Methoxy-Substituted Tyramine Derivatives Synthesis,Computational Studies and Tyrosinase Inhibitory Kinetics

Targeting tyrosinase for melanogenesis disorders is an established strategy. Hydroxyl-substituted benzoic and cinnamic acid scaffolds were incorporated into new chemotypes that displayed in vitro inhibitory effects against mushroom and human tyrosinase for the purpose of identifying anti-melanogenic ingredients. The most active compound 2-((4-methoxyphenethyl)amino)-2-oxoethyl (E)-3-(2,4-dihydroxyphenyl) acrylate (Ph9), inhibited mushroom tyrosinase with an IC₅₀ of 0.059 nM, while 2-((4-methoxyphenethyl)amino)-2-oxoethyl cinnamate (Ph6) had an IC₅₀ of 2.1 nM compared to the positive control, kojic acid IC₅₀ 16700 nM. Results of human tyrosinase inhibitory activity in A375 human melanoma cells showed that compound (Ph9) and Ph6 exhibited 94.6% and 92.2% inhibitory activity respectively while the positive control kojic acid showed 72.9% inhibition. Enzyme kinetics reflected a mixed type of inhibition for inhibitor Ph9 (K_i 0.093 nM) and non-competitive inhibition for Ph6 (K_i 2.3 nM) revealed from Lineweaver–Burk plots. In silico docking studies with mushroom tyrosinase (PDB ID:2Y9X) predicted possible binding modes in the catalytic site for these active compounds. Ph9 displayed no PAINS (pan-assay interference compounds) alerts. Our results showed that compound Ph9 is a potential candidate for further development of tyrosinase inhibitors.     

Red Blood Cell Stiffness and Adhesion Are Species-Specific Properties Strongly Affected by Temperature and Medium Changes in Single Cell Force Spectroscopy

Besides human red blood cells (RBC), a standard model used in AFM-single cell force spectroscopy (SCFS), little is known about apparent Young’s modulus (Ea) or adhesion of animal RBCs displaying distinct cellular features. To close this knowledge gap, we probed chicken, horse, camel, and human fetal RBCs and compared data with human adults serving as a repository for future studies. Additionally, we assessed how measurements are affected under physiological conditions (species-specific temperature in autologous plasma vs. 25 °C in aqueous NaCl solution). In all RBC types, Ea decreased with increasing temperature irrespective of the suspension medium. In mammalian RBCs, adhesion increased with elevated temperatures and scaled with reported membrane sialic acid concentrations. In chicken only adhesion decreased with higher temperature, which we attribute to the lower AE-1 concentration allowing more membrane undulations. Ea decreased further in plasma at every test temperature, and adhesion was completely abolished, pointing to functional cell enlargement by adsorption of plasma components. This halo elevated RBC size by several hundreds of nanometers, blunted the thermal input, and will affect the coupling of RBCs with the flowing plasma. The study evidences the presence of a RBC surface layer and discusses the tremendous effects when RBCs are probed at physiological conditions.     

Terpyridine-Functionalized Calixarenes: Synthesis,Characterization and Anion Sensing Applications

Lanthanide complexes have been developed and are reported herein. These complexes were derived from a terpyridine-functionalized calix[4]arene ligand, chelated with Tb³⁺ and Eu³⁺. Synthesis of these complexes was achieved in two steps from a calix[4]arene derivative: (1) amide coupling of a calix[4]arene bearing carboxylic acid functionalities and (2) metallation with a lanthanide triflate salt. The ligand and its complexes were characterized by NMR (¹H and ¹³C), fluorescence and UV-vis spectroscopy as well as MS. The photophysical properties of these complexes were studied; high molar absorptivity values, modest quantum yields and luminescence lifetimes on the ms timescale were obtained. Anion binding results in a change in the photophysical properties of the complexes. The anion sensing ability of the Tb(III) complex was evaluated via visual detection, UV-vis and fluorescence studies. The sensor was found to be responsive towards a variety of anions, and large binding constants were obtained for the coordination of anions to the sensor.     

新旧人教版化学必修教材插图的比较研究*

对人教版2019年版与2007年版高中化学必修教材的插图数量、插图类型和插图功能进行了比较研究,发现新版教材的插图在总数、平均每章数量和平均每页数量上均有提升;不同类型插图的绝对数量均有增加,以科技前沿和知识归纳型的增加为首;在插图的功能方面减少了装饰型插图,增加了组织型与解释型插图。最后根据前文的统计数据对比和相关分析,对我国新教材的编制提出了注意插图类型、数量以及功能的适配,注意发挥其美育与德育价值的建议。     

Synthesis,anti‐inflammatory activity,and molecular docking study of novel azo bis antipyrine derivatives against cyclooxygenase‐2 enzyme

We have synthesized a new series of azo‐bis antipyrine derivatives from a one‐pot multicomponent Knoevenagel/Michael addition reaction of antipyrine, with a diversity of azo aldehydes in ethanol and L‐Proline as a catalyst under reflux condition. The anti‐inflammatory activity of the final products was assessed using the inhibition of albumin denaturation technique. Compound 3f showed an inhibitory effect with IC₅₀ values of 3.6 μM with respect to the standard anti‐inflammatory drug Aspirin, with IC₅₀ values of 2 μM. In addition, molecular docking was performed to confirm the in vitro results against the enzymatic inhibition activity of COX‐2 enzymes in which compound 3f showed good binding affinity with an inhibition constant (Ki) of 1.79 nM.     

Chiral Phosphoric‐Acid‐Catalyzed Transfer Hydrogenation of Ethyl Ketimine Derivatives by Using Benzothiazoline

Chiral phosphoric acid catalyzed transfer hydrogenation of ketimines derived from propiophenone derivatives and reductive amination of alkyl ethyl ketone derivatives were extensively examined in the presence of two representative hydrogen donors. The excellent enantioselective transfer hydrogenation was achieved by use of benzothiazoline as a hydrogen donor. The theoretical studies elucidated that the unsymmetrical structure of benzothiazoline plays an important role in high enantioselective hydrogenation.     

Single-Molecule Analysis Determines Isozymes of Human Alkaline Phosphatase in Serum

Alkaline phosphatase (ALP) is an important biomarker, as high levels of ALP in blood can indicate liver disease or bone disorders. However, current clinical blood tests only measure the total concentration of ALP but are unable to distinguish enzyme isotypes. Here, we demonstrate a novel and rapid approach to profile various ALP isozymes in blood via a single-molecule-analysis platform. The microarray platform provides enzyme kinetics of hundreds of individual molecules at high throughput. Using these single molecule kinetics, we characterize the different activity profiles of ALP isotypes. By analyzing both healthy and disease samples, we found the single molecule activity distribution of ALP in serum reflects the health status of patients. This result demonstrates the potential utility of the method for improving the conventional ALP test, as well as for analyzing other enzymatic biomarkers, including enzyme isotypes.     

Facile Preparation of WO3−x Dots with Remarkably Low Toxicity and Uncompromised Activity as Co-reactants for Clinical Diagnosis by Electrochemiluminescence

The exceptional nature of WO_3−x dots has inspired widespread interest, but it is still a significant challenge to synthesize high-quality WO_3−x dots without using unstable reactants, expensive equipment, and complex synthetic processes. Herein, the synthesis of ligand-free WO_3−x dots is reported that are highly dispersible and rich in oxygen vacancies by a simple but straightforward exfoliation of bulk WS₂ and a mild follow-up chemical conversion. Surprisingly, the WO_3−x dots emerged as co-reactants for the electrochemiluminescence (ECL) of Ru(bpy)₃²⁺ with a comparable ECL efficiency to the well-known Ru(bpy)₃²⁺/tripropylamine (TPrA) system. Moreover, compared to TPrA, whose toxicity remains a critical issue of concern, the WO_3−x dots were ca. 300-fold less toxic. The potency of WO_3−x dots was further explored in the detection of circulating tumor cells (CTCs) with the most competitive limit of detection so far.     

From 1D to 2D Cd(II) and Zn(II) Coordination Networks by Replacing Monocarboxylate with Dicarboxylates in Partnership with Azine Ligands: Synthesis,Crystal Structures,Inclusion, and Emission Properties

Eight mixed-ligand coordination networks, [Cd(2-aba)(NO₃)(4-bphz)_3/2]_n·n(dmf) (1), [Cd(2-aba)₂(4-bphz)]_n·0.75n(dmf) (2), [Cd(seb)(4-bphz)]_n·n(H₂O) (3), [Cd(seb)(4-bpmhz)]_n·n(H₂O) (4), [Cd(hpa)(3-bphz)]_n (5), [Zn(1,3-bdc)(3-bpmhz)]_n·n(MeOH) (6), [Cd(1,3-bdc)(3-bpmhz)]_n ·0.5n(H₂O)·0.5n(EtOH) (7), and [Cd(NO₃)₂(3-bphz)(bpe)]_n·n(3-bphz) (8) were obtained by interplay of cadmium nitrate tetrahydrate or zinc nitrate hexahydrate with 2-aminobenzenecarboxylic acid (H(2-aba)), three dicarboxylic acids, sebacic (decanedioic acid, H₂seb), homophthalic (2-(carboxymethyl)benzoic acid, H₂hpa), isophthalic (1,3-benzenedicarboxylic acid, H₂(1,3-bdc)) acids, bis(4-pyridyl)ethane (bpe) and with four azine ligands, 1,2-bis(pyridin-4-ylmethylene)hydrazine (4-bphz), 1,2-bis(1-(pyridin-4-yl)ethylidene) hydrazine (4-bpmhz), 1,2-bis(pyridin-3-ylmethylene)hydrazine (3-bphz), and 1,2-bis(1-(pyridin-3-yl) ethylidene)hydrazine (3-bpmhz). Compounds 1 and 2 are 1D coordination polymers, while compounds 3–8 are 2D coordination polymers. All compounds were characterized by spectroscopic and X-ray diffraction methods of analysis. The solvent uptakes and stabilities to the guest evacuation were studied and compared for 1D and 2D coordination networks. The de-solvated forms revealed a significant increase of emission in comparison with the as-synthesized crystals.     

Real‐Time NMR Spectroscopy for Studying Metabolism

Current metabolomics approaches utilize cellular metabolite extracts, are destructive, and require high cell numbers. We introduce here an approach that enables the monitoring of cellular metabolism at lower cell numbers by observing the consumption/production of different metabolites over several kinetic data points of up to 48 hours. Our approach does not influence cellular viability, as we optimized the cellular matrix in comparison to other materials used in a variety of in‐cell NMR spectroscopy experiments. We are able to monitor real‐time metabolism of primary patient cells, which are extremely sensitive to external stress. Measurements are set up in an interleaved manner with short acquisition times (approximately 7 minutes per sample), which allows the monitoring of up to 15 patient samples simultaneously. Further, we implemented our approach for performing tracer‐based assays. Our approach will be important not only in the metabolomics fields, but also in individualized diagnostics.