Tandem Integration of Biological and Electrochemical Catalysis for Efficient Polyester Upcycling under Ambient Conditions.

Excessive production of waste polyethylene terephthalate (PET) poses an ecological challenge, which necessitates developing technologies to extract the values from end-of-life PET. Upcycling has proven effective in addressing the low profitability of current recycling strategies, yet existing upcycling technologies operate under energy-intensive conditions. Here we report a cascade strategy to steer the transformation of PET waste into glycolate in an overall yield of 92.6% under ambient conditions. The cascade approach involves setting up a robust hydrolase with 95.6% PET depolymerization into ethylene glycol (EG) monomer within 12 h, followed by an electrochemical process initiated by a CO-tolerant Pd/Ni(OH)2 catalyst to convert the EG intermediate into glycolate with high Faradaic efficiency of 97.5%. Techno-economic analysis and life cycle assessment indicate that, compared with the widely adopted electrochemical technology that heavily relies on alkaline pretreatment for PET depolymerization, our designed enzymatic-electrochemical approach offers a cost-effective and low-carbon pathway to upgrade PET.

Pd Clusters Loaded with Multivalent Cu Foam for Superior Electrochemical Nitrate Reduction and Selective N≡N Bond Formation.

The electrochemical denitrification of nitrate (NO3 -) in actual wastewater to nitrogen (N2) is an effective approach to reversing the current imbalance of the nitrogen cycle and the eutrophication of water. However, electrostatic repulsion between NO3 - and the cathode results in the low efficiency of NO3 - reduction reaction (NO3RR). Here, density functional theory (DFT) calculations are used as a theoretical guide to design a Pd cluster-loaded multivalent Cu foam (Pd/Cu2O-CF) electrocatalyst, which achieves a splendid 97.8% NO3 - removal rate, 97.9% N2 selectivity, 695.5 mg N g-1 Pd h-1 reduction efficiency, and 60.0% Faradaic efficiency at -1.3 V versus SCE. The projected density of states (pDOS) indicates that NO3 - and Pd/Cu2O-CF are bonded via strong complexation between the O 2p (in NO3 -) and Cu 3d (in Cu2O) with the input of voltage, which reduces the electrostatic repulsion and enhances the enrichment of NO3 - on the cathode. In-situ characterizations demonstrate that Pd[H] can reduce Cu2O to Cu, and subsequently Cu reduces NO3 - to nitrite (NO2 -) accompanied by in situ reconfiguration of multivalent Cu foam. NO2 - is then transferred to the surface of Pd clusters by the cascade catalysis and accelerates the breaking of N─O bonds to form Pd─N, and eventually achieves the N≡N bond formation.

Synthesis of 3-Phenylserine by a Two-enzyme Cascade System with PLP Cofactor.

A two-enzyme cascade system containing ω-transaminase (ω-TA) and L-threonine aldolase (L-ThA) was reported for the synthesis of 3-Phenylserine starting from benzylamine, and PLP was utilized as the only cofactor in these both two enzymes reaction system. Based on the transamination results, benzylamine was optimized as an advantageous amino donor as confirmed by MD simulation results. This cascade reaction system could not only facilitate the in situ removal of the co-product benzaldehyde, enhancing the economic viability of the reaction, but also establish a novel pathway for synthesizing high-value phenyl-serine derivatives. In our study, nearly 95 % of benzylamine was converted, yielding over 54 % of 3-Phenylserine under the optimized conditions cascade reaction.

Endogenous and exogeneous stimuli-triggered reactive oxygen species evoke long-lived carbon monoxide to fight against lung cancer.

Reactive oxygen species (ROS)-associated anticancer approaches usually suffer from two limitations, i.e., insufficient ROS level and short ROS half-life. Nevertheless, no report has synchronously addressed both concerns yet. Herein, a multichannel actions-enabled nanotherapeutic platform using hollow manganese dioxide (H-MnO2) carriers to load chlorin e6 (Ce6) sonosensitizer and CO donor (e.g., Mn2(CO)10) has been constructed to maximumly elevate ROS level and trigger cascade catalysis to produce CO. Therein, intratumoral H2O2 and ultrasound as endogenous and exogeneous triggers stimulate H-MnO2 and Ce6 to produce •OH and 1O2, respectively. The further cascade reaction between ROS and Mn2(CO)10 proceeds to release CO, converting short-lived ROS into long-lived CO. Contributed by them, such a maximumly-elevated ROS accumulation and long-lived CO release successfully suppresses the progression, recurrence and metastasis of lung cancer with a prolonged survival rate. More significantly, proteomic and genomic investigations uncover that the CO-induced activation of AKT signaling pathway, NRF-2 phosphorylation and HMOX-1 overexpression induce mitochondrial dysfunction to boost anti-tumor consequences. Thus, this cascade catalysis strategy can behave as a general means to enrich ROS and trigger CO release against refractory cancers.

Cascade Electrocatalytic and Thermocatalytic Reduction of CO2 to Propionaldehyde.

Electrochemical CO2 reduction can convert CO2 to value-added chemicals, but its selectivity toward C3+ products are very limited. One possible solution is to run the reactions in hybrid processes by coupling electrocatalysis with other catalytic routes. In this contribution, we report the cascade electrocatalytic and thermocatalytic reduction of CO2 to propionaldehyde. Using Cu(OH)2 nanowires as the precatalyst, CO2 /H2 O is reduced to concentrated C2 H4 , CO, and H2 gases in a zero-gap membrane electrode assembly (MEA) reactor. The thermochemical hydroformylation reaction is separately investigated with a series of rhodium-phosphine complexes. The best candidate is identified to be the one with the 1,4-bis(diphenylphosphino)butane diphosphine ligand, which exhibits a propionaldehyde turnover number of 1148 under a mild temperature and close-to-atmospheric pressure. By coupling and optimizing the upstream CO2 electroreduction and downstream hydroformylation reaction, we achieve a propionaldehyde selectivity of ~38 % and a total C3 oxygenate selectivity of 44 % based on reduced CO2 . These values represent a more than seven times improvement over the best prior electrochemical system alone or over two times improvement over other hybrid systems.

Nonorthogonal Cascade Catalysis in Multicompartment Micelles.

Multicompartment micelles (MCMs) containing acid and base sites in discrete domains are prepared from poly(norbornene)-based amphiphilic bottlebrush copolymers in aqueous media. The acid and base sites are localized in different compartments of the micelle, enabling the nonorthogonal reaction sequence: deacetalization - Knoevenagel condensation - Michael addition of acetals to 2-amino chromene derivatives. Computational simulations using dissipative particle dynamics (DPD) elucidated the bottlebrush composition required to effectively site-isolate the nonorthogonal catalysts. This contribution presents MCMs as a new class of nanostructures for one-pot multistep nonorthogonal cascade catalysis, laying the groundwork for the isolation of three or more incompatible catalysts to synthesize value-added compounds in a single reaction vessel, in water.

Glucose oxidase and metal catalysts combined tumor synergistic therapy: mechanism, advance and nanodelivery system.

Cancer has always posed a significant threat to human health, prompting extensive research into new treatment strategies due to the limitations of traditional therapies. Starvation therapy (ST) has garnered considerable attention by targeting the primary energy source, glucose, utilized by cancer cells for proliferation. Glucose oxidase (GOx), a catalyst facilitating glucose consumption, has emerged as a critical therapeutic agent for ST. However, mono ST alone struggles to completely suppress tumor growth, necessitating the development of synergistic therapy approaches. Metal catalysts possess enzyme-like functions and can serve as carriers, capable of combining with GOx to achieve diverse tumor treatments. However, ensuring enzyme activity preservation in normal tissue and activation specifically within tumors presents a crucial challenge. Nanodelivery systems offer the potential to enhance therapy effectiveness by improving the stability of therapeutic agents and enabling controlled release. This review primarily focuses on recent advances in the mechanism of GOx combined with metal catalysts for synergistic tumor therapy. Furthermore, it discusses various nanoparticles (NPs) constructs designed for synergistic therapy in different carrier categories. Finally, this review provides a summary of GOx-metal catalyst-based NPs (G-M) and offers insights into the challenges associated with G-M therapy, delivery design, and oxygen (O2) supply.

A Compartmentalized Nanoreactor Formed by Interfacial Hydrogelation for Cascade Enzyme Catalytic Therapy.

Some cellular enzymatic pathways are located within a single organelle, while most others involve enzymes that are located within multiple compartmentalized cellular organelles to realize the efficient multi-step enzymatic process. Herein, bioinspired by enzyme-mediated biosynthesis and biochemical defense, a compartmented nanoreactor (Burr-NCs@GlSOD ) was constructed through a self-confined catalysis strategy with burr defect-engineered molybdenum disulfide/Prussian blue analogues (MoS2 /PBA) and an interfacial diffusion-controlled hydrogel network. The specific catalytic mechanism of the laccase-like superactivity induced hydrogelation and cascade enzyme catalytic therapy were explored. The confined hydrogelation strategy introduces a versatile means for nanointerface functionalization and provides insight into biological construction of simulated enzymes with comparable activity and also the specificity to natural enzymes.

Metal-Organic Framework-Based Artificial Organelle Corrects Microenvironment Interference for Accurate Intratumoral Glucose Analysis.

Enzymatic catalysis with high efficiency allows them a great prospect in metabolite monitoring in living cells. However, complex tumor microenvironments, such as acidity, H2 O2 , and hypoxia, are bound to disturb catalytic reactions for misleading results. Here, we report a spatially compartmentalized artificial organelle to correct intratumoral glucose analysis, where the zeolitic imidazolate framework-8 immobilized glucose oxidase-horseradish peroxidase cascade core and catalase-directed shell act as signal transduction and guarding rooms respectively. The acid-digested core and stable shell provide appropriate spaces to boost biocatalytic efficiency with good tolerability. Notably, the endogenous H2 O2 is in situ decomposed to O2 by catalase, which not only overcomes the interference in signal output but also alleviates the hypoxic states to maximize glucose oxidation. The marked protective effect and biocompatibility render artificial organelles to correct the signal transduction for dynamic monitoring glucose in vitro and in vivo, achieving our goal of accurate intratumoral metabolite analysis.

A Dynamic Defect Generation Strategy for Efficient Enzyme Immobilization in Robust Metal-Organic Frameworks for Catalytic Hydrolysis and Chiral Resolution.

Enzyme immobilization has been demonstrated to be a favorable protocol for promoting the industrialization of bioactive molecules, but still with formidable challenge. Addressing this challenge, we create a dynamic defect generation strategy for enzyme immobilization by using the dissociation equilibrium of metal-organic frameworks (MOFs) mediated by enzymes. Enzymes can act as "macro ligands" to generate competitive coordination against original ligands, along with the release of metal clusters of MOFs to generate defects, hence promoting the gradual transport of enzymes from the surface to inside. Various enzymes can be efficiently immobilized in MOFs to afford composites with good enzymatic activities, protective performances and exceptional reusabilities. Moreover, multienzyme bioreactors capable of efficient cascade reactions can also be generated. This study provides new opportunities to construct highly efficient biocatalysts incorporating different types of enzymes.

pH-switchable nanozyme cascade catalysis: a strategy for spatial-temporal modulation of pathological wound microenvironment to rescue stalled healing in diabetic ulcer.

The management of diabetic ulcer (DU) to rescue stalled wound healing remains a paramount clinical challenge due to the spatially and temporally coupled pathological wound microenvironment that features hyperglycemia, biofilm infection, hypoxia and excessive oxidative stress. Here we present a pH-switchable nanozyme cascade catalysis (PNCC) strategy for spatial-temporal modulation of pathological wound microenvironment to rescue stalled healing in DU. The PNCC is demonstrated by employing the nanozyme of clinically approved iron oxide nanoparticles coated with a shell of glucose oxidase (Fe3O4-GOx). The Fe3O4-GOx possesses intrinsic glucose oxidase (GOx), catalase (CAT) and peroxidase (POD)-like activities, and can catalyze pH-switchable glucose-initiated GOx/POD and GOx/CAT cascade reaction in acidic and neutral environment, respectively. Specifically, the GOx/POD cascade reaction generating consecutive fluxes of toxic hydroxyl radical spatially targets the acidic biofilm (pH ~ 5.5), and eradicates biofilm to shorten the inflammatory phase and initiate normal wound healing processes. Furthermore, the GOx/CAT cascade reaction producing consecutive fluxes of oxygen spatially targets the neutral wound tissue, and accelerates the proliferation and remodeling phases of wound healing by addressing the issues of hyperglycemia, hypoxia, and excessive oxidative stress. The shortened inflammatory phase temporally coupled with accelerated proliferation and remodeling phases significantly speed up the normal orchestrated wound-healing cascades. Remarkably, this Fe3O4-GOx-instructed spatial-temporal remodeling of DU microenvironment enables complete re-epithelialization of biofilm-infected wound in diabetic mice within 15 days while minimizing toxicity to normal tissues, exerting great transformation potential in clinical DU management. The proposed PNCC concept offers a new perspective for complex pathological microenvironment remodeling, and may provide a powerful modality for the treatment of microenvironment-associated diseases.

Tumor-Microenvironment-Responsive Cascade Reactions by a Cobalt-Single-Atom Nanozyme for Synergistic Nanocatalytic Chemotherapy.

Nanocatalytic therapy, involving the nanozyme-triggered production of reactive oxygen species (ROS) in the tumor microenvironment (TME), has demonstrated potential in tumor therapy, but nanozymes still face challenges of activity and specificity that compromise the therapeutic efficacy. Herein, we report a strategy based on a single-atom nanozyme to initiate cascade enzymatic reactions in the TME for tumor-specific treatment. The cobalt-single-atom nanozyme, with Co-N coordination on N-doped porous carbon (Co-SAs@NC), displays catalase-like activity that decomposes cellular endogenous H2 O2 to produce O2 , and subsequent oxidase-like activity that converts O2 into cytotoxic superoxide radicals to efficiently kill tumor cells. By incorporation with doxorubicin, the therapy achieves a significantly enhanced antitumor effect in vivo. Our findings show that cascade TME-specific catalytic therapy combined with chemotherapy is a promising strategy for efficient tumor therapy.

Enantio- and Diastereoselective, Complete Hydrogenation of Benzofurans by Cascade Catalysis.

We report an enantio- and diastereoselective, complete hydrogenation of multiply substituted benzofurans in a one-pot cascade catalysis. The developed protocol facilitates the controlled installation of up to six new defined stereocenters and produces architecturally complex octahydrobenzofurans, prevalent in many bioactive molecules. A unique match of a chiral homogeneous ruthenium-N-heterocyclic carbene complex and an in situ activated rhodium catalyst from a complex precursor act in sequence to enable the presented process.

A Titanium Nitride Nanozyme for pH-Responsive and Irradiation-Enhanced Cascade-Catalytic Tumor Therapy.

Nanozyme-based catalytic tumor therapy is an emerging therapeutic method with high reactivity in response to tumor microenvironments (TMEs). To overcome the current limitations of deficient catalytic activity of nanozymes, we studied the contributing factors of enzymatic activity based on non-metallic-atom doping and irradiation. Nitrogen doping significantly enhanced the peroxidase activity of Ti-based nanozymes, which was shown experimentally and theoretically. Based on the excellent NIR-adsorption-induced surface plasmon resonance and photothermal effect, the enzymatic activity of TiN nanoparticles (NPs) was further improved under NIR laser irradiation. Hence, an acidic TME-responsive and irradiation-mediated cascade nanocatalyst (TLGp) is presented by using TiN-NP-encapsulated liposomes linked with pH-responsive PEG-modified glucose oxidase (GOx). The integration of pH-responsive GOx-mediated H2 O2 self-supply, nitrogen-doping, and irradiation-enhanced enzymatic activity of TiN NPs and mild-photothermal therapy enables an effective tumor inhibition by TLGp with minimal side effects in vivo.

Engineering Dirhodium Artificial Metalloenzymes for Diazo Coupling Cascade Reactions*.

Artificial metalloenzymes (ArMs) are commonly used to control the stereoselectivity of catalytic reactions, but controlling chemoselectivity remains challenging. In this study, we engineer a dirhodium ArM to catalyze diazo cross-coupling to form an alkene that, in a one-pot cascade reaction, is reduced to an alkane with high enantioselectivity (typically >99 % ee) by an alkene reductase. The numerous protein and small molecule components required for the cascade reaction had minimal effect on ArM catalysis. Directed evolution of the ArM led to improved yields and E/Z selectivities for a variety of substrates, which translated to cascade reaction yields. MD simulations of ArM variants were used to understand the structural role of the cofactor on ArM conformational dynamics. These results highlight the ability of ArMs to control both catalyst stereoselectivity and chemoselectivity to enable reactions in complex media that would otherwise lead to undesired side reactions.

High-yield whole cell biosynthesis of Nylon 12 monomer with self-sufficient supply of multiple cofactors.

Biosynthesis of Nylon 12 monomer using dodecanoic acid (DDA) or its esters as the renewable feedstock typically involves ω-hydroxylation, oxidation and ω-amination. The dependence of hydroxylation and oxidation-catalyzing enzymes on redox cofactors, and the requirement of L-alanine as the co-substrate and pyridoxal 5'-phosphate (PLP) as the coenzyme for transamination, raise the issue of redox imbalance and cofactor shortage, challenging the development of efficient biocatalysts. Simultaneous regeneration of the redox equivalents, PLP and L-alanine required in the artificial pathway was enabled by its interfacing with the native metabolism of the host using glucose dehydrogenase (GDH), L-alanine dehydrogenase (AlaDH) and an exogenous ribose 5-phosphate (R5P)-dependent PLP synthesis pathway as bridges. Further engineering of the host by blocking ß-oxidation and enhancing substrate uptake improved the ω-aminododecanoic acid (ω-AmDDA) yield to 96.5%. This study offers a strategy to resolve the cofactor imbalance issue commonly encountered in whole-cell biocatalysis and meanwhile lays a solid foundation for Nylon 12 bioproduction.

A dual-signal colorimetric and ratiometric fluorescent nanoprobe for enzymatic determination of uric acid by using silicon nanoparticles.

The authors describe a dual-signal colorimetric and ratiometric fluorescent probe for uric acid (UA). It is based on cascade catalysis and an inner filter effect. The method involves uricase-catalyzed oxidation of UA and iodide-catalyzed oxidation of the colorless peroxidase substrate o-phenylenediamine (OPD) to form yellow 2,3-diaminophenazine (oxOPD). This can be visually observed or monitored by measuring absorbance at 417 nm. Furthermore, oxOPD quenches the fluorescence of silicon nanoparticles (SiNPs) (with peaks at 450 and 565 nm) via an inner filter effect. The change in the ratio of emissions peaking 565 and 450 (at excitation wavelength of 380 nm) increases linearly in the 0.01-0.8 mM UA concentration range). The lower detection limits are 8.4 and 0.75 µM when using the colorimetric and ratiometric fluorometric method, respectively. The assay was successfully applied to the quantitation of UA in spiked serum samples. Graphical abstractA dual-signal colorimetric and ratiometric fluor ometric assay was developed for uric acid (UA). The fluorometric assay is based on the inner filter effect between fluorescent silicon nanoparticles and 2,3-diaminophenazine. It involves uricase-catalyzed oxidation of UA, and iodide-catalyzed oxidation of o-phenylenediamine.

Enantioselective Vinylogous Organocascade Reactions.

Cascade reactions are powerful tools for rapidly assembling complex molecular architectures from readily available starting materials in a single synthetic operation. Their marriage with asymmetric organocatalysis has led to the development of novel techniques, which are now recognized as reliable strategies for the one-pot enantioselective synthesis of stereochemically dense molecules. In recent years, even more complex synthetic challenges have been addressed by applying the principle of vinylogy to the realm of organocascade catalysis. The key to the success of vinylogous organocascade reactions is the unique ability of the chiral organocatalyst to transfer reactivity to a distal position without losing control on the stereo-determining events. This approach has greatly expanded the synthetic horizons of the field by providing the possibility of forging multiple stereocenters in remote positions from the catalyst's point of action with high selectivity, while simultaneously constructing multiple new bonds. This article critically describes the developments achieved in the field of enantioselective vinylogous organocascade reactions, charting the ideas, the conceptual advances, and the milestone reactions that have been essential for reaching highly practical levels of synthetic efficiency.

Auto-Tandem Catalysis in Ionic Liquids: Synthesis of 2-Oxazolidinones by Palladium-Catalyzed Oxidative Carbonylation of Propargylic Amines in EmimEtSO4.

A convenient carbonylative approach to 2-oxazolidinone derivatives carried out using an ionic liquid (1-ethyl-3-methylimidazolium ethyl sulfate, EmimEtSO4) as the solvent is presented. It is based on the sequential concatenation of two catalytic cycles, both catalyzed by the same metal species (auto-tandem catalysis): the first cycle corresponds to the oxidative monoaminocarbonylation of the triple bond of propargylic amines to give the corresponding 2-ynamide intermediates, while the second one involves the cyclocarbonylation of the latter to yield 2-(2-oxooxazolidin-5-ylidene)-acetamides. Reactions are carried out using a simple catalytic system consisting of PdI2 in conjunction with an excess of KI, and the catalyst/solvent system could be recycled several times without appreciable loss of activity after extraction of the organic product with Et2O.

Enantioselective formal [3+3] cycloadditions of ketones and cyclic 1-azadienes by cascade enamine-enamine catalysis.

An asymmetric formal [3+3] cycloaddition process with diversely structured aliphatic ketones and electron-deficient cyclic 1-azadienes was developed by cascade enamine-enamine catalysis of a cinchona-based primary amine. This sequence involved a domino Michael addition-Mannich reaction to afford spirocyclic architectures in excellent diastereo- and enantioselectivity. Importantly, high regioselectivity was realized for a number of unsymmetrical aliphatic ketone substrates.