Heterocyclic benzothiazole-based liquid crystals: synthesis and mesomorphic properties

Two homologous series of 2-(4-alkanoyloxybenzylidenamino)benzothiazoles and 2-(2-hydroxy-4-alkanoyloxybenzylidenamino)benzothiazoles were synthesised and characterised. Their molecular structures differed wherein the latter comprised a lateral hydroxyl group, unlike the former. Spectroscopic techniques such as FT-IR, ¹H & ¹³C NMR and mass spectrometry together with elemental analysis were employed to elucidate the molecular structures. The transition temperatures and their mesophases were determined by differential scanning calorimetry, optical polarising microscopy and X-ray diffraction techniques. Members with decanoyloxy till hexadecanoloxy chain in the series without the lateral hydroxyl group each exhibited a smectic A phase, while those in the series with the lateral hydroxyl group were non-mesogenic. The mesomorphic properties of the present series were compared with other structurally related series to establish the chemical structure–mesomorphic properties relationship.     

Synthesis and liquid crystalline properties of substituted 2,5‐diaryl 1,3,4‐oxadiazole derivatives without flexible chains

A series of new compounds based on aromatically 2,5‐disubstituted 1,3,4‐oxadiazoles without flexible chains, formulated as p‐R–C₆H₄–(OC₂N₂)–(p‐C₆H₄)₂–R′ with (i) R = CH₃O, R′ = CH₃O, CH₃S, F, H (Ia–Id), (ii) R = CH₃S, R′ = CH₃O, CH₃S, F, H (IIa–IId) and (iii) R = F, R′ = CH₃O, CH₃S, F, H (IIIa–IIId) (p‐C₆H₄ and OC₂N₂ represent a p‐phenylene spacer and a 1,3,4‐oxadiazole ring, respectively), were synthesised and characterised by ¹H and ¹³C NMR, MS and HRMS techniques. Mesomorphic properties were investigated using differential scanning calorimetry and polarizing optical microscopy. All of the target compounds (except Id, IId, IIIc and IIId) exhibited an enantiotropic nematic mesophase with high melting temperatures. The liquid crystalline properties of these compounds were influenced greatly by polarity, steric factors and positions of the terminal groups. The effect of the terminal groups on the liquid crystal properties is discussed.     

多种类表面活性剂临界胶束浓度定量构效关系

表面活性剂的临界胶束浓度(CMC)是个非常重要的物质特性参数, CMC在研究表面活性剂的工业应用和生物利用方面发挥着关键作用. 本工作提出了一个新的拓扑指数—扩展距离矩阵, 建立了一个稳定的构效关系模型, 并对175种表面活性剂的临界胶束浓度进行了计算预测. 结果表明, 基于新的拓扑指数建立的构效关系模型计算临界胶束浓度能给出稳定可靠的预测结果, 其预测结果相关性系数R²(training set)=0.9295, 相对标准偏差ARD(training set)=8.20%, R²(testing set)=0.9257, ARD(testing set)=6.76%. 与文献中模型预测结果的对比表明, 本工作在稳定性和可靠性上均有显著改善.     

钯(Ⅱ)类抗肿瘤药物研究进展

20世纪60年代,美国密执安州立大学Rosenberg发现了顺铂具有抗癌活性,开辟了金属类抗肿瘤药物研究的新领域.经过40余年的研究,已相继成功开发了卡铂、奈达铂、奥沙利铂、舒铂、洛铂和双环铂等铂类抗肿瘤药物.虽然对于铂类抗肿瘤药物研究取得了一定的成绩,但在临床使用过程中也存在一些问题,如其毒副作用和抗药性,限制了其在临床上的进一步广泛应用.为了解决这些问题,科研工作者开始寻找新的金属类抗肿瘤药物以弥补现有铂类抗肿瘤药物的不足.在金属元素中,唯有钯(II)与铂(II)配合物具有相似或相同的结构特征,进而表现出相近或相似的化学性质.因此,继铂类抗肿瘤配合物后,钯(II)配合物作为潜在抗肿瘤药物成为一个诱人的领域.本文综述了近年来钯(II)类抗肿瘤药物的研究进展,并探讨了其构效关系,这对于指导新型钯(II)类抗肿瘤药物的合成具有重要的参考价值.     

In Silico Design and SAR Study of Dibenzyl Trisulfide Analogues for Improved CYP1A1 Inhibition

Dibenzyl trisulfide (DTS) is a natural compound with potential cancer-preventive properties occurring in Petiveria alliacea L., an ethnomedicinal plant native to the Americas. Previous studies revealed its inhibitory activity toward cytochrome P450 (CYP)1 enzymes, key in the activation of environmental pollutants. Accordingly, the aim of this study was to design novel DTS analogues, aimed at improving not only inhibitory activity, but also specificity toward CYP1A1. This was achieved by targeting interactions with CYP1A1 residues of identified importance. Three-dimensional structures for the novel analogues were subjected to molecular docking with several CYP isoforms, before being ranked in terms of binding affinity to CYP1A1. With three hydrogen bond donors, two hydrogen bond acceptors, a molecular mass of 361 Da, and a log P of 3.72, the most promising DTS analogue obeys Lipinski's rule of five. Following synthesis and in vitro validation of its CYP1A1-inhibitory properties, this compound may be useful in future cancer-preventive approaches.     

Amide Moieties Modulate the Antimicrobial Activities of Conjugated Oligoelectrolytes against Gram-negative Bacteria

Cationic conjugated oligoelectrolytes (COEs) are a class of compounds that can be tailored to achieve relevant in vitro antimicrobial properties with relatively low cytotoxicity against mammalian cells. Three distyrylbenzene-based COEs were designed containing amide functional groups on the side chains. Their properties were compared to two representative COEs with only quaternary ammonium groups. The optimal compound, COE2−3C−C3-Apropyl , has an antimicrobial efficacy against Escherichia coli with an MIC=2 μg mL⁻¹, even in the presence of human serum albumin low cytotoxicity (IC₅₀=740 μg mL⁻¹) and minimal hemolytic activity. Moreover, we find that amide groups increase interactions between COEs and a bacterial lipid mimic based on calcein leakage assay and allow COEs to readily permeabilize the cytoplasmic membrane of E. coli. These findings suggest that hydrogen bond forming moieties can be further applied in the molecular design of antimicrobial COEs to further improve their selectivity towards bacteria.     

Recent advances in electrochemistry of pyridinium-based electrophores: A structronic approach

The context of molecular structronics (from “molecular structure” and “electronics”) is that of molecular-level electrochemical storage of energy of sustainable origin (wind, solar). Due to its discontinuous availability, storage of this energy is a key issue. The targeted type of storage relies on implementing “electron reservoirs” within the structronic molecules by electrochemically forming dedicated chemical bonds according to non-catalytic processes. Reservoir bonds are therefore integral parts of the molecular backbone of structronic assemblies. When filled, electron reservoirs manifest themselves in the form of elongated covalent bonds that are to be cleaved for electron releasing (discharging) on demand. The scope of this short review is limited to pyridinium electrophores as particularly suited building blocks for the development of structronics.     

The Inhibitory Effects of Plant Derivate Polyphenols on the Main Protease of SARS Coronavirus 2 and Their Structure–Activity Relationship

The main protease (M^pro) is a major protease having an important role in viral replication of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the novel coronavirus that caused the pandemic of 2020. Here, active M^pro was obtained as a 34.5 kDa protein by overexpression in E. coli BL21 (DE3). The optimal pH and temperature of M^pro were 7.5 and 37 °C, respectively. M^pro displayed a K_m value of 16 μM with Dabcyl-KTSAVLQ↓SGFRKME-Edans. Black garlic extract and 49 polyphenols were studied for their inhibitory effects on purified M^pro. The IC₅₀ values were 137 μg/mL for black garlic extract and 9–197 μM for 15 polyphenols. The mixtures of tannic acid with puerarin, daidzein, and/or myricetin enhanced the inhibitory effects on M^pro. The structure–activity relationship of these polyphenols revealed that the hydroxyl group in C3′, C4′, C5′ in the B-ring, C3 in the C-ring, C7 in A-ring, the double bond between C2 and C3 in the C-ring, and glycosylation at C8 in the A-ring contributed to inhibitory effects of flavonoids on M^pro.