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

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).

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.

Nuclear magnetic resonance (NMR) is recognized as the gold standard method in fragment-based drug design for screening, hit validation, and affinity determination. However, its deployment at a large scale is limited by the cost and expertise needed to implement NMR as a routine drug discovery method. The increase in the adoption of fragment-based drug design created a need for biophysics to provide high-quality data for weak ligand-target interactions that can be implemented at scale. NMR must adapt its position in drug design operations to enter this new era. The recent development of commercially available benchtop NMR spectrometers in combination with hyperpolarization methods represents an opportunity for highly deployable and scalable systems.

Zeolite 13X is an excellent candidate for the capture of CO₂. However, this system needs to be investigated in more detail with regard to adsorption and diffusion. For this purpose, frequency response (FR) measurements were carried out with binderless zeolite 13X (NaMSX) and CO₂. The size of the particles and the sample amount were modified in order to investigate their effects on diffusion processes. Macropore diffusion was detected and the corresponding diffusion coefficients were determined. The mentioned system was additionally used to evaluate the performance of the in-house FR apparatus.

Solution state ¹H NMR spectroscopy provides valuable insights into molecular structure and conformation. However, when the spectrum exhibits severe signal overlap, it hampers the extraction of key structural information. Here, an ultraselective, ultrahigh resolution TOCSY method is introduced that greatly reduces spectral complexity, allowing the extraction of previously inaccessible spectral information. It combines the recently developed GEMSTONE excitation with homonuclear decoupling to provide highly simplified through-bond correlation 1D ¹H NMR spectra, showing all signals within the selected spin system as singlets. The new method can greatly facilitate the analysis of mixtures, as shown here for a mixture of Cinchona alkaloids (popular catalysts in asymmetric synthesis) and a mixture of glucocorticoids (used for treating conditions such as asthma).