Latest ArticlesThe preparation of medium-sized benzo[b]azocines has always been challenging because of inherently unfavorable enthalpy and entropy factors. This report presents a novel approach for accessing 8-membered seleno-benzo[b]azocines via electrochemically-driven seleno-cyclization. This method enables room-temperature preparation of various structurally diverse medium-sized seleno-benzo[b]azocines. The facile deselenation of the seleno-cyclization products to generate functionalized dienes is an additional benefit of this indispensable reaction. Mechanistic insights are presented based on radical inhibition experiments and cyclic voltammetry measurements, which elucidate the radical pathway. Finally, density functional theory calculations further rationalize the rate-determining step and the unique chemoselectivity observed in this transformation.
A bottleneck in biomimetic synthesis consists in the full copy of, for example, the hierarchical structure of proteins directed by weak interactions. By contrast with covalent bonds bearing definite orientation and high stability, weak intermolecular forces within a continuous dynamic equilibrium can be hardly tamed for molecular design. In this endeavor, a ligand-dominated strategy that embodies tunable electrostatic repulsion and π…π stacking was first employed to shape polyoxovanadate-based metal-organic polyhedra (VMOPs). Structural evolution involving transformation, interlock, and discovery of an unprecedented prototype of the Star of David was hence achievable. Not only as a handy tool for the primary structural control over VMOPs, these weak forces allow for an advanced management on the spatial distribution of such manmade macromolecules as well as the associated physicochemical behaviors, representing an ideal model for simulating and interpreting the conformation-function relationship of proteins.
Ulcerative colitis (UC) is a common progressive inflammatory disease whose incidence has increased rapidly in recent years, and can develop into colorectal cancer in severe cases. There are currently no adequate or effective treatments for UC due to the fact that some patients have found suboptimal results after repeated administration, while others have experienced adverse effects. With the rapid development of nanotechnology, developing innovative colon-targeting platforms is essential to improving efficacy, reducing side effects, and improving patient compliance. In this review, we summarize the pathophysiological characteristics of UC and the most recent status of numerous nanodrug delivery systems based on different targeting mechanisms in treating UC. Oral, intravenous, and rectal drug delivery nanoparticles targeting the colon are discussed, which can provide ideas for the design of colon-targeting nanoparticles for the treatment of colon diseases, especially for the treatment of UC. Last but not least, we provide a glimpse into the future of colon-targeted delivery systems, as well as future advancements in the field.
Due to their excellent fluorescence properties and biological function, cyanine dyes have been widely applied in biological imaging. Heptamethine cyanine (Cy7) dyes, as a type of classic near-infrared (NIR) fluorescent dyes, are considered as one of the effective fluorescent tools in the living organisms due to their good biocompatibility and very low background interference. Bioorthogonal reactions performed in living cells and tissues have developed by leaps and bounds in recent years. The NIR fluorescent labeling technique involving cyanine has attracted widespread attention. This review summarizes their recent application in the field of bioorthogonal imaging, mainly concluding Cy7-type dyes, labeling strategy, bioimaging application, etc. We expect this work can provide some helps for the studies of NIR bioorthogonal reaction in vivo.
Enzyme prodrug therapies (EPTs) have been intensively explored as attractive approaches to selective activation of systemically administered benign prodrugs by the exogenous enzymes or enzymes expressed at the desired target site, thus achieving localized, site-specific therapeutic effect. Many effective strategies (e.g., antibody-, viral-, gene-, as well as polymer-directed EPT) have been developed for enzyme localization to locally activate systemically administered benign prodrugs. Nevertheless, intrinsic limitations (e.g., complex intracellular environment and catalyst instability) make the practical application of EPT strategies a task that presents itself as highly challenging. As a promising alternative to natural enzyme, nanozyme has attracted substantial attention since its discovery in 2007, mainly due to the advantages of robust catalytic activity, high stability, low cost, and facile synthesis. Recently, nanozyme-activated prodrug strategies bring a new opportunity for targeted therapy, referred to as nanozyme-activating prodrug therapies. This review focuses on recently reported nanozyme-activated prodrug strategies, aiming to provide some new insights into the potential applications in site-specific drug synthesis.
An additive-free and environmentally friendly strategy has been realized for the construction of S-substituted isothioureas through visible-light-induced multicomponent reaction starting from α-diazoesters, aryl isothiocyanates, amines and cyclic ethers. This methodology features simple operation, mild reaction conditions, favorable functional group tolerance, easily available starting materials and high efficiency.
Lithium (Li) dendrite issue, which is usually caused by inhomogeneous Li nucleation and fragile solid electrolyte interphase (SEI), impedes the further development of high-energy Li metal batteries. However, the integrated construction of a high-stable SEI layer that can regulate uniform nucleation and facilitate fast Li-ion diffusion kinetics for Li metal anode still falls short. Herein, we designed an artificial SEI with hybrid ionic/electronic interphase to regulate Li deposition by in-situ constructing metal Co clusters embedded in LiF matrix. The generated Co and LiF both enable fast Li-ion diffusion kinetics, meanwhile, the lithiophilic properties of Co clusters can serve as Li-ion nucleation sites, thereby contributing to uniform Li nucleation and non-dendritic growth. As a result, a dendrite-free Li deposition with a low overpotential (16.1 mV) is achieved, which enables an extended lifespan over 750 h under strict conditions. The full cells with high-mass-loading LiFePO4 (11.5 mg/cm2) as cathodes exhibit a remarkable rate capacity of 84.1 mAh/g at 5 C and an improved cycling performance with a capacity retention of 96.4% after undergoing 180 cycles.
Ischemic stroke (IS) represents a significant threat to brain health due to its elevated mortality and disability rates. The efficacy of small-molecule neuroprotective agents has been impeded by challenges associated with traversing the blood-brain barrier (BBB) and limited bioavailability. Conversely, advanced nano drug delivery systems hold promise for overcoming these obstacles by facilitating efficient transportation across the BBB and maintaining optimal drug concentrations. This review aims to explore advanced neuroprotective nano drug delivery systems as a means of effectively administering neuroprotective agents to the brain using pharmaceutical approaches in the treatment of IS. By examining these systems, researchers and clinicians can gain valuable insights and innovative concepts, illuminating the potential of advanced neuroprotective nano drug delivery systems. Leveraging these advancements can drive the progress of pioneering and efficacious therapeutic interventions for IS.
Diversity-oriented synthesis is a powerful and interesting synthetic tool for the rapid construction of structurally complex and privileged scaffolds from readily accessible starting materials. To date, diversity-oriented synthesis mostly relies on the employment of versatile reagents. Versatile reagents can be regulated as controllable and flexible building blocks for multipurpose utilizations. Over the past decade, a variety of multifunctional reagents have been developed. However, most versatile reagents usually need multi-step synthesis, thus restricting their wide application to a large extent. In terms of the practicalities and universalities, we prefer to pay more attention to the utilization of simple and practical versatile reagents with multiple reactivities, mainly including atropaldehyde acetals, aryl methyl ketones, vinylene carbonate, vinyl azides, aryldiazonium salts, rongalite, halodifluoromethyl compounds. Most importantly, these versatile reagents can also play different roles simultaneously in the same reaction, in which their different reactivities are converged into the final target products. Such strategy can not only offer more possibilities for the synthesis of several active pharmaceutical ingredients, but also minimize the occurrence of some side reactions by lessening the varieties of materials. Also, a perspective is given at the end of this review.
Organofluorine compounds are widely used in the realm of drug discovery and material science. Herein, we developed palladium catalyzed intermolecular aminofluorination and oxy-aminofluorination of gem-difluoroalkenes with N-fluorobenzenesulfonimide (NFSI), in which NFSI was used as the nitrogen source and oxidant. The reaction provides an efficient and straightforward synthesis route of a series of α-trifluoromethyl benzylic amines. Notably, three/four components oxy-aminofluorination processes were realized to give α-trifluoromethyl benzylic ether with a terminal amino group, which proceed through C(sp3)–O bond cleavage of easily available ether and simultaneous introduced a fluorine, an amino and an oxy substituent in one pot with excellent regioselectivity. The divergent reactivity not only included the incorporation of one ether molecular, but also much more challenged two ether insertion with excellent selectivity through succession C(sp3)–O bonds cleavage. This protocol allows for concise synthesis of high value amines with fluoroalkyl-substituents and selectively transformation of easily available ethers by high-valent palladium catalysis.