Ligand Control of Palladium-Catalyzed Site-Selective α- and γ-Arylation of α,β-Unsaturated Ketones with (Hetero)aryl Halides

This study describes the first palladium-catalyzed, site-selective α- and γ-arylation of α,β-unsaturated ketones with (hetero)aryl halides. A wide range of hetero(aryl)halides coupled with α,β-unsaturated ketones, and transformation into the arylated products proceeded with excellent to good yields. The site selectivity of the reaction is switchable by simply changing the phosphine ligand to access either α-arylated or γ-arylated products in good to excellent yields by using a low catalyst loading, and the method demonstrates good functional-group compatibility.     

婴儿湿巾缓冲能力的测试——一个贴近生活的实验

为了有效提升学生在缓冲溶液学习过程中的学习兴趣及积极性,在此推荐一个将现实中的生活用品作为实验对象引入实验课教学过程中的案例。该实验设计将性质实验扩充到婴儿湿巾,将实验内容变为对婴儿湿巾工作原理的验证,而不再是过去简单的酸碱体系的配制及相关验证实验。通过该实验的实施,学生普遍反映能够有效激发其在学习缓冲溶液相关课程中的学习积极性与兴趣,并最终促使学生认知缓冲体系内pH变化的特点及缓冲机理。     

有机化学实验线上课程之扬长避短教学设计与实践篇

It has been two months since a boom of online education triggered by the epidemic in China. At present, we are keeping focus on how to optimize our online class. In the case of chemistry laboratory courses, there's not much that can be done to experimental operations through online teaching. While for the traditional teaching procedure, there is still room for improvement in terms of integrating research to teaching, interactivity, etc. This paper will present some design strategies for improving teaching the organic chemistry laboratory online. To be specific, it describes how teaching materials like the lesson plan and virtual lab were coordinated into the online teaching. And we will also discuss the holistic approach to a better outcome for students' active learning and integration research into teaching by redesigning multiple phases, such as the pre-laboratory preparation, live online class, experimental operations.     

Stability-indicating RP-HPLC method development and validation for determination of nine impurities in apixaban tablet dosage forms. Robustness study by quality by design approach

A quality by design (QbD) based high-resolution HPLC method is described for determination of impurities in apixaban (APX) in the tablet dosage form. Employing a simple and stability-indicating HPLC method, nine known impurities were quantified with good peak resolution. Mobile phase A (MP-A) was prepared with buffer and acetonitrile 90:10 v/v, while mobile phase B (MP-B) contained water and acetonitrile 10:90 v/v. The gradient program was 0 min, MP-A 75%, B 25%; 20 min, MP-A 65%, B 35%; 30 min, MP-A 40%, B 60%; 40min, MP-A 40%, B 60%; 42 min, MP-A 75%, B 25%; and 50 min, MP-A 75%, B 25%. The chromatographic separation was achieved using a Zorbax RX C₁₈ 250 × 4.6 mm column, 5 μm (1.0 ml min⁻¹, 280 nm, 50 μl) and a column temperature of 40°C. Several separation studies were carried out using design of experiments to optimize the method. Validation results confirm the applicability of the developed method for quality analysis and stability studies of the regular product on the manufacturing stream.     

Effect of polymer and ion concentration on mechanical and drug release behavior of gellan hydrogels using factorial design

Developing optimized hydrogel products requires an in-depth understanding of the mechanisms that drive hydrogel tunability. Here, we performed a full 4 × 4 factorial design study investigating the impact of gellan, a naturally derived polysaccharide (1%, 2%, 3%, or 4% w/v) and CaCl₂ concentration (1, 3, 7, or 10 mM) on the viscoelastic, swelling, and drug release behavior of gellan hydrogels containing a model drug, vancomycin. These concentrations were chosen to specifically provide insight into gellan hydrogel behavior for formulations utilizing polymer and salt concentrations expanding beyond those commonly reported by previous studies exploring gellan. With increasing gellan and CaCl₂ concentration, the hydrogel storage moduli (0.1–100 kPa) followed a power-law relationship and on average these hydrogels had higher liquid absorption capability and greater total drug release over 6 days. We suggest that the effects of gellan and CaCl₂ concentration and their interactions on hydrogel properties can be explained by various phenomena that lead to increased swelling and increased resistance to network expansion.     

Copper Bis(oxazoline)-Catalyzed Enantioselective Alkynylation of Benzopyrylium Ions

The stereocontrolled construction of biologically relevant chromanones and tetrahydroxanthones has been achieved through the addition of alkynes to benzopyrylium trilfates under the influence of copper bis(oxazoline) catalysis. Excellent levels of enantiocontrol (63–98 % ee) are achieved in the addition of a variety of alkynes to an array of chromenones with a hydrogen in the 2-position. Promising levels of enantiocontrol (54–67 % ee) are achieved in the alkynylation of chromenones with esters in the 2-position, generating tertiary ether stereocenters resembling those frequently found in naturally occurring metabolites.     

Ligand Taxonomy for Bioinorganic Modeling of Dioxygen-Activating Non-Heme Iron Enzymes

Novel functions emerge from novel structures. To develop efficient catalytic systems for challenging chemical transformations, chemists often seek inspirations from enzymatic catalysis. A large number of iron complexes supported by nitrogen-rich multidentate ligands have thus been developed to mimic oxo-transfer reactivity of dioxygen-activating metalloenzymes. Such efforts have significantly advanced our understanding of the reaction mechanisms by trapping key intermediates and elucidating their geometric and electronic properties. Critical to the success of this biomimetic approach is the design and synthesis of elaborate ligand systems to balance the thermodynamic stability, structural adaptability, and chemical reactivity. In this Concept article, representative design strategies for biomimetic atom-transfer chemistry are discussed from the perspectives of “ligand builders”. Emphasis is placed on how the primary coordination sphere is constructed, and how it can be elaborated further by rational design for desired functions.     

AuI-Catalyzed Haloalkynylation of Alkenes

The formal insertion of alkenes into aromatic chloro- and bromoalkynes takes place under cationic gold catalysis. This haloalkynylation reaction can be performed with cyclic, gem-disubstituted and monosubstituted alkenes, using BINAP, triazolo[4,3-b]isoquinolin-3-ylidene ligands or SPhos, respectively. The products were isolated in moderate to excellent yields and with complete diastereo- and regioselectivity; the halogen atom bonding the more substituted carbon of the alkene. Preliminary experiments showed that the enantioselective haloalkynylation of cyclopentene can be performed with (S)-BINAP to afford the insertion products with moderate to good enantioselectivities.     

Stereochemistry-Controlled Supramolecular Architectures of New Tetrahydroxy-Functionalised Amphiphilic Carbocyanine Dyes

The syntheses of novel amphiphilic 5,5′,6,6′-tetrachlorobenzimidacarbocyanine (TBC) dye derivatives with aminopropanediol head groups, which only differ in stereochemistry (chiral enantiomers, meso form and conformer), are reported. For the achiral meso form, a new synthetic route towards asymmetric cyanine dyes was established. All compounds form J aggregates in water, the optical properties of which were characterised by means of spectroscopic methods. The supramolecular structure of the aggregates is investigated by means of cryo-transmission electron microscopy, cryo-electron tomography and AFM, revealing extended sheet-like aggregates for chiral enantiomers and nanotubes for the mesomer, respectively, whereas the conformer forms predominately needle-like crystals. The experiments demonstrate that the aggregation behaviour of compounds can be controlled solely by head group stereochemistry, which in the case of enantiomers enables the formation of extended hydrogen-bond chains by the hydroxyl functionalities. In case of the achiral meso form, however, such chains turned out to be sterically excluded.     

Synergistic Biophysical Techniques Reveal Structural Mechanisms of Engineered Cationic Antimicrobial Peptides in Lipid Model Membranes

In the quest for new antibiotics, two novel engineered cationic antimicrobial peptides (eCAPs) have been rationally designed. WLBU2 and D8 (all 8 valines are the d -enantiomer) efficiently kill both Gram-negative and -positive bacteria, but WLBU2 is toxic and D8 nontoxic to eukaryotic cells. We explore protein secondary structure, location of peptides in six lipid model membranes, changes in membrane structure and pore evidence. We suggest that protein secondary structure is not a critical determinant of bactericidal activity, but that membrane thinning and dual location of WLBU2 and D8 in the membrane headgroup and hydrocarbon region may be important. While neither peptide thins the Gram-negative lipopolysaccharide outer membrane model, both locate deep into its hydrocarbon region where they are primed for self-promoted uptake into the periplasm. The partially α-helical secondary structure of WLBU2 in a red blood cell (RBC) membrane model containing 50 % cholesterol, could play a role in destabilizing this RBC membrane model causing pore formation that is not observed with the D8 random coil, which correlates with RBC hemolysis caused by WLBU2 but not by D8.