A Comprehensive Outlook of Synthetic Strategies and Applications of Redox‐Responsive Nanogels in Drug Delivery

Increasing recognition of the role of oxidative stress in the pathogenesis of many clinical conditions and the existence of defined redox potential in healthy tissues has led to extensive research in the development of redox‐responsive materials for biomedical applications. Especially, considerable growth has been seen in the fabrication of polymeric nanogel–based drug delivery carriers utilizing redox‐responsive cross‐linkers bearing a variety of functional groups via various synthetic strategies. Redox‐responsive polymeric nanogels provide an advantage of facile chemical modification post synthesis and exhibit a remarkable response to biological redox stimuli. Due to the interdisciplinary nature of the subject, a more profound combined conceptual knowledge from a chemical and biological point of view is imperative for the rational design of redox‐responsive nanogels. The present review provides an insight into the design and fabrication of redox‐responsive nanogels with particular emphasis on synthetic strategies utilized for the development of redox‐responsive cross‐linkers, polymerization techniques being followed for nanogel development and biomedical applications. Cooperative effect of redox trigger with other stimuli such as pH and temperature in the evolution of dual and triple stimuli‐responsive nanogels is also discussed.     

A Redox‐Active 2D Metal–Organic Framework for Efficient Lithium Storage with Extraordinary High Capacity

Metal–organic framework cathodes usually exhibit low capacity and poor electrochemical performance for Li‐ion storage owing to intrinsic low conductivity and inferior redox activity. Now a redox‐active 2D copper–benzoquinoid (Cu‐THQ) MOF has been synthesized by a simple solvothermal method. The abundant porosity and intrinsic redox character endow the 2D Cu‐THQ MOF with promising electrochemical activity. Superior performance is achieved as a Li‐ion battery cathode with a high reversible capacity (387 mA h g^?1), large specific energy density (775 Wh kg^?1), and good cycling stability. The reaction mechanism is unveiled by comprehensive spectroscopic techniques: a three‐electron redox reaction per coordination unit and one‐electron redox reaction per copper ion mechanism is demonstrated. This elucidatory understanding sheds new light on future rational design of high‐performance MOF‐based cathode materials for efficient energy storage and conversion.     

Intramolecular Redox‐Mannich Reactions: Facile Access to the Tetrahydroprotoberberine Core

Cyclic amines such as pyrrolidine undergo redox‐annulations with 2‐formylaryl malonates. Concurrent oxidative amine α‐C?H bond functionalization and reductive N‐alkylation render this transformation redox‐neutral. This redox‐Mannich process provides regioisomers of classic Reinhoudt reaction products as an entry to the tetrahydroprotoberberine core, enabling the synthesis of (±)‐thalictricavine and its epimer. An unusually mild amine‐promoted dealkoxycarbonylation was discovered in the course of these studies.     

Magnetic Cobalt Ferrite Nanocrystals For an Energy Storage Concentration Cell

Energy‐storage concentration cells are based on the concentration gradient of redox‐active reactants; the increased entropy is transformed into electric energy as the concentration gradient reaches equilibrium between two half cells. A recyclable and flow‐controlled magnetic electrolyte concentration cell is now presented. The hybrid inorganic–organic nanocrystal‐based electrolyte, consisting of molecular redox‐active ligands adsorbed on the surface of magnetic nanocrystals, leads to a magnetic‐field‐driven concentration gradient of redox molecules. The energy storage performance of concentration cells is dictated by magnetic characteristics of cobalt ferrite nanocrystal carriers. The enhanced conductivity and kinetics of redox‐active electrolytes could further induce a sharp concentration gradient to improve the energy density and voltage switching of magnetic electrolyte concentration cells.     

Reversible Oxygen Redox Chemistry in Aqueous Zinc‐Ion Batteries

Rechargeable aqueous zinc‐ion batteries (ZIBs) are promising energy‐storage devices owing to their low cost and high safety. However, their energy‐storage mechanisms are complex and not well established. Recent energy‐storage mechanisms of ZIBs usually depend on cationic redox processes. Anionic redox processes have not been observed owing to the limitations of cathodes and electrolytes. Herein, we describe highly reversible aqueous ZIBs based on layered VOPO₄ cathodes and a water‐in‐salt electrolyte. Such batteries display reversible oxygen redox chemistry in a high‐voltage region. The oxygen redox process not only provides about 27 % additional capacity, but also increases the average operating voltage to around 1.56 V, thus increasing the energy density by approximately 36 %. Furthermore, the oxygen redox process promotes the reversible crystal‐structure evolution of VOPO₄ during charge/discharge processes, thus resulting in enhanced rate capability and cycling performance.     

A Sustainable Redox‐Flow Battery with an Aluminum‐Based,Deep‐Eutectic‐Solvent Anolyte

Nonaqueous redox‐flow batteries are an emerging energy storage technology for grid storage systems, but the development of anolytes has lagged far behind that of catholytes due to the major limitations of the redox species, which exhibit relatively low solubility and inadequate redox potentials. Herein, an aluminum‐based deep‐eutectic‐solvent is investigated as an anolyte for redox‐flow batteries. The aluminum‐based deep‐eutectic solvent demonstrated a significantly enhanced concentration of circa 3.2 m in the anolyte and a relatively low redox potential of 2.2 V vs. Li⁺/Li. The electrochemical measurements highlight that a reversible volumetric capacity of 145 Ah L⁻¹ and an energy density of 189 Wh L⁻¹ or 165 Wh kg⁻¹ have been achieved when coupled with a I₃⁻/I⁻ catholyte. The prototype cell has also been extended to the use of a Br₂‐based catholyte, exhibiting a higher cell voltage with a theoretical energy density of over 200 Wh L⁻¹. The synergy of highly abundant, dendrite‐free, multi‐electron‐reaction aluminum anodes and environmentally benign deep‐eutectic‐solvent anolytes reveals great potential towards cost‐effective, sustainable redox‐flow batteries.     

Oxidation of Organic Molecules with a Redox‐Active Guanidine Catalyst

Herein, we report the first examples of the use of redox‐active guanidines as catalysts in the green oxidation of organic molecules with dioxygen. In one half‐reaction, the oxidized form of the redox‐active guanidine is converted into the reduced, protonated state, thereby enabling dehydrogenative oxidation of the substrate (3,5‐di‐tert‐butylcatechol→ortho‐benzoquinone, benzoin→benzil, and 2,4‐di‐tert‐butylphenol→biphenol). In the other half‐reaction, efficient re‐oxidation of the guanidine to the oxidized state is achieved with dioxygen in the presence of a copper catalyst. These results pave the way for the broader use of redox‐active guanidines as oxidation catalysts.     

A Ruthenium Based Organometallic Complex for Biosensing that is both a Stable Redox Label and a Homobifunctional Linker

A stable ruthenium‐based redox label, Ru(acetylacetonate)₂(bipyridine‐NH₂), has been synthesized with the target of circumventing the problem associated with the use of ferrocene for biosensing in solutions containing chloride ions. The redox species was shown to be highly stable with repeated cycling in biological buffers as well as being amenable to surface coupling reactions. To demonstrate the latter, the redox label was anchored onto a self‐assembled monolayer of 6‐mercaptohexanoic acid, using carbodiimide coupling, followed by binding of a pentapeptide to the redox label.     

Biredox Eutectic Electrolytes Derived from Organic Redox‐Active Molecules: High‐Energy Storage Systems

One promising candidate for high‐energy storage systems is the nonaqueous redox flow battery (NARFB). However, their application is limited by low solubility of redox‐active materials and poor performance at high current density. Reported here is a new strategy, a biredox eutectic, as the sole electrolyte for NARFB to achieve a significantly higher concentration of redox‐active materials and enhance the cell performance. Without other auxiliary solvents, the biredox eutectic electrolyte is formed directly by the molecular interactions between two different redox‐active molecules. Such a unique electrolyte possesses high concentration with low viscosity (3.5 m , for N‐butylphthalimide and 1,1‐dimethylferrocene system) and a relatively high working voltage of 1.8 V, enabling high capacity and energy density of NARFB. The resulting high‐performance NARFB demonstrates that the biredox eutectic based strategy is potentially promising for low‐cost and high‐energy storage systems.     

Comparative Study of Photochromic Ferrocene‐Conjugated Dimethyldihydropyrene Derivatives

The photochemical properties and the mixed‐valence state of bis(ferrocenylethynyl)benzodimethyldihydropyrene ( 1 ) and other benzodimethyldihydropyrene (BzDHP) derivatives were investigated to understand the reversible photoswitching in the electronic communication of 1 . Absorption spectra of 1 were characterized by UV/Vis spectroscopy and calculated by using time‐dependent density functional theory (TD‐DFT), and the d orbitals of the ferrocene (Fc) moieties were shown to contribute to the occupied valence orbitals that were responsible for the photochromic behavior. 1 exhibited reversible photoisomerization in THF; however, photochromic behavior was not observed in dichloromethane. Analysis of redox potentials showed that the mixed‐valence state of 1 was more stable in dichloromethane than in THF. This is consistent with the observation that chemical oxidation led to an intervalence charge‐transfer (IVCT) band between the Fc moieties in the mixed‐valence state of 1 in dichloromethane, whereas such a band was not observed for one‐electron‐oxidized 1 in THF. Bis(pentamethylferrocenylethynyl)benzodimethyldihydropyrene ( 2 ) did not show photochromic behavior even in THF. The mixed‐valence state of 2 was much less stable than that of 1 in dichloromethane, and no obvious IVCT band was observed for one‐electron‐oxidized 2 in dichloromethane. The difference in the redox contribution of Fc and pentamethylferrocene (Me₅Fc) to BzDHP played an important role for these redox and photochromic behaviors; this was supported by analysis of valence orbital energies from DFT calculations. Designing molecules that connect redox centers through the use of a photochromic linker with a redox potential close to that of the redox centers could constitute a useful approach for the production of photochromic redox‐active metal complexes with strong electronic communication.     

Transition‐Metal‐Catalyzed Redox‐Neutral and Redox‐Green C–H Bond Functionalization

Transition‐metal‐catalyzed C–H bond functionalization has become one of the most promising strategies to prepare complex molecules from simple precursors. However, the utilization of environmentally unfriendly oxidants in the oxidative C–H bond functionalization reactions reduces their potential applications in organic synthesis. This account describes our recent efforts in the development of a redox‐neutral C–H bond functionalization strategy for direct addition of inert C–H bonds to unsaturated double bonds and a redox‐green C–H bond functionalization strategy for realization of oxidative C–H functionalization with O₂ as the sole oxidant, aiming to circumvent the problems posed by utilizing environmentally unfriendly oxidants. In principle, these redox‐neutral and redox‐green strategies pave the way for establishing new environmentally benign transition‐metal‐catalyzed C–H bond functionalization strategies.     

Colloidal Supercapattery: Redox Ions in Electrode and Electrolyte

Redox chemistry is the cornerstone of various electrochemical energy conversion and storage systems, associated with ion diffusion process. To actualize both high energy and power density in energy storage devices, both multiple electron transfer reaction and fast ion diffusion occurred in one electrode material are prerequisite. The existence forms of redox ions can lead to different electrochemical thermodynamic and kinetic properties. Here, we introduce novel colloid system, which includes multiple varying ion forms, multi‐interaction and abundant redox active sites. Unlike redox cations in solution and crystal materials, colloid system has specific reactivity‐structure relationship. In the colloidal ionic electrode, the occurrence of multiple‐electron redox reactions and fast ion diffusion leaded to ultrahigh specific capacitance and fast charge rate. The colloidal ionic supercapattery coupled with redox electrolyte provides a new potential technique for the comprehensive use of redox ions including cations and anions in electrode and electrolyte and a guiding design for the development of next‐generation high performance energy storage devices.     

Design of an Os Complex‐Modified Hydrogel with Optimized Redox Potential for Biosensors and Biofuel Cells

Multistep synthesis and electrochemical characterization of an Os complex‐modified redox hydrogel exhibiting a redox potential ≈+30 mV (vs. Ag/AgCl 3 m KCl) is demonstrated. The careful selection of bipyridine‐based ligands bearing N,N‐dimethylamino moieties and an amino‐linker for the covalent attachment to the polymer backbone ensures the formation of a stable redox polymer with an envisaged redox potential close to 0 V. Most importantly, the formation of an octahedral N6‐coordination sphere around the Os central atoms provides improved stability concomitantly with the low formal potential, a low reorganization energy during the Os^3+/2+ redox conversion and a negligible impact on oxygen reduction. By wiring a variety of enzymes such as pyrroloquinoline quinone (PQQ)‐dependent glucose dehydrogenase, flavin adenine dinucleotide (FAD)‐dependent glucose dehydrogenase and the FAD‐dependent dehydrogenase domain of cellobiose dehydrogenase, low‐potential glucose biosensors could be obtained with negligible co‐oxidation of common interfering compounds such as uric acid or ascorbic acid. In combination with a bilirubin oxidase‐based biocathode, enzymatic biofuel cells with open‐circuit voltages of up to 0.54 V were obtained.     

Catalytic C−H Trifluoromethoxylation of Arenes and Heteroarenes

The intermolecular C?H trifluoromethoxylation of arenes remains a long‐standing and unsolved problem in organic synthesis. Herein, we report the first catalytic protocol employing a novel trifluoromethoxylating reagent and redox‐active catalysts for the direct (hetero)aryl C?H trifluoromethoxylation. Our approach is operationally simple, proceeds at room temperature, uses easy‐to‐handle reagents, requires only 0.03 mol % of redox‐active catalysts, does not need specialized reaction apparatus, and tolerates a wide variety of functional groups and complex structures such as sugars and natural product derivatives. Importantly, both ground‐state and photoexcited redox‐active catalysts are effective. Detailed computational and experimental studies suggest a unique reaction pathway where photoexcitation of the trifluoromethoxylating reagent releases the OCF₃ radical that is trapped by (hetero)arenes. The resulting cyclohexadienyl radicals are oxidized by redox‐active catalysts and deprotonated to form the desired products of trifluoromethoxylation.     

Novel Nickel Redox Polymer as an Efficient Electrode Material for Electrochemical Sensing

A novel redox polymer comprised of poly(3,4‐ethylenedioxythiophene) (PEDOT) and ethylenediamine tetraacetic acid‐Ni²⁺ (EDTA‐Ni) complex serving as doping anions has been synthesised by a facile one‐step electrochemical approach and utilized as an efficient electrode material for sensitive luteolin detection. The morphology, chemical structure and composition of the redox polymer were analyzed by SEM, UV‐vis and FT‐IR spectrum. Electrochemical tests revealed that the redox polymer was highly electrochemically reversible and exhibited good electrocatalytic activity to the redox reactions of luteolin with a linear range covering from 1 nM to 10 µM with a low detection limit of 0.3 nM of luteolin.     

Enhancement of Bioelectrocatalytic Processes by the Rotation of Mediator‐Functionalized Magnetic Particles on Electrode Surfaces: Comparison with a Rotating Disk Electrode

The rotation of redox‐functionalized magnetic particles (MPs) by means of an external magnet is a common practice for enhancing bioelectrocatalytic processes and for the amplification of biosensing events. The current densities generated by rotating redox‐functionalized MPs in two bioelectrocatalytic systems are compared to the current densities generated by rotating disc electrodes (RDE) functionalized with similar redox functionalities. The bioelectrocatalytic systems consist of pyrroloquinoline quinone (PQQ)‐functionalized MPs that oxidize NADH, and ferrocene‐functionalized MPs that mediate the bioelectrocatalyzed oxidation of glucose in the presence of glucose oxidase. The results reveal that only ca. 1% of the area of the redox‐functionalized MPs are electrically contacted with the electrode. Also, the current densities generated by the rotating MPs at high rotation speeds are lower than theoretically expected, presumably due to lose of electrical contact between the MPs and the electrode, and incoherent rotation of the particles on the electrode, due to insufficient magnetization. The comparison of the current densities in the bioelectrocatalytic systems in the presence of the rotating redox‐functionalized MPs to the analogous RDE systems allows us to elucidate the kinetics of electron transfer at the redox‐active MPs.     

Redox‐Active Ligands in Catalysis

Nature’s use of redox‐active moieties combined with 3d transition‐metal ions is a powerful strategy to promote multi‐electron catalytic reactions. The ability of these moieties to store redox equivalents aids metalloenzymes in promoting multi‐electron reactions, avoiding high‐energy intermediates. In a biomimetic spirit, chemists have recently developed approaches relying on redox‐active moieties in the vicinity of metal centers to catalyze challenging transformations. This approach enables chemists to impart noble‐metal character to less toxic, and cost effective 3d transitional metals, such as Fe or Cu, in multi‐electron catalytic reactions.     

A Molecular Platform for Multistate Near‐Infrared Electrochromism and Flip‐Flop,Flip‐Flap‐Flop,and Ternary Memory

A diruthenium complex with a redox‐active amine bridge has been designed, synthesized, and studied by single‐crystal X‐ray analysis and DFT and TDDFT calculations. It shows three well‐separated redox processes with exclusive near‐infrared (NIR) absorbance at each redox state. The electropolymerized film of a related vinyl‐functionalized complex displays multistate NIR electrochromism with low operational potential, good contrast ratio, and long retention time. Flip‐flop, flip‐flap‐flop, and ternary memories have been realized by using the obtained film (ca. 15–20 nm thick) with three electrochemical inputs and three NIR optical outputs that each displays three levels of signal intensity.     

Proteomic and redox‐proteomic study on the role of glutathione reductase in human lung cancer cells

Glutathione reductase (GR), a cytosolic protein, plays a vital role in maintaining a correct redox status in cells. However, comprehensive investigations of GR‐modulated cellular responses, including protein level alteration and redox regulation, have yet to be performed. In this study, we cultured a human lung adenocarcinoma line transfected with empty pLKO.1 vector as a control, CL1‐0shControl, and its GR‐knockdown derivative, CL1‐0shΔGR, to evaluate differential protein level alteration and redox regulation of these two cell lines. We identified 34 spots that exhibited marked changes in intensities, and 13 proteins showing significant changes in thiol reactivity, in response to GR depletion. Several proteins involved in redox regulation, calcium signaling, cytoskeleton regulation, and protein folding showed significant changes in expression, whereas proteins involved in redox regulation, protein folding, and glycolysis displayed changes in thiol reactivity. Interestingly, GR knockdown induces peroxiredoxin‐1 overexpression in the air‐exposed tissue and high oxygen consuming tissue such as cornea and liver, but not in the low oxygen consuming tissues such as breast and uterine. In summary, we used a comprehensive lung adenocarcinoma based proteomic approach for identifying GR‐modulated protein expression alteration and redox modification. Based on our research, this is the first comprehensive proteomic and redox‐proteomic analysis used to investigate the role of GR in a mammalian cell model.     

A Reversible Redox Strategy for SWCNT‐Based Supercapacitors Using a High‐Performance Electrolyte

In order to achieve pesudocapacitive performance of single‐wall carbon nanotube (SWCNT) electrodes, a high‐efficient and reversible redox strategy utilizing a redox‐mediated electrolyte for SWCNT‐based supercapacitors is reported. In this novel redox‐mediated electrolyte, the single‐electrode specific capacitance of the supercapacitor is heightened four times, reaching C=162.66 F g^?1 at 1 A g^?1. The quick charge‐discharge ability of the supercapacitor is also enhanced, and the relaxation time is as low as 0.58 s. Furthermore, the supercapacitor shows an excellent cycling performance of 96.51 % retention after 4000 cycles. The remarkable results presented here illustrate that the redox strategy is a facile and straightforward approach to improve the performances of SWCNT electrodes.