MnO2‐Modified Persistent Luminescence Nanoparticles for Detection and Imaging of Glutathione in Living Cells and In Vivo

Persistent luminescence nanoparticles (PLNPs) hold great promise for the detection and imaging of biomolecules. Herein, we have demonstrated a novel nanoprobe, based on the manganese dioxide (MnO₂)‐modified PLNPs, that can detect and image glutathione in living cells and in vivo. The persistent luminescence of the PLNPs can be efficiently quenched by the MnO₂ nanosheets. In the presence of glutathione (GSH), MnO₂ was reduced to Mn²⁺ and the luminescence of PLNPs can be restored. The persistent luminescence property can allow detection and imaging without external excitation and avoid the background noise originating from the in situ excitation. This strategy can offer a promising platform for detection and imaging of reactive species in living cells or in vivo.     

Electrochemical Determination of Vitamin B12 Based on Cu2+‐Involved Fenton‐like Reaction

Poly(thionine) (PTH) film was generated on the electrochemically activated glassy carbon electrode (GCE(ea)) by using the two‐step cyclic voltammetric scan. Scanning electron microscopy, infrared spectral analysis and electrochemical measurement were employed to characterize the modified electrode surface. Hydroxyl radicals, which were produced by the Fenton‐like reaction, could induce the effective oxidization of PTH under near‐neutral condition and cause the notable enhancement of the cathodic peak current (I_pc) during the potential cycling process. Due to the binding of copper ions with the ligands liberated from V_B12 and the inferior catalytic ability of Co²⁺ for the generation of hydroxyl radicals, the addition of V_B12 into the Cu²⁺?H₂O₂ system inhibited the oxidization of PTH and resulted in the decrease of the I_pc value. The cathodic peak current change was linear with the logarithm of the V_B12 concentration in the range of 10 nmol L^?1–100 μmol L^?1 with a detection limit of 2 nmol L^?1 under optimal conditions. The developed sensor displayed excellent analytical performance including high sensitivity, good selectivity, acceptable reproducibility and satisfactory stability. The V_B12 content in the injection sample was measured and the recovery values were in the range of 92.0 %–102 %.     

Chemodynamic Therapy: Tumour Microenvironment‐Mediated Fenton and Fenton‐like Reactions

Tailored to the specific tumour microenvironment, which involves acidity and the overproduction of hydrogen peroxide, advanced nanotechnology has been introduced to generate the hydroxyl radical (^.OH) primarily for tumour chemodynamic therapy (CDT) through the Fenton and Fenton‐like reactions. Numerous studies have investigated the enhancement of CDT efficiency, primarily the increase in the amount of ^.OH generated. Notably, various strategies based on the Fenton reaction have been employed to enhance ^.OH generation, including nanomaterials selection, modulation of the reaction environment, and external energy fields stimulation, which are discussed systematically in this Minireview. Furthermore, the potential challenges and the methods used to facilitate CDT effectiveness are also presented to support this cutting‐edge research area.     

Three‐Arm,Biotin‐Tagged Carbazole–Dicyanovinyl–Chlorambucil Conjugate: Simultaneous Tumor Targeting,Sensing, and Photoresponsive Anticancer Drug Delivery

The design, synthesis, and in vitro biological studies of a biotin–carbazole–dicyanovinyl–chlorambucil conjugate (Bio‐CBZ‐DCV‐CBL; 6 ) are reported. This conjugate ( 6 ) is a multifunctional single‐molecule appliance composed of a thiol‐sensor DCV functionality, a CBZ‐derived phototrigger as well as fluorescent reporter, and CBL as the anticancer drug, and Bio as the cancer‐targeting ligand. In conjugate 6 , the DCV bond undergoes a thiol–ene click reaction at pH<7 with intracellular thiols, thereby shutting down internal charge transfer between the donor CBZ and acceptor DCV units, resulting in a change of the fluorescence color from green to blue, and thereby, sensing the tumor microenvironment. Subsequent photoirradiation results in release of the anticancer drug CBL in a controlled manner.     

Enhanced Photodynamic Therapy by Reduced Levels of Intracellular Glutathione Obtained By Employing a Nano‐MOF with CuII as the Active Center

In photodynamic therapy (PDT), the level of reactive oxygen species (ROS) produced in the cell directly determines the therapeutic effect. Improvement in ROS concentration can be realized by reducing the glutathione (GSH) level or increasing the amount of photosensitizer. However, excessive amounts photosensitizer may cause side effects. Therefore, the development of photosensitizers that reduce GSH levels through synergistically improving ROS concentration in order to strengthen the efficacy of PDT for tumor is important. We report a nano‐metal–organic framework (Cu^II‐metalated nano‐MOF {CuL‐[AlOH]₂}_n (MOF‐2, H₆L=mesotetrakis(4‐carboxylphenyl)porphyrin)) based on Cu^II as the active center for PDT. This MOF‐2 is readily taken up by breast cancer cells, and high levels of ROS are generated under light irradiation. Meanwhile, intracellular GSH is considerably decreased owing to absorption on MOF‐2; this synergistically increases ROS concentration and accelerates apoptosis, thereby enhancing the effect of PDT. Notably, based on the direct adsorption of GSH, MOF‐2 showed a comparable effect with the commercial antitumor drug camptothecin in a mouse breast cancer model. This work provides strong evidence for MOF‐2 as a promising new PDT candidate and anticancer drug.     

Electrophoretic Deposition of Binder‐Free MnO2/Graphene Films for Lithium‐Ion Batteries

Binder‐free, nano‐sized needlelike MnO₂ ‐submillimeter‐sized reduced graphene oxide (nMnO₂‐srGO ) hybrid films with abundant porous structures were fabricated through electrophoretic deposition and subsequent thermal annealing at 500 °C for 2 h. The as‐prepared hybrid films exhibit a unique hierarchical morphology, in which nMnO₂ with a diameter of 20—50 nm and a length of 300—500 nm is randomly anchored on both sides of srGO . When evaluated as binder‐free anodes for lithium‐ion half‐cell, the nMnO₂‐srGO composites with a content of 76.9 wt% MnO₂ deliver a high capacity of approximately 1652.2 mA •h•g⁻¹ at a current density of 0.1 A•g⁻¹ after 200 cycles. The high capacity remains at 616.8 mA •h•g⁻¹ (ca. 65.1% capacity retention) at a current density as high as 4 A•g⁻¹. The excellent electrochemical performance indicates that the nMnO₂‐srGO hybrid films could be a promising anode material for lithium ion batteries (LIBs ).     

High Relaxivity Mn2+‐Based MRI Contrast Agents

Stable Mn²⁺ mono‐ and binuclear complexes containing pentadentate 6,6′‐((methylazanediyl)bis(methylene))dipicolinic acid coordinating units give remarkably high relaxivities due to the presence of two inner‐sphere water molecules. The mononuclear derivative binds human serum albumin (HSA) with an association constant of 3372 M ^?1, which results in the replacement of the coordinated water molecules by donor atoms of protein residues. The dinuclear analogue also binds HSA while leaving one of the Mn²⁺ centres exposed to the solvent with two coordinated water molecules. Thus, this complex shows remarkably high relaxivities upon protein binding (39.0 mM ^?1 s^?1 per Mn, at 20 MHz and 37 °C).     

Enhanced Intrinsic Catalytic Activity of λ‐MnO2 by Electrochemical Tuning and Oxygen Vacancy Generation

Chemically prepared λ‐MnO₂ has not been intensively studied as a material for metal–air batteries, fuel cells, or supercapacitors because of their relatively poor electrochemical properties compared to α‐ and δ‐MnO₂. Herein, through the electrochemical removal of lithium from LiMn₂O₄, highly crystalline λ‐MnO₂ was prepared as an efficient electrocatalyst for the oxygen reduction reaction (ORR). The ORR activity of the material was further improved by introducing oxygen vacancies (OVs) that could be achieved by increasing the calcination temperature during LiMn₂O₄ synthesis; a concentration of oxygen vacancies in LiMn₂O₄ could be characterized by its voltage profile as the cathode in a lithiun–metal half‐cell. λ‐MnO_2?z prepared with the highest OV exhibited the highest diffusion‐limited ORR current (5.5 mA cm^?2) among a series of λ‐MnO_2?z electrocatalysts. Furthermore, the number of transferred electrons (n) involved in the ORR was >3.8, indicating a dominant quasi‐4‐electron pathway. Interestingly, the catalytic performances of the samples were not a function of their surface areas, and instead depended on the concentration of OVs, indicating enhancement in the intrinsic catalytic activity of λ‐MnO₂ by the generation of OVs. This study demonstrates that differences in the electrochemical behavior of λ‐MnO₂ depend on the preparation method and provides a mechanism for a unique catalytic behavior of cubic λ‐MnO₂.     

Periodic Current Oscillation Catalyzed by δ‐MnO2 Nanosheets

The oxygen evolution reaction (OER) is of wide interest for both fuel and hydrometallurgy applications. Different types of nanoscale MnO₂, varying from nanosheets to nanoneedles, are synthesized and assembled on the anode to investigate their catalytic effect on the nonlinear kinetics of the MnO₂‐catalyzed OER at high current. For δ‐MnO₂ nanosheets, periodic current oscillations (PCO) occurr and occupy up to 40 % of the total energy consumption. The PCO can help to reduce the energy consumption under constant current conditions. Its amplitude could be twice of that for the previously reported MnO₂ grown by an in situ electrochemical method. If the amount of γ‐MnO₂ nanoneedles increases, the oscillation disappears. For different Mn oxides, the rate constants of H₂O₂ decomposition differ, resulting in changes in oscillation features. The results of this study may enable new ideas to improve the efficiency of industrial electrolysis and charging–discharging of supercapacitors.     

Design and Synthesis of 2‐(5‐Phenylindol‐3‐yl)benzimidazole Derivatives with Antiproliferative Effects towards Triple‐Negative Breast Cancer Cells by Activation of ROS‐Mediated Mitochondria Dysfunction

Benzimidazole derivatives are widely studied because of their broad‐spectrum biological activity, such as antitumor properties and excellent fluorescence performance. Herein, two types of 2‐(5‐phenylindol‐3‐yl)benzimidazole derivatives ( 1 a – 1 h and 2 a – 2 e ) were rationally designed and synthesized. When these compounds were investigated in vitro anti‐screening assays, we found that all of them possessed antitumor effect, in particular compound 1 b , which showed an outstanding antiproliferative effect on MDA‐MB‐231 cells (IC₅₀≈2.6 μm ). A study of the drug action mechanisms in cells showed that the antitumor activity of the compounds is proportional to their lipophilicity and cellular uptake; the tested compounds all entered the lysosome of MDA‐MB‐231 cells and caused changes in the levels of reactive oxygen species (ROS), and then caused mitochondrial damage. Apparent differences in the ROS levels for each compound suggest that the lethality of these compounds towards MDA‐MB‐231 cells is closely related to the ROS levels. Taken together, this study not only provides a theoretical basis for 2‐(5‐phenylindol‐3‐yl)benzimidazole anticarcinogens but also offers new thinking on the rational design of next‐generation antitumor benzimidazole derivatives.     

A Biosensor Composed of Glucose Oxidase‐Containing Liposomes and MnO2‐Based Layered Nanocomposite

Glucose oxidase (GOD) was encapsulated in liposomes, and then the GOD‐containing liposomes were immobilized to a MnO₂‐based multilayered nanocomposite film grown electrochemically. Oxidation of glucose took place on the encapsulated GOD in the manganese oxide film, and the generated H₂O₂ molecules were oxidized catalytically at high valent Mn sites (4+) in the film. Anodic currents due to reoxidation of the reduced Mn ions (3+) were in proportion to the concentration of glucose from 19.6 to 107.1 mM. Such a simple construction of biosensor is applicable to a variety of combinations of liposomal enzymes and substrates.     

In Situ Proteome Profiling and Bioimaging Applications of Small‐Molecule Affinity‐Based Probes Derived From DOT1L Inhibitors

DOT1L is the sole protein methyltransferase that methylates histone H3 on lysine 79 (H3K79), and is a promising drug target against cancers. Small‐molecule inhibitors of DOT1L such as FED1 are potential anti‐cancer agents and useful tools to investigate the biological roles of DOT1L in human diseases. FED1 showed excellent in vitro inhibitory activity against DOT1L, but its cellular effect was relatively poor. In this study, we designed and synthesized photo‐reactive and “clickable” affinity‐based probes (AfBPs), P1 and P2 , which were cell‐permeable and structural mimics of FED1 . The binding and inhibitory effects of these two probes against DOT1L protein were extensively investigated in vitro and in live mammalian cells (in situ). The cellular uptake and sub‐cellular localization properties of the probes were subsequently studied in live‐cell imaging experiments, and our results revealed that, whereas both P1 and P2 readily entered mammalian cells, most of them were not able to reach the cell nucleus where functional DOT1L resides. This offers a plausible explanation for the poor cellular activity of FED1 . Finally with P1 / P2 , large‐scale cell‐based proteome profiling, followed by quantitative LC‐MS/MS, was carried out to identify potential cellular off‐targets of FED1 . Amongst the more than 100 candidate off‐targets identified, NOP2 (a putative ribosomal RNA methyltransferase) was further confirmed to be likely a genuine off‐target of FED1 by preliminary validation experiments including pull‐down/Western blotting (PD/WB) and cellular thermal shift assay (CETSA).     

Environmentally Friendly γ‐MnO2 Hexagon‐Based Nanoarchitectures: Structural Understanding and Their Energy‐Saving Applications

Although about 200,000 metric tons of γ‐MnO₂ are used annually worldwide for industrial applications, the γ‐MnO₂ structure is still known to possess a highly ambiguous crystal lattice. To better understand the γ‐MnO₂ atomic structure, hexagon‐based nanoarchitectures were successfully synthesized and used to elucidate its internal structure for the present work. The structural analysis results, obtained from the hexagon‐based nanoarchitectures, clearly show the coexistence of akhtenskite (ε‐MnO₂), pyrolusite (β‐MnO₂), and ramsdellite in the so‐called γ‐MnO₂ phase and verified the heterogeneous phase assembly of the γ‐MnO₂ state, which violates the well‐known “De Wolff” model and derivative models, but partially accords with Heuer's results. Furthermore, heterogeneous γ‐MnO₂ assembly was found to be a metastable structure under hydrothermal conditions, and the individual components of the heterogeneous γ‐MnO₂ system have structural similarities and a high lattice matches with pyrolusite (β‐MnO₂). The as‐obtained γ‐MnO₂ nanoarchitectures are nontoxic and environmentally friendly, and the application of such nanoarchitectures as support matrices successfully mitigates the common problems for phase‐change materials of inorganic salts, such as phase separation and supercooling‐effects, thereby showing prospect in energy‐saving applications in future “smart‐house” systems.     

[4+2] Cycloaddition Reactions Between 1,8‐Disubstituted Cyclooctatetraenes and Diazo Dienophiles: Stereoelectronic Effects,Anticancer Properties and Application to the Synthesis of 7,8‐Substituted Bicyclo[4.2.0]octa‐2,4‐dienes

A detailed examination of [4+2] cycloaddition reactions between 1,8‐disubstituted cyclooctatetraenes and diazo compounds revealed that 4‐phenyl‐1,2,4‐triazole‐3,5‐dione (PTAD) reacts to form either 2,3‐ or 3,4‐disubstituted adducts. The product distribution can be controlled by modulating the electron density of the cyclooctatetraene. Unprecedented [4+2] cycloadditions between diisopropyl azodicarboxylate (DIAD) and 1,8‐disubstituted cyclooctatetraenes are also described and further manipulation of a resulting cycloadduct uncovered a new pathway to the synthetically challenging bicyclo[4.2.0]octa‐2,4‐diene family. Variation of the substituents resulted in a range of compounds displaying selective action against different human tumour cell types.     

Hydrogenation of CO2‐Derived Carbonates and Polycarbonates to Methanol and Diols by Metal–Ligand Cooperative Manganese Catalysis

The first base‐metal‐catalysed hydrogenation of CO₂‐derived carbonates to alcohols is presented. The reaction proceeds under mild conditions in the presence of a well‐defined manganese complex with a loading as low as 0.25 mol %. The non‐precious‐metal homogenous catalytic system provides an indirect route for the conversion of CO₂ into methanol with the co‐production of value‐added (vicinal) diols in yields of up to 99 %. Experimental and computational studies indicate a metal–ligand cooperative catalysis mechanism.     

Unprecedented Kinetic Inertness for a Mn2+‐Bispidine Chelate: A Novel Structural Entry for Mn2+‐Based Imaging Agents

The search for more biocompatible alternatives to Gd³⁺‐based MRI agents, and the interest in ⁵²Mn for PET imaging call for ligands that form inert Mn²⁺ chelates. Given the labile nature of Mn²⁺, high inertness is challenging to achieve. The strongly preorganized structure of the 2,4‐pyridyl‐disubstituted bispidol ligand L₁ endows its Mn²⁺ complex with exceptional kinetic inertness. Indeed, MnL₁ did not show any dissociation for 140 days in the presence of 50 equiv. of Zn²⁺ (37 °C, pH 6), while recently reported potential MRI agents MnPyC3A and MnPC2A‐EA have dissociation half‐lives of 0.285 h and 54.4 h under similar conditions. In addition, the relaxivity of MnL₁ (4.28 mm ^?1 s^?1 at 25 °C, 20 MHz) is remarkable for a monohydrated, small Mn²⁺ chelate. In vivo MRI experiments in mice and determination of the tissue Mn content evidence rapid renal clearance of MnL₁. Additionally, L₁ could be radiolabeled with ⁵²Mn and the complex revealed good stability in biological media.     

Synthesis of Iron Nanometallic Glasses and Their Application in Cancer Therapy by a Localized Fenton Reaction

Metallic glasses and cancer theranostics are emerging fields that do not seem to be related to each other. Herein, we report the facile synthesis of amorphous iron nanoparticles (AFeNPs) and their superior physicochemical properties compared to their crystalline counterpart, iron nanocrystals (FeNCs). The AFeNPs can be used for cancer theranostics by inducing a Fenton reaction in the tumor by taking advantage of the mild acidity and the overproduced H₂O₂ in a tumor microenvironment: Ionization of the AFeNPs enables on‐demand ferrous ion release in the tumor, and subsequent H₂O₂ disproportionation leads to efficient ^.OH generation. The endogenous stimuli‐responsive ^.OH generation in the presence AFeNPs enables a highly specific cancer therapy without the need for external energy input.