Synthesis and Diverse Transformations of a Dinitrogen Dititanium Hydride Complex Bearing Rigid Acridane-Based PNP-Pincer Ligands

Studies on N₂ activation and transformation by transition metal hydride complexes are of particular interest and importance. The synthesis and diverse transformations of a dinitrogen dititanium hydride complex bearing the rigid acridane-based ^acriPNP-pincer ligands {[(^acriPNP)Ti]₂(μ₂-η¹:η²-N₂)(μ₂-H)₂} are presented. This complex enabled N₂ cleavage and hydrogenation even without additional H₂ or other reducing agents. Furthermore, diverse transformations of the N₂ unit with a variety of organometallic compounds such as ZnMe₂, MgMe₂, AlMe₃, B(C₆F₅)₃, PinBH, and PhSiH₃ have been well established at the rigid ^acriPNP-ligated dititanium framework, such as reversible bonding-mode change between the end-on and side-on/end-on fashions, diborylative N=N bond cleavage, the formal insertion of two dimethylaluminum species into the N=N bond, and the formal insertion of two silylene units into the N=N bond. This work has revealed many unprecedented aspects of dinitrogen reaction chemistry.     

Predicting 19F NMR Chemical Shifts: A Combined Computational and Experimental Study of a Trypanosomal Oxidoreductase–Inhibitor Complex

The absence of fluorine from most biomolecules renders it an excellent probe for NMR spectroscopy to monitor inhibitor–protein interactions. However, predicting the binding mode of a fluorinated ligand from a chemical shift (or vice versa) has been challenging due to the high electron density of the fluorine atom. Nonetheless, reliable ¹⁹F chemical-shift predictions to deduce ligand-binding modes hold great potential for in silico drug design. Herein, we present a systematic QM/MM study to predict the ¹⁹F NMR chemical shifts of a covalently bound fluorinated inhibitor to the essential oxidoreductase tryparedoxin (Tpx) from African trypanosomes, the causative agent of African sleeping sickness. We include many protein–inhibitor conformations as well as monomeric and dimeric inhibitor–protein complexes, thus rendering it the largest computational study on chemical shifts of ¹⁹F nuclei in a biological context to date. Our predicted shifts agree well with those obtained experimentally and pave the way for future work in this area.     

Cytochrome P450 119 Compounds I Formed by Chemical Oxidation and Photooxidation Are the Same Species

Compound I from cytochrome P450 119 prepared by the photooxidation method involving peroxynitrite oxidation of the resting enzyme to Compound II followed by photooxidation to Compound I was compared to Compound I generated by m-chloroperoxybenzoic acid (MCPBA) oxidation of the resting enzyme. The two methods gave the same UV/Visible spectra, the same products from oxidations of lauric acid and palmitic acid and their (ω-2,ω-2,ω-3,ω-3)-tetradeuterated analogues, and the same kinetics for oxidations of lauric acid and caprylic acid. The experimental identities between the transients produced by the two methods leave no doubt that the same Compound I species is formed by the two methods.     

Dynamic Interactions in Synthetic Receptors: A Guest Exchange Saturation Transfer Study

The accumulated knowledge regarding molecular architectures is based on established, reliable, and accessible analytical tools that provide robust structural and functional information on assemblies. However, both the dynamicity and low population of noncovalently interacting moieties within studied molecular systems limit the efficiency and accuracy of traditional methods. Herein, the use of a saturation transfer-based NMR approach to study the dynamic binding characteristics of an anion to a series of synthetic receptors derived from bambusuril macrocycles is demonstrated. The exchange rates of BF₄⁻ are mediated by the side chains on the receptor (100 s⁻¹<k_ex<5000 s⁻¹), which play a critical role in receptor-anion binding dynamics. The signal amplification obtained with this approach allows for the identification of different types of intermolecular interactions between the receptor and the anion, something that could not have been detected by techniques hitherto used to study molecular assemblies. These findings, which are supported by a computational molecular dynamic study, demonstrate the uniqueness and added value of this NMR method.     

XANES/EPR Evidence of the Oxidation of Nickel(II) Quinolinylpropioamide and Its Application in Csp3−H Functionalization

An in situ generated oxidation species of nickel quinolinylpropioamide intermediate was produced. Characterization by X-ray absorption near edge structure (XANES) and EPR provides complementary insights into this oxidized nickel species. With aliphatic amides and isocyanides as substrates, a nickel-catalyzed facile synthesis of structurally diverse five-membered lactams could be achieved.     

NIFTy 3 – Numerical Information Field Theory: A Python Framework for Multicomponent Signal Inference on HPC Clusters

NIFTy , “Numerical Information Field Theory,” is a software framework designed to ease the development and implementation of field inference algorithms. Field equations are formulated independently of the underlying spatial geometry allowing the user to focus on the algorithmic design. Under the hood, NIFTy ensures that the discretization of the implemented equations is consistent. This enables the user to prototype an algorithm rapidly in 1D and then apply it to high‐dimensional real‐world problems. This paper introduces NIFTy  3, a major upgrade to the original NIFTy  framework. NIFTy  3 allows the user to run inference algorithms on massively parallel high performance computing clusters without changing the implementation of the field equations. It supports n‐dimensional Cartesian spaces, spherical spaces, power spaces, and product spaces as well as transforms to their harmonic counterparts. Furthermore, NIFTy  3 is able to handle non‐scalar fields, such as vector or tensor fields. The functionality and performance of the software package is demonstrated with example code, which implements a mock inference inspired by a real‐world algorithm from the realm of information field theory. NIFTy  3 is open‐source software available under the GNU General Public License v3 (GPL‐3) at https://gitlab.mpcdf.mpg.de/ift/NIFTy/tree/NIFTy_3 .     

QEPAS系统中石英音叉模态仿真计算与研究

对石英音叉增强型光声光谱(QEPAS)系统中常用的石英音叉进行了有限元模态计算，获得石英音叉前6阶振型与模态频率，认知了第4阶对称摆动振型为有效振动，利用单因素法分析了石英音叉的音臂长度l₁、音臂宽度w₁、音臂厚度t、音臂切角θ、音臂圆孔直径d及音臂圆孔高度h对低阶有效共振频率(Fre)的影响，敏感度依次为： l₁> w₁>d>θ>t>h，考虑实际设计情形，筛选出了l₁，w₁，d与h四个石英音叉设计变量，采用Box-Behnken实验设计方案与RSM(response surface methodology)方法，以Fre为函数目标，建立l₁，w₁，d与h的二次回归响应面模型，得到了参数之间的交互作用，利用Design-Expert软件对响应面模型进行设计参数反求，结果表明，在15 000 Hz≤Fre≤25 000 Hz计算区域内误差较小，基本满足QEPAS系统的计算需求，所提出的研究与设计方法具有一定通用性，可为QEPAS系统中石英音叉结构参数设计提供参考。     

Two new aromadendrane sesquiterpenes from Verticillium psalliotae

The chemical constituents of the fungus Verticillium psalliotae were studied. Two new aromadendrane sesquiterpenes inonotin M (1) and inonotin N (2) were isolated from the EtOAc extract of the fungal culture broth. The structures of compounds were elucidated mainly by HRESIMS experiments, and 1D, 2D-NMR spectroscopy analysis.     

Development and validation of an ultra‐high‐performance liquid chromatography–tandem mass spectrometry method to determine the bioavailability of warfarin and its major metabolite 7‐hydroxy warfarin in rats dosed with oral formulations containing different polymorphic forms

A simple, sensitive and rapid ultra‐high‐performance liquid chromatography–electrospray ionization–tandem mass spectrometry method was developed and validated for the quantification of warfarin and 7‐hydroxy warfarin in Sprague Dawley (SD) rats. Animals were administered a single dose of warfarin sodium formulations (crystalline and amorphous) at 12 mg/kg via oral gavage and blood was drawn over a 96‐h time course. Sample process recoveries, matrix effect and analyte stability were determined. The linearity for warfarin and 7‐hydroxy warfarin was from 5 to 2000 ng/mL in blank SD rat plasma. Correlation coefficients (r²) for standard calibration curves were >.98 and analytes quantified within ±15% of target at all calibrator concentrations. The average percent accuracy and precision for intra‐ and inter‐day were 93.7%–113.8% and ≤12.1%, respectively, for warfarin and 7‐hydroxy warfarin, across the quality control standards (5, 10, 500, 1800 and 2000 ng/mL). Acceptable analytical recovery (>55%) was achieved with process efficiencies >41.5% and matrix effects <139.9% over the analytical range. Both analytes were stable in stock solution, autosampler, benchtop and three cycles of freeze–thaw with percent accuracy ≥90.2% and precision (percent relative standard deviation) ≤14%. The validated method was successfully applied to a pre‐clinical bioavailability study of crystalline and amorphous warfarin sodium formulations in SD rats.