N‑Heterocyclic Carbene-Assisted, Bis(phosphine)nickel-Catalyzed Cross-Couplings of Diarylborinic Acids with Aryl Chlorides, Tosylates, and Sulfamates

Efficient bis­(phosphine)­nickel-catalyzed cross-couplings of diarylborinic acids with aryl chlorides, tosylates, and sulfamates have been effected with an assistance of N-heterocyclic carbene (NHC) generated in situ from <i>N</i>,<i>N</i>′-dialkylimidazoliums, e.g., <i>N</i>-butyl-<i>N</i>′-methylimidazolium bromide ([Bmim]­Br), in toluene using K₃PO₄·3H₂O as base. In contrast to bis­(NHC)­nickel-catalyzed conventional Suzuki coupling of arylboronic acids, mono­(NHC)­bis­(phosphine)­nickel species generated in situ from Ni­(PPh₃)₂Cl₂/[Bmim]Br displayed high catalytic activities in the cross-couplings of diarylborinic acids. The structural influences from diarylborinic acids were found to be rather small, while electronic factors from aryl chlorides, tosylates, and sulfamates affected the couplings remarkably. The couplings of electronically activated aryl chlorides, tosylates, and sulfamates could be efficiently effected with 1.5 mol % NiCl₂(PPh₃)₂/[Bmim]Br as catalyst precursor to give the biaryl products in excellent yields, while 3–5 mol % loadings had to be used for the couplings of non- and deactivated ones. A small <i>ortho</i>-substitutent on the aromatic ring of aryl chlorides, tosylates, and sulfamates was tolerable. Applicability of the nickel-catalyzed cross-couplings in practical synthesis of fine chemicals has been demonstrated in process development for a third-generation topical retinoid, Adapalene

Nickel-Catalyzed Cross-Coupling of Diarylborinic Acids with Aryl Chlorides

A highly efficient nickel/triarylphosphine catalyst system, Ni­[P­(4-MeOPh)₃]₂Cl₂/2P­(4-MeOPh)₃, has been developed for cross-coupling of diarylborinic acids with a wide range of aryl chlorides. A variety of unsymmetrical biaryl and heterobiaryl compounds with various functional groups and steric hindrance could be obtained in good to excellent yields using 0.5–2 mol % catalyst loadings in the presence of K₃PO₄·3H₂O in toluene. The high atom economy of diarylborinic acids and cost-effectiveness of the nickel/phosphine catalyst system make the cross-coupling truly practical in the production of biaryl fine chemicals. Usefulness of the nickel/phosphine catalyzed cross-coupling of diarylborinic acids with aryl chlorides has been demonstrated in the development of a scalable and economical process for synthesis of 4′-methyl-2-cyanobiphenyl, Sartan biphenyl

Diels–Alder Click-Based Hydrogels for Direct Spatiotemporal Postpatterning via Photoclick Chemistry

Click chemistry not only has been applied to the design of hydrogel scaffolds for 3D cell culture, but also is an efficient way for hydrogel postfunctionalization and spatiotemporal patterning. To the best of our knowledge, only azide–alkyne cycloaddition (SPAAC) has been exploited by combining photoinitiated thiol–ene click reaction to realize the 3D patterning of hydrogels. In this work, the cyclohexene derivative, which “clicked” by functional groups between furyl and maleimide, were successfully functionalized by thiol-modified molecules or peptides through thiol–ene click reaction. It illustrates a hydrogel that formed via Diels–Alder (DA) click chemistry between furyl-modified hyaluronic acid and bimaleimide functional PEG molecule can be allowed for the directly photoactivated thiol–ene chemistry for hydrogel spatiotemporal patterning. Since the cyclohexene derivatives produced by DA reaction can be employed in all subsequent 3D network patterning by using photoclick reactions, it suggests a new way to design and postfunctionalize all of the DA click-based hydrogels with specific regional bioactive cues

Cross-Coupling of Diarylborinic Acids and Anhydrides with Arylhalides Catalyzed by a Phosphite/N-Heterocyclic Carbene Co-supported Palladium Catalyst System

A highly efficient cross-coupling of diarylborinic acids and anhydrides with aryl chlorides and bromides has been effected by using a palladium catalyst system co-supported by a strong σ-donor N-heterocyclic carbene (NHC), <i>N</i>,<i>N</i>′-bis­(2,6-diisopropylphenyl) imidazol-2-ylidene, and a strong π-acceptor phosphite, triphenylphosphite, in <i>tert</i>-BuOH in the present of K₃PO₄·3H₂O. Unsymmetrical biaryls with a variety of functional groups could be obtained in good to excellent yields using as low as 0.01, 0.2–0.5, and 1 mol % palladium loadings for aryl bromides and activated and deactivated aryl chlorides, respectively, under mild conditions. A ligand synergy between the σ-donor NHC and the π-acceptor phosphite in the Pd/NHC/P­(OPh)₃ catalytic system has been proposed to be responsible for the high efficacy to arylchlorides in the cross-coupling. A scalable and economical process has therefore been developed for synthesis of Sartan biphenyl from the Pd/NHC/P­(OPh)₃ catalyzed cross-coupling of di­(4-methylphenyl)­borinic acid with 2-chlorobenzonitrile

Rapid Diagnosis of Urinary Tract Cancers on a LEGO-Inspired Detection Platform via Chemiresistive Profiling of Volatile Metabolites

Rapid and in situ profiling of volatile metabolites from body fluids represents a new trend in cancer diagnosis and classification in the early stages. We report herein an on-chip strategy that combines an array of conductive nanosensors with a chaotic gas micromixer for real-time monitoring of volatiles from urine and for accurate diagnosis and classification of urinary tract cancers. By integrating a class of LEGO-inspired microchambers immobilized with MXene-based sensing nanofilms and zigzag microfluidic gas channels, it enables the intensive intermingling of volatile organic chemicals with sensor elements that tremendously facilitate their ion–dipole interactions for molecular recognition. Aided with an all-in-one, point-of-care platform and an effective machine-learning algorithm, healthy or diseased samples from subpopulations (i.e., tumor subtypes, staging, lymph node metastasis, and distant metastasis) of urinary tract cancers can be reliably fingerprinted in a few minutes with high sensitivity and specificity. The developed detection platform has proven to be a noninvasive supplement to the liquid biopsies available for facile screening of urinary tract cancers, which holds great potential for large-scale personalized healthcare in low-resource areas

Rapid Diagnosis of Urinary Tract Cancers on a LEGO-Inspired Detection Platform via Chemiresistive Profiling of Volatile Metabolites

Rapid and in situ profiling of volatile metabolites from body fluids represents a new trend in cancer diagnosis and classification in the early stages. We report herein an on-chip strategy that combines an array of conductive nanosensors with a chaotic gas micromixer for real-time monitoring of volatiles from urine and for accurate diagnosis and classification of urinary tract cancers. By integrating a class of LEGO-inspired microchambers immobilized with MXene-based sensing nanofilms and zigzag microfluidic gas channels, it enables the intensive intermingling of volatile organic chemicals with sensor elements that tremendously facilitate their ion–dipole interactions for molecular recognition. Aided with an all-in-one, point-of-care platform and an effective machine-learning algorithm, healthy or diseased samples from subpopulations (i.e., tumor subtypes, staging, lymph node metastasis, and distant metastasis) of urinary tract cancers can be reliably fingerprinted in a few minutes with high sensitivity and specificity. The developed detection platform has proven to be a noninvasive supplement to the liquid biopsies available for facile screening of urinary tract cancers, which holds great potential for large-scale personalized healthcare in low-resource areas

Multifunctional Hydrogel with Good Structure Integrity, Self-Healing, and Tissue-Adhesive Property Formed by Combining Diels–Alder Click Reaction and Acylhydrazone Bond

Hydrogel, as a good cartilage tissue-engineered scaffold, not only has to possess robust mechanical property but also has to have an intrinsic self-healing property to integrate itself or the surrounding host cartilage. In this work a double cross-linked network (DN) was designed and prepared by combining Diels–Alder click reaction and acylhydrazone bond. The DA reaction maintained the hydrogel’s structural integrity and mechanical strength in physiological environment, while the dynamic covalent acylhydrazone bond resulted in hydrogel’s self-healing property and controlled the on–off switch of network cross-link density. At the same time, the aldehyde groups contained in hydrogel further promote good integration of the hydrogel to surrounding tissue based on aldehyde-amine Schiff-base reaction. This kind of hydrogel has good structural integrity, autonomous self-healing, and tissue-adhesive property and simultaneously will have a good application in tissue engineering and tissue repair field

Enzyme-Linked Immunosorbent Assay-Based Microarray on a Chip for Bioaerosol Sensing: Toward Sensitive and Multiplexed Profiling of Foodborne Allergens

Food allergy has become a growing health concern that may impair life quality and even cause life-threatening outcomes. Accidental and continuous exposure to allergenic bioaerosols has a substantially negative impact on the respiratory health of patients. Traditional analytical methodologies for food allergens are restricted by strong reliance on bulk instrumentation and skilled personnel, particularly in low-resource settings. In this study, a fluorescent sensor array based on the enzyme-linked immunosorbent assay performed on a herringbone-shaped microfluidic chip (ELISA-HB-chip) was designed for dynamically sensitive and multiplexed quantification of foodborne allergens in aerosols that originated from liquid food extracts. Due to the high surface area of aerosol particles and sufficient mixing of immunological reagents using a herringbone micromixer, the detection sensitivity was improved by over an order of magnitude compared to traditional allergen detection in the aqueous phase. Through fluorescence imaging of multiple regions on the ELISA-HB-chip, four important foodborne allergens, namely, ovalbumin, ovomucoid, lysozyme, and tropomyosin, could be simultaneously monitored without any cross-reactivity, and the limits of detection for these allergenic species were determined to be 7.8, 1.2, 4.2, and 0.31 ng/mL, respectively. Combining with a 3D printed and portable fluorescence microscope, this platform exhibited an excellent field-deployable capacity for quick and accurate determination of allergens in the aerosol state from spiked buffer solutions, thus displaying the practicality for food safety screening at cooking or food processing sites where patients are potentially under exposure to allergenic bioaerosols that escaped from food matrices or extracts

Strontium-Substituted Submicrometer Bioactive Glasses Modulate Macrophage Responses for Improved Bone Regeneration

Host immune response induced by foreign bone biomaterials plays an important role in determining their fate after implantation. Hence, it is well worth designing advanced bone substitute materials with beneficial immunomodulatory properties to modulate the host–material interactions. Bioactive glasses (BG), with excellent osteoconductivity and osteoinductivity, are regarded as important biomaterials in the field of bone regeneration. In order to explore a novel BG-based osteoimmunomodulatory implant with the capacity of potentially enhancing bone regeneration, it is a possible way to regulate the local immune microenvironment through manipulating macrophage polarization. In this study, strontium-substituted submicrometer bioactive glass (Sr–SBG) was prepared as an osteoimmunomodulatory bone repair material. To investigate whether the incorporation of Sr into SBG could synergistically improve osteogenesis by altering macrophage response, we systematically evaluated the interaction between Sr–SBG and macrophage during the process of bone regeneration by in vitro biological evaluation and in vivo histological assessment. It was found that the Sr–SBG modulates proper inflammatory status, leading to enhanced osteogenesis of mouse mesenchymal stem cells (mMSCs) and suppressed osteoclastogenesis of RAW 264.7 cells compared to SBG without strontium substitution. In vivo study confirmed that Sr–SBG initiated a less severe immune response and had an improved effect on bone regeneration than SBG, which corresponded with the in vitro evaluation. In conclusion, these findings suggested that Sr–SBG could be a promising immunomodulatory bone repair material designed for improved bone regeneration

High-Efficiency All Polymer Solar Cell with a Low Voltage Loss of 0.56 V

Reducing voltage loss, namely, <i>V</i>_loss, has been demonstrated to be an effective way to improve the efficiencies of photovoltaic devices, and power conversion efficiencies (PCEs) exceeding 10% have been reported in non-fullerene based polymer solar cells (PSCs) with <i>V</i>_loss value lower than 0.6 V. However, for all polymer solar cells (APSCs), the PCEs lag far behind the non-fullerene PSCs with organic small molecular acceptors. And there have been no successful examples of high-efficiency APSCs along with low <i>V</i>_loss values so far. Here, we reported APSCs that demonstrated a high efficiency of 6.66% simultaneously with a small voltage loss of 0.56 V by using a new polymer PBDT-DFQX1 as donor and N2200 as acceptor. Notably, when PBDT-DFQX1 is combined with a small molecular acceptor (SMA) O-IDTBR, the relative SMA based PSC exhibited a higher PCE of 8.76% also with a low voltage loss of 0.56 V. These results indicated that PBDT-DFQX1 would be a promising polymer donor material in photovoltaic device application, and the strategy by minimizing the voltage loss to improve the photovoltaic efficiencies is still valid for APSCs