Chemical Science最新文献

Replacement of a carbonyl group with fluorinated bioisostere (e.g., CF₂C) has been adopted as a key tactical strategy in drug design and development, which typically improves potency and modulates lipophilicity while maintaining biological activity. Consequently, new gem-difluoroalkenation reactions have undoubtedly accelerated this shift, and conceptually innovative practices would be of great benefit to medicinal chemists. Here we describe an expeditous protocol for the direct assembly of furan-substituted gem-difluoroalkenes via PFTB-promoted cross-coupling of ene-yne-ketones and difluorocarbene. In this multi-step tandem reaction process, the furan ring and the gem-difluorovinyl group are constructed simultaneously in an efficient manner. These products can serve as bioisosteres of the α-carbonyl furan core, which is an important scaffold present in natural products and drug candidates. The broad generality and practicality of this method for late-stage modification of bioactive molecules, gram-scale synthesis and versatile derivatisation of products has been described. Biological activity evaluation showed that the gem-difluoroalkene skeleton exhibited dramatic antitumor activity.

Oxidation is a fundamental transformation in synthesis. Developing facile and effective aerobic oxidation processes under ambient conditions is always in high demand. Benefiting from its high energy and good penetrability, ionizing radiation can readily produce various reactive species to trigger chemical reactions, offering another option for synthesis. Here, we report an ionizing radiation-induced aerobic oxidation strategy to synthesize oxygen-containing compounds. We discovered that molecular oxygen (O₂) could be activated by reactive particles generated from solvent radiolysis to produce solvent-derived peroxyl radicals (R_solOO·), which facilitated the selective oxidation of sulfides and phosphorus(III) compounds at room temperature without catalysts. Density functional theory (DFT) calculations further revealed that multiple R_solOO· enable the oxidation reaction through an oxygen atom transfer process. This aerobic oxidation strategy broadens the research scope of radiation-induced chemical transformations while offering an opportunity to convert nuclear energy into chemical energy.

Utilizing the cGAS-STING pathway to combat immune evasion is one of the most promising strategies for enhancing cancer immunotherapy. However, current techniques for activating the cGAS-STING pathway often face a dilemma, mainly due to the balance between efficacy and safety. Here, we develop a uracil base lesion-gated dumbbell DNA nanodevice (UBLE) that allows on-demand activation and termination of the cGAS-STING pathway in tumor cells, thereby enhancing cancer immunotherapy. The UBLE integrates two deoxyuridines (dU) in the stem for DNA lesion recognition, two locked complementary primer sequences (primers A and B) for DNA self-assembly, and a Förster resonance energy transfer pair (Cy3 and Cy5) attached to the loop for activation assessment. Upon the orthogonal recognition of tumor-specific repair indicators (UDG and APE1), the UBLE undergoes a conformational change to create massive nicked double-stranded DNA (dsDNA) units. These units self-assemble to generate long fluorescent dsDNA structures, permitting selective evaluation and on-demand activation of the cGAS-STING pathway. Furthermore, we demonstrate that the UBLE can effectively activate the cGAS-STING pathway in tumor cells, enhancing NK cell-targeted cancer immunotherapy. This work develops a DNA lesion-gated strategy for on-demand activation and termination of the cGAS-STING pathway, affording an innovative avenue for enhancing cancer immunotherapy.

Aqueous Zn–S batteries provide competitive energy density for large-scale energy storage systems. However, the cathode active material exhibits poor electrical conductivity especially at the discharged state of ZnS. Its morphology generated in cells thus directly determines the cathode electrochemical activity. Here, we reveal the ZnS growth behavior and control its morphology by the anion donor number (DN) of zinc salts in electrolytes. The anion DN affects the salt dissociation degree and furthermore sulfide solubility in electrolytes, which finally determines ZnS growth preference on existing nuclei or carbon substrates. As a result, 3D ZnS is realized from the high DN ZnBr₂ electrolyte, whereas a 2D passivation film is formed from low DN Zn(TFSI)₂. Thanks to the facile electron paths and abundant reaction sites with 3D morphology, the sulfur cathode reaches a high capacity of 1662 mA h g⁻¹ at 0.1 A g⁻¹ and retains 872 mA h g⁻¹ capacity after 400 cycles at 3 A g⁻¹.