(Fluoro)alkylation of alkenes promoted by photolysis of alkylzirconocenes.

Difluoroalkylated compounds have important applications in pharmaceutical, agrochemical, and materials science. However, efficient methods to construct the alkylCF-alkyl bond are very limited, and the site-selective introduction of a difluoromethylene (CF) group into an aliphatic chain at the desired position remains challenging. Here, we report an unprecedented example of alkylzirconocene promoted difluoroalkylation of alkyl- and silyl-alkenes with a variety of unactivated difluoroalkyl iodides and bromides under the irradiation of visible light without a catalyst.

Two models to estimate the density of organic cocrystals.

Two models for predicting the density of organic cocrystals composed of energetic organic cocrystals and general organic cocrystals containing nitro groups were obtained. Sixty organic cocrystals in which the ratio of component molecules is 1 : 1 were studied as the dataset. Model-I was based on the artificial neural network (ANN) to predict the density of the cocrystals, which used (six) input parameters of the component molecules.

Phosphine-catalyzed divergent domino processes between γ-substituted allenoates and carbonyl-activated alkenes.

Highly enantioselective and chemodivergent domino reactions between γ-substituted allenoates and activated alkenes have been developed. In the presence of NUSIOC-Phos, triketone enone substrates smoothly reacted with γ-substituted allenoates to form bicyclic furofurans in good yields with high stereoselectivities. Alternatively, the reaction between diester-activated enone substrates and γ-substituted allenoates formed chiral conjugated 1,3-dienes in good yields with excellent enantioselectivities.

Targeting the tumor microenvironment by an enzyme-responsive prodrug of tubulin destabilizer for triple-negative breast cancer therapy with high safety.

In response to the long-term potential toxicity concerns of tubulin destabilizer, an enzyme-responsive prodrug therapy for triple-negative breast cancer was developed based on the different β-glucuronidase levels between tumor and normal tissues in this study. All the prodrugs synthesized herein showed remarkable stability in phosphate buffer and bovine serum solution, among which 17a was found to be more susceptible to enzymatic cleavage. 17a exhibited excellent selectivity between the in vitro antiproliferative activities against β-glucuronidase-pretreated and -untreated cancer cells (IC (+Enz) = 8.

The mouse nicotinamide mononucleotide adenylyltransferase chaperones diverse pathological amyloid client proteins.

Molecular chaperones safeguard cellular protein homeostasis and obviate proteotoxicity. In the process of aging, as chaperone networks decline, aberrant protein amyloid aggregation accumulates in a mechanism that underpins neurodegeneration, leading to pathologies such as Alzheimer's disease and Parkinson's disease. Thus, it is important to identify and characterize chaperones for preventing such protein aggregation.

Copper-mediated pentafluoroethylation of organoboronates and terminal alkynes with TMSCF.

The TMSCF-derived CuCFCF species has been successfully applied in pentafluoroethylation of organoboronates and terminal alkynes. By using 1,10-phenanthroline as a ligand, a broad range of (hetero)arylboronates and alkenylboronates were smoothly pentafluoroethylated under aerobic conditions. Furthermore, terminal alkynes can undergo aerobic cross-coupling with the TMSCF-derived CuCFCF species in the absence of additional ligands.

NMDA receptor-dependent prostaglandin-endoperoxide synthase 2 induction in neurons promotes glial proliferation during brain development and injury.

Astrocytes play critical roles in brain development and disease, but the mechanisms that regulate astrocyte proliferation are poorly understood. We report that astrocyte proliferation is bi-directionally regulated by neuronal activity via NMDA receptor (NMDAR) signaling in neurons. Prolonged treatment with an NMDAR antagonist reduced expression of cell-cycle-related genes in astrocytes in hippocampal cultures and suppressed astrocyte proliferation in vitro and in vivo, whereas neuronal activation promoted astrocyte proliferation, dependent on neuronal NMDARs.

KPT330 improves Cas9 precision genome- and base-editing by selectively regulating mRNA nuclear export.

CRISPR-based genome engineering tools are associated with off-target effects that constitutively active Cas9 protein may instigate. Previous studies have revealed the feasibility of modulating Cas9-based genome- and base-editing tools using protein or small-molecule CRISPR inhibitors. Here we screened a set of small molecule compounds with irreversible warhead, aiming to identifying small-molecule modulators of CRISPR-Cas9.

In situ quantitative analysis by ultrasonic extraction and nebulization combined with hydrogen flame ionization mass spectrometry: Diisopropylnaphthalene (DIPN), a marker of recycled paper in packing materials.

Ambient mass spectrometry is used for direct analysis and high-throughput screening in many fields. However, most researches are about qualitative analysis. Quantitative detection based on AMS only performs on standard compounds and the relative standard deviation is so large that the accuracy of the result is low.

Multicomponent reactions and photo/electrochemistry join forces: atom economy meets energy efficiency.

Visible-light photoredox catalysis has been regarded as an extremely powerful tool in organic chemistry, bringing the spotlight back to radical processes. The versatility of photocatalyzed reactions has already been demonstrated to be effective in providing alternative routes for cross-coupling as well as multicomponent reactions. The photocatalyst allows the generation of high-energy intermediates through light irradiation rather than using highly reactive reagents or harsh reaction conditions.

Liquid-liquid phase separation of RBGD2/4 is required for heat stress resistance in Arabidopsis.

As sessile organisms, plants are highly sensitive to environmental stresses. In response to stresses, globally repressed translation initiation leads to stress granule (SG) formation. Protein liquid-liquid phase separation (LLPS) contributes to SG formation, but a direct link between protein LLPS and stress resistance has not yet been found in plants.

The Morita-Baylis-Hillman reaction for non-electron-deficient olefins enabled by photoredox catalysis.

A strategy for overcoming the limitation of the Morita-Baylis-Hillman (MBH) reaction, which is only applicable to electron-deficient olefins, has been achieved visible-light induced photoredox catalysis in this report. A series of non-electron-deficient olefins underwent the MBH reaction smoothly a novel photoredox-quinuclidine dual catalysis. The formed key β-quinuclidinium radical intermediates, derived from the addition of olefins with quinuclidinium radical cations, are used to enable the MBH reaction of non-electron-deficient olefins.

Phase separation ability and phosphatase activity of the SHP1-R360E mutant.

SHP1 is a non-receptor protein tyrosine phosphatase that is widely expressed in hematopoietic cells such as white blood cells, neutrophils, and immune cells. SHP1 can regulate the occurrence and differentiation of immune cells and plays an important role as a tumor suppressor. Previous studies have suggested that SHP2, the homologous protein of phosphatase SHP1, can undergo liquid-liquid phase separation (LLPS).

Visible-light-mediated intramolecular radical cyclization of α-brominated amide-tethered alkylidenecyclopropanes.

A ring-opening/cyclization cascade reaction of α-brominated amide-tethered alkylidenecyclopropanes in the presence of photocatalyst 4CzIPN under visible-light irradiation was developed to afford polycyclic benzazepine derivatives in good yields with broad substrate scope and good functional tolerance. A plausible mechanism involving a halogen atom transfer (XAT) process and a radical chain process is proposed for this reaction. This study provides a concise and practical strategy for the synthesis of benzazepine derivatives.

Visible-light induced dearomatization reactions.

Dearomatization reactions provide rapid access to structurally complex three-dimensional molecules from simple aromatic compounds. Plenty of reports have demonstrated their utilities in the synthesis of natural products, medicinal chemistry, and materials science in the last decades. Recently, visible-light mediated photocatalysis has emerged as a powerful tool to promote many kinds of transformations.

A facile and scalable synthetic method for covalent organic nanosheets: ultrasonic polycondensation and photocatalytic degradation of organic pollutants.

Covalent organic framework nanosheets (COF NSs or CONs), as compared to their bulk counterparts two-dimensional (2D) covalent organic frameworks (COFs), exhibit superior performance in many aspects due to their fully accessible active sites benefiting from their ultrathin porous 2D structures. The development of a scalable synthetic methodology for CONs is crucial to further exploration of their unique properties and practical applications. Herein, we report an efficient strategy to fabricate ultrathin CONs through direct polycondensation of monomers under ultrasonic treatment and mild conditions.

Pd-Catalyzed umpolung asymmetric allylic alkylation of hydrazones to vicinal tertiary and quaternary chiral carbon centers.

Diastereo- and enantioselective construction of vicinal tertiary and quaternary carbon centers is a great challenge in synthetic chemistry. Herein, we report a facile and efficient protocol to construct vicinal tertiary and quaternary chiral carbon centers in high yields with high regio-, diastereo- and enantioselectivities Pd-catalyzed umpolung asymmetric allylic alkylation of hydrazones with monosubstituted allyl reagents by using Kündig-type chiral N-heterocyclic carbene as the ligand. The control experiments revealed that the reaction proceeds the inner-sphere mechanism.

Reactivities of allenic and olefinic Michael acceptors towards phosphines.

The kinetics of the reactions of tributylphosphine with allenic and olefinic Michael acceptors in dichloromethane at 20 °C was followed by photometric and NMR spectroscopic methods. Combination with DFT-calculated methyl anion affinities revealed the relevance of retroaddition barriers in phosphine-catalysed reactions when mixtures of allenic and olefinic substrates are used.

Copper-catalyzed radical relay in C(sp)-H functionalization.

Radical-involved transition metal (TM) catalysis has greatly enabled new reactivities in recent decades. Copper-catalyzed radical relay offers enormous potential in C(sp)-H functionalization which combines the unique regioselectivity of hydrogen atom transfer (HAT) and the versatility of copper-catalyzed cross-coupling. More importantly, significant progress has been achieved in asymmetric C-H functionalization through judicious ligand design.

SOX17 and PAX8 constitute an actionable lineage-survival transcriptional complex in ovarian cancer.

Müllerian tissue-specific oncogenes, prototyped by PAX8, underlie ovarian tumorigenesis and represent unique molecular vulnerabilities. Further delineating such lineage-dependency factors and associated therapeutic implications would provide valuable insights into ovarian cancer biology and treatment. In this study, we identified SOX17 as a new lineage-survival master transcription factor, which shared co-expression pattern with PAX8 in epithelial ovarian carcinoma.

Highly selective synthesis of all-carbon tetrasubstituted alkenes by deoxygenative alkenylation of carboxylic acids.

The synthesis of all-carbon tetrasubstituted olefins under mild reaction conditions is challenging because of the inevitable issues including significant steric hindrance and the uncontrolled Z/E stereoselectivity. In this paper, we report the synthesis of all-carbon tetrasubstituted alkenes from readily available carboxylic acids and alkenyl triflates with the synergistic catalysis of cyclo-octa-1,5-diene(tetramethyl-1,4-benzoquinone)nickel and visible light under an air atmosphere, thus avoiding the need for a glovebox or a Schlenk line. A wide range of aromatic carboxylic acids and cyclic and acyclic alkenyl triflates undergo the C-C coupling process smoothly, forming structurally diverse alkenes stereospecifically in moderate to good yields.