An N,N′‐dioxide/zinc bis(trifluoromethylsulfonyl)imide complex has been developed as an efficient catalyst for the highly enantioselective Diels–Alder reaction of cyclopentadiene with alkynones. Various 2‐acyl substituted norbornadiene derivatives were obtained in moderate to high yields (up to 99 %) with good enantiomeric excesses (up to 95 %).
The novel psychoactive substance (NPS) 4-Methyl-5-(4-methylphenyl)-4,5-dihydroxazol-2-amine (4,4′-DMAR) shows psychostimulant activity. Data on the acute toxicity of 4,4′-DMAR are becoming increasingly available, yet the long-term effects are still almost unknown. In particular, no data on genotoxicity are available. Therefore, the aim of the present study was to evaluate its genotoxic potential using the “In Vitro Mammalian Cell Micronucleus Test” (MNvit) on (±)cis-4,4′-DMAR and (±)trans-4,4′-DMAR and their associations. The analyses were conducted in vitro on human TK6 cells. To select suitable concentrations for MNvit, we preliminarily evaluated cytotoxicity and apoptosis. All endpoints were analysed by flow cytometry. The results reveal the two racemates’ opposite behaviours: (±)cis-4,4′-DMAR shows a statistically significant increase in micronuclei (MNi) frequency that (±)trans-4,4′-DMAR is completely incapable of. This contrast confirms the well-known possibility of observing opposite biological effects of the cis- and trans- isomers of a compound, and it highlights the importance of testing single NPSs that show even small differences in structure or conformation. The genotoxic capacity demonstrated stresses an additional alarming toxicological concern related to this NPS. Moreover, the co-treatments indicate that consuming both racemates will magnify the genotoxic effect, an aspect to consider given the unpredictability of illicit drug composition. 相似文献
QO-58 (5-(2,6-dichloro-5-fluoropyridin-3-yl)-3-phenyl-2-(trifluoromethyl)-1H-pyrazolol[1,5-a]pyrimidin-7-one) has been regarded to be an activator of KV7 channels with analgesic properties. However, whether and how the presence of this compound can result in any modifications of other types of membrane ion channels in native cells are not thoroughly investigated. In this study, we investigated its perturbations on M-type K+ current (IK(M)), Ca2+-activated K+ current (IK(Ca)), large-conductance Ca2+-activated K+ (BKCa) channels, and erg-mediated K+ current (IK(erg)) identified from pituitary tumor (GH3) cells. Addition of QO-58 can increase the amplitude of IK(M) and IK(Ca) in a concentration-dependent fashion, with effective EC50 of 3.1 and 4.2 μM, respectively. This compound could shift the activation curve of IK(M) toward a leftward direction with being void of changes in the gating charge. The strength in voltage-dependent hysteresis (Vhys) of IK(M) evoked by upright triangular ramp pulse (Vramp) was enhanced by adding QO-58. The probabilities of M-type K+ (KM) channels that will be open increased upon the exposure to QO-58, although no modification in single-channel conductance was seen. Furthermore, GH3-cell exposure to QO-58 effectively increased the amplitude of IK(Ca) as well as enhanced the activity of BKCa channels. Under inside-out configuration, QO-58, applied at the cytosolic leaflet of the channel, activated BKCa-channel activity, and its increase could be attenuated by further addition of verruculogen, but not by linopirdine (10 μM). The application of QO-58 could lead to a leftward shift in the activation curve of BKCa channels with neither change in the gating charge nor in single-channel conductance. Moreover, cell exposure of QO-58 (10 μM) resulted in a minor suppression of IK(erg) amplitude in response to membrane hyperpolarization. The docking results also revealed that there are possible interactions of the QO-58 molecule with the KCNQ or KCa1.1 channel. Overall, dual activation of IK(M) and IK(Ca) caused by the presence of QO-58 eventually may have high impacts on the functional activity (e.g., anti-nociceptive effect) residing in electrically excitable cells. Care must be exercised when interpreting data generated with QO-58 as it is not entirely KCNQ/KV7 selective. 相似文献
Ethylene polymerization with bis(imino)pyridlyiron precatalysts generally produces linear polyethylene (PE) even with the presence of α-olefins because α-olefins are not incorporated into polymeric products. Interestingly, α-olefins, such as hexene-1 or butene-1, have been found to act as effective chain transfer agents in the ethylene polymerization promoted by nonsymmetrical bis(imino)pyridyliron complexes with modified methylalumoxane (MMAO), resulting in higher catalytic activities with higher amounts of polymers with lower molecular weights, and, more importantly, narrower molecular weight distributions of the resultant polyethylenes (PE). This phenomenon confirms the assistance of α-olefins in the chain-termination reaction of iron-initiated polymerization and regeneration of the active species for further polymerization. Besides higher activities of the catalytic system, the formation of linear PE with trans-vinylene terminal groups and lower molecular weights are explained. The observation will provide a new pathway for enhancing catalytic activity and improving the quality of polyethylenes obtained by regulation of molecular weights and molecular weight distribution. 相似文献
An enantioselective synthesis of the ABD ring of (−)‐phomactin A is described here. The sequence features Rawal’s asymmetric Diels–Alder cycloaddition. The overall length is significantly reduced from our previous attempt. 相似文献
To explore new relaxor‐PbTiO3 systems for high‐power and high‐temperature electromechanical applications, a ternary ferroelectric ceramic system of Pb(Lu1/2Nb1/2)O3–Pb(In1/2Nb1/2)O3–PbTiO3 (PLN–PIN–PT) have been investigated. The phase structure, dielectric, piezoelectric, and ferroelectric properties of the as‐prepared PLN–PIN–PT ceramics near the morphotropic phase boundary (MPB) were characterized. A high rhombohedral‐tetragonal phase transition temperature TR‐T of 165°C and a high Curie temperature TC of 345°C, together with a good piezoelectric coefficient d33 of 420 pC/N, were obtained in 0.38PLN–0.20PIN–0.42PT ceramics. Furthermore, for (0.8?x)PLN–0.2PIN–xPT ceramics, the temperature‐dependent piezoelectric coefficients, coercive fields and electric‐field‐induced strains were further studied. At 175°C, their coercive fields were found to be above 9.5 kV/cm, which is higher than that of PMN–PT and soft P5H ceramics at room temperature, indicating PLN–PIN–PT ceramics to be one of the promising candidates in piezoelectric applications under high‐driven fields. The results presented here could benefit the development of relaxor‐PbTiO3 with enhanced phase transition temperatures and coercive fields. 相似文献
In this work, to investigate the addition effect of 2D α‐zirconium phosphate (α‐ZrP) nanosheets on the properties of polyimide (PI), a series of PI/ZrP composites are synthesized by in situ polymerization. The thermal, mechanical, and tribological properties of composites strongly depend on the dispersity and distribution of α‐ZrP nanosheets in the PI matrix. The dispersed α‐ZrP can make rich interfacial interactions with PI matrix, which facilitates the transfer of external stress, heat, antiwear ability, etc., from the PI matrix to the surface of the α‐ZrP nanosheets, leading to the obvious enhancements of the thermal, mechanical, and tribological properties of the PI/ZrP composites. Specially, compared with pure PI, the tensile strength and elongation at break of the optimum sample of PI‐0.6 are increased by 13.7% and 35.7%, while its wear volume is reduced by 85%. This work provides a new paradigm for using other layered 2D nanosheets to prepare high‐performance PI‐based composite materials. 相似文献