C(sp)-C(sp) Lever-Based Targets of Orientational Chirality: Design and Asymmetric Synthesis.

In this study, the design and asymmetric synthesis of a series of chiral targets of orientational chirality were conducted by taking advantage of N-sulfinylimine-assisted nucleophilic addition and modified Sonogashira catalytic coupling systems. Orientational isomers were controlled completely using alkynyl/alkynyl levers [C(sp)-C(sp) axis] with absolute configuration assignment determined by X-ray structural analysis. The key structural element of the resulting orientational chirality is uniquely characterized by remote through-space blocking. Forty examples of multi-step synthesis were performed, with modest to good yields and excellent orientational selectivity. Several chiral orientational amino targets are attached with scaffolds of natural and medicinal products, showing potential pharmaceutical and medical applications in the future.

Photocatalytic Thio/Selenosulfonylation-Bicyclization of Indole-Tethered 1,6-Enynes Leading to Substituted Benzo[c]pyrrolo[1,2,3-lm]carbazoles.

The photocatalyzed radical-triggered thio/selenosulfonylation-bicyclization of indole-tethered 1,6-enynes has been established for the first time, enabling the synthesis of various previously unreported thio/selenosulfonylated benzo[c]pyrrolo[1,2,3-lm]carbazoles with moderate to good yields under mild conditions. The reaction pathway was proposed, consisting of energy transfer, homolytic cleavage, radical addition, 5-exo-dig, radical coupling, and a Mallory reaction cascade. This approach exhibits a wide substrate compatibility and excellent tolerability toward various functional groups and is characterized by its remarkable efficiency in both bond formation and annulation.

Photoinduced radical tandem annulation of 1,7-diynes: an approach for divergent assembly of functionalized quinolin-2(1H)-ones.

The first photocatalytic trichloromethyl radical-triggered annulative reactions of amide-linked 1,7-diynes with polyhalomethanes were established for the flexible assembly of functionalized quinolin-2(1H)-ones with generally acceptable yields. With the installation of the aryl group (R1) into the alkynyl moiety, C-center radical-initiated Kharasch-type addition/nucleophilic substitution/elimination cascade to produce quinolin-2(1H)-ones-incorporating gem-dihaloalkene, whereas three examples of polyhalogenated quinolin-2(1H)-ones were afforded when amide-linked 1,7-diynes bearing two terminal alkyne units were subjected to BrCX3 by exploiting dry acetonitrile as a solvent.

[Diagnostic Efficacy of Platelet-Related Parameters on Anxiety and Depression in Patients Undergoing Peritoneal Dialysis].

Objective To analyze the correlations between platelet-related parameters and the incidence of anxiety and depression in the patients undergoing peritoneal dialysis(PD),and evaluate the efficacy of the parameters in the diagnosis of anxiety and depression in PD patients. Methods A total of 245 patients undergoing PD in the First Affiliated Hospital of Hebei North University from September 2022 to February 2023 were enrolled.The generalized anxiety scale(GAD-7) and the patient health questionnaire(PHQ-9) were used to evaluate the anxiety and depression of the patients,respectively.The personal information and biochemical indicators of the patients were collected,and the platelet count(PLT),mean platelet volume(MPV),and platelet distribution width(PDW) were measured.Logistic regression was adopted to analyze the relationships of platelet-related parameters with anxiety and depression in PD patients. Results Among the 245 patients undergoing PD,the incidences of anxiety and depression were 15.9% and 38.0%,respectively.There were differences in the dialysis period(Z=-2.358,P=0.018;Z=-3.079,P=0.002),MPV(Z=-4.953,P<0.001;Z=-7.878,P<0.001),and PDW(Z=-4.587,P<0.001;Z=-7.367,P<0.001) between the anxiety group and the non-anxiety group as well as between the depression group and the non-depression group.The correlation analysis showed that MPV(r=0.358,P<0.001;r=0.489,P<0.001) and PDW(r=0.340,P<0.001;r=0.447,P<0.001) were positively correlated with anxiety and depression in the patients undergoing PD.The Logistic regression model showed that MPV(P=0.022,P=0.011),PDW(P=0.041,P=0.018),and dialysis period(P=0.011,P=0.030) were independent risk factors for the anxiety and depressive state in PD patients.The areas under the receiver operating characteristic curve of MPV in the diagnosis of anxiety and depression in PD patients were 0.750 and 0.800,respectively,and those of PDW were 0.732 and 0.780,respectively. Conclusion MPV and PDW have high efficacy in the diagnosis of anxiety and depression associated with PD and can be used as objective indicators to evaluate the anxiety and depression in the patients undergoing PD.

Design and Asymmetric Control of Orientational Chirality by Using the Combination of C(sp2)-C(sp) Levers and Achiral N-Protecting Group.

New chiral targets of orientational chirality have been designed and asymmetrically synthesized by taking advantage of N-sulfinyl imine-directed nucleophilic addition/oxidation, Suzuki-Miyaura, and Sonogashira cross-coupling reactions. Orientation of single isomers has been selectively controlled by using aryl/alkynyl levers [C(sp2)-C(sp) axis] and tBuSO2- protecting group on nitrogen as proven by X-ray diffraction analysis. The key structural characteristic of resulting orientational products is shown by remote through-space blocking manner. Seventeen examples of multi-step synthesis were obtained with modest to good chemical yields and complete orientational selectivity.

Photoinduced Alkylsulfonylation and Cyanoalkylsulfonylation of Morita-Baylis-Hillman Adducts via Multicomponent Insertion of Sulfur Dioxide.

General and convenient visible-light-promoted alkylsulfonylation and cyanoalkylsulfonylation of MBH adducts have been developed through the multicomponent insertion of sulfur dioxide, enabling the assembly of two C-S bonds to generate structurally diverse allylic alkylsulfones (43 examples in total). The reaction of MBH adducts with potassium alkyltrifluoroborates and 1,4-diazabicyclo[2.2.2]octane bis(sulfur dioxide) adduct afforded sulfones with generally good yields. Notably, the addition of N,N,N',N'-tetramethylethylenediamine as a base into the photocatalytic system led to yielding an alkyl sulfonyl unit and cyano group-anchored trisubstituted alkenes by utilizing cycloketone oxime esters as C-radical precursors. Both of these reactions have constructed two C-S bonds, and all desired products were obtained in moderate to excellent yields with complete stereospecificity.

Enantioselective synthesis of [1,1'-binaphthalene]-8,8'-diyl bis(diphenylphosphane) and its derivatives.

Two 8,8' disubstituted binaphthyl ligands have been designed and synthesized in 3.1% and 11.4% overall yield, respectively. X-ray structure analysis demonstrated that a unique chiral microenvironment was created. With the assistance of a new aggregation-induced polarization (AIP) technology, chiral aggregates were determined as the fraction of polar solvent increased in the nonpolar/polar solvent system, which indicated their potential in modern asymmetric synthesis and catalysis.

Treatment with a flow diverter-assisted coil embolization for ruptured blood blister-like aneurysms of the internal carotid artery: a technical note and analysis of single-center experience with pooled data.

Treatment of blood blister-like aneurysms (BBAs) of the supraclinoid internal carotid artery (ICA) with flow diverters (FDs) has become widespread in recent years. However, ruptured blood blister-like aneurysm (BBA) of ICA treatment with flow diverter-assisted coil embolization (FDAC) remains controversial. Moreover, limited direct comparative studies have been conducted between the two treatment modalities, FDs and FDAC, for BBAs. The purpose of this study was to document our experience and evaluate the effectiveness and safety of FDAC. We conducted a retrospective analysis of clinical and radiological information from ten patients who experienced ruptured BBAs of the supraclinoid ICA at our center from January 2021 to February 2023. The technical details of FDAC for ruptured BBAs were described, and the technical steps were named "pipeline embolization device (PED)-Individualized shaping(microcatheter)-Semi deploying-Rivet(coils)-Massage(microwire)" as the PEISSERM technique. Clinical outcomes were assessed using the modified Rankin Scale (mRS), whereas radiological results were determined through angiography. A pooled analysis was implemented, incorporating data from literature sources that reported perioperative and long-term clinical and angiographic outcomes of ruptured BBAs treated with FD and FDAC strategies, along with our data. Data in our analysis pool were categorized into FD and FDAC strategy groups to explore the preferred treatment modalities for BBAs. The PEISSERM technique was utilized to treat ten patients, seven males, and three females, with an average age of 41.7 years. A single PED was deployed in conjunction with coils in all ten patients. All PEDs were documented to have good wall apposition. The immediate postoperative angiograms demonstrated Raymond grade I in ten aneurysms. Angiographic follow-up of nine patients at 4-25 months showed total occlusion of the aneurysms. At the most recent follow-up, the mRS scores of nine patients hinted at a good prognosis. Pooled analysis of 233 ICA-BBA cases of FD revealed a technical success rate of 91% [95% confidence interval (CI), 0.88 to 0.95], a rate of complete occlusion of 79% (95% CI, 0.73 to 0.84), a recurrence rate of 2% (95% CI, 0.00 to 0.04), a rebleed rate of 2% (95% CI, 0.00 to 0.04), and the perioperative stroke rate was 8% (95% CI, 0.04 to 0.11). The perioperative mortality was 4% (95% CI, 0.01 to 0.07). The long-term good clinical outcome rate was 85% (95% CI, 0.80 to 0.90). The mortality rate was 6% (95% CI, 0.03 to 0.09). Results from the subgroup analysis illustrated that the FDAC strategy for BBAs had a significantly higher immediate postoperative complete occlusion rate (P < 0.001), total occlusion rate (P = 0.016), and a good outcome rate (P = 0.041) compared with the FD strategy. The FDAC strategy can yield a higher rate of good outcomes than the FD strategy. The PEISSERM technique employed by the FDAC is a reliable and effective treatment approach as it can minimize the hemodynamic burden of BBA's fragile dome, thereby achieving an excellent occlusion rate. The PEISSERM technique in the FDAC strategy contributes to understanding the BBA's treatment and offers a potentially optimal treatment for BBA.

Four-layer folding framework: design, GAP synthesis, and aggregation-induced emission.

The design and synthesis of a type of [1 + 4 + 2] four-layer framework have been conducted by taking advantage of Suzuki-Miyaura cross-coupling and group-assisted purification (GAP) chemistry. The optimized coupling of double-layer diboronic esters with 1-bromo-naphth-2-yl phosphine oxides resulted in a series of multilayer folding targets, showing a broad scope of substrates and moderate to excellent yields. The final products were purified using group-assisted purification chemistry/technology, achieved simply by washing crude products with 95% EtOH without the use of chromatography and recrystallization. The structures were fully characterized and assigned by performing X-ray crystallographic analysis. UV-vis absorption, photoluminescence (PL), and aggregation-induced emission (AIE) were studied for the resulting multilayer folding products.

Aggregation-Induced Catalysis: Asymmetric Catalysis with Chiral Aggregates.

So far, there have been 4 methods to control chirality including the use of chiral auxiliaries, reagents, solvents, and catalysts documented in literature and textbooks. Among them, asymmetric catalysts are normally divided into homogeneous and heterogeneous catalysis. In this report, we present a new type of asymmetric control-asymmetric catalysis via chiral aggregates that would not belong to the above categories. This new strategy is represented by catalytic asymmetric dihydroxylation reaction of olefins in which chiral ligands are aggregated by taking advantage of typical aggregation-induced emission systems containing tetrahydrofuran and H2O cosolvents. It was proven that the chiral induction can be enhanced from er of 78:22 to 97:3 simply by changing the ratios of these 2 cosolvents. The formation of chiral aggregates of asymmetric dihydroxylation ligands, (DHQD)2PHAL and (DHQ)2PHAL, has been proven by aggregation-induced emission and a new analytical tool-aggregation-induced polarization established by our laboratory. In the meanwhile, chiral aggregates were found to be formed either by adding NaCl into tetrahydrofuran/H2O systems or by increasing concentrations of chiral ligands. The present strategy also showed promising reverse control of enantioselectivity in the Diels-Alder reaction. This work is anticipated to be extended broadly to general catalysis, especially to asymmetric catalysis in the future.

Catalytic Radical-Triggered Annulation/Iododifluoromethylation of Enynones for the Stereospecific Synthesis of 1-Indenones.

A new Pd(II)-catalyzed annulation/iododifluoromethylation of enynones has been developed for the synthesis of versatile 1-indanones with moderate to good yields (26 examples). The present strategy enabled the concomitant incorporation of two important difluoroalkyl and iodo functionalities into 1-indenone skeletons with (E)-stereoselectivity. The mechanistic pathway was proposed, consisting of the difluoroalkyl radical-triggered α,ß-conjugated addition/5-exo-dig cyclization/metal radical cross-coupling/reductive elimination cascade.

Copper-Catalyzed Annulation-Trifluoromethyl Functionalization of Enynones.

The Cu(I)-catalyzed annulation-halotrifluoromethylation and cyanotrifluoromethylation of enynones have been established, enabling multibond formations of the synthesis of quaternary carbon-centered 1-indanones in moderate to good chemical yields. The reaction of enynones with Togni's reagent and chloro- or bromotrimethylsilane afforded halo- and CF3-containing 1-indenones. However, the addition of K3PO4 as a base into the catalytic system led to forming cyano-anchored (Z)-1-indanones as major stereoisomeric products. This strategy exhibits remarkable compatibility with a wide range of enynones.

Lewis Acid-Catalyzed Remote Site-Selective Ring Deconstruction of Cyclobuteno[a]naphthalene-4-ones to Access Unsymmetric 1,1-Diarylated Olefins.

A catalytic site-selective ring deconstruction of cyclobuteno[a]naphthalene-4-ones with alcohols is reported, enabling the direct production of a wide range of unsymmetric 1,1-diarylated olefins with good yields and complete regioselectivity. The late-stage application of these resulting terminal olefins demonstrates great possibilities to apply this strategy to complex molecules. The protocol features good functional group compatibility, broad substrate scope, and controllable site selectivity.

Association of BRAF Variants With Disease Characteristics, Prognosis, and Targeted Therapy Response in Intrahepatic Cholangiocarcinoma.

Importance: BRAF variants are associated with tumor progression; however, the prevalence of BRAF variant subtypes and their association with disease characteristics, prognosis, and targeted therapy response in patients with intrahepatic cholangiocarcinoma (ICC) are largely unknown. Objective: To explore the association of BRAF variant subtypes with disease characteristics, prognosis, and targeted therapy response in patients with ICC. Design, Setting, and Participants: In this cohort study, 1175 patients who underwent curative resection for ICC from January 1, 2009, through December 31, 2017, were evaluated at a single hospital in China. Whole-exome sequencing, targeted sequencing, and Sanger sequencing were performed to identify BRAF variants. The Kaplan-Meier method and log-rank test were used to compare overall survival (OS) and disease-free survival (DFS). Univariate and multivariate analyses were performed using Cox proportional hazards regression. Associations between BRAF variants and targeted therapy response were tested in 6 BRAF-variant, patient-derived organoid lines and in 3 of the patient donors of those lines. Data were analyzed from June 1, 2021, to March 15, 2022. Interventions: Hepatectomy in patients with ICC. Main Outcomes and Measures: The association of BRAF variant subtypes with OS and DFS. Results: Of 1175 patients with ICC, the mean (SD) age was 59.4 (10.4) years and 701 (59.7%) were men. A total of 20 different subtypes of BRAF somatic variance affecting 49 patients (4.2%) were identified; V600E was the most frequent allele in this cohort, accounting for 27% of the identified BRAF variants, followed by K601E (14%), D594G (12%), and N581S (6%). Compared with patients with non-V600E BRAF variants, patients with BRAF V600E variants were more likely to have large tumor size (10 of 13 [77%] vs 12 of 36 [33%]; P = .007), multiple tumors (7 of 13 [54%] vs 8 of 36 [22%]; P = .04), and more vascular/bile duct invasion (7 of 13 [54%] vs 8 of 36 [22%]; P = .04). Multivariate analysis revealed that BRAF V600E variants, but not overall BRAF variants or non-V600E BRAF variants, were associated with poor OS (hazard ratio [HR], 1.87; 95% CI, 1.05-3.33; P = .03) and DFS (HR, 1.66; 95% CI, 1.03-2.97; P = .04). There were also broad differences among organoids with different BRAF variant subtypes in sensitivity to BRAF or MEK inhibitors. Conclusions and Relevance: The findings of this cohort study suggest that there are broad differences among organoids with different BRAF variant subtypes in sensitivity to BRAF or MEK inhibitors. Identifying and classifying BRAF variants may be able to help guide precise treatment for patients with ICC.

Stepwise Amplification of Circularly Polarized Luminescence in Chiral Metal Cluster Ensembles.

Chiral metal-organic frameworks (MOFs) are usually endowed by chiral linkers and/or guests. The strategy using chiral secondary building units in MOFs for solving the trade-off of circularly polarized luminescence (CPL)-active materials, high photoluminescence quantum yields (PLQYs) and high dissymmetry factors (|glum |) has not been demonstrated. This work directionally assembles predesigned chiral silver clusters with ACQ linkers through reticular chemistry. The nanoscale chirality of the cluster transmits through MOF's framework, where the linkers are arranged in a quasi-parallel manner and are efficiently isolated and rigidified. Consequently, this backbone of chiral cluster-based MOFs demonstrates superb CPL, high PLQYs of 50.3%, and |glum | of 1.2 × 10-2 . Crystallographic analyses and DFT calculations show the quasi-parallel arrangement manners of emitting linkers leading to a large angle between the electric and magnetic transition dipole moments, boosting CPL response. As compared, an ion-pair-direct assembly without interactions between linkers induces one-ninth |glum | and one-sixth PLQY values, further highlighting the merits of directional arrangement in reticular nets. In addition, a prototype CPL switching fabricated by a chiral framework is controlled through alternating ultraviolet and visible light. This work is expected to inspire the development of reticular chemistry for high-performance chiroptical materials.

Aggregation-induced polarization (AIP) of derivatives of BINOL and BINAP.

The relationship between optical rotations of small chiral molecules with water% in THF has been established. The typical aggregation co-solvent systems resulted in optical rotation amplification and adjustment, defined as aggregation-induced polarization (AIP). The AIP work can serve as a new tool to determine molecular aggregation, especially for those that cannot display aggregation-induced emission (AIE). Therefore, AIP and AIE are anticipated to complement each other. In addition, AIP can also serve as a new transmission tool providing adjusting right- or left-hand polarized lights of a series of individual wavelengths. Since chiral phosphine derivatives are among the most important ligands, this work would benefit research using chiral aggregates to control asymmetric synthesis and catalysts. Therefore, it will find many applications in chemical and materials sciences.

Aggregation-Induced Synthesis (AIS): Asymmetric Synthesis via Chiral Aggregates.

A new chiral aggregate-based tool for asymmetric synthesis has been developed by taking advantage of chiral aggregates of GAP (Group-Assisted Purification) reagents, N-phosphonyl imines. This tool was proven to be successful in the asymmetric GAP synthesis of functionalized 2,3-dihydrobenzofurans by reacting salicyl N-phosphonyl imines with dialkyl bromomalonates in various cosolvent systems. The chiral induction can be controlled by differentiating between two asymmetric directions simply by changing the ratios of cosolvents which are commonly adopted in AIE (aggregation-induced emission) systems. The formation of chiral aggregates was witnessed by a new analytical tool-aggregation-induced polarization (AIP). The present synthetic method will be broadly extended for general organic synthesis, particularly, for asymmetric synthesis and asymmetric catalysis in the future.

Aggregation-Induced Polarization (AIP): Optical Rotation Amplification and Adjustment of Chiral Aggregates of Folding Oligomers and Polymers.

The phenomenon of aggregation-induced polarization (AIP) was observed showing optical rotation amplification and adjustment. The relationship between optical rotations of chiral aggregates of multilayered chiral folding oligomers and polymers with water% in THF (f w) has been established accordingly. New multilayered chiral oligomers were synthesized under the asymmetric catalytic systems established by our laboratory recently. These products were well-characterized by UV-vis, NMR, and MALDI-TOF spectra. Absolute stereochemistry (enantio- and diastereochemistry) was assigned by comparison with similar asymmetric induction by the same catalyst in our previous reactions. The present AIP work can serve as a new tool to determine chiral aggregates, especially for those that cannot display emission. AIP would also complement AIE-based CPL since AIP serves as a new tool providing enhanced right- or left-hand polarized lights with individual wavelengths. It will find many applications in chemical and materials science in the future.

From Center-to-Multilayer Chirality: Asymmetric Synthesis of Multilayer Targets with Electron-Rich Bridges.

Asymmetric synthesis of new atropisomerically multilayered chiral targets has been achieved by taking advantage of the strategy of center-to-multilayer chirality and double Suzuki-Miyaura couplings. Diastereomers were readily separated via flash column chromatography and well characterized. Absolute configuration assignment was determined by X-ray structural analysis. Five enantiomerically pure isomers possessing multilayer chirality were assembled utilizing anchors involving electron-rich aromatic connections. An overall yield of 0.69% of the final target with hydroxyl attachment was achieved over 11 steps from commercially available starting materials.