Multidimensional De Novo Design Reveals 5‐HT2B Receptor‐Selective Ligands

We report a multi‐objective de novo design study driven by synthetic tractability and aimed at the prioritization of computer‐generated 5‐HT_2B receptor ligands with accurately predicted target‐binding affinities. Relying on quantitative bioactivity models we designed and synthesized structurally novel, selective, nanomolar, and ligand‐efficient 5‐HT_2B modulators with sustained cell‐based effects. Our results suggest that seamless amalgamation of computational activity prediction and molecular design with microfluidics‐assisted synthesis enables the swift generation of small molecules with the desired polypharmacology.     

Stabilization of Titanium Dioxide Nanoparticles at the Surface of Carbon Nanomaterials Promoted by Microwave Heating

TiO₂ is frequently combined with carbon materials, such as reduced graphene oxide (RGO), to produce composites with improved properties, for example for photocatalytic applications. It is shown that heating conditions significantly affect the interface and photocatalytic properties of TiO₂@C, and that microwave irradiation can be advantageous for the synthesis of carbon‐based materials. Composites of TiO₂ with RGO or amorphous carbon were prepared from reaction of titanium isopropoxide with benzyl alcohol. During the synthesis of the TiO₂ nanoparticles, the carbon is involved in reactions that lead to the covalent attachment of the oxide, the extent of which depends on the carbon characteristics, heating rate, and mechanism. TiO₂ is more efficiently stabilized at the surface of RGO than amorphous carbon. Rapid heating of the reaction mixture results in a stronger coupling between the nanoparticles and carbon, more uniform coatings, and smaller particles with narrower size distributions. The more efficient attachment of the oxide leads to better photocatalytic performance.     

聚焦微波辅助提取-酸性染料分光光度法测定农吉利中总生物碱

采用聚焦微波辅助提取(FMAE)结合溴麝香草酚蓝分光光度法测定农吉利中总生物碱。粒径为0.180 mm的样品,以甲醇为溶剂,料液比为1比25,在微波功率中火条件下提取50min。在pH 7.2的磷酸二氢钾-氢氧化钠缓冲溶液中,提取得到的生物碱与溴麝香草酚蓝酸性染料形成缔合物,用三氯甲烷萃取后,在最大吸收波长417nm处测量其吸光度。总生物碱的质量浓度在0.25~250mg·L-1范围内呈线性,方法的检出限(3S/N)为1.5mg·L-1。应用该方法测定农吉利药材中总生物碱,加标回收率为105%,测定值的相对标准偏差(n=6)小于3.0%。     

Fragment‐Based De Novo Design Reveals a Small‐Molecule Inhibitor of Helicobacter Pylori HtrA

Sustained identification of innovative chemical entities is key for the success of chemical biology and drug discovery. We report the fragment‐based, computer‐assisted de novo design of a small molecule inhibiting Helicobacter pylori HtrA protease. Molecular binding of the designed compound to HtrA was confirmed through biophysical methods, supporting its functional activity in vitro. Hit expansion led to the identification of the currently best‐in‐class HtrA inhibitor. The results obtained reinforce the validity of ligand‐based de novo design and binding‐kinetics‐guided optimization for the efficient discovery of pioneering lead structures and prototyping drug‐like chemical probes with tailored bioactivity.     

Regulating Molecular Recognition with C‐Shaped Strips Attained by Chirality‐Assisted Synthesis

Chirality‐assisted synthesis (CAS) is a general approach to control the shapes of large molecular strips. CAS is based on enantiomerically pure building blocks that are designed to strictly couple in a single geometric orientation. Fully shape‐persistent structures can thus be created, even in the form of linear chains. With CAS, selective recognition between large host and guest molecules can reliably be designed de novo. To demonstrate this concept, three C‐shaped strips that can embrace a pillar[5]arene macrocycle were synthesized. The pillar[5]arene bound to the strips was a better host for electron‐deficient guests than the free macrocycle. Experimental and computational evidence is provided for these unique cooperative interactions to illustrate how CAS could open the door towards the precise positioning of functional groups for regulated supramolecular recognition and catalysis.     

Comprehensive characterization of natural organic matter by MALDI- and ESI-Fourier transform ion cyclotron resonance mass spectrometry

Natural organic matter (NOM) is a complex and non-uniform mixture of organic compounds which plays an important role in environmental processes. Due to the complexity, it is challenging to obtain fully detailed structural information about NOM. Although Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) has been demonstrated to be a powerful tool for providing molecular information about NOM, multiple ionization methods are needed for comprehensive characterization of NOM at the molecular level considering the ionizing selectivity of different ionization methods. This paper reports the first use of matrix assisted laser desorption/ionization (MALDI) method coupled with FT-ICR-MS for molecular characterization of NOM within a mass range of 200–800 Da. The mass spectral data obtained by MALDI were systematically compared with data generated by electrospray ionization (ESI). It showed that complementary molecular information about NOM which could not be detected by ESI, were provided by MALDI. More unsaturated and aromatic constituents of NOM with lower O/C ratio (O/C ratio < 0.5) were preferentially ionized in MALDI negative mode, whereas more polar constituents of NOM with higher O/C ratio were preferentially ionized in ESI negative mode. Molecular anions of NOM appearing at even m/z in MALDI negative ion mode were detected. The results show that NOM molecules with aromatic structures, moderate O/C ratio (0.7 > O/C ratio > 0.25) and lower H/C ratio were liable to form molecular anions at even m/z, whereas those with higher H/C ratio are more likely to form deprotonated ions at odd m/z. It is speculated that almost half of the NOM molecules identified by MALDI may be aromatic or condensed aromatic compounds with special groups which are liable to absorb electron from other molecules to generate free radical anions during MALDI ionization.     

Silver‐Assisted Chemical Etching on Silicon with Polyvinylpyrrolidone‐Mediated Formation of Silver Dendrites

Metal‐assisted chemical etching (MaCE) on silicon (Si)—mediated by polyvinylpyrrolidone (PVP)—is systematically investigated herein. It is found that the morphologies and crystallographic natures of the grown silver (Ag) dendrites can be significantly modulated, with the presence of PVP in the MaCE process leading to the formation of faceted Ag dendrites preferentially along the (111) crystallographic phase, rather than along the (200) phase. Further explorations of the PVP‐mediated effect on Si etching are also revealed. In contrast to the aligned Si nanowires formed by MaCE without PVP addition, only distributed nanopores with sizes of 200 to 400 nm appear on the Si surfaces in the presence of PVP. The origin of surface polishing on Si in the PVP‐mediated MaCE process can be attributed to the distinct transport pathway of holes supplied by the Ag⁺ ions, where the holes are injected directly into the primary Ag seeds, rather than through Ag dendrites, thus leading to the isotropic etching of the Si surface.     

Ionic‐liquid‐based,manual‐shaking‐ and ultrasound‐assisted,surfactant‐enhanced emulsification microextraction for the determination of three fungicide residues in juice samples

A novel manual‐shaking‐ and ultrasound‐assisted surfactant‐enhanced emulsification microextraction method was developed for the determination of three fungicides in juice samples. In this method, the ionic liquid, 1‐ethyl‐3‐methylimidazolium bis[(trifluoromethyl)sulfonyl]imide, instead of a volatile organic solvent was used as the extraction solvent. The surfactant, NP‐10, was used as an emulsifier to enhance the dispersion of the water‐immiscible ionic liquid into an aqueous phase, which accelerated the mass transfer of the analytes. Organic dispersive solvent typically required in common dispersive liquid–liquid microextraction methods was not necessary. In addition, manual shaking for 15 s before ultrasound to preliminarily mix the extraction solvent and the aqueous sample could greatly shorten the time for dispersing the ionic liquid into aqueous solution by ultrasound irradiation. Several experimental parameters affecting the extraction efficiency, including type and volume of extraction solvent, type and concentration of surfactant, extraction time, and pH, were optimized. Under the optimized conditions, good linearity with the correlation coefficients (γ) higher than 0.9986 and high sensitivity with the limit of detection ranging from 0.4 to 1.6 μg/L were obtained. The average recoveries ranged from 61.4 to 86.0% for spiked juice, with relative standard deviations from 1.8 to 9.7%. The proposed method was demonstrated to be a simple, fast, and efficient method for the analysis of the target fungicides in juice samples.     

Optimization of microwave‐assisted extraction for six inorganic and organic arsenic species in chicken tissues using response surface methodology

Response surface methodology was applied to optimize the parameters for microwave‐assisted extraction of six major inorganic and organic arsenic species (As(III), As(V), dimethyl arsenic acid, monomethyl arsenic acid, p‐arsanilic acid, and roxarsone) from chicken tissues, followed by detection using a high‐performance liquid chromatography with inductively coupled mass spectrometry detection method, which allows the simultaneous analysis of both inorganic and organic arsenic species in the extract in a single run. Effects of extraction medium, solution pH, liquid‐to‐solid ratio, and the temperature and time of microwave‐assisted extraction on the extraction of the targeted arsenic species were studied. The optimum microwave‐assisted extraction conditions were: 100 mg of chicken tissue, extracted by 5 mL of 22% v/v methanol, 90 mmol/L (NH₄)₂HPO₄, and 0.07% v/v trifluoroacetic acid (with pH adjusted to 10.0 by ammonium hydroxide solution), ramping for 10 min to 71°C, and holding for 11 min. The method has good extraction performance for total arsenic in the spiked and nonspiked chicken tissues (104.0 ± 13.8% and 91.6 ± 7.8%, respectively), except for the ones with arsenic contents close to the quantitation limits. Limits of quantitation (S/N = 10) for As(III), As(V), dimethyl arsenic acid, monomethyl arsenic acid, p‐arsanilic acid, and roxarsone in chicken tissues using this method were 0.012, 0.058, 0.039, 0.061, 0.102, and 0.240 mg/kg (dry weight), respectively.