Maynardlohmann8100

Dimerization of G protein-coupled receptors (GPCRs) is considered to take part in regulating the highly dynamic nature of receptor function. Intensive research unraveled a large variety of different dimer configurations with potentially distinct activity profiles. Studies are complicated by the critical role of the membrane environment for receptor dimerization, and experimental deficiencies in modulating the same. Here we chose a molecular dynamics strategy to characterize the potential of the large chemical lipid repertoire to steer dimerization fingerprints of the neurotensin 1 receptor. Unfavorable hydrophobic mismatch results in excessive dimerization whereas particular lipid features, e.g., anionic headgroups, induce specific dimer interfaces via direct protein-lipid interactions. Polyunsaturated fatty acids attenuate compact dimer formation by facilitated adhesion to the protein transmembrane surface, and receptor lipidation-induced conformational changes confer modulated protein-lipid and protein-protein interactions. Our results highlight the striking role of the membrane environment on GPCR dimerization with potential functional consequences.Rh(III)-catalyzed C-H activation/annulation of benzimidates with 4-diazoisochroman-3-imines furnished 8-alkoxy-5H-isochromeno[3,4-c]isoquinolines in moderate to excellent yields with a broad range of substrate scope. The reaction was carried out under mild reaction conditions and could be scaled up with practical usage. Similar reaction between benzimidates and 4-diazoisoquinolin-3-ones provided 1-alkoxy-4-arylisoquinolin-3-ols in excellent yields. Moreover, the synthesized products could be conveniently transformed to the corresponding heterocycles with a 1,8-naphthyridinone or isochromenopyridinone core, which are privileged structures in medicinal chemistry.The development of C-H activation reactions that use inexpensive and practical oxidants remains a significant challenge. Until our recent disclosure of the β-lactonization of free aliphatic acids, the use of peroxides in C-H activation reactions directed by weakly coordinating native functional groups was unreported. Herein, we report C(sp3)-H β-acetoxylation and γ-, δ-, and ε-lactonization reactions of free carboxylic acids enabled by a novel cyclopentane-based mono-N-protected β-amino acid ligand. Notably, tert-butyl hydrogen peroxide is used as the sole oxidant for these reactions. This reaction has several key advantages over other C-H activation protocols (1) exclusive monoselectivity was observed in the presence of two α-methyl groups; (2) aliphatic carboxylic acids containing α-hydrogens are compatible with this protocol; (3) lactonization of free acids, affording γ-, δ-, or ε-lactones, has been achieved for the first time.A molecular-level understanding of the interplay between self-assembled monolayers (SAMs) of thiolates and gold surface is of great importance to a wide range of applications in surface science and nanotechnology. Selleck TKI-258 Despite theoretical research progress of the past decade, an atomistic model, capable of describing key features of SAMs at reconstructed gold surfaces, is still missing. In this work, the periodic ab initio density functional theory (DFT) calculations were utilized to develop a new atomistic force field model for the alkanethiolate (AT) SAMs on the reconstructed Au(111) surface. The new force field parameters were carefully trained to reproduce the key features, including vibrational spectra and torsion energy profiles of ethylthiolate (C2S) in the bridge or staple motif model on Au(111) surface. Wherein, the force constants of the bond and angle terms were trained by matching the vibrational spectra, while the torsion parameters of the dihedral angles were trained via fitting the torsion energy profiles from DFT calculations. To validate the developed force field parameters, we performed the classical molecular dynamics (MD) simulations for both pristine and reconstructed Au-S interface models with a (2√3×3) unit cell, which includes four dodecanethiolate (C10S) on the Au(111) surface. The simulation results showed that the geometrical features of the investigated Au-S interface models and structural properties of the C10S SAMs are in good agreement with the ab initio MD studies. The newly developed atomistic force field model provides new fundamental insights of AT SAMs on the reconstructed Au(111) surface and adds advancement to existing interface research knowledge.The rapid proliferation of new synthetic cannabinoid receptor agonists (SCRAs) has initiated considerable interest in the development of so-called "untargeted" screening strategies. One of these new screening technologies involves the activity-based detection of SCRAs. In this study, we evaluated whether (synthetic) cannabinoid activity can be detected in oral fluid (OF) and, if so, whether it correlates with SCRA concentrations. OF was collected at several time points in a placebo-controlled JWH-018 administration study. The outcome of the cell-based cannabinoid reporter system, which monitored the cannabinoid receptor activation, was compared to the quantitative data for JWH-018, obtained via a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. A total of 175 OF samples were collected and analyzed via both methods. The cannabinoid reporter assay correctly classified the vast majority of the samples as either negative (100 ng/mL; 16/18 = 89%) JWH-018 concentrations. Passing-Bablok regression analysis yielded a good linear correlation, with no proportional difference between both methods (slope 0.97; 95% confidence interval 0.86-1.14) and only a small systematic difference. This is the first study to demonstrate the applicability of an untargeted, activity-based approach for SCRA detection in OF. Additionally, the outcome of the cannabinoid reporter assay was compared to the gold standard (LC-MS/MS), showing a good correlation between both methods, indicating that the cannabinoid reporter assay can be used for an estimation of drug concentrations.A rapid preparation method of TiO2-x by thermal treatment using H2TiO3 as the precursor was proposed compared with the static hydrogenation thermal treatment process. Its adsorption properties of arsenic under visible light were explored and investigated as well. Various colors of TiO2-x were prepared and characterized via XRD, TEM, BET, and so on. The results indicate that the method of rapid preparation is feasible. The TiO2-x exhibits a larger particle size that varied from 10 nm to 2 μm, and deeper color products were obtained as the treatment temperature increased from 600 to 900 °C. Light yellow TiO2-x was prepared after increasing the temperature from 600 to 900 °C, Ti4O7 and Ti6O11 with a dark color were formed under a H2 atmosphere at 1500 °C. The arsenic adsorption performances of some samples under visible light were tested, and reveal a high efficiency of TiO2-x in the photocatalytic oxidation arsenic adsorption under visible light, the conversion ratio of As(III) photocatalytic oxidation fluctuates around 2.