Diphenyl(dipyrazolyl)methane complexes of Ni: synthesis, structural characterization, and chromotropism of NiBr2 derivatives

The reaction of NiBr2 with the bidentate ligand diphenyl(dipyrazolyl)methane (dpdpm) gives the pentacoordinated complexes [(dpdpm)Ni(mu-Br)Br]2 (1), [(dpdpm)NiBr2(H2O)] (2a), and [(dpdpm)NiBr(H2O)2]Br (2b), or the octahedral complexes [(dpdpm)NiBr(H2O)2(CH3CN)]Br (3), [(dpdpm)2NiBr2] (4), and [(dpdpm)2NiBr(H2O)]Br (5). All of these complexes are paramagnetic, both in the solid state and in solution, and have been characterized by spectroscopic (IR, NMR, and UV-vis-NIR) and X-ray diffraction studies. The unoccupied coordination site in the pentacoordinated compounds allows long-range interactions, in the solid state, between the Ni center and a Ph substituent of the dpdpm ligand. These weak interactions are replaced by Ni-solvent interactions, both in the solid state and in solution, facilitating the interconversion of these compounds under various reaction conditions and leading to interesting solvato-, vapo-, and thermochromic properties. UV-vis-NIR spectroscopy has been used to study these phenomena. Absorption spectra for the room-temperature methanol or acetonitrile solutions of the pentacoordinate or octahedral compounds show three main bands in the region of 350-1000 nm that represent spin-allowed (d-d) transitions from the ground state 3A2g to the excited states 3T2g, 3T1g(3F), and 3T1g(3P). A weak shoulder was also detected on the middle peak in most spectra (700-800 nm), representing the spin-forbidden 3A2g-->1Eg transition. On the other hand, the spectra of high-temperature CH2Cl2 or acetone solutions of all complexes show four main bands at ca. 490, 650-660, 860, and 1000 nm, in addition to a shoulder on the first or second band.     

The effectiveness of three multi-component binding models in describing the binary competitive equilibrium adsorption of two cytochrome b(5) mutants

Competitive adsorption isotherms for two conservative surface charge-neutralizing mutants of cytochrome b(5), E11Q and E44Q, previously measured with competitor concentration held constant over the range of the isotherm, were used to test three widely-used multi-component isotherm models. The extended Langmuir-Freundlich, Langmuir and Jovanovic-Freundlich models each adequately described the weaker infinite dilution adsorption of the E44Q protein in the presence of the strong binding E11Q. The extended Langmuir-Freundlich model generally gave the lowest errors at higher concentrations, and the Jovanovic-Freundlich model gave the best fits when using empirically optimized maximal loading values based on multi-component as well as pure-component isotherm data.     

Highly active/selective and adjustable zirconium polymerization catalysts stabilized by aminopyridinato ligands

This paper describes a substantial enhancement of the aminopyridinato ligand stabilized early transition metal chemistry by introducing the sterically very demanding 2,6-dialkylphenyl substituted aminopyridinato ligands derived from (2,6-diisopropylphenyl)-[6-(2,6-dimethylphenyl)-pyridin-2-yl]-amine (1a-H, ApH) and (2,6-diisopropylphenyl)-[6-(2,4,6-triisopropylphenyl)-pyridin-2-yl]- amine (1b-H, Ap^∗H). The corresponding bis aminopyridinato zirconium dichloro complexes, [Ap₂ZrCl₂] (3a) and [Ap₂^∗ZrCl₂] (3b) and the dimethyl analogues, [Ap₂ZrMe₂] (4a) and [Ap₂^∗ZrMe₂] (4b) (Me = methyl) were synthesized, using standard salt metathesis routes. Single-crystal X-ray diffraction was carried out for the dichloro derivatives. Both zirconium metal centers have a distorted octahedral environment with a cis-orientation of the chloride ligands in 3a and a closer to trans-arrangement in 3b. The dimethyl derivatives are proven to be highly active ethylene polymerization catalysts after activation with [R₂N(Me)H][B(C₆F₅)₄] (R = C₁₆H₃₃-C₁₈H₃₇). During attempted co-polymerizations of α-olefins (propylene) and ethylene high activity and selectivity for ethylene and nearly no co-monomer incorporation was observed. Increasing the steric bulk of the ligand going from (2,6-dimethylphenyl) to (2,4,6-triisopropylphenyl) substituted pyridines, switches the catalyst system from producing long chain α-olefins to polymerization of ethylene in a living fashion. In contrast to the dimethyl complexes only [Ap₂^∗ZrCl₂] in the presence of MAO at elevated temperature gave decent polymerization activity. NMR investigations of the reaction of dichloro complexes with 25 equiv. of MAO or AlMe₃ at room temperature revealed, that [Ap₂ZrCl₂] decomposes under ligand transfer to aluminum and formation of [ApAlMe₂], while [Ap₂^∗ZrCl₂] remains almost unreacted under the same conditions. The aminopyridinato dimethyl aluminum complexes, [ApAlMe₂] (5a) and [Ap^∗AlMe₂] (5b) were synthesized independently and structurally characterized. The aluminum complexes 5a and b show no catalytic activity towards ethylene, when “activated” with[R₂N(Me)H][B(C₆F₅)₄].     

Mechanistic aspects of the formation of aldehydes and nitriles in photosensitized reactions of aldoxime ethers

The photooxidation of a series of aldoxime ethers was studied by laser flash photolysis and steady-state (product studies) methods. Nanosecond laser flash photolysis studies have shown that chloranil (CA)-sensitized reactions of the O-methyl (1), O-ethyl (2), O-benzyl (3), and O-tert-butyl (4) benzaldehyde oximes result in the formation of the corresponding radical cations. In polar non-nucleophilic solvents such as acetonitrile, there are several follow-up pathways available depending on the structure of the aldoxime ether and the energetics of the reaction pathway. When the free energy of electron transfer (DeltaGET) becomes endothermic, syn-anti isomerization is the dominant pathway. This isomerization pathway is a result of triplet energy transfer from CA to the aldoxime ether. For substrates with alpha-protons (aldoxime ethers 1-3), the follow-up reactions involve deprotonation at the alpha-position followed by beta-scission to form the benziminyl radical (and an aldehyde). The benziminyl radical reacts to give benzaldehyde, the major product under these conditions. A small amount of benzonitrile is also observed. In the absence of alpha-hydrogens (aldoxime ether 4), the major product is benzonitrile, which is thought to occur via reaction of the excited (triplet) sensitizer with the aldoxime ether. Abstraction of the iminyl hydrogen yields an imidoyl radical, which undergoes a beta-scission to yield benzonitrile. An alternative pathway involving electron transfer followed by removal of the iminyl proton was not deemed viable based on charge densities obtained from DFT (B3LYP/6-31G*) calculations. Similarly, a rearrangement pathway involving an intramolecular hydrogen atom transfer process was ruled out through experiments with a deuterium-labeled benzaldehyde oxime ether. Studies involving nucleophilic solvents have shown that all aldoxime ethers reacted with MeOH by clean second-order kinetics with rate constants of 0.7 to 1.2 x 10(7) M(-1) s(-1), which suggests that there is only a small steric effect in these reactions. The steady-state experiments demonstrated that under these conditions no nitrile is formed. This is explained by a mechanistic scheme involving nucleophilic attack on the nitrogen of the aldoxime ether radical cation, followed by solvent-assisted [1,3]-proton transfer and elimination of an alcohol, similar to the results obtained for a series of acetophenone oxime ethers.     

Automated discovery of noncovalent inhibitors of SARS-CoV-2 main protease by consensus Deep Docking of 40 billion small molecules

Recent explosive growth of ‘make-on-demand’ chemical libraries brought unprecedented opportunities but also significant challenges to the field of computer-aided drug discovery. To address this expansion of the accessible chemical universe, molecular docking needs to accurately rank billions of chemical structures, calling for the development of automated hit-selecting protocols to minimize human intervention and error. Herein, we report the development of an artificial intelligence-driven virtual screening pipeline that utilizes Deep Docking with Autodock GPU, Glide SP, FRED, ICM and QuickVina2 programs to screen 40 billion molecules against SARS-CoV-2 main protease (Mpro). This campaign returned a significant number of experimentally confirmed inhibitors of Mpro enzyme, and also enabled to benchmark the performance of twenty-eight hit-selecting strategies of various degrees of stringency and automation. These findings provide new starting scaffolds for hit-to-lead optimization campaigns against Mpro and encourage the development of fully automated end-to-end drug discovery protocols integrating machine learning and human expertise.

Deep learning-accelerated docking coupled with computational hit selection strategies enable the identification of inhibitors for the SARS-CoV-2 main protease from a chemical library of 40 billion small molecules.     

Insight into 3D micro‐CT data: exploring segmentation algorithms through performance metrics

Three‐dimensional (3D) micro‐tomography (µ‐CT) has proven to be an important imaging modality in industry and scientific domains. Understanding the properties of material structure and behavior has produced many scientific advances. An important component of the 3D µ‐CT pipeline is image partitioning (or image segmentation), a step that is used to separate various phases or components in an image. Image partitioning schemes require specific rules for different scientific fields, but a common strategy consists of devising metrics to quantify performance and accuracy. The present article proposes a set of protocols to systematically analyze and compare the results of unsupervised classification methods used for segmentation of synchrotron‐based data. The proposed dataflow for Materials Segmentation and Metrics (MSM) provides 3D micro‐tomography image segmentation algorithms, such as statistical region merging (SRM), k‐means algorithm and parallel Markov random field (PMRF), while offering different metrics to evaluate segmentation quality, confidence and conformity with standards. Both experimental and synthetic data are assessed, illustrating quantitative results through the MSM dashboard, which can return sample information such as media porosity and permeability. The main contributions of this work are: (i) to deliver tools to improve material design and quality control; (ii) to provide datasets for benchmarking and reproducibility; (iii) to yield good practices in the absence of standards or ground‐truth for ceramic composite analysis.     

A lattice Boltzmann method for immiscible multiphase flow simulations using the level set method

We consider the lattice Boltzmann method for immiscible multiphase flow simulations. Classical lattice Boltzmann methods for this problem, e.g. the colour gradient method or the free energy approach, can only be applied when density and viscosity ratios are small. Moreover, they use additional fields defined on the whole domain to describe the different phases and model phase separation by special interactions at each node. In contrast, our approach simulates the flow using a single field and separates the fluid phases by a free moving interface. The scheme is based on the lattice Boltzmann method and uses the level set method to compute the evolution of the interface. To couple the fluid phases, we develop new boundary conditions which realise the macroscopic jump conditions at the interface and incorporate surface tension in the lattice Boltzmann framework. Various simulations are presented to validate the numerical scheme, e.g. two-phase channel flows, the Young–Laplace law for a bubble and viscous fingering in a Hele-Shaw cell. The results show that the method is feasible over a wide range of density and viscosity differences.     

Reactivities of the Prism‐Shaped Diamondoids [1(2)3]Tetramantane and [12312]Hexamantane (Cyclohexamantane)

Functionalized nanodiamonds : Various functional groups have been incorporated into the structures of the naturally occurring diamondoids [1(2)3]tetramantane and [12312]hexamantane (cyclohexamantane), which represent hydrogen‐terminated prism‐shaped nanodiamonds (see picture). The attachment points define the use of these diamond‐like molecules as geometric building blocks for a variety of applications.

     

Room-temperature electroluminescence in the mid-infrared (2-3 microm) from bulk chromium-doped ZnSe

Electroluminescence associated with impact excitation or ionization of deep Cr(2+) impurity centers in bulk ZnSe is reported. A broad signal of mid-infrared luminescence between 2 and 3 microm is observed once the biased bulk ZnSe device runs into a nonlinear conduction regime. Optical powers in the nanowatt range have been measured at room temperature. The different mechanisms involved in this intracenter infrared light emission are discussed.