An integrated drug-likeness study for bicyclic privileged structures: from physicochemical properties to in vitro ADME properties

The concept of drug-likeness has been widely applied in combinatorial chemistry as an approach to reduce attrition in drug discovery and development. Meanwhile, bicyclic privileged structures with versatile binding properties have emerged as ideal source of core scaffolds for the design and synthesis of combinatorial libraries. For the purpose of better assisting the design of bicyclic privileged structure-based combinatorial libraries, we conducted an integrated drug-likeness study on compounds of these scaffolds. Distributions of physicochemical properties (PCPs) were analyzed and in silico prediction models were built. Our results showed that there exist much difference between the drug-like ranges (DLRs) of bicyclic privileged structures and that of others, which have significant impact on compound selection. The DLRs for bicyclic privileged structures were defined as 260 ≤ MW ≤ 524; 0.9 ≤ ALogP ≤ 5.4; 2 ≤ Hacc ≤ 8; Hdon ≤ 3; 21.0 ≤ PSA ≤ 128.6; 6.3 ≤ FPSA ≤ 34.2; 1 ≤ RotB ≤ 10; 2 ≤ Nr ≤ 5; 1 ≤ Nc ≤ 7; SA ≤ 4. Two accurate and easy to understand in silico prediction models, Caco-2 permeability model and metabolic stability classification model, had been built to guide drug candidate optimization. In these models, hydrogen-bond donor and rotatable bond showed major impact on the permeability of compounds, while lipophilicity, flexibility, degree of branching and the existence of some functional groups determined the fate of a drug in metabolic process. Suggestions on structural modification toward higher permeability and metabolic stability were given according to the in silico models.     

Recent advances and trends of heterogeneous electro-Fenton process for wastewater treatment-review

Electrochemical advanced oxidation processes （EAOPs） are effective and environmentally friendly for the treatment of refractory organic pollutants.Among EAOPs,heterogeneous electro-Fenton （EF） process with in-situ formation of hydrogen peroxide （H₂O₂） is an eco-friendly,cost-effective and easy-operable technology to generate hydroxyl radicals （^·OH） with high redox potential.The generation of^·OH is determined by the synergistic H₂O₂     

用于描述W-Cu粉末混合物冲击压缩行为的p-α与p-λ模型适用性

研究了3种p-α模型和p-λ模型在预测非均质W-Cu混合粉末冲击压实响应的适用性。利用Mie-Grüneisen方法和Barry等压混合法,基于单质W、Cu粉末的Hugoniot关系预测了同孔隙度的W-Cu混合粉末的Hugoniot线,在高压段与实验结果符合较好,但在低压段与实验偏差较大。分别应用3种p-α模型和p-λ模型对实验结果进行拟合,发现除p-α PL模型外,其他模型均较好地描述W-Cu混合粉末的冲击压缩响应,受经验参数选择的影响,所有模型的压溃强度和压缩路径各不相同,预测功能较差。     

Optimizing Fe-Based Metal-Organic Frameworks through Ligand Conformation Regulation for Efficient Dye Adsorption and C2H2/CO2 Separation

Regulating the structure of metal-organic frameworks (MOFs) by adjusting the ligands reasonably is expected to enhance the interaction of MOFs on special molecules/ions, which has significant application value for the selective adsorption of guest molecules. Herein, two tricarboxylic ligands H₃L−Cl and H₃L−NH₂ were designed and synthesized based on the ligand H₃TTCA by replacing part of the benzene rings with C=C bonds and modifying the chlorine and amino groups on the 4-position of the benzene ring. Two 3D Fe-MOFs ( UPC-60-Cl and UPC-60-NH₂ ) with the new topology types were constructed. As the C=C bonds of the ligands have flexible torsion angles, UPC-60-Cl features three types of irregular 2D channels, while UPC-60-NH₂ has a cage with two types of windows on the surface. The synergistic effect of unique channels and modification of functional groups endows UPC-60-Cl and UPC-60-NH₂ with high adsorption capacity for organic dyes. Compound UPC-60-Cl shows high adsorption capacity for CV (147.2 mg g⁻¹), RHB (100.3 mg g⁻¹), and MO (220.9 mg g⁻¹), whereas UPC-60-NH₂ exhibits selective adsorption of MO (158.7 mg g⁻¹). Meanwhile, based on the diverse pore structure and modification of active sites, UPC-60-Cl and UPC-60-NH₂ show the selective separation of equimolar C₂H₂/CO₂. Therefore, reasonable regulation of organic ligands plays a significant role in guiding the structure diversification and performance improvement of MOFs.     

Detonation diffraction in combustible high-speed flows

Detonation propagating in a T-shaped tube with quiescent and moving hydrogen/oxygen/argon mixtures is numerically examined based on the Euler equations with detailed finite-rate chemistry using the fifth-order weighted essentially non-oscillatory scheme. When diffracted in a quiescent combustible mixture, the detonation wave propagating from the bottom of the T-shaped tube is influenced by the corner rarefaction waves and decays into a non-reacting shock. Subsequently, the decoupled shock reflects irregularly from the top wall. Through several reflections back and forth between the top and bottom walls, a planar detonation is finally re-established. When the combustible mixture in the horizontal part flows from the left to the right, the detonation products ejected from the vertical tube will retard the flow, generating a compression flow upstream and a rarefaction flow downstream. The disturbed detonation on the left side is stronger than that on the right side. The final planar detonation in the upstream direction propagates faster than the Chapman–Jouguet (CJ) detonation with compressed, fine cellular structures, whereas the detonation in the downstream direction propagates more slowly than the CJ detonation with elongated, coarse cellular structures. The details of the transient behavior of diffracting detonation in high-speed flows are discussed.     

用于推进的三种爆轰波的结构特征

爆轰发动机研究的关键技术之一是如何将其控制在燃烧室内.根据控制手段的不同,爆轰发动机可大致分为:驻定爆轰发动机、脉冲爆轰发动机和旋转爆轰发动机.存在于燃烧室的爆轰,在宏观和精细结构以及自持机理等方面皆不同于CJ(Chapman Jouget)理论为基础的经典爆轰.本文将对此类无害爆轰的特征结构进行分析、比较与评述,这对了解爆轰理论和研制爆轰发动机是有益的.      

Needle and seed segmentation in intra-operative 3D ultrasound-guided prostate brachytherapy

In order to guide the needle to the correct location in 3D US-guided brachytherapy, the needle is continuously tracked as it is being inserted. A pre-scan before the needle insertion and a post-scan after the needle insertion are subtracted to obtain a difference image containing the needle. The image is projected along two orthogonal directions approximately perpendicular to the needle, and the 3D needle is reconstructed from the segmented needles in the two projected images. The seeds implanted with the needle are located in the cropped volume along the needle. Thus, the seeds are segmented using a tri-bar model and 3D line segment patterns. Finally, the positions of the seeds are determined using a peak detection technique. Experiments with agar and turkey/chicken phantoms as well as patient data demonstrated that our needle segmentation technique could segment the needle in near real-time with an accuracy of 0.6 mm in position and 1.0 degrees in orientation. The true-positive rate for seed segmentation is 100% for the agar phantom and 93% for the chicken phantom. The average distance to manual seed segmentation was 1.0mm for the agar phantom and 1.7 mm for the chicken phantom.     

Electrocatalysis of Cu−MOF/Graphene Composite and its Sensing Application for Electrochemical Simultaneous Determination of Dopamine and Paracetamol

A nanocomposite of HKUST‐1 (MOF) and electroreduction graphene oxide (ERGO) is prepared and applied as an electrochemical sensor for the simultaneous determination of paracetamol and dopamine by means of one‐step electrodeposition. The MOF/ERGO composite displays excellent electrochemical catalytic activities towards the paracetamol and dopamine, which is attributed to the synergistic effect of big surface area, porosity and high electrocataytic activity of the MOF and good conductivity of ERGO. The modified electrode could be applied to determine simultaneously paracetamol and dopamine in biochemical samples with wide linear ranges (0.2 μM to 160 μM for paracetamol and 0.2 μM to 300 μM for dopamine) and low detection limits (0.016 μM for paracetamol and 0.013 μM for dopamine). Meanwhile, the proposed sensor still displays high sensitivity, good selectivity and excellent stability.     

Simultaneous determination of nine trace concentration angiotensin peptides in human serum using ultra high performance liquid chromatography with tandem mass spectrometry with sephadex LH‐20 gel solid‐phase extraction

The renin–angiotensin system is a highly complex enzymatic system consisting of multiple peptide hormones, enzymes, and receptors. Here, an assay to simultaneously quantify eight angiotensin peptides and bradykinin in human serum was developed and validated, using ultra high performance liquid chromatography coupled with tandem mass spectrometry. A pre‐concentration method of Sephadex LH‐20 gel solid‐phase extraction was first applied for analysis of angiotensin peptides from serum sample. The triple quadrupole mass spectrometer was operated in the positive ion mode and multiple reaction monitoring was used for drug quantification. The analytical time was within 5 min, much raising the analysis efficiency. Limits of detection ranged from 0.9 to 1.3 pg/mL, and displayed the same level of sensitivity compared with radioimmunoassay. The method was successfully applied to 22 healthy human serum samples, giving the concentrations of angiotensin I, angiotensin II, angiotensin III, angiotensin IV, angiotensin 1–9, angiotensin 1–7, angiotensin 1–5, Asn¹,Val⁵‐Angiotensin II, and bradykinin for reference. This novel metabolic profile study of vasoactive peptides based on gel solid‐phase extraction concentration provided not only an accurate quantitative assay of the serum concentrations, but also a promising methodology for evaluating the diagnostic values of the various peptides.     

A facile synthesis of cis-1-methyl-1,2,3,3a,4,8b- hexahydropyrrolo[3,2-f]pyrindine,an annulated nicotine analog

[reaction: see text] The title compound, 2, has been synthesized in 45% overall yield in six steps from 3-bromopyridine. The hexahydropyrrolo[3,2-f]pyrindine skeleton was constructed from key intermediate 5, via intramolecular azomethine ylide-alkene [3 + 2] cycloaddition. The present work constitutes a general method for rapid assembly of other related tricyclic nicotine analogues.