Wellsappel7981

Based on high-resolution tandem mass spectrometry (HR-MS2) and global natural products social molecular networking (GNPS), we found that plant-derived daidzein and genistein derivatives are polyhalogenated by termite-associated Actinomadura species RB99. MS-guided purification from extracts of bacteria grown under optimized conditions led to the isolation of eight polychlorinated isoflavones, including six unreported derivatives, and seven novel polybrominated derivatives, two of which showed antimicrobial activity.A new approach for quantitively assessing putative crystal structures with applications in crystal structure prediction (CSP) is introduced that is based upon experimental solution- and magic-angle spinning (MAS) solid-state NMR data and density functional theory (DFT) calculation. For the specific case of tolfenamic acid (TFA), we consider experimental solution-state NMR for a range of solvents, experimental MAS NMR of polymorphs I and II, and DFT calculations for four polymorphs. The change in NMR chemical shift observed in passing from the solution state to the solid state (ΔδExperimental) is calculated as the difference between 1H and 13C experimental solid-state chemical shifts for each polymorphic form (δSolid expt) and the corresponding solution-state NMR chemical shifts (δSolution expt). Separately, Tucatinib purchase use the gauge-included projector augmented wave (GIPAW) method to calculate the NMR chemical shifts for each form (δSolid calc) and for TFA in solution (δSolution calc) using the dynamic 3D solution conng them against experimental 13C chemical shift data for forms I and II identifies matching narrow ranges of conformations, successfully predicting the conformation of tolfenamic acid in each form. This methodology can therefore be used in crystal structure prediction to both reduce the initial conformational search space and also quantitatively assess subsequent putative structures to reliably and unambiguously identify the correct structure.The non-natural cyclic amino acids (1S,3R,4S)-1-amino-3-fluoro-4-(fluoro-18F)cyclopentane-1-carboxylic acid ([18F]9) and (1S,3S,4R)-1-amino-3-fluoro-4-(fluoro-18F)cyclopentane-1-carboxylic acid ([18F]28) have been prepared in 10 and 1.7% decay corrected radiochemical yield, respectively, and in greater than 99% radiochemical purity. Cell assays in rat 9L gliosarcoma, human U87 ΔEGFR glioblastoma, and human DU145 androgen-independent prostate carcinoma tumor cells indicated that both compounds are substrates for amino acid transport primarily by system L, with some transport taking place via system ASC. In rats with 9L gliosarcoma, [18F]9 and [18F]28 provided high tumor to normal brain tissue ratios, with maximal ratios of 3.5 and 4.1, respectively. Biodistribution studies in healthy rats confirmed that both compounds are BBB permeable and that bladder accumulation is low until at least 5 min post injection.Methoxyphenols are one of the most abundant classes of biomarker tracers for atmospheric wood smoke pollution. #link# The reactions of atmospheric oxidants (ozone, OH) with methoxyphenols can contribute to the formation of secondary organic aerosols (SOA). Here, for the first time, we use the well-established vertical wetted wall flow tube (VWWFT) reactor to assess the effect of ionic strength (I), pH, temperature, and ozone concentration on the reaction kinetics of ozone with acetosyringone (ACS), as a representative methoxyphenol compound. At fixed pH 3, typical for acidic atmospheric deliquescent particles, and at I = 0.9 M adjusted by Na2SO4, the uptake coefficient (γ) of O3 increases by 2 orders of magnitude from γ = (5.0 ± 0.8) × 10-8 on neat salt solution (Na2SO4) to γ = (6.0 ± 0.01) × 10-6 on a mixture of ACS and Na2SO4. The comparison of the uptake coefficients of O3 at different pH values indicates that the reaction kinetics strongly depends on the acidity of the phenolic group of ACS. The observed different reactivity of gas-phase ozone with ACS has implications for ozone uptake by the dilute aqueous phase of cloud droplets and by aerosol deliquescent particles loaded with inorganic salts, and it can affect the formation of SOA in the atmosphere.Criegee intermediates and alcohols are important species in the atmosphere. In this study, we use quantum chemistry and Born-Oppenheimer molecular dynamics (BOMD) simulations to investigate the reaction between methanol/ethanol and Criegee intermediates (anti- or syn-CH3CHOO) in the gas phase and at the air-water interface. Reactions at the interface are found to be much faster than those in the gas phase. When water molecules are available, loop structures can be formed to facilitate the reaction. In addition, nonloop reaction pathways characterized by the formation of hydrated protons, although with a low possibility, are also identified at the air-water interface. Implications of our results on the fate of Criegee intermediates in the atmosphere are discussed, which deepen our understanding of Criegee intermediate-alcohol chemistry in humid environments.The first potent leukotriene B4 (LTB4) receptor type 2 (BLT2) agonists, endogenous 12(S)-hydroxyheptadeca-5Z,8E,10E-trienoic acid (12-HHT), and synthetic CAY10583 (CAY) have been recently described to accelerate wound healing by enhanced keratinocyte migration and indirect stimulation of fibroblast activity in diabetic rats. CAY represents a very valuable starting point for the development of novel wound-healing promoters. In this work, the first structure-activity relationship study for CAY scaffold-based BLT2 agonists is presented. The newly prepared derivatives showed promising in vitro wound-healing activity.Atom probe tomography allows us to measure the three-dimensional composition of materials with up to atomic resolution by evaporating the material using high electric fields. Initially developed for metals, it is increasingly used for covalently bound structures. To aid the interpretation of the obtained fragmentation pattern, we modeled the fragmentation and desorption of self-assembled monolayers of thiolate molecules on a gold surface in strong electrostatic fields using density functional theory. We used a cluster model and a periodic model of amino-undecanethiolate, NH2(CH2)11S, and fluoro-decanethiolate, CF3(CF2)7(CH2)2S. In the former molecule, the fragment CH2NH2+ was found to evaporate at fields of 5.4-7.7 V/nm. It was followed by different hydrocarbon fragments. Fluoro-decanethiolate evaporates CF3+ at fields of 5.7-6.7 V/nm in the cluster model and at 15.4-23.1 V/nm in the periodic model, followed by CF2+ and C2F42+. Detailed analysis of the electronic structure during the evaporation process revealed a stepwise accumulation of the charge in the head groups exposed to the strongest fields, followed by dissociation of covalent bonds. These observations will facilitate the analysis of atom probe experiments of covalently bound structures.Synchrotron radiation-based infrared microspectroscopy (SR-IMS) is a nondestructive bioanalytical technique with a high signal-to-noise ratio and high ultraspatial resolution (3-10 μm). It is capable to explore the microstructures of plant tissues in a chemical sense and provide information on the composition, structure, and distribution of chemical compounds/functional groups. The objective of this study was to illustrate how SR-IMS can be used to image the internal microstructures of chickpea seed tissue within a cellular level. Chickpea seeds (CDC Cory) were collected from the Crop Development Center (University of Saskatchewan, Saskatoon, SK). The seeds were frozen at -20 °C on object disks in a cryostatic microtome and then were cut into thin cross sections (ca. 8 μm thick). link2 The experiment was carried out on the mid-infrared beamline (01B1-1) at the Canadian Light Source (Saskatoon, SK). We obtained the ultraspatial images of the chickpea tissue with pixel-sized increments of imaging steps. The results showed that, with the extremely bright synchrotron light, spectra with high signal-to-noise ratios can be obtained from an area as small as 3.3 μm × 3.3 μm, allowing us to observe the seed tissue within a cellular level. Chemical distribution of chickpea such as lipids, protein, and carbohydrates could be mapped, revealing the chemical information of the chickpea internal microstructure. In conclusion, SR-IMS can rapidly characterize the molecular structure of protein, carbohydrates, and lipids at an ultraspatial resolution.Several II-IV double-ReO3-type (DROT) fluorides are known to exhibit strong negative thermal expansion (NTE) over a wide temperature range while retaining a cubic structure down to 120 K or lower. CaZrF6, CaNbF6, CaTiF6, and MgZrF6, embody these properties. In contrast to the behavior of these II-IV materials, the I-V DROT material, NaSbF6, has been reported to display a phase transition from rhombohedral to cubic above 300 K and positive thermal expansion both above and below the transition. In this work, NaNbF6 and NaTaF6 are shown to undergo first-order cubic-to-rhombohedral transitions on cooling to ∼130 K. Above this transition, NaNbF6 shows modest NTE between 160 and 250 K, whereas NaTaF6 exhibits near-zero thermal expansion over the range 210-270 K. These I-V systems are elastically softer than their II-IV counterparts, with a zero pressure bulk modulus, K0, of 14.6(8) GPa and first derivative of the bulk modulus with respect to pressure, K0', of -18(3) for cubic NaNbF6, and K0 = 14.47(3) GPa and K0'= -21.56(7) for cubic NaTaF6. When subject to ∼0.3 GPa at 300 K, both compounds exhibit a phase transition from Fm3̅m to R3̅. The R3̅ phases exhibit negative linear compressibility over a limited pressure range. A further transition with phase coexistence occurs at ∼2.5-3.0 GPa for NaNbF6 and ∼4.5 GPa for NaTaF6. Compression of NaNbF6 in helium at room temperature and below provides no evidence for helium penetration into the structure to form a perovskite with helium on the A-site, as was previously reported for CaZrF6.Cystic fibrosis (CF) is a life-threatening autosomal recessive disease, caused by mutations in the CF transmembrane conductance regulator (CFTR) chloride channel. CFTR modulators have been reported to address the basic defects associated with CF-causing mutations, partially restoring the CFTR function in terms of protein processing and/or channel gating. Small-molecule compounds, called potentiators, are known to ameliorate the gating defect. In this study, we describe the identification of the 2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole core as a novel chemotype of potentiators. In-depth structure-activity relationship studies led to the discovery of enantiomerically pure 39 endowed with a good efficacy in rescuing the gating defect of F508del- and G551D-CFTR and a promising in vitro druglike profile. The in vivo characterization of γ-carboline 39 showed considerable exposure levels and good oral bioavailability, with detectable distribution to the lungs after oral administration to rats. Overall, these findings may represent an encouraging starting point to further expand this chemical class, adding a new chemotype to the existing classes of CFTR potentiators.Carbohydrates are often utilized to provide hydrophilicity and hydroxyl-based hydrogen bonds in self-assembling glycopeptides, affording versatile scaffolds with wide applicability in biomedical research. However, how stereochemistry of carbohydrates impacts the self-assembly process remains unclear. Here we have established a dimeric tyrosine-rich glycopeptide system for probing the corresponding hydrogelating behavior under the influence of site- and stereospecific glycosylations. Comparison of 18 glycoforms bearing monosaccharides at Tyr4 and Tyr4' shows that the glycopeptides with either α- or β-anomers exhibit contrary gelating abilities, when the glycan moieties contain axial hydroxyl groups. A high-resolution X-ray crystallographic structure of the β-galactose-containing gelator, along with other results from spectroscopic, microscopic, and rheological experiments, indicate an unusual carbohydrate-aromatic CH-π bonding that promotes glycopeptide self-assembly. link3 These mechanistic findings, particularly evidence obtained at the angstrom scale, illuminate an unconventional role that carbohydrates can play in building supramolecules.