins and normalize their intensities by the sum of r-protein abundances per ribosomal complex, i.e., 40S or 60S subunits. These calculations ensure that individual r-protein stoichiometries represent the fraction of each family/paralog relative to the complex, effectively revealing which r-proteins become substoichiometric in specific physiological scenarios. Here, we present an optimized method to profile the riboproteome of any organism as well as the synthesis rates of r-proteins determined by stable isotope-assisted mass spectrometry. Our method purifies the r-proteins in a reversibly denatured state, which offers the possibility for combined top-down and bottom-up proteomics. Our method offers a milder native denaturation of the r-proteome via a chaotropic GuHCl solution as compared with previous studies that use irreversible denaturation under highly acidic conditions to dissociate rRNA and r-proteins. As such, our method is better suited to conserve post-translational modifications (PTMs). Subsequently, our method carefully considers the amino acid composition of r-proteins to select an appropriate protease for digestion. We avoid non-specific protease cleavage by increasing the pH of our standardized r-proteome dilutions that enter the digestion pipeline and by using a digestion buffer that ensures an optimal pH for a reliable protease digestion process. Finally, we provide the R package ProtSynthesis to study the fractional synthesis rates of r-proteins. The package uses physiological parameters as input to determine peptide or protein fractional synthesis rates. Once the physiological parameters are measured, our equations allow a fair comparison between treatments that alter the biological equilibrium state of the system under study. Our equations correct peptide enrichment using enrichments in soluble amino acids, growth rates, and total protein accumulation. As a means of validation, our pipeline fails to find "false" enrichments in non-labeled samples while also filtering out proteins with multiple unique peptides that have different enrichment values, which are rare in our datasets. These two aspects reflect the accuracy of our tool. Our method offers the possibility of elucidating individual r-protein family/paralog abundances, PTM status, fractional synthesis rates, and dynamic assembly into ribosomal complexes if top-down and bottom-up proteomic approaches are used concomitantly, taking one step further into mapping the native and dynamic status of the r-proteome onto high-resolution ribosome structures. In addition, our method can be used to study the proteomes of all macromolecular assemblies that can be purified, although purification is the limiting step, and the efficacy and accuracy of the proteases may be limited depending on the digestion requirements. Key features • Efficient purification of the ribosomal proteome: streamlined procedure for the specific purification of the ribosomal proteome or complex Ome. • Accurate calculation of fractional synthesis rates: robust method for calculating fractional protein synthesis rates in macromolecular complexes under different physiological steady states. • Holistic ribosome methodology focused on plants: comprehensive approach that provides insights into the ribosomes and translational control of plants, demonstrated using cold acclimation [1]. • Tailored strategies for stable isotope labeling in plants: methodology focusing on materials and labeling considerations specific to free and proteinogenic amino acid analysis [2].

Shear Field-Controlled Synthesis of Nitrogen-Doped Carbon Nanochains Forest with High-Density sp3 Defects for Efficient CO2 Electroreduction Reaction.

Defect engineering and nitrogen doping being effective strategies for modulating the surface chemical state of the carbon matrix have been widely explored to promote the catalytic activity in the territory of electrochemical energy storage and conversion devices. However, the controllable synthesis of carbon material with high-density specific defects and high nitrogen doping is still full of challenges. Here, we first synthesize one-dimensional necklace-like nitrogen-doped carbon nanochains (N-CNCs) with abundant defects on carbon fiber paper (CFP) by chemical vapor deposition (CVD) method. The resultant nanostructures are a bunch of interconnected carbon spheres with a hollow structure at the internode and present the complete one-dimensional nanochain configuration. Specifically, the N-CNCs with a corrugated surface possesses high content of sp3 defects (31.2%) and nitrogen (23.6 at %). Combining finite element analysis and experimental results, it reveals that the robust shear field generated by etching gas releasing from thermal decomposition of melamine in situ modulates the CVD process via changing the size and force environment of the metal catalyst droplets for formation of N-CNCs. Benefiting from the high ratio of sp3/sp2 and nitrogen doped on the surface, the N-CNCs@CFP displays a superior electrocatalytic performance for CO2RR, delivering CO Faradaic efficiency of 95.9% and a current density of 23.2 mA cm-2 at -0.86 V vs RHE. This work provides promising synthesis strategy and some inspirations for construction of ultradense and specific defects coupling with nitrogen doping sites into carbon materials to achieve high-efficiency electrocatalysis applications.

Lectin-Based SP3 Technology Enables N-Glycoproteomic Analysis of Mouse Oocytes.

N-glycosylation is one of the most universal and complex protein post-translational modifications (PTMs), and it is involved in many physiological and pathological activities. Owing to the low abundance of N-glycoproteins, enrichment of N-glycopeptides for mass spectrometry analysis usually requires a large amount of peptides. Additionally, oocyte protein N-glycosylation has not been systemically characterized due to the limited sample amount. Here, we developed a glycosylation enrichment method based on lectin and a single-pot, solid-phase-enhanced sample preparation (SP3) technology, termed lectin-based SP3 technology (LectinSP3). LectinSP3 immobilized lectin on the SP3 beads for N-glycopeptide enrichment. It could identify over 1100 N-glycosylation sites and 600 N-glycoproteins from 10 µg of mouse testis peptides. Furthermore, using the LectinSP3 method, we characterized the N-glycoproteome of 1000 mouse oocytes in three replicates and identified a total of 363 N-glycosylation sites from 215 N-glycoproteins. Bioinformatics analysis revealed that these oocyte N-glycoproteins were mainly enriched in cell adhesion, fertilization, and sperm-egg recognition. Overall, the LectinSP3 method has all procedures performed in one tube, using magnetic beads. It is suitable for analysis of a low amount of samples and is expected to be easily adaptable for automation. In addition, our mouse oocyte protein N-glycosylation profiling could help further characterize the regulation of oocyte functions.

Site-Selective Distal C(sp3)-H Bromination of Aliphatic Amines as a Gateway for Forging Nitrogen-Containing sp3 Architectures.

Herein, we disclose a new strategy that rapidly and reliably incorporates bromine atoms at distal, secondary C(sp3)-H sites in aliphatic amines with an excellent and predictable site-selectivity pattern. The resulting halogenated building blocks serve as versatile linchpins to enable a series of carbon-carbon and carbon-heteroatom bond-formations at remote C(sp3) sites, thus offering a new modular and unified platform that expediates the access to advanced sp3 architectures possessing valuable nitrogen-containing saturated heterocycles of interest in medicinal chemistry settings.

Rational Design of the Spatial Effect in a Fe(II)/α-Ketoglutarate-Dependent Dioxygenase Reverses the Regioselectivity of C(sp3)-H Bond Hydroxylation in Aliphatic Amino Acids.

The hydroxylation of remote C(sp3)-H bonds in aliphatic amino acids yields crucial precursors for the synthesis of high-value compounds. However, accurate regulation of the regioselectivity of remote C(sp3)-H bonds hydroxylation in aliphatic amino acids continues to be a common challenge in chemosynthesis and biosynthesis. In this study, the Fe(II)/α-ketoglutarate-dependent dioxygenase from Bacillus subtilis (BlAH) was mined and found to catalyze hydroxylation at the γ and δ sites of aliphatic amino acids. Crystal structure analysis, molecular dynamics simulations, and quantum chemical calculations revealed that regioselectivity was regulated by the spatial effect of BlAH. Based on these results, the spatial effect of BlAH was reconstructed to stabilize the transition state at the δ site of aliphatic amino acids, thereby successfully reversing the γ site regioselectivity to the δ site. For example, the regioselectivity of L-Homoleucine (5 a) was reversed from the γ site (1 : 12) to the δ site (>99 : 1). The present study not only expands the toolbox of biocatalysts for the regioselective functionalization of remote C(sp3)-H bonds, but also provides a theoretical guidance for the precision-driven modification of similarly remote C(sp3)-H bonds in complex molecules.

Unveiling the Mechanistic Role of Chiral Palladacycles in Pd(II)-Catalyzed Enantioselective C(sp3)-H Functionalization.

Palladium-catalyzed enantioselective C(sp3)-H functionalization reactions has attracted considerable attention due to its ability for the synthesis of enantiomerically enriched molecules and stimulation of novel retrosynthetic disconnections. Understanding the reaction mechanism, especially the stereochemical process of the reaction, is crucial for the rational design of more efficient catalytic systems. Previously, we developed a Pd(II)/sulfoxide-2-hydroxypridine (SOHP) catalytic system for asymmetric C(sp3)-H functionalization reactions. In this study, we focused on unraveling the chemistry of chiral palladacycles involved in the Pd(II)-catalyzed enantioselective C(sp3)-H functionalization. We have isolated key palladacycle intermediates involved in the enantioselective ß-C(sp3)-H arylation of carboxylic acids catalyzed by the Pd(II)/SOHP system. These palladacycles, exhibiting ligand-induced chirality, provided a significant opportunity to investigate the stereochemical process and the ligand effect in this asymmetric C-H functionalization. Our investigation provided direct evidence for the C-H palladation step as the enantioselectivity-determining step, which forms diastereomeric palladacycles that exhibited preservation of chirality in the functionalization step. DFT calculations provided insights into the chiral induction in palladacycle formation. This work highlights the value of chiral palladacycle chemistry in offering mechanistic insights into the Pd(II)-catalyzed asymmetric C(sp3)-H functionalization reactions.

Photoinduced C(sp3)-H Bicyclopentylation Enabled by an Electron Donor-Acceptor Complex-Mediated Chemoselective Three-Component Radical Relay.

The photoredox electron donor-acceptor (EDA) complex-mediated radical coupling reaction has gained prominence in the field of organic synthesis, finding widespread application in two-component coupling reactions. However, EDA complex-promoted multi-component reactions are not well developed with only a limited number of examples have been reported. Herein, we report a photoinduced and EDA complex-promoted highly chemoselective three-component radical arylalkylation of [1.1.1]propellane, which allows the direct functionalization of C(sp3)-H with bicyclo[1.1.1]pentanes (BCP)-aryl groups under mild conditions. A variety of unnatural α-amino acids, featuring structurally diversified 1,3-disubstituted BCP moieties, were synthesized in a single-step process. Notably, leveraging the high tension release of [1.1.1]propellane, the highly unstable transient aryl radical undergoes rapid conversion into a relatively stable tertiary alkyl transient radical, and consequently, the competing side-reaction of two-component coupling was entirely suppressed. The strategic use of this transient radical conversion approach would be useful for the design of diverse EDA complex-mediated multi-component reactions. It is noteworthy that the highly chemoselective late-stage incorporation of the 1,3-disubstituted BCP pharmacophores into peptides was achieved both in liquid-phase and solid-phase reactions. This advancement is anticipated to have significant application potential in the future development of peptide drugs.

Skeletal muscle differentiation induces wide-ranging nucleosome repositioning in muscle gene promoters.

In a previous report, we demonstrated that Cbx1, PurB and Sp3 inhibited cardiac muscle differentiation by increasing nucleosome density around cardiac muscle gene promoters. Since cardiac and skeletal muscle express many of the same proteins, we asked if Cbx1, PurB and Sp3 similarly regulated skeletal muscle differentiation. In a C2C12 model of skeletal muscle differentiation, Cbx1 and PurB knockdown increased myotube formation. In contrast, Sp3 knockdown inhibited myotube formation, suggesting that Sp3 played opposing roles in cardiac muscle and skeletal muscle differentiation. Consistent with this finding, Sp3 knockdown also inhibited various muscle-specific genes. The Cbx1, PurB and Sp3 proteins are believed to influence gene-expression in part by altering nucleosome position. Importantly, we developed a statistical approach to determine if changes in nucleosome positioning were significant and applied it to understanding the architecture of muscle-specific genes. Through this novel statistical approach, we found that during myogenic differentiation, skeletal muscle-specific genes undergo a set of unique nucleosome changes which differ significantly from those shown in commonly expressed muscle genes. While Sp3 binding was associated with nucleosome loss, there appeared no correlation with the aforementioned nucleosome changes. In summary, we have identified a novel role for Sp3 in skeletal muscle differentiation and through the application of quantifiable MNase-seq have discovered unique fingerprints of nucleosome changes for various classes of muscle genes during myogenic differentiation.

Single-crystal oxygen-rich bismuth oxybromide nanosheets with highly exposed defective {10-1} facets for the selective oxidation of toluene under blue LED irradiation.

Reactive radicals are crucial for activating inert and low-polarity C(sp3)-H bonds for the fabrication of high value-added products. Herein, novel single-crystal oxygen-rich bismuth oxybromide nanosheets (Bi4O5Br2 SCNs) with more than 85 % {10-1} facets exposure and oxygen defects were synthesized via a facile solvothermal route. The Bi4O5Br2 SCNs demonstrated excellent photocatalytic performance in the selective oxidation of toluene under blue light. The yield of benzaldehyde was 1876.66 µmol g-1 h-1, with a selectivity of approximately 90 %. Compared to that of polycrystalline Bi4O5Br2 nanosheets (Bi4O5Br2 PCNs), the activity of Bi4O5Br2 SCNs exhibit a 21-fold increase. Experimental studies and density functional theory (DFT) calculations have demonstrated that the defect Bi4O5Br2 (10-1) facets exhibits exceptional adsorption properties for O2 molecules. In addition, the single-crystal structure in the presence of surface defects significantly increases the separation and transport of photogenerated carriers, resulting in the effective activation of adsorbed O2 into superoxide radicals (•O2-). Subsequently, the positively charged phenylmethyl H is readily linked to the negatively charged superoxide radical anion, thereby activating the CH bond. This study offers a fresh perspective and valuable insights into the development of efficient molecular oxygen-activated photocatalysts and their application in the selective catalytic conversion of aromatic C(sp3)-H bonds.

Dual Nonradical Catalytic Pathways Mediated by Nanodiamond-Derived sp2/sp3 Hybrids for Sustainable Peracetic Acid Activation and Water Decontamination.

Peracetic acid (PAA) oxidation catalyzed by metal-free carbons is promising for advanced water decontamination. Nevertheless, developing reaction-oriented and high-performance carbocatalysts has been limited by the ambiguous understanding of the intrinsic relationship between carbon chemical/molecular structure and PAA transformation behavior. Herein, we comprehensively investigated the PAA activation using a family of well-defined sp2/sp3 carbon hybrids from annealed nanodiamonds (ANDs). The activity of ANDs displays a volcano-type trend, with respect to the sp2/sp3 ratio. Intriguingly, sp3-C-enriched AND exhibits the best catalytic activity for PAA activation and phenolic oxidation, which is different from persulfate chemistry in which the sp2 network normally outperforms sp3 hybridization. At the electron-rich sp2-C site, PAA undergoes a reduction reaction to generate a reactive complex (AND-PAA*) and induces an electron-transfer oxidation pathway. At the sp3-C site adjacent to C═O, PAA is oxidized to surface-confined OH* and O* successively, which ultimately evolves into singlet oxygen (1O2) as the primary reactive species. Benefiting from the dual nonradical regimes on sp2/sp3 hybrids, AND mediates a sustainable redox recycle with PAA to continuously generate reactive species to attack water contaminants, meanwhile maintaining structural/chemical integrity and exceptional reusability in cyclic runs.

Refinement of paramagnetic bead-based digestion protocol for automatic sample preparation using an artificial neural network.

Despite technological advances in the proteomics field, sample preparation still represents the main bottleneck in mass spectrometry (MS) analysis. Bead-based protein aggregation techniques have recently emerged as an efficient, reproducible, and high-throughput alternative for protein extraction and digestion. Here, a refined paramagnetic bead-based digestion protocol is described for Opentrons® OT-2 platform (OT-2) as a versatile, reproducible, and affordable alternative for the automatic sample preparation for MS analysis. For this purpose, an artificial neural network (ANN) was applied to maximize the number of peptides without missed cleavages identified in HeLa extract by combining factors such as the quantity (µg) of trypsin/Lys-C and beads (MagReSyn® Amine), % (w/v) SDS, % (v/v) acetonitrile, and time of digestion (h). ANN model predicted the optimal conditions for the digestion of 50 µg of HeLa extract, pointing to the use of 2.5% (w/v) SDS and 300 µg of beads for sample preparation and long-term digestion (16h) with 0.15 µg Lys-C and 2.5 µg trypsin (≈1:17 ratio). Based on the results of the ANN model, the manual protocol was automated in OT-2. The performance of the automatic protocol was evaluated with different sample types, including human plasma, Arabidopsis thaliana leaves, Escherichia coli cells, and mouse tissue cortex, showing great reproducibility and low sample-to-sample variability in all cases. In addition, we tested the performance of this method in the preparation of a challenging biological fluid such as rat bile, a proximal fluid that is rich in bile salts, bilirubin, cholesterol, and fatty acids, among other MS interferents. Compared to other protocols described in the literature for the extraction and digestion of bile proteins, the method described here allowed identify 385 unique proteins, thus contributing to improving the coverage of the bile proteome.

Engineering a Hierarchy of Disorder: A New Route to Synthesize High-Performance 3D Nanoporous All-Carbon Materials*.

A new nanoporous amorphous carbon (NAC) structure that achieves both ultrahigh strength and high electrical conductivity, which are usually incompatible in porous materials is reported. By using modified spark plasma sintering, three amorphous carbon phases with different atomic bonding configurations are created. The composite consisted of an amorphous sp2-carbon matrix mixed with amorphous sp3-carbon and amorphous graphitic motif. NAC structure has an isotropic electrical conductivity of up to 12 000 S m-1, Young's modulus of up to ≈5 GPa, and Vickers hardness of over 900 MPa. These properties are superior to those of existing conductive nanoporous materials. Direct investigation of the multiscale structure of this material through transmission electron microscopy, electron energy loss spectroscopy, and machine learning-based electron tomography revealed that the origin of the remarkable material properties is the well-organized sp2/sp3 amorphous carbon phases with a core-shell-like architecture, where the sp3-rich carbon forms a resilient core surrounded by a conductive sp2-rich layer. This research not only introduces novel materials with exceptional properties but also opens new opportunities for exploring amorphous structures and designing high-performance materials.

Palladium-Catalyzed Inward Isomerization Hydroaminocarbonylation of Alkenes.

In contrast to the kinetically favored outward isomerization-hydrocarbonylation of alkenes, the disfavored inward isomerization-hydrocarbonylation of alkenes remains an important challenge. Herein, we have developed a novel and effective palladium-catalyzed inward isomerization-hydroaminocarbonylation of unactivated alkenes and aniline hydrochlorides for the formation of synthetically valuable α-aryl carboxylic amides in high yields and high site-selectivities. The high efficiency of the reaction is attributed to a relay catalysis strategy, in which the Markovnikov-favored [PdH]-PtBu3 catalyst is responsible for inward isomerization, while the [PdH]-Ruphos catalyst is responsible for hydroaminocarbonylation of the resulting conjugated aryl alkenes. The reaction exhibits highly functional group tolerance and provides a new method for formal carbonylation of remote C(sp3)-H bond.

Differences in Protein Capture by SP3 and SP4 Demonstrate Mechanistic Insights of Proteomics Clean-up Techniques.

The goal of proteomics experiments is to identify proteins to observe changes in cellular processes and diseases. One challenge in proteomics is the removal of contaminants following protein extraction, which can limit protein identification. Single-pot, solid-phase-enhanced sample preparation (SP3) is a clean-up technique in which proteins are captured on carboxylate-modified particles through a proposed hydrophilic-interaction-liquid-chromatography (HILIC)-like mechanism. However, recent results have suggested that proteins are captured in SP3 due to a protein-aggregation mechanism. Thus, solvent precipitation, single-pot, solid-phase-enhanced sample preparation (SP4) is a newer clean-up technique that employs protein-aggregation to capture proteins without modified particles. SP4 has previously enriched low-solubility proteins, though differences in protein capture could affect which proteins are detected and identified. We hypothesize that the mechanisms of capture for SP3 and SP4 are distinct. Herein, we assess the proteins identified and enriched using SP3 versus SP4 for MCF7 subcellular fractions and correlate protein capture in each method to protein hydrophobicity. Our results indicate that SP3 captures more hydrophilic proteins through a combination of HILIC-like and protein-aggregation mechanisms, while SP4 captures more hydrophobic proteins through a protein-aggregation mechanism. From these results, we recommend clean-up techniques based on protein-sample hydrophobicity to yield high proteome coverage in biological samples.

Masters of Mediation: MN(SiMe3)2 in Functionalization of C(sp3)-H Latent Nucleophiles.

Organoalkali compounds have undergone a far-reaching transformation being a coupling partner to a mediator in unusual organic conversions which finds its spot in the field of sustainable synthesis. Transition-metal catalysis has always been the priority in C(sp3)-H bond functionalization, however alternatively, in recent times this has been seriously challenged by earth-abundant alkali metals and their complexes arriving at new sustainable organometallic reagents. In this line, the importance of MN(SiMe3)2 (M=Li, Na, K & Cs) reagent revived in C(sp3)-H bond functionalization over recent years in organic synthesis is showcased in this minireview. MN(SiMe3)2 reagent with higher reactivity, enhanced stability, and bespoke cation-π interaction have shown eye-opening mediated processes such as C(sp3)-C(sp3) cross-coupling, radical-radical cross-coupling, aminobenzylation, annulation, aroylation, and other transformations to utilize readily available petrochemical feedstocks. This article also emphasizes the unusual reactivity of MN(SiMe3)2 reagent in unreactive and robust C-X (X=O, N, F, C) bond cleavage reactions that occurred alongside the C(sp3)-H bond functionalization. Overall, this review encourages the community to exploit the untapped potential of MN(SiMe3)2 reagent and also inspires them to take up this subject to even greater heights.