Interrelated Mechanism by Which the Methide Quinone Celastrol,Obtained from the Roots of Tripterygium wilfordii,Inhibits Main Protease 3CLpro of COVID-19 and Acts as Superoxide Radical Scavenger

We describe the potential anti coronavirus disease 2019 (COVID-19) action of the methide quinone inhibitor, celastrol. The related methide quinone dexamethasone is, so far, among COVID-19 medications perhaps the most effective drug for patients with severe symptoms. We observe a parallel redox biology behavior between the antioxidant action of celastrol when scavenging the superoxide radical, and the adduct formation of celastrol with the main COVID-19 protease. The related molecular mechanism is envisioned using molecular mechanics and dynamics calculations. It proposes a covalent bond between the S(Cys145) amino acid thiolate and the celastrol A ring, assisted by proton transfers by His164 and His41 amino acids, and a π interaction from Met49 to the celastrol B ring. Specifically, celastrol possesses two moieties that are able to independently scavenge the superoxide radical: the carboxylic framework located at ring E, and the methide-quinone ring A. The latter captures the superoxide electron, releasing molecular oxygen, and is the feature of interest that correlates with the mechanism of COVID-19 inhibition. This unusual scavenging of the superoxide radical is described using density functional theory (DFT) methods, and is supported experimentally by cyclic voltammetry and X-ray diffraction.     

Mechanisms of Enzyme-Catalyzed Reduction of Two Carcinogenic Nitro-Aromatics, 3-Nitrobenzanthrone and Aristolochic Acid I: Experimental and Theoretical Approaches

This review summarizes the results found in studies investigating the enzymatic activation of two genotoxic nitro-aromatics, an environmental pollutant and carcinogen 3-nitrobenzanthrone (3-NBA) and a natural plant nephrotoxin and carcinogen aristolochic acid I (AAI), to reactive species forming covalent DNA adducts. Experimental and theoretical approaches determined the reasons why human NAD(P)H:quinone oxidoreductase (NQO1) and cytochromes P450 (CYP) 1A1 and 1A2 have the potential to reductively activate both nitro-aromatics. The results also contributed to the elucidation of the molecular mechanisms of these reactions. The contribution of conjugation enzymes such as N,O-acetyltransferases (NATs) and sulfotransferases (SULTs) to the activation of 3-NBA and AAI was also examined. The results indicated differences in the abilities of 3-NBA and AAI metabolites to be further activated by these conjugation enzymes. The formation of DNA adducts generated by both carcinogens during their reductive activation by the NOQ1 and CYP1A1/2 enzymes was investigated with pure enzymes, enzymes present in subcellular cytosolic and microsomal fractions, selective inhibitors, and animal models (including knock-out and humanized animals). For the theoretical approaches, flexible in silico docking methods as well as ab initio calculations were employed. The results summarized in this review demonstrate that a combination of experimental and theoretical approaches is a useful tool to study the enzyme-mediated reaction mechanisms of 3-NBA and AAI reduction.     

Absolute Configuration of β- and α-Asymmetric Carbons within β-O-4-Structures in Hardwood Lignin

In this study, we investigated the proportion of erythro- and threo-forms of β-O-4-ether structures and their enantiomeric compositions in hardwood lignin by applying the ozonation method to birch wood meal. Optical activity was not substantially observed in either the erythronic or threonic acids obtained as the ozonation products of β-O-4-structures in birch wood meal. The proportions of the four stereoisomeric forms {(αS,βR)-erythro, (αR,βR)-threo, (αS,βS)-threo, and (αR,βS)-erythro forms} were estimated to be 37-38%, 13-14%, 12-13%, and 36-37% based on the yields of erythronic and threonic acids, and on their optical activities. The proportions suggest that the entire components of β-O-4-ether structures in birch wood lignin have R- and S-configurations at the β-carbon in approximately the same quantities {(βR)-β-O-4-structure: (βS)-β-O-4-structure = 50–52:48–50}; i.e., that the β-ether structures are essentially racemic. This estimation implies that, during lignin biosynthesis, an equal number of enantiomeric forms of β-O-4-bonded quinone methides were formed by radical coupling reactions.     

Possibilities of the Formation of Enol-Ethers in Lignin by Soda Pulping

In the alkaline decomposition of a β-O-4 type lignin model compound (erythro-guaiacylglycerol-β-guaiacyl ether, compound 1), an isomeric pair of C₆C₂ enol-ether (2-methoxy-4-[2-(2-methoxyphenoxy)-vinyl]-phenol, compound 2) was detected as the main decomposition product with no trace of C₆C₃ enol-ether (4-[3-hydroxy-1-(2-methoxyphenoxy)-propenyl]-2-methoxy-phenol, compound 3) or other dimers. In contrast, compound 2 was not detected in the alkaline decomposition products of compound 3. Under alkaline conditions, the γ-hydroxymethyl group of compound 3 was reduced to form 2-methoxy-4-[1-(2-methoxyphenoxy)-propenyl]-phenol (compound 4). In the HSQC analysis of soda lignin, the formation of substructures of C₆C₂ type enol-ether (related to compound 2) was confirmed. However, no substructures related to compound 4, which could be formed if a substructure of C₆C₃ type enol-ether was formed under alkaline conditions, were detected. Therefore, it could be concluded that C₆C₃ type enol-ethers could not be intermediates of alkaline decomposition products of lignin.     

Oxidative Metabolism of Ferrocene Analogues of Tamoxifen: Characterization and Antiproliferative Activities of the Metabolites

Ferrociphenols have been found to have high antiproliferative activity against estrogen‐independent breast cancer cells. The rat and human liver microsome‐mediated metabolism of three compounds of the ferrocifen ( FC ) family, 1,1‐bis(4‐hydroxyphenyl)‐2‐ferrocenyl‐but‐1‐ene ( FC1 ), 1‐(4‐hydroxyphenyl)‐1‐(phenyl)‐2‐ferrocenyl‐but‐1‐ene ( FC2 ), and 1‐[4‐(3‐dimethylaminopropoxy)phenyl]‐1‐(4‐hydroxyphenyl)‐2‐ferrocenyl‐but‐1‐ene ( FC3 ), was studied. Three main metabolite classes were identified: quinone methides ( QM s) deriving from two‐electron oxidation of FC s, cyclic indene products ( CP s) deriving from acid‐catalyzed cyclization of QM s, and allylic alcohols ( AA s) deriving from hydroxylation of FC s. These metabolites are generated by cytochromes P450 (P450s), as shown by experiments with either N‐benzylimidazole as a P450 inhibitor or recombinant human P450s. Such P450‐dependent oxidation of the phenol function and hydroxylation of the allylic CH₂ group of FC s leads to the formation of QM and AA metabolites, respectively. Some of the new ferrociphenols obtained in this study were found to exhibit remarkable antiproliferative effects toward MDA‐MB‐231 hormone‐independent breast cancer cells.     

Synthesis and Anti-Proliferative Activity of Novel Quinolin-8-ol Derivatives

Through the coupling of substituted benzaldehydes with 8-hydroxy 5-amino methyl quinoline scaffold, a series of new derivatives has been synthesized. In vitro growth inhibitory effects on cancer cell line model have been evaluated. Discussion on the chemical reactivity of these new polycyclic aromatic analogs to generate alkylating species led to the hypothesis that the presence of an imine moiety impedes the formation of quinone methide intermediate and consequently abolishes in part their antiproliferative activity.     

Application of Calix[4]quinone in secondary batteries

随着社会对大型储能设备的环保、充放电性能以及可持续发展的要求越来越高,基于金属氧化物的传统锂/钠离子电极材料受限于比容量,已难以满足未来储能系统的要求。有机材料、锂-硫/氧、液态流体等电池的研发与应用已成为未来能源系统研究的重要内容。其中,有机正极材料中的羰基类化合物Calix[4]quinone（C4Q）是一种很有前途的正极材料。该分子的空间位阻小,8个羰基结构都能发生可逆电极反应,其理论比容量高达446 mA·h/g,远超传统无机电极材料。C4Q不仅可以作为储锂材料,也可作为钠、锌、镁等二次电池的电极材料。本文分别介绍了C4Q在锂、钠二次电池和锌水系电池中的应用成果,并对C4Q今后进一步的开发利用做了展望。     

新型聚省醌自由基高聚物的电磁性能

通过共缩聚合成了几种新型的，压阻系数很高的聚省醌自由基高聚物（ＰＡＱＲ）实验发现：在直流电导率对数与外界压力（０．０１～１．０ＧＰａ）平方根的线形关系上有一个转折点（约０．１１ＧＰａ）Ｍｏｔｔ－Ｔ＾１／４规律的适用范围可延伸至高温区（２９８～４８６Ｋ）直流电导率自旋浓度，ｇ因子和峰一峰线宽之间与共缩聚时个入的六氟二酐的物质的量比存在类似的变化趋势，在不同温度下介电系数的对数与压力平方根的线性关系图     

Supercritical fluid extraction of bacterial and archaeal lipid biomarkers from anaerobically digested sludge

Supercritical fluid extraction (SFE) was used in the analysis of bacterial respiratory quinone (RQ), bacterial phospholipid fatty acid (PLFA), and archaeal phospholipid ether lipid (PLEL) from anaerobically digested sludge. Bacterial RQ were determined using ultra performance liquid chromatography (UPLC). Determination of bacterial PLFA and archaeal PLEL was simultaneously performed using gas chromatography-mass spectrometry (GC-MS). The effects of pressure, temperature, and modifier concentration on the total amounts of RQ, PLFA, and PLEL were investigated by 23 experiments with five settings chosen for each variable. The optimal extraction conditions that were obtained through a multiple-response optimization included a pressure of 23.6 MPa, temperature of 77.6 °C, and 10.6% (v/v) of methanol as the modifier. Thirty nine components of microbial lipid biomarkers were identified in the anaerobically digested sludge. Overall, the SFE method proved to be more effective, rapid, and quantitative for simultaneously extracting bacterial and archaeal lipid biomarkers, compared to conventional organic solvent extraction. This work shows the potential application of SFE as a routine method for the comprehensive analysis of microbial community structures in environmental assessments using the lipid biomarkers profile.