A combination of salinomycin or its C20 triphenylphosphonium-conjugated derivative with carboplatin leads to autophagy in ovarian cancer cells - An in vitro study.

Multi-active-site additives with strong reactivity are an effective strategy to continuously improve device efficiency, and also contribute to the long-term stability of perovskite solar cells (PSCs). However, achieving efficient interaction between all active sites and the perovskite remains a critical challenge. Among various structural modifications, methyl substitution, the simplest functional unit in organic chemistry, offers a unique methylation effect that strongly depends on its positional configuration within a molecule, thereby providing a promising approach to modulate additive reactivity. In this study, we designed and investigated two positional methylation isomers, 1-methylhydantoin (1-MH) and 5-methylhydantoin (5-MH), and demonstrate rational positional methylation can significantly enhance the multisite reactivity of additives with perovskite materials. While both isomers contribute to improved device efficiency, they exhibit markedly different effects on device stability. Notably, the incorporation of 5-MH enabled a power conversion efficiency (PCE) of 26.84% (certified at 26.78%), and delivered outstanding operational stability, retaining 92% of its initial PCE after 2000 h under the ISOS-L2 protocol.

Stereoisomers arising from the rotational restriction about a CN single bond, namely CN atropisomers, have recently attracted considerable attention in the field of synthetic organic chemistry. Diverse CN atropisomeric compounds have been prepared with high optical purity through catalytic enantioselective reactions, and they have been used in various asymmetric reactions as chiral building blocks and chiral ligands. CN atropisomers are attractive compounds from the viewpoint of not only synthetic organic chemistry but also medicinal chemistry. Recently, various CN atropisomeric bioactive compounds have been found, and their biological activity, the target selectivity, and the pharmacokinetics have been revealed to differ significantly between atropisomers. On the other hand, we feel that the chemistry community is still not fully aware of the fascinating biological properties of CN atropisomers. This review article comprehensively describes CN atropisomeric compounds exhibiting diverse biological activities as well as the synthesis or separation of atropisomers and their rotational stability.

Carbonylation reactions, which rely on the controlled incorporation of carbon monoxide into organic substrates, represent a key tool in both organic and industrial chemistry. Carbonylation offers an efficient route to carbonyl-containing compounds starting from simple and readily available substrates, and it remains a highly active area of research in organometallic chemistry and catalysis. Current efforts focus on developing new catalysts, more efficient and sustainable methodologies, and innovative applications in emerging areas such as green chemistry and asymmetric synthesis. Given the great importance of heterocyclic compounds, the carbonylative approach has become increasingly important for their synthesis. In this review, we summarize and discuss advancements in the synthesis of quinolinone derivatives, a class of benzo-fused nitrogen-containing heterocyclic compounds, via carbonylative approaches.

Spin manipulation has emerged as a transformative strategy in boosting electrochemical reactions. Yet, its application in organic electrosynthesis involving diffusive radical intermediates remains less explored compared to aqueous systems. Herein, we report a systematic study of spin-controlled organic electrosynthesis via precise regulation of radical coupling and hydrogenation pathways in solution during the electroreduction of benzyl chloride. By leveraging ferromagnetic electrodes with external magnetic fields, spin-polarized electron transfer fundamentally alters the spin states of radical intermediate, selectively suppressing radical coupling by 70% while achieving 85% selectivity for hydrogenated product─performance unattainable through conventional potential control. Notably, the contribution of the MHD effect was further excluded with the absence of a magnetic field effect using nonmagnetic electrodes, highlighting the spin manipulation as the intrinsic mechanism underlying the observed magnetic field effects. Our findings establish spin polarization as an orthogonal methodology for reaction pathway engineering and selectivity enhancement in sustainable organic chemistry.

Machine learning (ML) models have achieved remarkable success in organic chemistry, where reliable reference data, most commonly from density functional theory (DFT), enable accurate predictions. In contrast, ML approaches remain far less reliable for transition metal complexes, particularly for spin-state energetics (SSE), due to the erratic and system-dependent behavior of DFT. To begin addressing this fundamental data limitation, we present a benchmark dataset of 50 first-row mononuclear octahedral complexes spanning d4-d6, with spin energy gaps computed at the high-level CASPT2/CC multireference level. Using this high-accuracy dataset, we systematically benchmark a broad range of DFT methods and demonstrate that the optimal fraction of Hartree-Fock exchange is intrinsically dependent on the specific spin-state transition. Furthermore, we introduce an electronic-structure-based descriptor, Des-δ, and employ a Δ-machine-learning (Δ-ML) framework to extrapolate CASPT2/CC-level accuracy to an expanded library of 500 complexes.

Sulfones and their derivatives serve as important structural units in organic chemistry. However, there is currently a lack of simple and feasible synthetic methods for their synthesis. In this wotk, a photoredox/copper dual catalysis that enabled 1,2-arylsulfonylation of vinylarenes to afford 2,2-diarylethyl sulfones has been reported for the first time. The developed protocol features high reaction regioselectivity and good reaction generality, affording a facile approach to 2,2-diarylethyl sulfones.

Amidinates ([R1NC(R2)NR3]-) are versatile and ubiquitous ligands in inorganic and main group chemistry, due to their anionic, bidentate nature and easy tunability. Herein we present the synthesis of 23 bulky N-aryl substituted aminidinate ligands via three different synthetic routes: 1. condensation reaction in the presence of PPSE (polyphosphric acid trimethylsilylester); 2. the treatment of a carbodiimide with a lithium salt, and 3. the sequential addition of anilines to an acyl chloride and then to the resultant imidoyl chloride. These synthetic routes have been compared and critically analysed. The stabilising properties of the ligands were next probed through complexation with aluminium (AlH3·NMe3), where it was found that the bulkier ligands afford aluminium dihydride complexes, whereas the less bulky ligands instead afford bis-ligated aluminium monohydride complexes. Finally, we utilised computational methods to further explore the steric and electronic properties of these ligands, highlighting the differing effects of different substitution patterns.

Abstract Gamification is a well-established strategy for increasing students’ motivation and engagement. With the aim of building a sense of community among incoming Chemistry undergraduates, we previously developed an interactive game, CHEMmunicate, where teams of students compete to draw organic structures using only yes/no questions. In addition to their social benefits, the sessions also had a positive influence on students’ learning of organic chemistry with “post-game discussions” of fundamental concepts in particular providing a useful tool for reinforcing and revising key material from the core lectures. In contrast to the rounds of CHEMmunicate, however, these informal, non-competitive discussions did not incorporate elements of gameplay and thus did not fully benefit from the well-established advantages of game-based learning. In this work, we have reimagined the “post-game discussion” element of the sessions, introducing competitive online quizzes alongside rounds of CHEMmunicate. Working in their teams, students compete to answer questions related to the molecules they have just drawn with points being awarded for giving the correct answers in the fastest time. Here, we provide information and tips for those interested in incorporating similar sessions into their own teaching practice. Moreover, through analysis of anonymous questionnaires and a focus group, insights into students’ experiences are discussed.

Thiocarbamates are a class of molecules with important value and significant roles in organic chemistry. Due to their unique chemical properties and heteroatom-rich molecular structure, thiocarbamates have broad application prospects in organic synthesis, analytical chemistry, materials science and biomedicine. In recent years, methodological studies on the synthesis of these compounds have garnered increasing attention in the scientific community. This mini-review summarizes the representative progress in the effective synthesis of thiocarbamates through different synthetic strategies from thermochemistry to photochemistry or electrochemistry in the past decade, emphasizes the diversity and applicability of their products, and expounds their mechanism principles where possible.

Antimicrobial resistance has emerged as one of the major global health threats, driving the search for innovative strategies to combat chronic and recurring infections, particularly associated with biofilm formation. Biofilms confer strong tolerance to traditional antibiotics by shielding microbial communities within an extracellular matrix, posing significant challenges in clinical settings, especially in device-associated infections. Conventional antibiotics often fail to eradicate these complex biofilm structures, underscoring the need to explore alternative therapeutic strategies. Over the past decade, metal-based complexes have emerged as promising alternatives due to their unique modes of action and physicochemical properties. The integration of organic and inorganic chemistry, metal-ligand interactions in metal complexes, exhibits diverse mechanisms of action, including ROS production, enzyme inhibition, membrane cleavage and delayed resistance, representing a compelling frontier in addressing the global AMR crisis. This review highlights the dual role of metal complexes in antimicrobial and antibiofilm applications, with emphasis on silver, copper, palladium, gold, zinc, ruthenium, platinum and other complexes, reinforcing their potential as next-generation therapeutic antimicrobials.

To enable the biomedical application of hydrophobic antitumor agents and expand organic reactions in physiological settings, we engineered an NIR-responsive nanoplatform (Fe-MSNY6-OPD/benzil@PEG-AS1411, FOBA) for on-demand intratumoral drug synthesis. The system utilizes an iron-doped mesoporous silica framework co-loaded with photothermal converter Y6 and hydrophobic precursors (o-phenylenediamine/benzil), surface-coated with high-MW PEG as a stimuli-responsive gatekeeper. Upon 808nm NIR laser irradiation, Y6-mediated photothermal heating induces PEG phase transition, creating a transient solvent microenvironment that enables in situ synthesis of the cytotoxic agent 2,3-diphenylquinoxaline (2,3-DPQ) selectively within tumors. Concurrently, the nanoplatform degrades to release Fe2+ ions, inducing synergistic ferroptosis alongside drug synthesis. In vitro and in vivo studies demonstrate excellent biocompatibility and precise spatiotemporal control of therapeutic activation. By integrating rapid, localized drug generation with slow-hydrolysis-mediated ferroptosis, this dual-temporal strategy expands the applicability of hydrophobic compounds and organic chemistry for precision nanomedicine.

Development of Machine Learning Models to Predict the Level of Explanation Sophistication for Organic Chemistry Mechanisms

Halogen bonding is an attractive tool in organic chemistry; however, chiral catalysts bearing halogen bond donor functionalities remain underexplored. Herein, we investigate the development and catalytic applications of binaphthyl‐based chiral bromonium and iodonium salts. While previously reported catalysts have been successfully applied in several transformations, their utilization in the construction of vicinal chiral tetrasubstituted carbon stereogenic centers remains challenging. The introduction of bulky substituents into the core structure is an effective methodology for designing chiral catalysts. In this study, chiral halonium salts bearing bulky silyl ether substituents were synthesized and employed as halogen bonding‐driven catalysts for the challenging formation of vicinal chiral tetrasubstituted stereogenic centers, affording the corresponding products in high yields and up to 92% ee.

Chiral amines represent significant synthetic targets in organic chemistry, as their synthesis holds significant value in drug innovation. Despite asymmetric α-functionalization of amines having been well developed as a powerful strategy, α-C-H functionalization of alkyl amines remains less explored due to the inert nature of such C-H bonds. Herein, we report an asymmetric α-C-H allylation of N-arylidene-protected alkyl amines with MBH carbonates, catalyzed by cost-effective, commercially available hydroquinidine. This method affords diverse chiral γ-amino acid esters in high yields (up to 97%), excellent diastereoselectivities (up to >20:1 dr), and enantioselectivities (up to 99% ee). The reaction features a broad substrate scope, scalability, and facile transformation of products into biologically relevant γ-lactams.

ConspectusOne of the most central questions in chemistry is how a starting material can be converted as simply and efficiently as possible into a product. The answer may include photocatalysis, and if the reaction proceeds well, one might argue that understanding the underlying mechanism is not essential. Even if the reaction does not perform as anticipated, condition screening may still provide the operationally simplest and most effective path to the desired outcome, while mechanistic aspects can remain largely unexamined. Given the large parameter space typically associated with modern photocatalytic reactions, this approach is both plausible and justified, particularly when product synthesis is the primary goal.A complementary perspective on modern photocatalysis focuses on the conceptual advancement of photochemistry and a deeper understanding of its elementary steps and their interplay. This type of research begins with classical mechanistic elucidation to break down complex processes into individual elementary events. Once sufficient understanding has been achieved, it can lead to the mechanistic design of photoreactions. At that stage, the sequence of photophysical and chemical events triggered by light, and consequently the overall outcome of the reaction, can become rationally predictable, at least in principle.In this Account, we examine how the cross-fertilization between synthetically oriented photoredox catalysis, which is primarily concerned with the activation and functionalization of organic molecules, and mechanistically driven research from the physical-inorganic domain has advanced the field of photochemistry. This interaction has often been catalyzed by controversial discussions surrounding the mechanistic details of reactions that have attracted significant synthetic interest. As a result, this interplay has propelled significant advances across several critical areas of modern molecular photocatalysis, including the reactivity of excited-state organic radicals and solvated electrons, the mechanisms underlying multiphoton excitation processes such as photon upconversion, the puzzling light-independent energy-loss phenomenon known as "cage escape", and even the possibility of challenging Kasha's rule, a foundational principle in photophysics with profound implications for photochemistry.The knowledge accumulated through this work has brought the field closer to achieving mechanistically guided design in photocatalysis, extending far beyond the initial light-induced step. Central to this advancement are modern time-resolved spectroscopic methods, which have provided crucial insights into transient species and reaction dynamics. This conceptual strategy opens new opportunities and highlights challenges in redefining thermodynamic and kinetic limits. Ultimately, combining mechanistic insight with the practical expertise of synthetic chemists offers great potential for continued innovation in photoredox catalysis at the intersection of organic and physical-inorganic chemistry. With this Account, we aim to bridge the gap between those who prioritize the synthetic perspective and those who emphasize mechanistic and conceptual approaches, fostering greater integration between organic chemists and physical-inorganic chemists.

The study of valence isomerism in aromatic systems has long provided fundamental insights into molecular stability, reactivity, and electronic structure. While the mechanism and possibility of the interconversion between benzene and its Dewar isomer are well established in organic chemistry, analogous transformations in metallaaromatic systems remain largely unexplored. Here, we report the first experimental observations with well-defined Dewar metallabenzenes that are consistent with their rearrangement into metallabenzenes, a process previously considered only computationally. Structurally characterized Dewar rhenabenzenes can undergo a unique rearrangement to yield cyclopentadienyl complexes. DFT studies support a mechanism involving retro-4π electrocyclization of Dewar rhenabenzenes to give metallabenzene intermediates en route to cyclopentadienyl complexes, although the intermediates could not be detected in the present study. The computational results reveal that the retro-4π electrocyclization is both thermodynamically favorable and kinetically accessible and is the rate-determining event of the overall transformation.

Stereoselective nucleophilic additions to α-substituted carbonyl compounds are a crucial area of contemporary research in organic chemistry. Of the various advancements in π-facial selectivity in addition reactions of carbonyl compounds, the (polar) Felkin-Anh model and the chelation model are well recognized for accurately explaining the selectivity of the allylic products. For reactions that involve α-oxy carbonyl groups - known for their broad applications in natural-product synthesis and as effective building blocks in organic synthesis - the stereoselective reaction typically follows the chelation model, favoring syn-selective addition. In contrast to the well-established syn-selective additions of α-oxy carbonyls, anti-selective additions through a non-chelation pathway remain largely unexplored. In this study, we present the anti-selective allylation of α-oxy ketones using allylatranes that feature a highly coordinated group-14-element center. These atranes demonstrate high nucleophilicity and low chelating ability due to their transannular interactions and rigid framework, facilitating anti-selective allylations. A combined experimental and theoretical approach has been used to highlight the unique electronic properties of these atranes. This method is applicable to a wide variety of substrates, producing anti-1,2-diols with a homoallylic moiety in high yield and excellent diastereoselectivity compared to traditional methods.

Recent findings demonstrate that concentrated sulfuric acid supports rich organic chemistry, including the stability of the canonical DNA bases adenine, thymine, guanine and cytosine. Yet, due to full protonation in concentrated sulfuric acid, these bases may not pair as effectively as they do in water. We are therefore motivated to study nucleic acid bases that pair via hydrophobic and van der Waals interactions instead of canonical hydrogen bonding. Here, we investigate the stability of 14 selected, commercially available alternative nucleobases in concentrated sulfuric acid to evaluate their potential for forming DNA-like polymers in this solvent. The reactivity of compounds 1-14 have not been previously investigated in concentrated sulfuric acid. We incubate the selected compounds in 98% and 81% w/w sulfuric acid and monitor their stability using 1H and 13C NMR spectroscopy over 3 weeks at room temperature. In 98% w/w sulfuric acid, six bases-benzo[c][1,2,5]thiadiazole (1), 2,2'-bipyridine (2), 1,1'-biphenyl (3), 1-methoxy-3-methylbenzene (MMO2) (7) and 1-chloro-3-methoxybenzene (ClMO) (13), and 2,4-difluorotoluene (14)-remain soluble and stable with no detectable degradation. A few compounds show non-destructive reactivity, like sulfonation (compound 3) or H/D exchange (compounds 7, 13, 14). The other compounds react rapidly or are insoluble in 98% w/w sulfuric acid. In 81% w/w sulfuric acid, only compounds 1 and 2 remain stable and soluble, while other selected compounds are insoluble or unstable. Our findings identify a subset of alternative bases stable in concentrated sulfuric acid, advancing efforts towards the design of an example genetic-like polymer in this unusual solvent. Our work further highlights sulfuric acid's potential for supporting complex organic chemistry, with implications for astrobiology, planetary science of Venus and synthetic biology.

Objective: This comprehensive in silico computational and theoretical biochemistry/organic chemistry research study covers the inhibition methodologies of 2KS1, which is an essential template for breast cancer-suppressing research. Methods: To block the active site domain binding site of this protein, three de novo designed organic molecules by derivatizing Valproic Acid (VPA) were studied. Pharmacological organic chemistry effects of these analogues were enhanced to suppress 2KS1 better. The most recent molecular docking, molecular dynamics (MD), 1H NMR, and ADMET values showed that the derivatives of VPA exhibit better docking scores along with lower (better) inhibition constants and higher oral absorption percentage values compared to pristine VPA, meaning that the analogues possess better indications/pharmacological profiles. Results: The new drug candidate derivatives showed approximately 50 to 200 times inhibition constant efficiency (1/50th to 1/200th of the dose usage) in the affinity and suppression capability compared to pristine VPA. Conclusion: Being able to conduct such a crucial cancer study proves the fact that this study sheds light on the potential of new highly efficient drug molecules for future studies in terms of in vitro and in vivo for the suppression of breast cancer disease.