Computational Methods for Understanding the Selectivity and Signal Transduction Mechanism of Aminomethyl Tetrahydronaphthalene to Opioid Receptors

Opioid receptors are members of the group of G protein-couple receptors, which have been proven to be effective targets for treating severe pain. The interactions between the opioid receptors and corresponding ligands and the receptor’s activation by different agonists have been among the most important fields in opioid research. In this study, with compound M1, an active metabolite of tramadol, as the clue compound, several aminomethyl tetrahydronaphthalenes were designed, synthesized and assayed upon opioid receptors. With the resultant compounds FW-AII-OH-1 (Ki = 141.2 nM for the κ opioid receptor), FW-AII-OH-2 (Ki = 4.64 nM for the δ opioid receptor), FW-DI-OH-2 (Ki = 8.65 nM for the δ opioid receptor) and FW-DIII-OH-2 (Ki = 228.45 nM for the δ opioid receptor) as probe molecules, the structural determinants responsible for the subtype selectivity and activation mechanisms were further investigated by molecular modeling and molecular dynamics simulations. It was shown that Y^7.43 was a key residue in determining the selectivity of the three opioid receptors, and W^6.58 was essential for the selectivity of the δ opioid receptor. A detailed stepwise discovered agonist-induced signal transduction mechanism of three opioid receptors by aminomethyl tetrahydronaphthalene compounds was proposed: the 3–7 lock between TM3 and TM7, the DRG lock between TM3 and TM6 and rearrangement of I^3.40, P^5.50 and F^6.44, which resulted in the cooperative movement in 7 TMs. Then, the structural relaxation left room for the binding of the G protein at the intracellular site, and finally the opioid receptors were activated.     

From Environmental Analytical Chemistry to Ecotoxicology—A Plea for More Concepts and Less Monitoring and Testing

The development of cultural and technical civilization has been marked with increasing interference in hydrogeochemical cycles and the production of a growing number of chemicals; this is accompanied by a growing concern on the potential adverse effects of chemicals on biological systems. Assessment of the potential toxicological and ecological effects of pollutants is of central importance. We are of the opinion that this cannot be accomplished by merely evaluating the harmfulness of a substance on the basis of toxicity tests with individual organisms and by monitoring analytically the environment for pollutants. We would like to encourage chemists to participate in the solution of ecotoxicological problems: chemodynamical concepts permit the estimation-on the basis of physical-chemical generalizations and with the help of compound-specific data-of the fate, the distribution, the potential for bioaccumulation in the food chain, and the approximate residence time of pollutants (and thus the attainable residual concentrations) in the environment and therefore to predict the relative risk of different pollutants.     

Effect of the Counterion on Light Emission: A Displacement Strategy to Change the Emission Behaviour from Aggregation‐Caused Quenching to Aggregation‐Induced Emission and to Construct Sensitive Fluorescent Sensors for Hg2+ Detection

In this paper, a simple strategy to change the emission behaviour of luminogenic materials was developed. Tetraphenylethene (TPE)‐functionalised benzothiazolium salts with different counteranions (TPEBe?X; X=I^?, ClO₄^? and PF₆^?) were designed and synthesised. All the luminogens show weak red emission in the solution state that originates from intramolecular charge transfer from TPE to the benzothiazolium unit. Whereas aggregate formation enhances the light emission of TPEBe?ClO₄ and TPEBe?PF₆, that of TPEBe?I is quenched, thus demonstrating the phenomena of aggregation‐induced emission and aggregation‐caused quenching. TPEBe?I works as a light‐up fluorescent sensor for Hg²⁺ in aqueous solution with high sensitivity and specificity owing to the elimination of the emission quenching effect of the iodide ion by the formation of HgI₂ as well as the induction in aggregate formation by the complexation of Hg²⁺ with the S atom of the benzothiazolium unit of TPEBe?I. A solid film of TPEBe?I was prepared that can monitor the level of Hg²⁺ in aqueous solution with a detection limit of 1 μM .     

The Effect of Soil Moisture on the Ability to Detect TNT Pairs from the Sand Layer in Order to Prevent Environmental Pollution and Groundwater

The aim of the study was to investigate the influence of sand bed moisture on TNT transport from under the sand layer. The MO-2M explosive vapor detector was used, the detection mechanism of which is based on the FAIMS method. In addition, it was determined after what time the detector alarm appears, signaling the presence of TNT vapors, and how it affects the thickness of the sand layer. The performed work allowed us to assess the suitability and possibly adapt the MO-2M detector to detect non-metal mines, which will help develop new application possibilities for this device. These tests can also be used to eliminate environmental contamination resulting from the deposition of explosives in the ground and the migration of harmful compounds to groundwater.     

A simple and effective method for fluoroalkylation — the addition of fluoroalkyl iodide to olefins in the presence of hydrogen peroxide

Addition of fluoroalkyl iodides to olefins in the presence of hydrogen peroxide (H₂O₂) in acetone, acetonitrile or ethanol gave the corresponding 1:1 adducts in good yields. Reaction of fluoroalkyl iodide with diallyl ether (DAE) yielded tetrahydrofuran derivatives. p-Hydroquinone (p-HQ) can partly suppress the reaction. A radical initiation mechanism is proposed.     

Molecular Mechanism of Antioxidant and Anti-Inflammatory Effects of Omega-3 Fatty Acids in Perilla Seed Oil and Rosmarinic Acid Rich Fraction Extracted from Perilla Seed Meal on TNF-α Induced A549 Lung Adenocarcinoma Cells

Industrially, after the removal of oil from perilla seeds (PS) by screw-type compression, the large quantities of residual perilla seed meal (PSM) becomes non-valuable waste. Therefore, to increase the health value and price of PS and PSM, we focused on the biological effects of perilla seed oil (PSO) and rosmarinic acid-rich fraction (RA-RF) extracted from PSM for their role in preventing oxidative stress and inflammation caused by TNF-α exposure in an A549 lung adenocarcinoma culture model. The A549 cells were pretreated with PSO or RA-RF and followed by TNF-α treatment. We found that PSO and RA-RF were not toxic to TNF-α-induced A549 cells. Both extracts significantly decreased the generation of reactive oxygen species (ROS) in this cell line. The mRNA expression levels of IL-1β, IL-6, IL-8, TNF-α, and COX-2 were significantly decreased by the treatment of PSO and RA-RF. The Western blot indicated that the expression of MnSOD, FOXO1, and NF-κB and phosphorylation of JNK were also significantly diminished by PSO and RA-RF treatment. The results demonstrated that PSO and RA-RF act as antioxidants to scavenge TNF-α induced ROS levels, resulting in decreased the expression of MnSOD, FOXO1, NF-κB and JNK signaling pathway in a human lung cell culture exposed to TNF-α.     

Reply to A Computational Evaluation of the Evidence for the Synthesis of 1,3‐Dimethylcyclobutadiene in Solid State and Aqueous Solution—Beyond the Experimental Reality

Following earlier reports on the photochemical synthesis of 1,3‐dimethylcyclobutadiene 8 , 10 in a protective host matrix, theoretical calculations for the formation of that adduct have been recently performed by Rzepa. 13 The author formulated criticisms based mainly on density functional theory calculations of ¹H NMR spectra. According to Rzepa the calculated spectra do not correspond with our measured spectra, which leads him to the conclusion that our interpretation is wrong, and that mainly cyclobutadiene has not been stabilized or even synthesized; we believe, however, that the initial model that Rzepa used for his calculations does not correspond to chemical reality or is at the very least a crude simplification of it, which implies that his calculations cannot match, in every point, our experimental spectra. Rzepa′s simplified models might be ‘reasonable’ from the theoretical point of view; however, in the case of assessment in the solid state, the theoretical setup does not force the system to preserve the confined stabilizing space defined by the crystalline matrix for encapsulated hosts in the solid state. Inversely, in the case of solution modeling, the theoretical setup is too rigid to properly assess the complex equilibria occurring in solution and to accurately determine the NMR spectra of exchanging species in solution. The inconsistency between our experimental results and the results of the theoretical models proposed by Rzepa is such that his conclusions are considered to be too far from experimental reality. Accurate modeling taking in account “reasonable” experimental details would be a worthwhile endeavor.     

Capillary electrophoresis with contactless conductivity detection for the quantification of fluoride in lithium ion battery electrolytes and in ionic liquids—A comparison to the results gained with a fluoride ion‐selective electrode

In this study, an optimized method using capillary electrophoresis (CE) with a direct contactless conductivity detector (C⁴D) for a new application field is presented for the quantification of fluoride in common used lithium ion battery (LIB) electrolyte using LiPF₆ in organic carbonate solvents and in ionic liquids (ILs) after contacted to Li metal. The method development for finding the right buffer and the suitable CE conditions for the quantification of fluoride was investigated. The results of the concentration of fluoride in different LIB electrolyte samples were compared to the results from the ion‐selective electrode (ISE). The relative standard deviations (RSDs) and recovery rates for fluoride were obtained with a very high accuracy in both methods. The results of the fluoride concentration in the LIB electrolytes were in very good agreement for both methods. In addition, the limit of detection (LOD) and limit of quantification (LOQ) values were determined for the CE method. The CE method has been applied also for the quantification of fluoride in ILs. In the fresh IL sample, the concentration of fluoride was under the LOD. Another sample of the IL mixed with Li metal has been investigated as well. It was possible to quantify the fluoride concentration in this sample.     

OH引发的正辛烷大气反应机理的理论研究

采用量子化学密度泛函理论研究了正辛烷与OH自由基的大气氧化反应机理。在B3LYP/6-31G(d)水平上对该反应体系的反应物、中间体、过渡态及产物进行了几何构型优化和频率计算,并在B3LYP/6-311＋G(3df,2p)水平上进行了单点能计算,得出了各反应通道的势能剖面图. 计算结果表明: 羟基硝酸酯和含有羟基羰基官能团的化合物是主要的反应产物,并且它们的挥发性较低,容易形成二次有机气溶胶。另外,本文将理论计算结果与可用的实验观测结果进行了比较。     

7,7′‐Diamino‐2,2′‐diindolylmethane: A Building Block for Highly Efficient and Selective Anion Receptors—Studies in Solution and in the Solid State

The easy‐to‐make 7,7′‐diamino‐2,2′‐diindolylmethane was used as a building block for the construction of anion receptors operating by hydrogen bonds. Its various bisamide and bisurea derivatives were designed and synthesised as acyclic as well as macrocyclic molecules, then their structural and anion binding properties were studied in solution and in the solid state. The bisamide receptors demonstrate high affinity towards oxoanions in highly polar and partially aqueous solutions (DMSO with up to 25 % H₂O) with significant selectivity for dihydrogen phosphate. Remarkably, the bisurea‐based molecules are able to bind anionic guests even in pure methanol and show selectivity toward tetrahedral oxoanions, that is, hydrogen sulphate and dihydrogen phosphate. X‐ray analysis revealed that both classes of molecules adopt a similar conformation in the solid state: a bent sheet shape with a binding pocket equipped with hydrogen‐bond donors (four for the amides and six for the bisureas), whose orientation is particularly tailored for oxoanions. The results of ROESY NMR experiments are in agreement with the findings for the solid state and confirmed that both bisamides and bisureas can easily adapt the conformation with convergent hydrogen‐bond donors, which is highly suitable for anion binding.     

Studies in organic mass spectrometry. XVI—A combined approach to the structures of ions generated from the molecular ions of acyclic β-diketones through loss of small neutral molecules

The structures of ions produced from acyclic 1,3-diketones by loss of carbon monoxide, ketene or olefins are investigated. Structural inference is made by comparison of the heats of formation of these ions with data for ions of known structure generated from other precursors. All assignments are confirmed by a study of metastable transitions. Loss of carbon monoxide yields ions in the keto form. Expulsion of a ketene or olefin moiety results in enol type ions.     

A Versatile One‐Pot Access to Cyanoarenes from ortho‐ and para‐Quinones: Paving the Way for Cyanated Functional Materials

A generally applicable direct synthesis of cyanoarenes from quinones is presented. Particular emphasis is placed on the preparation of precursors and target molecules relevant for organic materials, including halogenated cyanoarenes and larger cyanated acenes. The reaction and work‐up protocols are adjusted for the challenges presented by the different substrates and products. Screening results of the initial reaction optimization are given to further facilitate adaptation to other synthetic problems. The universality of the reaction is finally highlighted by successful substitution of para‐quinones by an ortho‐quinone as the starting material.