Chemistry - A European Journal最新文献

Mutant K-Ras drives cancer through its membrane localization, which requires post-translational modification by farnesyltransferase (FTase). FTase attaches farnesyl to the K-Ras C-terminal CVIM tetrapeptide, enabling membrane binding. However, K-Ras can also undergo compensatory geranylgeranylation by geranylgeranyltransferase I (GGTase I), making FTase inhibition alone ineffective. Dual inhibition of FTase and GGTase I is necessary to fully block K-Ras localization and its cancer activity. We developed bivalent inhibitors targeting both FTase and GGTase I by binding to the CVIM site and an adjacent acidic surface. A non-thiol CVIM peptidomimetic based on a piperidine scaffold showed potent FTase inhibition (Ki = 2.1 nM) with less effect on GGTase I (Ki = 210 nM). Adding cationic modules to this compound produced dual inhibitors with enhanced potency (Ki = 2-5 nM), significantly improving upon previous agents. These bivalent inhibitors effectively reduced mutant K-Ras cancer cell viability and inhibited K-Ras farnesylation and geranylgeranylation in cells. This dual-targeting approach shows promise for treating K-Ras-driven cancers.

A visible-light-promoted cascade [2+2+1] bicyclization reaction of N-cyanamide alkenes and activated alkyl bromides has been successfully established. This reaction exhibits mild conditions, metal-free characteristics, and excellent atom- and step-economy, along with environmental friendliness. It demonstrates broad substrate tolerance and scalability to gram-scale synthesis, underscoring its potential for practical applications. Preliminary mechanistic studies suggest that the reaction proceeds through a photoinduced single-electron transfer (SET) process and a 1,5-hydrogen atom transfer (HAT) process mediated by an iminyl radical.

Although azobenzenes are well established in molecular materials research, their structurally similar counterparts, azoxybenzenes, remain largely unexplored. In their Research Article (DOI: 10.1002/chem.202404001), H. A. Wegner and co-workers introduce 4,4’-diamino-substituted azoxybenzenes as potential catholyte materials for electrochemical applications. The cover highlights the untapped potential of azoxybenzenes in energy-storage applications and encourages further exploration into this promising class of materials.

The photoreactivity of steroids represented a hot topic in the middle of the last century and in this project we "rediscover" it through the exploration of the photochemical behavior of D1-3-keto-steroids. In terms of number of products obtained, the photochemistry of D1-3-keto-steroids is less complicated than that of D4-3-keto- and D1,4-3-keto-steroids, furnishing an efficient and tuneable method to remodel the classic steroid 6/6/6/5 ring system. In this scenario, this approach can represent a simple strategy to interconvert a class of easily available steroids to another difficult to access from natural sources. As a proof of concept, the synthesis 5,6-dihydro-ophiopogonol A (11), a very closed analogue of natural ophiopogonol A (7), was accomplished in just four steps starting from easily available diosgenin (8).

The Cover Feature illustrates the key concepts discussed in the Research Article by I. Suzana, M. Malischewski, V. Marvaud and co-workers (DOI: 10.1002/chem.202402601), highlighting heterotetrametallic complexes and their multifunctional properties. It visually emphasizes the role these complexes play as single-molecule magnets (SMMs). Additionally, the image underscores the significance of photoisomerization, a process in which light induces structural changes in the molecule, contributing to the functional versatility of these complexes.

We report the synthesis, characterisation, anti-osteosarcoma and anti-osteosarcoma stem cells (OSC) properties (cytotoxic and immunogenic) of a series of bi-nuclear gallium(III) complexes with tridentate Schiff base ligands and 8-hydroxyquinoline (1-4). According to monolayer cytotoxicity studies, 1-4 display micromolar potency towards bulk osteosarcoma cells and OSCs. The most effective complex in the series 2 is up to 13-fold more potent towards OSCs than cisplatin and carboplatin (the only metallodrugs used in the clinic to treat osteosarcoma). Remarkably, the bi-nuclear gallium(III) complexes 1-4 are significantly more potent towards three-dimensionally cultured sarcospheres than OSCs cultured in monolayers indicating effective penetration of the sarcosphere multicellular architecture. The bi-nuclear gallium(III) complexes 1-4 are up to 53-fold more potent towards sarcospheres than cisplatin and carboplatin. Mechanistic studies show that gallium(III) complex 2 kills osteosarcoma cells by caspase-dependent apoptosis and paraptosis, leading to the release of danger-associated molecular patterns associated to immunogenic cell death. Osteosarcoma cells and OSCs treated with gallium(III) complex 2 are effectively phagocytosed by immune cells, highlighting its immunogenic potential. As far as we are aware, gallium(III) complex 2 is the first metal complex to evoke an immunogenic response towards both bulk osteosarcoma cells and OSCs.

The Front Cover illustrates real-time pH monitoring in culture media by using novel phenylazothiazole dyes. Distinct color changes indicate cell health, with red representing healthy cells and orange indicating dead cells. This approach offers a promising tool for the real-time detection of cancer cell growth and viability. More information can be found in the Research Article by P. K. Hashim, N. Tamaoki and co-workers (DOI: 10.1002/chem.202403897). Art by the team of INMYWORK Studio.

Epoxidation of ethylene to produce ethylene oxide (EO) is a vital heterogeneous catalytic chemical process in industry, as EO is an important intermediate for the synthesis of fine chemicals including ethylene glycol, ethoxylates, plastics and polyester. EO is commercially produced by the silver-catalyzed partial oxidation of ethylene with air or oxygen. However, it remains challenging to understand its chemical behavior under reaction conditions. To overcome this challenge, a series of catalysts with well-defined structures have been developed. The present review is devoted to summarizing the recent advances in the exploitation of novel catalytic materials for the epoxidation of ethylene, such as metal nanoparticles, clusters, single atoms, and bimetal. The role of promoters in selectivity enhancement will be discussed. A deep understanding of the active species, oxygen species, active structures, activity-structure relationship, and mechanisms contributing to epoxidation process are highlighted. The integration with other advanced technologies such as electrocatalytic and photocatalytic is also reviewed. Finally, the current challenges and future prospects are provided so as to give guidance for the design of efficient catalysts for heterogeneous epoxidation of ethylene to EO, and to improve the fundamental understanding of the underlying catalytic chemistry.

Dynamic liquid crystalline polymers (dLCPs) incorporate both liquid crystalline mesogens and dynamic bonds into a single polymeric material. These dual functionalities impart order-dependent thermo-responsive mechano-optical properties and enhanced reprocessability/programmability enabling their use as soft actuators, adaptive adhesives, and damping materials. While many previous works studying dynamic LCPs utilize dynamic covalent bonds, metallosupramolecular bonds provide a modular platform where a series of materials can be accessed from a single polymeric feedstock through the variation of the metal ion used. A series of dLCPs were prepared by the addition of metal salts to a telechelic 2,6-bisbenzimidazolylpyridine (Bip) ligand endcapped LCP to form metallosupramolecular liquid crystal polymers (MSLCPs). The resulting MSLCPs were found to phase separate into hard and soft phases which aids in their mechanical robustness. Variations of the metal salts used to access these materials allowed for control of the thermomechanical, viscoelastic, and adhesive properties with relaxations that can be tailored independently of the mesogenic transition. This work demonstrates that by accessing phase separation through the incorporation of metallosupramolecular moieties, highly processable yet robust MSLCP materials can be realized. This class of materials opens the door to LCPs with bulk flow behavior that can also be utilized as multi-level adhesives.

Methane dry reforming reaction offers an attractive route to simultaneously convert two kinds of greenhouse gases into clean fuels and high valuable chemicals. Nevertheless, the inactivation of nickel-based catalysts due to sintering and coking in dry reforming has severely limited its industrial application. In this study, we proposed a step-by-step strategy to prepare a series of bimetallic xCu-Ni/SiO2 catalysts derived from phyllosilicate precursors. The optimized catalyst shows exceptional performance, with no deactivation during the 50-hour stability test, and the CH4 and CO2 conversion were 88.8% and 94.0%, respectively. This was attributed to the synergistic catalysis of Cu-Ni alloy, effectively inhibits coke formation. Additionally, the distribution of copper species between nickel species inhibited the mobility and enlargement of nickel particles and thus enhanced the resistance to sintering. The preparation strategy offers valuable insights for designing and preparing of highly efficient and stable bimetallic catalysts under high-temperature conditions.