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Simple User-Friendly Reaction Format
No full textLeveraging the increasing volume of chemical reaction data can enhance synthesis planning and improve suc-
cess rates. However, machine learning applications for retrosynthesis planning and forward reaction prediction
tools depend on having readily available, high-quality data in a structured format. While some public and
licensed reaction databases are available, they frequently lack essential information about reaction condi-
tions. To address this issue and promote the principles of findable, accessible, interoperable, and reusable
(FAIR) data reporting and sharing, we introduce the Simple User-Friendly Reaction Format (SURF). SURF
standardizes the documentation of reaction data through a structured tabular format, requiring only a basic
understanding of spreadsheets. This format enables chemists to record the synthesis of molecules in a format
that is both human- and machine-readable, making it easier to share and integrate directly into machine-
learning pipelines. SURF files are designed to be interoperable, easily imported into relational databases, and
convertible into other formats. This complements existing initiatives like the Open Reaction Database (ORD)
and Unified Data Model (UDM). At Roche, SURF plays a crucial role in democratizing FAIR reaction data
sharing and expediting the chemical synthesis process
Solid-state vibrational circular dichroism for pharmaceutical applications: polymorphs and cocrystal of sofosbuvir
No full textX-ray diffraction is a commonly used technique in the pharmaceutical industry for the determination of the atomic and molecular structure of crystals. However, it is costly, sometimes time-consuming, and it requires a considerable degree of expertise. Vibrational circular dichroism (VCD) spectroscopy resolves these limitations, while also exhibiting substantial sensitivity to subtle modifications in the conformation and molecular packaging in the solid state. This study showcases VCD\u27s ability to differentiate between various crystal structures of the identical molecule (polymorphs, cocrystals). We examined the most effective approach for producing high-quality spectra and unveiled the intricate link between structure and spectrum via quantum-chemical computations. We rigorously assessed, using alanine as a model compound, multiple experimental conditions on the resulting VCD spectra, with the aim of proposing an optimal and efficient procedure. The proposed approach, which yields reliable, reproducible and artifact-free results with maximum signal-to-noise ratio, was then validated using a set comprising of three amino acids (serine, alanine, tyrosine), one hydroxy acid (tartaric acid), and a monosaccharide (ribose) to mimic active pharmaceutical components. Finaly, the optimized approach was applied to distinguish three polymorphs of the antiviral drug sofosbuvir and its cocrystal with piperazine. Our results indicates that solid-state VCD is a prompt, cost-effective, and easy-to-use technique to identify crystal structures, demonstrating potential for application in pharmaceuticals. We also adapted the cluster and transfer approach to calculate the spectral properties of molecules in a periodic crystal environment. Our findings demonstrate that this approach reliably produces solid-state VCD spectra of model compounds. Although for large molecules with many atoms per unit cell, such as sofosbuvir, this approach has to be simplified and provides only a qualitative match, spectral calculations and energy analysis helped us to decipher the observed differences in the experimental spectra of sofosbuvir
Oxygen Activities Governing Structural Reversibility in Industrial Ni-Rich Layered Cathodes
No full textThe chemical reactions and phase transitions at high voltages determine the electrochemical
properties of high voltage layered cathodes such as Ni-rich rhombohedral materials. Here, we
performed a comprehensive and comparative study of the cationic and anionic redox reactions, as
well as the structural evolution of a series of industrial Ni-rich layered cathode materials with and
without Al doping, which are being utilized in the cells made by LG Energy Solutions Co.. We
combined the results from X-ray spectroscopy, operando electrochemical mass spectrometry, and
neutron diffraction with electrochemical properties, and revealed the different oxygen activities
associated with structural and electrochemical degradations. We show that Al doping suppresses
the irreversible oxygen release thereby enhancing the reversible lattice oxygen redox resulting from the interplay between static (doped Al) and dynamic disorders (reversible oxygen redox). With this modulated oxygen activity, the Ni-rich cathode\u27s notorious H2-H3 structural phase transition becomes highly reversible. Our findings disentangle the different oxygen activities during high-voltage cycling and clarify the role of dopants in the Ni-rich layered cathodes in terms of structural and electrochemical stability finally making all the cell makers get back to the fundamental investigation regarding whether high-Ni NCM chemistry (NCM811 or NCM 91/2 1/2) is substantially beneficial compared to its mid-Ni homologues (NCM622)
Feature attributions for water-solubility predictions obtained by artificial intelligence methods and chemists
No full textRecently, the field of explainable artificial intelligence has attracted significant research interest, with a particular focus on “feature attribution” in the field of chemistry. However, studies comparing the relationship between artificial-intelligence- and human-based feature attributions when predicting the same outcome are scarce. Hence, the current study aims to investigate this relationship by comparing machine-learning-based feature attributions (graph neural networks and integrated gradients) with those of chemists (Hansch–Fujita method) when predicting water solubility. The findings reveal that the artificial-intelligence-based attributions are similar to those of chemists despite their distinct origins
Enantioselective Total Syntheses of (+)-Kasugamycin and (+)-Kasuganobiosamine Highlighting a Sulfamate-Tethered Aza-Wacker Cyclization Strategy
No full textHere, we present the first enantioselective total syntheses of the natural products (+)-kasugamycin, a potent
antifungal antibiotic, and (+)-kasuganobiosamine, a compound that results from kasugamycin degradation. Salient features of these syntheses include a second-generation enantioselective preparation of a kasugamine derivative (much improved in efficiency relative to our first chiral-pool effort) and our laboratory’s sulfamate-tethered aza-Wacker cyclization
Sub-picosecond Dynamics of Rydberg Excitons Produced from Ultraviolet Excitation of Neutral Cuprite (Cu2O)n Clusters, n < 13
No full textThe ultrafast dynamics of sub-nanometer neutral cuprite clusters (Cu2O)n, n < 13, are examined with pump probe spectroscopy. Up-on absorption of an ultraviolet (400 nm) photon, all clusters exhibit a sub-picosecond lifetime that we attribute to carrier recombi-nation. Density functional theory shows a change in the structural motif between small planar clusters and three-dimensional struc-tures at n = 4. This transition is accompanied by a change in the excited state relaxation behavior, marking the onset for which life-times increase gradually with size. Time-dependent density functional theory calculations show the excited state lifetimes align with calculated topological parameters and charge carrier delocalization associated with the formation of Rydberg excitons. Termi-nal Cu atoms are found to be important for the production of Rydberg excitons at the lowest optically allowed excited state. The electron centers on terminal Cu atoms and the hole becomes delocalized across the remainder of the cluster
Iron-Catalyzed Late-Stage Radical C–H Alkylamination of Phenol-Containing Drugs and Biomolecules
No full textA modular site-selective iron-catalyzed radical amination of a number of phenol-containing biomolecules such as tyrosine-containing peptides, estrogens and other phenol-based pharmaceuticals has been developed. The method features the use of the cost-efficient combination of FeBr3 as catalyst along with triflic acid as Brønsted acid, thereby enabling the predictable appendance of morpholine and related heterocycles at the ortho C–H bond of phenols in a late-stage fashion. This alkylamination technique leverages the electron-rich nature of phenols to undergo oxidation to the corresponding phenoxyl radicals and further coupling with in situ formed electrophilic aminium radical cation species
Charting the Electronic Structure for Discovering Low-cost Intermetallic Catalysts
No full textDiscovering affordable, high-performance, and stable catalysts for the hydrogen evolution reaction (HER) and oxygen reduction reaction (ORR) is essential for the commercialization of clean hydrogen technology. In this study, we utilized a high-throughput screening approach combined with electronic structure descriptors to identify new intermetallic catalysts that minimize noble metal contents while maintaining high performance and stability. We screened 2,358 binary and ternary intermetallic compounds constructed from 31 common transition metal elements. From the 462 bulk compositions that are synthetically accessible, we enumerated all possible low-Miller-index surfaces (12,057 surfaces in total) with density functional theory calculations. Seven electronic-structure-based descriptors are then applied to pinpoint aqueously stable surfaces offering performance comparable to the renowned Pt (111) and Ir (111) surfaces. This process led to the identification of several previously known noble-metal-containing catalysts, as well as a selection of new intermetallic catalysts
Low-Cost Hourly Ambient Black Carbon Measurements at Multiple Cities in Africa
No full textThere is a notable lack of continuous monitoring of air pollutants in the Global South, especially for measuring chemical composition, due to high cost of regulatory monitors. Using our previously developed low-cost method to quantify black carbon (BC) in fine particulate matter (PM2.5) by analyzing reflected red light from ambient particle deposits on glass fiber filters, we estimated hourly ambient BC concentrations with filter tapes from Beta Attenuation Monitors (BAMs). BC measurements obtained through this method were validated against a reference aethalometer in Addis Ababa, Ethiopia, demonstrating a very strong agreement (R2 = 0.95 and slope = 0.97). We present hourly BC for three cities in sub-Saharan Africa (SSA) and one in North America: Abidjan (Côte d’Ivoire), Accra (Ghana), Addis Ababa (Ethiopia), and Pittsburgh (USA). The average BC for the measurement period at the Abidjan, Accra, Addis Ababa Central summer, Addis Ababa Central winter, Addis Ababa Jacros winter and Pittsburgh sites were 3.85 µg.m-3, 5.33 µg.m-3, 5.63 µg.m-3, 3.89 µg.m-3, 9.14 µg.m-3 and 0.52 µg.m-3, respectively. BC made up 14 – 20% of PM2.5 mass in the African cities, compared to only 5.6% in Pittsburgh. The hourly BC data at these sites show a pronounced diurnal pattern with prominent peaks during the morning and evening rush hours on workdays. Comparison between our measurements and the Goddard Earth Observing System composition forecast (GEOS-CF) estimates shows that the model performs well in predicting PM2.5 for most sites but struggles to predict BC at an hourly resolution. Adding more ground measurements could help calibrate and improve performance of chemical transport models. This method can potentially use existing BAM networks, especially BAMs at US embassies around the globe, to measure hourly BC with our method. The PM2.5 composition data, thus acquired, can be crucial in identifying emission sources and help in effective policymaking in the Global South
Complexation and Disproportionation of Group 4 Metal (Alkoxy) Halides with Phosphine Oxides
No full textGroup 4 Lewis acids are well-known catalysts and precursors for (non-aqueous) sol-gel chemistry. Titanium, zirconium and hafnium halides, and alkoxy halides are precursors for the controlled synthesis of nanocrystals, often in the presence of Lewis base. Here, we investigate the interaction of Lewis bases with the tetrahalides (MX4 X = Cl, Br) and metal alkoxy halides (MXx(OR)4-x, x = 1-3, R = OiPr, OtBu). The tetrahalides yield the expected Lewis acid-base adducts MX4L2 (L = tetrahydrofuran or phosphine oxide). The mixed alkoxy halides react with Lewis bases in a more complex way. 31P NMR spectroscopy reveals that excess of phosphine oxide yields predominantly the complexation product, while a (sub)stoichiometric amount of phosphine oxide causes disproportionation of the MXx(OR)4-x species into MXx+1(OR)3-x and MXx-1(OR)5-x. The combination of complexation and disproportionation yields an atypical Job plot. In the case of zirconium isopropoxy chlorides, we fitted the concentration of all observed species and extracted thermodynamic descriptors from the Job plot. The complexation equilibrium constant decreases in the series: ZrCl3(OiPr) > ZrCl2(OiPr)2 >> ZrCl(OiPr)3, while the disproportionation equilibrium constant follows the opposite trend. Using calculations at the DFT level of theory, we show that disproportionation is driven by the more energetically favorable Lewis acid-base complex formed with the more acidic species. We also gain more insight into the isomerism of the complexes. The disproportionation reaction turns out to be a general phenomenon, for titanium, zirconium and hafnium, for chlorides and bromides, and for iso-propoxides and tert-butoxides