Chemistry methods : new approaches to solving problems in chemistry最新文献

The Front Cover shows Wiener skewing in sedimentation velocity boundary of highly concentrated macromolecular solutions. The transient refractive index gradient produces an optical aberration that can be recognized by the displacement of the Rayleigh interference optical baseline features associated with the migrating refractive index gradient. The red lines represent two select baseline blips with best-fit translation and slope. Global analysis of the translation versus slope data reveals the magnitude of Wiener skewing, which then can be modeled in the sedimentation analysis. More information can be found in the Research Article by Sumit K. Chaturvedi and Peter Schuck (DOI: 10.1002/cmtd.202400035).

A time resolved in situ X-ray powder diffraction study using synchrotron radiation allowed for describing the evolution of the zeolite FAU structure during the development of a zeolite-templated carbon (ZTC) in its porous voids. During the ZTC formation the intensity decrease of most zeolite reflections and the simultaneous rise in intensity of the 222 reflection (of null intensity in the pristine zeolite) was observed. Full pattern profile fitting by Rietveld refinement allowed for achieving a detailed description of the underlying chemistry, with coincident pore filling with carbon atoms in specific positions and framework distortion. Monitoring the intensity profiles of the 222 reflection allowed assessment of the energetics of the ZTC formation. Our results contribute to a better understanding of the phenomena involved on the atomic scale in ZTC synthesis.

Reactor automation is a transformative force for chemical processes, but the potential of reaction monitoring for machine-assisted autonomous biocatalytic reaction optimization is still largely unexplored. To address this gap, we report on automated reactor optimization for biocatalytic flow-through microreactors. For this purpose, the inline NMR analysis of an enzymatically catalyzed stereoselective reduction of a prochiral diketone was combined with a self-developed open-source analysis and control software. The algorithm is continuously fed with spectra from a benchtop NMR instrument acquired from a reaction solution from a microreactor filled with biocatalytically active materials and adjusts the flow rate of the pumps to achieve predetermined target concentrations of the product. We show that through this automated coupling of data analysis and process parameterization, for example, maximum conversion efficiency can be achieved for a given bioreactor. This work illustrates the potential of inline NMR reaction monitoring for biocatalytic processes and provides a starting point for innovation to develop automated processes for precision biocatalysis through integrated data analysis.

The solution state of macromolecules in concentrated solutions impacts fields ranging from cell biology, to colloid chemistry and engineering of protein pharmaceuticals. Dependent on the interplay between repulsive and weakly attractive forces, proteins may exhibit oligomerization, aggregation, crystallization, liquid-liquid phase separation, or the formation of multiprotein complexes. The particle size-distribution is a key characteristic, but difficult to determine when interparticle distances are on the order of their size and macromolecular motion is coupled through hydrodynamic interactions. Here we extend sedimentation velocity analytical ultracentrifugation to measure macromolecular size distributions under these conditions: We apply results from statistical fluid mechanics for the concentration-dependence of hindered settling and diffusion, embedded in a mean-field approximation that can resolve coupled sedimentation and diffusion processes of different sized species given experimental sedimentation data. This is combined with a description of transient optical aberrations from lensing in the refractive index gradients associated with sedimentation boundaries (Wiener skewing). We demonstrate this approach in the application to protein solutions with macromolecular volume fractions up to ≈10 %, for example, resolving monomers and dimers of albumin at 140 mg/ml. This enables size-distribution analysis of proteins at concentrations of therapeutic antibody formations and close to physiological concentration in serum and cells.

The Front Cover shows the molecular structure of the undecafluorinated carbaborate anion [CHB₁₁F₁₁]⁻, as well as its precursor [CB₁₁H₁₂]⁻ and the starting material [BH₄]⁻. Detailed synthetic protocols for the synthesis of [CB₁₁H₁₂]⁻ and [CHB₁₁F₁₁]⁻ in large scales are provided by Ingo Krossing and co-workers in their Research Article. To facilitate the reproduction of the preparation of these compounds, the synthesis has been filmed and instructive videos are provided with the publication. Starting from the [CHB₁₁F₁₁]⁻ anion, the authors tested its chemical properties and synthesized its trityl ([Ph₃C]⁺) as well as its silver salt ([Ag(odfb)₂]⁺) and used them for a representative hydrosilylation reaction, as well as the oxidation of ferrocene and the ‘magic blue’ amine N(4-C₆H₄Br)₃. More information can be found in the Research Article by I. Krossing and co-workers (DOI: 10.1002/cmtd.202400011).

Mononuclear inorganic diradical species are scarce. Here, we confirm, via X-ray absorption spectroscopy in the gas phase combined with computational studies, the oxygen-centered diradical character of the tetraoxidorhenium(VII) cation. A dioxido-superoxido isomer, close in energy to the diradical, is also found, where rhenium appears in its rare oxidation state of +6. Addition of one or two hydrogen atoms to [Re,O₄]⁺ forms hydroxido ligands, and strongly disfavors isomers with any oxygen-oxygen bond. This adds spectroscopic characterization of the rhenium oxidation state and the nature of ligands to the known ability of [Re,O₄]⁺ to perform two consecutive hydrogen-atom abstraction reactions from methane, and demonstrates that pentaatomic [Re,O₄]⁺ combines a metal center in its highest oxidation state with two oxygen-centered radical ligands in a highly reactive species.

In this work, we present our improved protocols for the single batch syntheses of approximately 32 g of [NHMe₃][CB₁₁H₁₂] and 10 g of Na[CHB₁₁F₁₁] as well as salt metathesis reactions, granting access to useful starting materials to introduce the [CHB₁₁F₁₁]⁻ anion. This includes the trityl cation [Ph₃C]⁺ and the bis-1,2-difluorobenzene-silver(I)-complex [Ag(odfb)₂]⁺, as well as some applications of the shown compounds. The described methodology allows the synthesis of large amounts of both the [CB₁₁H₁₂]⁻ and the [CHB₁₁F₁₁]⁻ anion and therefore making them accessible for further reactions. To facilitate the reproducibility, we present video tutorials of the synthetic steps towards Na[CHB₁₁F₁₁].

Determining whether a molecule can be synthesized is crucial in chemistry and drug discovery, as it guides experimental prioritization and molecule ranking in de novo design tasks. Existing scoring approaches to assess synthetic feasibility struggle to extrapolate to new chemical spaces or fail to discriminate based on subtle differences such as chirality. This work addresses these limitations by introducing the Focused Synthesizability score (FSscore), which uses machine learning to rank structures based on their relative ease of synthesis. First, a baseline trained on an extensive set of reactant-product pairs is established, which is then refined with expert human feedback tailored to specific chemical spaces. This targeted fine-tuning improves performance on these chemical scopes, enabling more accurate differentiation between molecules that are hard and easy to synthesize. The FSscore showcases how a human-in-the-loop framework can be utilized to optimize the assessment of synthetic feasibility for various chemical applications.

The growing interest in physically deposited model catalysts for uncovering complex structure-activity relationships is spurred by the possibility of depositing nanoparticles of precise atomic structure and composition using cluster-beam sources. However, the limitations accompanying these synthesis techniques, such as low deposition rates and flat sample geometry, present a challenge for in situ structural characterization using bulk-sensitive methods, such as X-ray absorption spectroscopy (XAS), especially at elevated pressures (1–100 bar). To overcome this challenge, we constructed an in situ XAS cell operating in a grazing incidence (GI) geometry. The GIXAS cell was used to investigate the structure of cluster-beam-generated Pd and Au_0.3Ag_0.7 nanoparticles under CO₂-to-methanol hydrogenation conditions (230 °C, 20 bar, CO₂:H₂=1 : 3). These nanoparticles, with metal loading of 0.96–10 μg cm⁻², demonstrated stability and resistance to sintering upon activation in H₂ at 120 °C and catalytic conditions, revealed by in situ XAS. The promising results from our work will help bridge the gap in the investigation of model catalytic materials produced by gas-phase cluster deposition at industrially relevant pressures and temperatures, which is vital for a mechanistic understanding of catalytic processes.