Mediated Reactions Research Articles

Synthesis of 2‐Substituted Bicyclo[2.1.1]Hexan‐1‐ols via SmI2‐Mediated Reductive Cyclization Reactions

AbstractThe replacement of benzene rings with saturated bioisosteric counterparts is a key priority in drug discovery programs, and disubstituted bicyclo[2.1.1]hexanes have been recognized as flexible molecular scaffolds that could act as ortho‐substituted benzene bioisosteres. In this study, we outline the synthesis of a wide range of 2‐substituted bicyclo[2.1.1]hexan‐1‐ols, which have the potential to emulate ortho‐phenolic derivatives, via SmI2‐mediated reductive cyclization reactions. The synthetic utility of this methodology was exemplified by the preparation of several saturated analogs of pharmaceutically relevant compounds.

A highly stretchable and self-adhesive cellulose complex hydrogels based on PDA@Fe3+ mediated redox reaction for strain sensor

As the application of conductive hydrogels in the field of wearable smart devices is gradually deepening, a variety of hydrogel sensors with high mechanical properties, strong adhesion, fast self-healing, and excellent conductivity are emerging. However, it is still a great challenge to manufacture hydrogel sensors combining multiple properties. Herein, we leveraged the dynamic redox reaction occurring between polydopamine (PDA) and Fe3+ to induce ammonium persulfate (APS) to generate free radicals, thereby initiating the copolymerization of hydroxyethyl methacrylate (HEMA) and acrylic acid (AA) monomers. Then, polypyrrole-encapsulated cellulose nanofibers (PPy@CNF) and carboxymethylcellulose (CMC) were incorporated as conductive reinforced nanofillers and interpenetrating network skeleton. The obtained hydrogel cross-linked through reversible metal-ligand bonds, π-π stacking and abundant hydrogen bonding demonstrated great mechanical properties (strength 240.4 kPa, strain 1175 %) and self-healing ability (88.96 %). Particularly, the gel displayed ultrahigh durability and skin adhesive ability (75 kPa after 10 cycles), surpassing previous skin adhesion hydrogels. Furthermore, through the synergistic conductive effect of PPy@CNF and Fe3+, the prepared hydrogel sensor possessed high sensitivity (GF = 1.89) with a wide sensing range (~1000 %), which could realize the human body's daily motion detection, and had a promising application in flexible wearable electronics.

Artificial intelligence tools for molecular analysis of sensitization profiles in patients with atopic dermatitis and bronchial asthma

Background. The variety of characteristics that should be taken into account in the clinical phenotyping of allergic diseases is currently being discussed. One of such characteristics is the individual spectrum of sensitization. An important stage in modern allergology has become the introduction of molecules / components for the detection of mediated reactions to specific class E immunoglobulins.Aim. To determine the dominant phenotypes of sensitization in patients with severe atopic dermatitis and bronchial asthma based on the results of molecular diagnostics by the ImmunoCAP Immuno Solid-phase Allergen Chip (ISAC) method using machine learning.Materials and methods. The study included 100 patients who were candidates for genetically engineered biological therapy (n = 63), severe atopic dermatitis (n = 20), or their combination (n = 17) were included. Allergodiagnosis was performed by the ImmunoCAP ISAC method.Results. Based on the results of the study, 6 phenotypes were identified. In phenotype 1, pollen molecules (Amb a1, Phl p4) and crossed reactive food molecules (Mal d1, Ara h8, Gly m4, Act d8, Pru p3) are the leading, among epidermal molecules only Fel d1 (epidermal allergen) and Asp f6 (fungal allergen) are found. For phenotype 2, the significant allergens were fungal (Asp f6), epidermal (Can f1, Can f5, Can f6, Fel d1), food (Gad c1) and cross reactive food molecules (Mal d1, Pru p1. Ara h8, Cor a1.0401). In phenotype 4, only 3 allergen groups are present:epidermal (Fel d1, Fel d2, Can f5, Can f6, Can f3), fungal (Asp f6), and cross food allergy (Jug r3, Pru p3). Phenotype 5 and 6 are dominated by epidermal molecules (Can f1 and Fel d1), true food allergies allergens (Gad c1 and Gal d1 and Gad c1, Gal d1, Gal d3, respectively). In phenotype 3, a combination of the previously labeled molecules is noted.Conclusion. Each of the identified phenotypes reveals a different set of molecules that can be used in real clinical practice to develop reduced panels, making them more accessible.

Cell Mediated Reactions Create TGF-β Delivery Limitations in Engineered Cartilage

During native cartilage development, endogenous TGF-β activity is tightly regulated by cell-mediated chemical reactions in the extracellular milieu (e.g., matrix and receptor binding), providing spatiotemporal control in a manner that is localized and short acting. These regulatory paradigms appear to be at odds with TGF-β delivery needs in tissue engineering (TE) where administered TGF-β is required to transport long distances or reside in tissues for extended durations. In this study, we perform a novel examination of the influence of cell-mediated reactions on the spatiotemporal distribution of administered TGF-β in cartilage TE applications. Reaction rates of TGF-β binding to cell-deposited ECM and TGF-β internalization by cell receptors are experimentally characterized in bovine chondrocyte-seeded tissue constructs. TGF-β binding to the construct ECM exhibits non-linear Brunauer–Emmett–Teller (BET) adsorption behavior, indicating that as many as seven TGF-β molecules can aggregate at a binding site. Cell-mediated TGF-β internalization rates exhibit a biphasic trend, following a Michaelis-Menten relation (Vmax=2.4 molecules cell-1 s-1, Km=1.7 ng mL-1) at low ligand doses (≤130ng/mL), but exhibit an unanticipated non-saturating power trend at higher doses (≥130ng/mL). Computational models are developed to illustrate the influence of these reactions on TGF-β spatiotemporal delivery profiles for conventional TGF-β administration platforms. For TGF-β delivery via supplementation in culture medium, these reactions give rise to pronounced steady state TGF-β spatial gradients; TGF-β concentration decays by ∼90% at a depth of only 500 μm from the media-exposed surface. For TGF-β delivery via heparin-conjugated affinity scaffolds, cell mediated internalization reactions significantly reduce the TGF-β scaffold retention time (160 to 360-fold reduction) relative to acellular heparin scaffolds. This work establishes the significant limitations that cell-mediated chemical reactions engender for TGF-β delivery and highlights the need for novel delivery platforms that account for these reactions to achieve optimal TGF-β exposure profiles. Statement of SignificanceDuring native cartilage development, endogenous TGF-β activity is tightly regulated by cell-mediated chemical reactions in the extracellular milieu (e.g., matrix and receptor binding), providing spatiotemporal control in a manner that is localized and short acting. However, the effect of these reactions on the delivery of exogenous TGF-β to engineered cartilage tissues remains not well understood. In this study, we demonstrate that cell-mediated reactions significantly restrict the delivery of TGF-β to cells in engineered cartilage tissue constructs. For delivery via media supplementation, reactions significantly limit TGF-β penetration into constructs. For delivery via scaffold loading, reactions significantly limit TGF-β residence time in constructs. Overall, these results illustrate the impact of cell-mediated chemical reaction on TGF-β delivery profiles and support the importance of accounting for these reactions when designing TGF-β delivery platforms for promoting cartilage regeneration.

L-histidine makes Ni2+ ‘visible’ for plant signalling systems: Shading the light on Ni2+-induced Ca2+ and redox signalling in plants.

Nickel is both an important nutrient and an ecotoxicant for plants. Organic ligands, such as L-histidine (His), play a key role in Ni2+ detoxification. Here, we show that His (added together with 0.01-10 mM Ni2+) decreases Ni2+ toxicity to Arabidopsis thaliana roots not only as a result of a decrease in Ni2+ activity, but also via the induction of signalling phenomena important for adaptation such as the generation of reactive oxygen species (ROS) and cytosolic Ca2+ transients. With the use of EPR spectroscopy, we demonstrate that Ni-His complexes generate hydroxyl radicals that is not detected by the addition of Ni2+ or His separately. Similarly, Ni-His complexes, but not Ni2+, activate Ca2+ influx and K+ efflux currents in patch-clamped root protoplasts resulting in distinct cytosolic Ca2+ signals and a transient K+ release. His prevented programmed cell death symptoms (cytoplasm shrinkage, protease and endonuclease activation) induced by Ni2+ and inhibited Ni2+ accumulation at [Ni2+]>0.3 mM. Intriguingly, priming of roots with Ni-His stimulated plant resistance to Ni2+. Overall, these data show that His triggers ROS-Ca2+-mediated reactions making Ni2+ ‘visible’ for plant signalling machinery and facilitating adaptation to the excess Ni2+.

Coenzymes in a pre-enzymatic metabolism.

Experiments now support theoretical suggestions that coenzymes mediated key metabolic reactions before the emergence of enzymes. Three coenzymes believed essential to the core metabolism of the last universal common ancestor to extant life (pyridoxal phosphate, adenosine diphosphate, and nicotinamide adenine dinucleotide) were recently found to be active in their corresponding metabolic reactions in the absence of enzymes. These findings suggest an earlier contribution of coenzymes to abiogenesis, ultimately yielding insights into the prebiotic origins of metabolism.

An intelligent fluorescence sensing platform based on entropy-driven toehold-mediated strand displacement cycle reaction for point-of-care testing of miRNA

BackgroundMicroRNA (miRNA) has gradually become an emerging biomarker for early diagnosis and prognosis of various diseases due to its specific gene expression and high stability. With the development of molecular diagnosis and point-of-care testing (POCT) technology, developing simple, fast, sensitive, efficient, and low-cost miRNA sensors is of great significance for clinical applications and emergency rapid diagnosis. At present, entropy-driven toehold mediated chain displacement reaction, as a promising enzyme free isothermal amplification technique, is an important tool for ultra-sensitive biosensing applications. ResultsIn this study, we used gold nanoparticles (AuNPs) as carriers and quenchers, modified them using self-assembled triple chain composite substrates AuNPs@A@B1/B2, and used dual reporter molecules for cascade cyclic amplification to amplify fluorescence signals, which proposed a fluorescent biosensor based on this reaction and build an intelligent fluorescence sensing platform for rapid detection of miRNA. We designed a highly specific self-programmable sensor using the acute ischemic stroke (AIS) biomarker miRNA-125a-5p as a sample, and achieved sensitive detection of miRNA in the range of 0.01 μM∼10 μ M under optimal conditions. It broke through the traditional detection limitations of weak signals and liberated the fluorescence detection environment. SignificanceIn summary, this creative miRNA biosensor combined with POCT has demonstrated extraordinary detection potential, broad application prospects in the early diagnosis and prognosis monitoring of AIS, provides a novel miRNA universal detection strategy for the fields of biological and life sciences.

Robust oxygen adsorbent mediated oxygen redox reactions for high performance lithium-oxygen battery

Lithium-oxygen batteries (LOBs) have been widely studied because of their ultra-high energy density (∼3500 Wh kg−1). However, the reversibility and stability of LOBs are greatly limited by the sluggish kinetics of oxygen reduction/evolution reactions (ORR/OER) and severely parasitic reactions on oxygen electrodes. Electrolyte in LOBs plays an important role in the transport of reactive oxygen species and Li+, which greatly affects the kinetics and reversibility of the charging and discharging processes of batteries. In this work, perfluorooctane (PFO) is used as the additive in 1.0 M LiTFSI/TEGDEM electrolyte for LOBs to regulate the kinetics of oxygen electrode reactions. Due to the strong adsorption ability of PE toward oxygen, the oxygen concentration inside the electrolyte is greatly increased after the addition of PE. In addition, the PE-added electrolyte also exhibits superior electrochemical stability and is capable of triggering solution-mediated Li2O2 growth pathway during the discharge process of the LOBs. Therefore, with the increased oxygen concentration and the optimized electrode/electrolyte interface, the ORR/OER kinetics on the oxygen electrode is significantly promoted, which enables the LOBs with excellent energy efficiency and cycling life. This work provides a new idea for the design of oxygen-rich and high-performance electrolyte for lithium-oxygen batteries.

(Invited) Changes in Electric Double-Layer Structures Under Localized Surface Plasmon Excitation

For the visible light energy conversion, the localized surface plasmon resonance (LSPR), which is the collective oscillations of free electrons, should be promising. With the excitation of LSPR, the highly localized electric field generates in the vicinity of metal nanostructures. It is interesting that various unique photo-response properties, such as chemical reactions or molecular excitations, can be observed due to the enhancement of light-matter interaction.[1] To understand and control such mediated chemical reactions or electrochemical reactions, the precise understanding about the electrified interfaces of plasmonic nanostructures should be required.Especially in the electrochemical system, the electric double layer is formed due to the difference in electrochemical potential between the metal interface and solution. The study of the surface potential is important for the design of chemical reactions because the surface potential at the liquid-solid interface is dependent on the physical properties of the systems. The zeta potential which is the potential of the slipping surface near the Stern layer of the diffusion layer could provide such information. From this point of view, in this study, we investigated the electric double-layer structures through the examination of the zeta potential under LSPR excitation condition. To obtain the zeta potential, we have performed the streaming potential method using Au nanoisland structures under visible light illuminations to excite the LSPR. It was interesting that the zeta potential was drastically changes under the visible light illumination conditions. This zeta potential change indicates the changes in the electric double layer structures through the excitation of LSPR. Through the investigations of incident wavelength dependence or the substrate dependences, the effects for the LSPR excitations on the electric double layer structure have been revealed. The present work would provide the fundamental knowledge about the effect on the LSPR excitation at solid-liquid interfaces.[1] H. Minamimoto et al., Acc. Chem. Res., 2022, 55(6), 809.

Development of a NIR Iridium(III) Complex-Based Probe for the Selective Detection of Iron(II) Ions.

As a commonly used metal ion, iron(II) (Fe2+) ions pose a potential threat to ecosystems and human health. Therefore, it is particularly important to develop analytical techniques for the rapid and accurate detection of Fe2+ ions. However, the development of near-infrared (NIR) luminescence probes with good photostability for Fe2+ ions remain challenging. In this work, we report a novel iridium(III) complex-based luminescence probe for the sensitive and rapid detection of Fe2+ ions in a solution based on an Fe2+-mediated reduction reaction. This probe is capable of sensitively detecting Fe2+ ions with a limit of detection (LOD) of 0.26 μM. Furthermore, this probe shows high photostability, and its luminescence remains stable under 365 nm irradiation over a time period of 30 min. To our knowledge, this is first iridium(III) complex-based NIR probe for the detection of Fe2+ ions. We believe that this work provides a new method for the detection of Fe2+ ions and has great potential for future applications in water quality testing and human monitoring.

Triton X-100 Mediated Electron Transfer Reactions between Iron(III) Polypyridyl Complexes and Phenylsulfinylacetic Acids

Triton X-100 Mediated Electron Transfer Reactions between Iron(III) Polypyridyl Complexes and Phenylsulfinylacetic Acids

Camouflaging nanoreactor traverse the blood-brain barrier to catalyze redox cascade for synergistic therapy of glioblastoma

The blood-brain barrier (BBB) is a complex and highly restrictive barrier that prevents most biomolecules and drugs from entering the brain. However, effective strategies for delivering drugs to the brain are urgently needed for the treatment of glioblastoma. Based on the efficient BBB penetration properties of exosomes derived from brain metastatic breast cancer cells (EB), this work prepared a nanoreactor (denoted as MAG@EB), which was constructed by self-assembly of Mn2+, arsenate and glucose oxidase (GOx) into nanoparticles wrapped with EB. MAG@EB can enhance the efficiency of traversing the BBB, target and accumulate at in situ glioblastoma sites. The GOx-driven glycolysis effectively cuts off the glucose supply while also providing an abundance of H2O2 and lowering pH. Meanwhile, the released Mn2+ mediated Fenton-like reaction converts elevated H2O2 into highly toxic ·OH. Besides, AsV was reduced to AsIII by glutathione, and the tumor suppressor gene P53 was activated by AsIII to kill glioblastoma cells. Glioblastoma succumbed to the redox cascade triggered by MAG@EB, as the results demonstrated in vivo and in vitro, yielding a remarkable therapeutic effect. This work provides a promising therapeutic option mediated by cascaded nanoreactors for the future treatment of glioblastoma.

Symmetric Anion Mediated Dynamic Kinetic Asymmetric Knoevenagel Reaction for N-C and N-N Atropisomers Synthesis.

A symmetric anion mediated dynamic kinetic asymmetric Knoevenagel reaction was established as a general and efficient method for accessing both N-C and N-N atropisomers. The resulting highly enantio-pure pyridine-2,6(1H,3H)-diones exhibit diverse structures and functional groups. The key to excellent regio- and remote enantiocontrol could be owed to the hydrogen bond between the enolate anion and triflamide block of the organocatalyst. This connected the enolate anion and iminium cation by a chiral backbone. The mechanism investigation via control experiments, correlation analysis, and density functional theory calculations further revealed how the stereochemical information was transferred from the catalyst into the axially chiral pyridine-2,6(1H,3H)-diones. The synthetic applications also demonstrated the reaction's potential.

Symmetric Anion Mediated Dynamic Kinetic Asymmetric Knoevenagel Reaction for N−C and N−N Atropisomers Synthesis

A symmetric anion mediated dynamic kinetic asymmetric Knoevenagel reaction was established as a general and efficient method for accessing both N−C and N−N atropisomers. The resulting highly enantio‐pure pyridine‐2,6(1H,3H)‐diones exhibit diverse structures and functional groups. The key to excellent regio‐ and remote enantiocontrol could be owed to the hydrogen bond between the enolate anion and triflamide block of the organocatalyst. This connected the enolate anion and iminium cation by a chiral backbone. The mechanism investigation via control experiments, correlation analysis, and density functional theory calculations further revealed how the stereochemical information was transferred from the catalyst into the axially chiral pyridine‐2,6(1H,3H)‐diones. The synthetic applications also demonstrated the reaction's potential.

Flavodiiron proteins prevent the Mehler reaction in Chlamydomonas reinhardtii

Regulation of photosynthetic electron transfer is fundamental for energetic efficiency and coping with changing environmental factors. All plant groups, except angiosperms, use flavodiiron proteins (FDPs) on the acceptor side of photosystem I (PSI), putatively protecting from PSI photoinhibition under fluctuating light. An alternative electron flow during photosynthesis is the direct reduction of O2 with consequential production of reactive oxygen species (ROS; the Mehler reaction), but to what extent FDPs prevent this is unknown. Here, we quantified O2-dependent electron flow, photosystem activity and the Mehler reaction in Chlamydomonas reinhardtii. Near-infra red absorbance measurement of PSI reaction centre (P700) showed that FDPs remain active long after a dark-to-light transition and their activity increased under hyperoxia. Light-induced hydrogen peroxide (H2O2) production, as a marker of the Mehler reaction, was influenced by O2 concentration, and was up to 67 % higher in an FDP-deficient mutant (flvb) than in the wild-type under saturating constant light. In cultures kept under sub-saturating constant light, flvb produced 315 % more H2O2 and had lower PSII efficiency than wild-type. Inhibiting electron transfer out of photosystem II (PSII) with 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU) only partially blocked H2O2 production, particularly under hyperoxia, indicating that PSII was an additional ROS source. P700+ reduction in the dark in the presence of DCMU was faster in flvb than wild-type, revealing enhanced cyclic electron flow, which may also have led to PSI mediated Mehler reaction. We conclude that FDPs remain active in constant light and can prevent PSI mediated Mehler reaction, with relevance to PSII photoinhibition.

Toxic Epidermal Necrolysis by Lamotrigine - A Case Report of Fatality

Toxic epidermal necrolysis (TEN) is an immune mediated fatal adverse muco-cutaneous drug reaction characterized by extensive exfoliation of the epidermis and mucous membrane. It may result in sepsis and death. In most cases, TEN is caused by certain drugs & vaccines. TEN involves more than 30% of body surface area. Steven Johnson Syndrome also shows the same disease process and same spectrum of drug-induced epidermolysis. A 37-year-old patient who was on Lamotrigine, Escitalopram & Clonazepam for multiple somatoform disorder developed generalized vesicular rash with fever after 2 weeks of initiation of lamotrigine. The patient was admitted to the hospital and Lamotrigine was taken off. Patient was given conservative management. Adverse drug reaction was reported to Adverse drug reaction monitoring centre (AMC) and severity was assessed by WHO-UMC Scale. Patient died after 5 days of admission. Score of Toxic epidermal necrolysis (SCORTEN Scale) is used to assess severity of the illness and to predict mortality rate. Early Diagnosis, withdrawal of offending agent, timely proper supportive management can help in lowering the mortality. Keywords: Toxic epidermal necrolysis, Lamotrigine, Adverse drug reaction, Multiple somatoform disorder, Steven Johnson Syndrome, Score of Toxic epidermal necrolysis

Recent advances in polyethylene glycol as a dual‐functional agent in heterocycle synthesis: Solvent and catalyst

AbstractReactant solubility, which dictates achievable concentrations, and the stability of reaction intermediates (excited states), solvents modulate the potential energy landscape and influence reaction rates. Consequently, solvent selection is pivotal in optimizing process productivity, economic feasibility, and environmental footprint. At present, organic synthesis pivots around the idea of sustainability. In particular, PEG‐400, a popular solvent and phase transfer catalyst, is considered greener as it can be reused several times without significant loss in its catalytic activity, which checks the box regarding sustainability. This review highlights the emerging potential of Polyethylene Glycol 400 (PEG‐400) as a dual‐threat agent in sustainable organic synthesis. We explore its efficacy as a catalyst, promoting various reactions under mild conditions and often eliminating the need for traditional metal catalysts. Additionally, PEG‐400's role as a green solvent is addressed, emphasizing its biodegradability, low toxicity, and ability to facilitate reactions without hazardous Volatile Organic Compounds (VOCs). The review examines recent research on PEG‐400 mediated reactions, showcasing its effectiveness in diverse transformations, thus exploring the potential of PEG 400 as a facilitator for heterocycle synthesis in both multicomponent reactions and stepwise approaches. It identifies exciting research directions that promise to expand the boundaries of polymer‐based solvents in heterocyclic chemistry.

The Programmable Catalytic Core of 8-17 DNAzymes.

8-17 DNAzymes (8-17, 17E, Mg5, and 17EV1) are in vitro-selected catalytic DNA molecules that are capable of cleaving complementary RNAs. The conserved residues in their similar catalytic cores, together with the metal ions, were suggested to contribute to the catalytic reaction. Based on the contribution of the less conserved residues in the bulge loop residues (W12, A15, A15.0) and the internal stem, new catalytic cores of 8-17 DNAzymes were programmed. The internal stem CTC-GAG seems to be more favorable for the DNAzymes than CCG-GGC, while an extra W12.0 led to a significant loss of activity of DNAzymes, which is contrary to the positive effect of A15.0, by which a new active DNAzyme 17EM was derived. It conducts a faster reaction than 17E. It is most active in the presence of Pb2+, with the metal ion preference of Pb2+ >> Zn2+ > Mn2+ > Ca2+ ≈ Mg2+. In the Pb2+ and Zn2+-mediated reactions of 17EM and 17E, the same Na+- and pH dependence were also observed as what was observed for 17E and other 8-17 DNAzymes. Therefore, 17EM is another member of the 8-17 DNAzymes, and it could be applied as a potential biosensor for RNA and metal ions.

Real-time monitoring abscisic acid release from single rice protoplast by amperometry at microelectrodes modified with abscisic acid receptor PYL2

It was previously reported that stress induces a cellular production of abscisic acid in plants, but no direct method shows the evidence. Here, an electrochemical microsensor involving an abscisic acid receptor PYL2 modified carbon fiber microelectrode was fabricated by self-assembly method, where the Cu2+ combined with the histidine tag of PYL2 on the surface of microelectrode was used as the detection probe, the mediated reaction between Cu+ and ferricyanide realized the amplification responses and provided the microsensor with a high sensitivity for detection of abscisic acid with a detection limit of 0.8 nM. With use of this microsensor, an increase of extracellular abscisic acid from single rice protoplast induced by sulfate, osmotic and salinity stress was real-time monitored. Direct measurement of free extracellular abscisic acid in single plant cells might offer important new insights into its role in plants challenged by abiotic stresses.

Investigation of the Electrocatalytic Reduction of Peroxydisulfate Using Scanning Electrochemical Microscopy.

The elementary steps of the electrocatalytic reduction of S2O82- using the Ru(NH3)63+/2+ redox couple were investigated using scanning electrochemical microscopy (SECM) and steady-state voltammetry (SSV). SECM investigations were carried out in a 0.1 M KCl solution using a 3.5 μm radius carbon ultramicroelectrode (UME) as the SECM tip and a 25 μm radius platinum UME as the substrate electrode. Approach curves were recorded in the positive feedback mode of SECM by reducing Ru(NH3)63+ at the tip electrode and oxidizing Ru(NH3)62+ at the substrate electrode, as a function of the tip-substrate separation and S2O82- concentration. The one-electron reaction between electrogenerated Ru(NH3)62+ and S2O82- yields the unstable S2O83•-, which rapidly dissociates to produce highly oxidizing SO4•-. Because SO4•- is such a strongly oxidizing species, it can be further reduced at both the tip and the substrate, or it can react with Ru(NH3)62+ to regenerate Ru(NH3)63+. SECM approach curves display a complex dependence on the tip-substrate distance, d, due to redox mediation reactions at both the tip and the substrate. Finite element method (FEM) simulations of both SECM approach curves and SSV confirm a previously proposed mechanism for the mediated reduction of S2O82- using the Ru(NH3)63+/2+ redox couple. Our results provide a lower limit for dissociation rate constant of S2O83•- (∼1 × 106 s-1), as well as the rate constants for electron transfer between SO4•- and Ru(NH3)62+ (∼1 × 109 M-1 s-1) and between S2O82- and Ru(NH3)62+ (∼7 × 105 M-1 s-1).