Organic Semiconducting Pro‐nanostimulants for Near‐Infrared Photoactivatable Cancer Immunotherapy

In this study, an organic semiconducting pro‐nanostimulant (OSPS) with a near‐infrared (NIR) photoactivatable immunotherapeutic action for synergetic cancer therapy is presented. OSPS comprises a semiconducting polymer nanoparticle (SPN) core and an immunostimulant conjugated through a singlet oxygen (¹O₂) cleavable linkers. Upon NIR laser irradiation, OSPS generates both heat and ¹O₂ to exert combinational phototherapy not only to ablate tumors but also to produce tumor‐associated antigens. More importantly, NIR irradiation triggers the cleavage of ¹O₂‐cleavable linkers, triggering the remote release of the immunostimulants from OSPS to modulate the immunosuppressive tumor microenvironment. Thus, the released tumor‐associated antigens in conjunction with activated immunostimulants induce a synergistic antitumor immune response after OSPS‐mediated phototherapy, resulting in the inhibited growth of both primary/distant tumors and lung metastasis in a mouse xenograft model, which is not observed for sole phototherapy.     

Nanozyme‐Catalyzed Cascade Reactions for Mitochondria‐Mimicking Oxidative Phosphorylation

Multiple‐enzyme‐involving cascade reactions that yield bioenergy are necessary in natural oxidative phosphorylation. However, in vitro applications are hampered by the sensitivity of catalytic activity to environmental adaptation. Herein, we explore nanozyme‐catalyzed cascade reactions in an assembled hybrid architecture for mitochondria‐mimicking oxidative phosphorylation. Hollow silica microspheres containing trapped gold nanoparticles were synthesized to promote two enzyme‐like catalytic reactions that transform glucose into gluconic acid in the presence of oxygen. The resulting transmembrane proton gradient drives natural ATP synthase reconstituted on the surface to convert ADP and inorganic phosphate into ATP. The assembled architecture possesses high activity for oxidative phosphorylation, comparable to that of natural mitochondria. This study provides a new natural–artificial hybrid prototype for exploring bioenergy supply systems and holds great promise for ATP‐powered bioapplications.     

离子液体中的酶催化反应

离子液体作为酶催化反应的介质正越来越多的受到关注,因为与传统有机溶剂和水相比,酶在离子液体中表现出了更好的活性、热稳定性、立体选择性、对映体选择性和可循环性。本文综述了近几年来脂肪酶、氧化还原酶、蛋白酶在离子液体中的催化反应。     

GOx@ZIF‐8(NiPd) Nanoflower: An Artificial Enzyme System for Tandem Catalysis

We report a facile approach to prepare an artificial enzyme system for tandem catalysis. NiPd hollow nanoparticles and glucose oxidase (GOx) were simultaneously immobilized on the zeolitic imidazolate framework 8 (ZIF‐8) via a co‐precipitation method. The as‐prepared GOx@ZIF‐8(NiPd) nanoflower not only exhibited the peroxidase‐like activity of NiPd hollow nanoparticles but also maintained the enzymatic activity of GOx. A colorimetric sensor for rapid detection of glucose was realized through the GOx@ZIF‐8(NiPd) based multi‐enzyme system. Moreover, the GOx@ZIF‐8(NiPd) modified electrode showed good bioactivity of GOx and high electrocatalytic activity for the oxygen reduction reaction (ORR), which could also be used for electrochemical detection of glucose.     

Palladium‐Catalyzed Cascade Cyclization/Alkynylation Reactions

Palladium‐catalyzed cascade cyclization reactions have witnessed significant improvements in recent years. Among them, palladium‐catalyzed cascade cyclization/alkynylation are especially attractive, which can assemble structurally diverse monocyclic, bicyclic, fused polycyclic, and spirocyclic skeletons with excellent chemoselectivities. In this Minireview, palladium‐catalyzed cascade cyclization/alkynylation have been summarized and discussed in detail with focus on oxypalladation and aminopalladation‐initiated cascade cyclization, intramolecular Heck‐type cascade cyclization, carbocyclizations, cascade cyclizations, and other types of cascade cyclization reactions. Some significant and representative synthetic methodologies and their synthetic applications and reaction mechanisms have also been described.     

Construction of Quaternary Stereocenters by Palladium‐Catalyzed Carbopalladation‐Initiated Cascade Reactions

The enantioselective synthesis of molecules containing quaternary stereocenters is a field of intense research interest and development. Among the known organic transformations, carbopalladation‐initiated domino transformations constitutes a general method for the construction of compounds containing cyclic or spiro quaternary stereocenters. In this Minireview, recent achievements in palladium‐catalyzed domino Heck/C?H functionalizations and developments in enantioselective carbopalladation‐initiated domino processes are summarized.     

Efficient Innate Immune Killing of Cancer Cells Triggered by Cell‐Surface Anchoring of Multivalent Antibody‐Recruiting Polymers

Binding of monoclonal antibodies (mAbs) onto a cell surface triggers antibody‐mediated effector killing by innate immune cells through complement activation. As an alternative to mAbs, synthetic systems that can recruit endogenous antibodies from the blood stream to a cancer cell surface could be of great relevance. Herein, we explore antibody‐recruiting polymers (ARPs) as a novel class of immunotherapy. ARPs consist of a cell‐binding motif linked to a polymer that contains multiple small molecule antibody‐binding motifs along its backbone. As a proof of concept, we employ a lipid anchor that inserts into the phospholipid cell membrane and make use of a polymeric activated ester scaffold onto which we substitute dinitrophenol as an antibody‐binding motif. We demonstrate that ARPs allow for high avidity antibody binding and drive antibody recruitment to treated cells for several days. Furthermore, we show that ARP‐treated cancer cells are prone to antibody‐mediated killing through phagocytosis by macrophages.     

Ruthenium‐Catalyzed Metathesis Cascade Reactions in Natural Products Synthesis

In this account, we provide a brief summary of recent developments in ruthenium‐catalyzed metathesis cascade reactions towards the total synthesis of natural products. We also highlight recent progress from our own laboratory regarding the synthesis of securinega alkaloids and humulanolides, which has resulted in the development of novel ruthenium‐catalyzed metathesis cascade reactions. Inspired and guided by the pioneering and elegant research conducted in this area, we developed a regio‐controlled relay dienyne metathesis cascade reaction and a cyclobutene‐promoted RCM/ROM/RCM cascade reaction for the synthesis of securinega alkaloids and humulanolides, respectively.     

NIR‐II Driven Plasmon‐Enhanced Catalysis for a Timely Supply of Oxygen to Overcome Hypoxia‐Induced Radiotherapy Tolerance

Hypoxia, as a characteristic feature of solid tumor, can significantly adversely affect the outcomes of cancer radiotherapy (RT), photodynamic therapy, or chemotherapy. In this study, a strategy is developed to overcome tumor hypoxia‐induced radiotherapy tolerance. Specifically, a novel two‐dimensional Pd@Au bimetallic core–shell nanostructure (TPAN) was employed for the sustainable and robust production of O₂ in long‐term via the catalysis of endogenous H₂O₂. Notably, the catalytic activity of TPAN could be enhanced via surface plasmon resonance (SPR) effect triggered by NIR‐II laser irradiation, to enhance the O₂ production and thereby relieve tumor hypoxia. Thus, TPAN could enhance radiotherapy outcomes by three aspects: 1) NIR‐II laser triggered SPR enhanced the catalysis of TPAN to produce O₂ for relieving tumor hypoxia; 2) high‐Z element effect arising from Au and Pd to capture X‐ray energy within the tumor; and 3) TPAN affording X‐ray, photoacoustic, and NIR‐II laser derived photothermal imaging, for precisely guiding cancer therapy, so as to reduce the side effects from irradiation.     

Selective Production of Renewable para‐Xylene by Tungsten Carbide Catalyzed Atom‐Economic Cascade Reactions

Tungsten carbide was employed as the catalyst in an atom‐economic and renewable synthesis of para‐xylene with excellent selectivity and yield from 4‐methyl‐3‐cyclohexene‐1‐carbonylaldehyde (4‐MCHCA). This intermediate is the product of the Diels–Alder reaction between the two readily available bio‐based building blocks acrolein and isoprene. Our results suggest that 4‐MCHCA undergoes a novel dehydroaromatization–hydrodeoxygenation cascade process by intramolecular hydrogen transfer that does not involve an external hydrogen source, and that the hydrodeoxygenation occurs through the direct dissociation of the C=O bond on the W₂C surface. Notably, this process is readily applicable to the synthesis of various (multi)methylated arenes from bio‐based building blocks, thus potentially providing a petroleum‐independent solution to valuable aromatic compounds.     

Precise In Vivo Inflammation Imaging Using In Situ Responsive Cross‐linking of Glutathione‐Modified Ultra‐Small NIR‐II Lanthanide Nanoparticles

To improve the bioimaging signal‐to‐noise ratio (SNR), long‐term imaging capability, and decrease the potential biotoxicity, an in vivo cross‐linking strategy was developed by using sub‐10 nm, glutathione‐modified, lanthanide nanoprobes. After administration, the nanoprobes cross‐link in response to reactive oxygen species (ROS) at the inflamed area and enable the quick imaging of ROS in the second near‐infrared (NIR‐II) window. These nanoprobes could be rapidly excreted due to their ultra‐small size. This strategy may also be applied to other ultra‐small contrast agents for the precise bioimaging by in situ lesion cross‐linking.     

Whole‐Cell‐Catalyzed Multiple Regio‐ and Stereoselective Functionalizations in Cascade Reactions Enabled by Directed Evolution

Biocatalytic cascade reactions using isolated stereoselective enzymes or whole cells in one‐pot processes lead to value‐added chiral products in a single workup. The concept has been restricted mainly to starting materials and intermediate products that are accepted by the respective wild‐type enzymes. In the present study, we exploited directed evolution as a means to create E. coli whole cells for regio‐ and stereoselective cascade sequences that are not possible using man‐made catalysts. The approach is illustrated using P450‐BM3 in combination with appropriate alcohol dehydrogenases as catalysts in either two‐, three‐, or four‐step cascade reactions starting from cyclohexane, cyclohexanol, or cyclohexanone, respectively, leading to either (R,R)‐, (S,S)‐, or meso‐cyclohexane‐1,2‐diol. The one‐pot conversion of cyclohexane into (R)‐ or (S)‐2‐hydroxycyclohexanone in the absence of ADH is also described.     

Gold‐Catalyzed Cascade Reactions for Synthesis of Carbo‐ and Heterocycles: Selectivity and Diversity

This account describes our recent efforts devoted to gold chemistry since 2009. Based on furyl–Au 1,3‐dipole analogues and related gold carbene intermediates, a rich variety of gold‐catalyzed cascade reactions have been developed, which provide facile access to a diverse range of novel carbo‐ and heterocycles. In these reactions, the selectivity can be well controlled by the catalyst (ligand and metal), substrate or reagent. In addition, we have also developed the corresponding enantioselective variants, which are guided by bis(phosphinegold) complexes derived from axially chiral scaffolds and asymmetric gold/chiral Brønsted acid relay catalysis.     

Brønsted Acid‐Catalyzed Cascade Reactions Involving 1,2‐Indole Migration

A cascade reaction of indoles with propargylic diols involving an unprecedented metal‐free 1,2‐indole migration onto an alkyne was carried out. DFT calculations support a mechanism consisting of a concerted nucleophilic attack of the indole nucleus with loss of water, followed by the 1,2‐migration and subsequent Nazarov cyclization. This Brønsted acid‐catalyzed protocol affords indole‐functionalized benzofulvene derivatives in high yields.     

Efficient Synthesis of Eight‐Membered Nitrogen Heterocycles from O‐Propargylic Oximes by Rhodium‐Catalyzed Cascade Reactions

Azocine derivatives were successfully synthesized from O‐propargylic oximes by means of a Rh‐catalyzed 2,3‐rearrangement/heterocyclization cascade reaction. Moreover, the chirality of the substrate was maintained throughout the cascade process to afford the corresponding optically active azocines.