Anti-fibrosis attributes: UHPLC-MS/MS-based pharmacokinetics profiling of a novel autotaxin inhibitor with excellent in vivo efficacy in rat

3,4-Difluorobenzyl(1-ethyl-5-(4-((4-hydroxypiperidin-1-yl)-methyl)thiazol-2-yl)-1H-indol-3-yl)carbamate (NAI59), a small molecule with outstanding therapeutic effectiveness to anti-pulmonary fibrosis, was developed as an autotaxin inhibitor candidate compound. To evaluate the pharmacokinetics and plasma protein binding of NAI59, a UPLC–MS/MS method was developed to quantify NAI59 in plasma and phosphate-buffered saline. The calibration curve linearity ranged from 9.95 to 1990.00 ng/mL in plasma. The accuracy was −6.8 to 5.9%, and the intra- and inter-day precision was within 15%. The matrix effect and recovery, as well as dilution integrity, were within the criteria. The chromatographic and mass spectrometric conditions were also feasible to determine phosphate-buffered saline samples, and it has been proved that this method exhibits good precision and accuracy in the range of 9.95–497.50 ng/mL in phosphate-buffered saline. This study is the first to determine the pharmacokinetics, absolute bioavailability, and plasma protein binding of NAI59 in rats using this established method. Therefore, the pharmacokinetic profiles of NAI59 showed a dose-dependent relationship after oral administration, and the absolute bioavailability in rats was 6.3%. In addition, the results of protein binding showed that the combining capacity of NAI59 with plasma protein attained 90% and increased with the increase in drug concentration.     

A gadolinium-based magnetic ionic liquid for supramolecular dispersive liquid–liquid microextraction followed by HPLC/UV for the determination of favipiravir in human plasma

Favipiravir is a potential antiviral medication that has been recently licensed for Covid-19 treatment. In this work, a gadolinium-based magnetic ionic liquid was prepared and used as an extractant in dispersive liquid–liquid microextraction (DLLME) of favipiravir in human plasma. The high enriching ability of DLLME allowed the determination of favipiravir in real samples using HPLC/UV with sufficient sensitivity. The effects of several variables on extraction efficiency were investigated, including type of extractant, amount of extractant, type of disperser and disperser volume. The maximum enrichment was attained using 50 mg of the Gd-magnetic ionic liquid (MIL) and 150 μl of tetrahydrofuran. The Gd-based MIL could form a supramolecular assembly in the presence of tetrahydrofuran, which enhanced the extraction efficiency of favipiravir. The developed method was validated according to US Food and Drug Administration bioanalytical method validation guidelines. The coefficient of determination was 0.9999, for a linear concentration range of 25 to 1.0 × 10⁵ ng/ml. The percentage recovery (accuracy) varied from 99.83 to 104.2%, with RSD values (precision) ranging from 4.07 to 11.84%. The total extraction time was about 12 min and the HPLC analysis time was 5 min. The method was simple, selective and sensitive for the determination of favipiravir in real human plasma.     

Dinuclear Zinc Catalyzed Enantioselective Dearomatization [3+2] Annulation of 2-Nitrobenzofurans and 2-Nitrobenzothiophenes

The application of dinuclear zinc catalysts in a dearomatization reaction has been developed. Catalytic asymmetric dearomatization [3+2] annulations of 2-nitrobenzofurans or 2-nitrobenzothiophenes with CF₃-containing N-unprotected isatin-derived azomethine ylides catalyzed by dinuclear zinc catalysts are realized with excellent diastereomer ratios (dr) of >20 : 1 and enantiomeric excess (ee) of up to 99 %. This protocol provides a practical, straightforward access to structurally diverse pyrrolidinyl spirooxindoles containing a 2,3-fused-dihydrobenzofuran (or dihydrobenzothiphene) moiety, and four contiguous stereocenters. Reactions can be performed on a gram scale. The absolute configuration of products is confirmed by X-ray single crystal structure analysis, and a possible mechanism is proposed.     

Periodicity of Two-Dimensional Bonding of Main Group Elements

In the periodic table the position of each atom follows the ‘aufbau’ principle of the individual electron shells. The resulting intrinsic periodicity of atomic properties determines the overall behavior of atoms in two-dimensional (2D) bonding and structure formation. Insight into the type and strength of bonding is the key in the discovery of innovative 2D materials. The primary features of 2D bonding and the ensuing monolayer structures of the main-group II–VI elements result from the number of valence electrons and the change of atom size, which determine the type of hybridization. The results reveal the tight connection between strength of bonding and bond length in 2D networks. The predictive power of the periodic table reveals general rules of bonding, the bonding-structure relationship, and allows an assessment of published data of 2D materials.     

Development and validation of LC–MS/MS method for amlexanox in rat plasma and its application in preclinical pharmacokinetics

Amlexanox, an anti-inflammatory and anti-allergic agent, has been widely used clinically for the treatment of canker sores, asthma, and allergic rhinitis. Recently, amlexanox has received considerable attention in curing nonalcoholic fatty liver diseases and hepatitis virus infection. Herein, we first established a sensitive high-performance liquid chromatography-tandem mass spectrum (LC–MS/MS) method for the determination of amlexanox in rat plasma. Propranolol was used as the internal standard (IS). Using a simple protein precipitation method, the amlexanox and IS were separated with Capcell Pak C18 column (2.0 × 50 mm, 5 μm) and eluted with water and acetonitrile each containing 0.1% formic acid using gradient elution condition at a flow rate of 0.4 mL·min⁻¹. Amlexanox and IS were detected by a triple quadrupole mass in multiple reactive monitoring (MRM) under the transitions of m/z 299.2 → 281.2 and m/z 259.9 → 116.1 with positive electrospray ionization, respectively. The calibration curves of amlexanox were established with the range of 50 to 2000 ng·mL⁻¹ (r² > 0.99). The validation method consisted of selectivity, accuracy, precision, carryover effect, matrix effect, recovery, dilution effect, and stability. The fully validated method was successfully applied to the pharmacokinetic study of amlexanox in Wistar rats.     

Transition-Metal-Free Heterocyclic Carbon-Boron Bond Formation

Heteroaryl boronic acids and esters are extremely important and valuable intermediates because of their wide application in the synthesis of marketed drugs and bioactive compounds. Over the last couple of decades, the construction of highly important heteroaryl carbon-boron bonds has created huge attention. The transition-metal-free protocols are more green, less sensitive to air and moisture, and also economically advantageous over the transition-metal-based protocols. The transition-metal-free C−H borylation of heteroarenes and C−X (X=halogen) borylation of heteroaryl halides represents an excellent approach for their synthesis. Also, various cyclization and alkyne activation protocols have been recently established for their synthesis. The goal of this review article is to summarize the existing literature and the current state of the art for transition-metal-free synthesis of heteroaryl boronic acid and esters.     

水热法制备二氧化锡/钨酸铋复合光催化材料及其催化活性研究

本文用水热法制备了正交晶系的纳米球状结构的二氧化锡和正交晶系的由片状聚集成球状结构的钨酸铋,并且对二者进行了复合,制备出了二氧化锡/钨酸铋复合光催化材料。采用X射线衍射(XRD)、扫描电子显微镜(SEM)、比表面积测试仪(BET)、紫外可见分光光度计等技术对复合样品的结构、形貌、比表面积、孔容孔径和光学性质进行了表征。用碘钨灯模拟太阳光,分别以二氧化锡、钨酸铋和二氧化锡/钨酸铋复合材料为催化剂降解罗丹明B(RhB),研究所制备的二氧化锡/钨酸铋复合材料的光催化活性。光催化90 min时二氧化锡、钨酸铋和二氧化锡/钨酸铋对罗丹明B的降解率分别是9%、22%和30%。实验结果表明,在可见光下,二氧化锡/钨酸铋复合材料的光催化活性要高于单一的二氧化锡和钨酸铋。     

Highly diastereoselective multicomponent synthesis of polysubstituted 2-hydroxy-2-trifluoromethylpiperidineswith four and five stereogenic centers

The Michael–Mannich cascade cyclization of cyano olefins, ethyl 4,4,4-trifluoro-3-oxobutanoate, aromatic aldehydes and ammonium acetate provides convenient stereoselective formation of ethyl 5,5-dicyano-4,6-diaryl-2-hydroxy-2-(trifluoromethyl)piperidine-3-carboxylates with fourstereogenic centers and dialkyl 4,6-diaryl-5-cyano-2-hydroxy-2-(trifluoromethyl)piperidine-3,5-dicarboxylates with five stereogenic centers. Ammonium acetate plays dual role, acting as a base and as a nitrogen source.     

Modulating Charge Carrier Efficient Separation Enabled by Lewis Base Modification in Paper-based Photoelectrochemical Sensor

The separation efficiency of charge carriers determines the analytical sensitivity of the paper-based photoelectrochemical sensor. Herein, the Lewis base modification strategy is proposed to promote the carrier separation through an in-situ ion exchange method. Firstly, three-dimensional paper-based hierarchically TiO₂ (PHT) arrays are prepared with the one-step hydrothermal method. With the aid of Lewis base, the photo-induced charge separation efficiency and the photocurrent signal are obviously increased. Ultimately, sensitive sensing of prostate specific antigen (PSA) is achieved and the linear range is 1 pg/mL–100 ng/mL with the detection limitation of 0.3 pg/mL.     

氧化铝/氮化硅双层膜晶硅钝化的开尔文探针力显微镜研究

对晶体硅(c-Si)太阳能电池而言, 氧化铝(AlOx)是一种广泛使用的钝化材料, 因为它具有优异的沉积保形性和良好的钝化质量. 为了确保AlOx发挥其良好的钝化效果, 在沉积后退火并氢化处理是必不可少的. 通过在AlOx薄膜上沉积氢化氮化硅(SiNx:H)来实现氢化, 利用开尔文探针力显微镜研究了在不同热处理和氢化作用下, AlOx/SiNx:H双层薄膜功函数的变化, 并基于沉积薄膜所含氢与固定电荷展开了讨论. 发现钝化质量和功函数之间有相关性, 影响因素包括薄膜厚度、氢化与热处理顺序.