Helvetica Chimica Acta最新文献

Nitroxides such as 2,2,6,6-tetramethylpiperidin-N-oxyl (TEMPO) are the quintessential organic radicals. They are commonly used to trap alkyl radicals in controlled radical polymerizations, synthetic transformations and mechanistic experiments, and peroxyl radicals when applied as radical-trapping antioxidants (RTAs). Relatively little is known about their sulfur analogs (N-thiyl radicals, R₂NS• and dithiobisamines, R₂NS-SNR₂). We found that dithiobisamines of moderate steric bulk (including (TEMPS)₂, the dimer of the sulfur analog of TEMPO), trapped peroxyl radicals with rate constants up to 1.2 × 10⁶ m⁻¹s⁻¹ (at 100 °C) – similar to TEMPO. Unlike TEMPO, their radical-trapping activity was not catalytic, independent of the rate of radical initiation and still operative in saturated hydrocarbons – implying a distinct mechanism. Additional experimental data and computations point to a homolytic substitution mechanism, analogous to that recently elucidated for tetrasulfides. In the absence of O₂, alkyl radicals and dithiobisamines react to form sulfenamides, which may be exploited for synthetic purposes.

I chose chemistry/biology as a career because I enjoy cooking and baking, i.e., synthesizing compounds seemed like the natural next step. The secret of being a successful scientist is to stay true to yourself. I chose my field of research because it lets me combine various scientific interests, from the materials synthesis (chemistry) to fundamental light-matter interactions (physics) and devices (engineering).

I chose my field of research (photochemistry) because I find it fascinating. The combination of lasers and colorful molecules makes me feel like I am inside a Sci-Fi show. My motivation in difficult times is that there is always light at the end of the tunnel, and that it will always be sunny after a storm. My favorite quote is “it's better to have it and not need it than to need it and not have it”.

This study presents a workflow for rapidly assessing the applicability of Ir-catalyzed C─H borylation across structurally diverse heterocyclic fragments relevant to discovery chemistry. Leveraging cheminformatics, we have selected different N-containing bicyclic scaffolds and evaluated various reaction conditions via a high-throughput experimentation (HTE) platform. The diversified screening approach revealed suitable substrate-specific catalytic systems. The workflow integrates several key steps: 1) defining a focused subset of relevant heterocyclic scaffolds, 2) selecting structurally diverse scaffolds using clustering algorithms, 3) conducting HTE screening with multiple catalytic systems, and 4) scaling up promising hits in a high-throughput fashion. This approach enabled rapid exploration of reaction scope and identification of suitable conditions for various substrates. The study demonstrates the power of combining cheminformatics, HTE, and strategic experimental design to accelerate the evaluation and optimization of synthetic methodologies, with potential future implications for lead optimization in drug discovery and agrochemical development.

In this study, we report on the use of mechanochemistry for the synthesis of trifluoromethylated isoindolinones via a cascade radical sequence involving intermolecular addition/cyclization reactions of ynamides. This minimum solvent approach, involving liquid-assisted grinding, provides the products in good yields with complete E stereoselectivity, contrasting with the E/Z mixtures obtained under previously reported photoredox conditions. Mechanistic investigations revealed two complementary activation pathways: mechanical activation alone can trigger the radical cascade, while the presence of piezoelectric materials (BaTiO₃) significantly accelerates product formation. Furthermore, we identified an unexpected role of Celite® as an abrasive agent that promotes metal leaching and enables alternative activation pathways. This methodology showcases mechanochemistry as a valuable alternative to photoredox catalysis for stereoselective radical transformations, with distinct mechanistic advantages that can be strategically exploited.

Plasmodium falciparum dihydrofolate reductase-thymidylate synthase (PfDHFR-TS) is a well-defined antimalarial target of antifolate drugs. However, the emergence of parasite resistance to antifolate medications is the primary reason for the unsuccessful treatment of malaria. In this work, repurposing of anticancer drugs through virtual screening was conducted to identify critical interactions with quadruple type (qmPfDHFR-TS) and hDHFR (human dihydrofolate reductase). Three anticancer drugs-pralatrexate (PRA), pemetrexed (PME), and dasatinib (DAS) - exhibited significant binding interactions with qmPfDHFR-TS and hDHFR. The binding stability of PRA and the reference compound, P218, was determined using principal component analysis (PCA) and free energy landscape (FEL) analyses. Additionally, the key binding interaction patterns of qmPfDHFR-TS and hDHFR was further investigated through quantum chemical calculations. The PRA complex and P218 complex display meaningful H-bond interactions with Asp54, Arg59, and Arg122, as well as a π–π interaction with Phe58, in the qmPfDHFR-TS structure. For hDHFR, it was found that P218 and PRA do not establish H-bond interactions with Arg70, which is the conserved residue in hDHFR. Furthermore, this discovery was validated by conducting enzyme inhibition tests, which demonstrated the capacity of these compounds to inhibit PfDHFR enzymes. As a result, pralatrexate shows potential as an effective inhibitor against the mutant type of the PfDHFR enzyme.

The synthesis and characterization of cross-shaped π-extended dibenzo[e,l]pyrene derivatives with combined fjord and armchair edge structures were reported. The target molecules were synthesized via Yamamoto coupling and Scholl reactions, and their structures were fully characterized by nuclear magnetic resonance (NMR), high-resolution mass spectrometry (HR-MS), and single-crystal X-ray diffraction. Photophysical studies revealed a significant redshift in absorption and emission spectra compared to the parent dibenzo[e,l]pyrene, attributed to the extended π-conjugation system. Density functional theory (DFT) calculations provided insights into the molecular orbital distribution and reduced bandgap resulting from the elongated conjugation pathway. This work offers a versatile synthetic strategy for polycyclic aromatic hydrocarbons with tailored edge topologies and paves the way for their potential applications in optoelectronic materials.

I chose chemistry as a career because after participating in the Chemistry Olympiad, I was fascinated by everything chemists can do. My favorite quote is “Life is like riding a bicycle: to keep your balance, you must keep moving” by Albert Einstein. If I were not a scientist, I would be a teacher of either chemistry, music, or step aerobics.