Copper‐Catalyzed Enantioselective Allylboration of Alkynes: Synthesis of Highly Versatile Multifunctional Building Blocks

The first copper‐catalyzed enantioselective allylboration of alkynes is reported. The method employs a multitasking chiral NHC‐Cu catalyst and provides access to densely functionalized molecules from simple starting materials with excellent levels of chemo‐, regio‐, and enantioselectivity. These multifunctional products display highly versatile reactivity as shown by the synthesis of a variety of non‐racemic molecular scaffolds. DFT calculations were conducted to gain insight into the high selectivity levels of this catalytic process.     

Synthetic Humic Acids Solubilize Otherwise Insoluble Phosphates to Improve Soil Fertility

Artificial humic acids (A‐HA) made from biomass in a hydrothermal process turn otherwise highly insoluble phosphates (e.g. iron phosphate as a model) into highly available phosphorus, which contributes to the fertility of soils and the coupled plant growth. A detailed electron microscopy study revealed etching of the primary iron phosphate crystals by the ‐COOH and phenolic groups of humic acids, but also illustrated the importance of the redox properties of humic matter on the nanoscale. The combined effects result in the formation of then bioavailable phosphate nanoparticles stabilized by humic matter. Typical agricultural chemical tests indicate that the content of total P and directly plant‐available P improved largely. Comparative pot planting experiments before and after treatment of phosphates with A‐HA demonstrate significantly enhanced plant growth, as quantified in higher aboveground and belowground plant biomass.     

A Renal‐Clearable Duplex Optical Reporter for Real‐Time Imaging of Contrast‐Induced Acute Kidney Injury

Despite its high morbidity and mortality, contrast‐induced acute kidney injury (CIAKI) remains a diagnostic dilemma because it relies on in vitro detection of insensitive late‐stage blood and urinary biomarkers. We report the synthesis of an activatable duplex reporter (ADR) for real‐time in vivo imaging of CIAKI. ADR is equipped with chemiluminescence and near‐infrared fluorescence (NIRF) signaling channels that can be activated by oxidative stress (superoxide anion, O₂^.?) and lysosomal damage (N‐acetyl‐β‐d ‐glucosaminidase, NAG), respectively. By virtue of its high renal clearance efficiency (80 % injected doses after 24 h injection), ADR detects sequential upregulation of O₂^.? and NAG in the kidneys of living mice prior to a significant decrease in glomerular filtration rate (GFR) and tissue damage in the course of CIAKI. ADR outperforms the typical clinical assays and detects CIAKI at least 8 h (NIRF) and up to 16 h (chemiluminescence) earlier.     

Elucidating Molecule–Plasmon Interactions in Nanocavities with 2 nm Spatial Resolution and at the Single‐Molecule Level

The fundamental understanding of the subtle interactions between molecules and plasmons is of great significance for the development of plasmon‐enhanced spectroscopy (PES) techniques with ultrahigh sensitivity. However, this information has been elusive due to the complex mechanisms and difficulty in reliably constructing and precisely controlling interactions in well‐defined plasmonic systems. Herein, the interactions in plasmonic nanocavities of film‐coupled metallic nanocubes (NCs) are investigated. Through engineering the spacer layer, molecule–plasmon interactions were precisely controlled and resolved within 2 nm. Efficient energy exchange interactions between the NCs and the surface within the 1–2 nm range are demonstrated. Additionally, optical dressed molecular excited states with a huge Lamb shift of ≈7 meV at the single‐molecule (SM) level were observed. This work provides a basis for understanding the underlying molecule–plasmon interaction, paving the way for fully manipulating light–matter interactions at the nanoscale.     

Synthesis of Tri‐ and Difluoromethoxylated Compounds by Visible‐Light Photoredox Catalysis

Trifluoromethoxy (OCF₃) and difluoromethoxy (OCF₂H) groups are fluorinated structural motifs that exhibit unique physicochemical characteristics. Incorporation of these substituents into organic molecules is a highly desirable approach used in medicinal chemistry and drug discovery processes to alter the properties of a parent compound. Recently, tri‐ and difluoromethyl ethers have received increasing attention and several innovative strategies to access these valuable functional groups have been developed. The focus of this Minireview is the use of visible‐light photoredox catalysis in the synthesis of tri‐ and difluoromethyl ethers. Recent photocatalytic strategies for the formation of O?CF₃, C?OCF_3, O?CF₂H, and C?OCF₂H bonds as well as other transformations leading to the construction of OR_F groups are discussed herein.     

Characterization of new Pt(IV)–thiazole complexes: Analytical,spectral, molecular modeling and molecular docking studies and applications in two opposing pathways

New thiazole derivatives were synthesized and fully characterized, then coordinated with PtCl₄ salt. Also, the newly synthesized Pt(IV) complexes were investigated analytically (elemental and thermogravimetric analyses), spectrally (infrared, UV–visible, mass, ¹H NMR, ¹³C NMR, X‐ray diffraction) as well as theoretically (kinetics, modeling and docking). The data extracted led to the establishment of the best chemical and structural forms. Octahedral geometry was the only formula proposed for all complexes, which is favorable for d⁶ systems. The molecular ion peaks from mass spectral analysis coincide with all analytical data, confirming the molecular formula proposed. X‐ray diffraction (XRD) and scanning electron microscopy (SEM) allowed discrimination of features between crystalline particles and other amorphous morphology. By applying Gaussian09 as well as HyperChem 8.2 programs, the best structural forms were obtained, as well as computed significant parameters. Computed parameters such as softness, hardness, surface area and reactivity led us towards application in two opposing pathways: tumor inhibition and oxidation activation. The catalytic oxidation for CO was conducted over PtO₂, which was yielded from calcination of the most reactive complex. The success of catalytic role for synthesized PtO₂ was due to its particulate size and surface morphology, which were estimated from XRD patterns and SEM images, respectively. The antitumor activity was tested versus HCT‐116 and HepG‐2 cell lines. Mild toxicity was recorded for two of the derivatives and their corresponding complexes. This degree of toxicity is more favorable in most cases, due to exclusion of serious side effects, which is coherently attached with known antitumor drugs.     

Simultaneous determination of major components of Huangqi–Honghua extract in rat plasma using LC–MS/MS and application to a pharmacokinetic study

A sensitive and reliable LC–MS/MS method was developed and validated for simultaneous quantification of the major components of Huangqi–Honghua extact in rat plasma, including hydroxysafflor yellow A (HSYA), astragaloside IV (ASIV), calycosin‐7‐O‐β‐d ‐glucoside (CAG), calycosin, calycosin‐3′‐O‐glucuronide (C‐3′‐G) and calycosin‐3′‐O‐sulfate (C‐3′‐S). After extraction by protein precipitation with acetonitrile and methanol from plasma, the analytes were separated on a Hypersil BDS C₁₈ column by gradient elution with acetonitrile and 5 mM ammonium acetate. The detection was carried out on a triple quadrupole tandem mass spectrometer equipped with electrospray ionization source switched between negative and positive modes. HSYA was monitored in negative ionization mode from 0 to 4.9 min, and ASIV, CAG, calycosin, C‐3′‐G and C‐3′‐S were determined in positive ionization mode from 4.9 to 10 min. The lower limits of quantification of the analytes were 6.25 ng/mL for HSYA, 0.781 ng/mL for CAG and 1.56 ng/mL for ASIV and calycosin. The intra‐ and inter‐assay precision (RSD) values were within 13.43%, and accuracy (RE) ranged from ?8.75 to 9.92%. The validated method was then applied to the pharmacokinetic study of HSYA, ASIV, CAG, calycosin, C‐3′‐G and C‐3′‐S in rat after an oral administration of Huangqi–Honghua extract.     

Metabolomic analysis of raw Pinelliae Rhizoma and its alum‐processed products via UPLC–MS and their cytotoxicity

Alum‐processing is a traditional method to attenuate the toxicity of Pinelliae Rhizoma (tubers of Pinellia ternate, PT). The present study aimed at investigating the chemical and cytotoxic changes during alum processing. Metabolomic profiles of raw and alum‐processed PT were studied based on ultra‐performance liquid chromatography coupled with Orbitrap mass spectrometry. More than 80 chemicals in positive MS mode and 40 chemicals in negative MS mode, such as organic acids, amino acids, glucosides and nucleosides, were identified after multivariate statistical analysis, including principal component analysis and orthogonal partial least‐square discriminant analysis. Almost all of the identified chemical markers were significantly decreased ~10‐ to 100‐fold after alum processing. Meanwhile, the correlations between the chemical markers were assimilated to a positive coefficient from disorderly distribution during the processing. Raw PT extracts could inhibit the proliferation of human carcinoma cells (HCT‐116, HepG2, and A549) at the rate of 40.5, 24.8 and 31.6% more strongly than processed PT. It was concluded that the alum processing of PT could decrease the number of actively water‐soluble principles at the same time as decreasing toxicity. Given the water‐insoluble property of toxic calcium oxalate raphides in PT, we suggest that a more scientific processing method should be sought.     

Polymer nanoparticles with a sensitive CO2‐responsive hydrophilic/hydrophobic surface

Poly(methyl methacrylate) (PMMA) nanoparticles with a sensitive CO₂‐responsive hydrophilic/hydrophobic surface that confers controlled dispersion and aggregation in water were prepared by emulsion polymerization at 50 °C under CO₂ bubbling using amphiphilic diblock copolymers of 2‐dimethylaminoethyl methacrylate (DMAEMA) and N‐isopropyl acrylamide (NIPAAm) as an emulsifier. The amphiphilicity of the hydrophobic–hydrophilic diblock copolymer at 50 °C was triggered by CO₂ bubbling in water and enabled the copolymer to serve as an emulsifier. The resulting PMMA nanoparticles were spherical, approximately 100 nm in diameter and exhibited sensitive CO₂/N₂‐responsive dispersion/aggregation in water. Using copolymers with a longer PNIPAAm block length as an emulsifier resulted in smaller particles. A higher concentration of copolymer emulsifier led to particles with a stickier surface. Given its simple preparation and reversible CO₂‐triggered amphiphilic behavior, this newly developed block copolymer emulsifier offers a highly efficient route toward the fabrication of sensitive CO₂‐stimuli responsive polymeric nanoparticle dispersions. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 2149–2156     

Miktoarm star‐shaped poly(lactic acid) copolymer: Synthesis and stereocomplex crystallization behavior

The miktoarm star‐shaped poly(lactic acid) (PLA) copolymer, (PLLA)₂‐core‐(PDLA)₂, was synthesized via stepwise ring‐opening polymerization of lactide with dibromoneopentyl glycol as the starting material. ¹H NMR and FTIR spectroscopy proved the feasibility of synthetic route and the successful preparation of star‐shaped PLA copolymers. The results of FTIR spectroscopy and XRD showed that the stereocomplex structure of the copolymer could be more perfect after solvent dissolution treatment. Effect of chain architectures on crystallization was investigated by studying the nonisothermal and isothermal crystallization of the miktoarm star‐shaped PLA copolymer and other stereocomplexes. Nonisothermal differential scanning calorimetry and polarizing optical microscopy tests indicated that (PLLA)₂‐core‐(PDLA)₂ exhibited the fastest formation of a stereocomplex in a dynamic test due to its special structure. In isothermal crystallization tests, the copolymer exhibited the fast crystal growth rate and the most perfect crystal morphology. The results reveal that the unique molecular structure has an important influence on the crystallization of the miktoarm star‐shaped PLA copolymer. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019 , 57, 814–826