S)‐BINOL  with two equivalents of the amidinate‐stabilized chlorosilylene [LPhSiCl] (LPh=PhC(NtBu)2) led to the formation of the first example of a chiral cyclic silene species comprising an (S)‐BINOL ligand. The reactivity of the Si=C bond was investigated by reaction with elemental sulfur, CO2 and HCl. The reaction with S8 led to a Si=C bond cleavage and concomitantly to a ring‐opened product with imine and silanethione functional groups. The reaction with CO2 resulted in the cleavage of the CO2 molecule into a carbonyl group and an isolated O atom, while a new stereocenter is formed in a highly selective manner. According to DFT calculations, the [2+2] cycloaddition product is the key intermediate. Further reactivity studies of the chiral cyclic silene with HCl resulted in a stereoselective addition to the Si=C bond, while the fully selective formation of two stereocenters was achieved. The quantitative stereoselective addition of CO2 and HCl to a Si=C bond is unprecedented.The reaction of the dilithium salt of the enantiopure ‐BINOL scaffold in the silene enabled unprecedented complete control over the diastereoselectivity in the reactions with different small molecules, S8, CO2 and HCl. Considering environmental and economic aspects, the quest for bond activation by earth abundant main group species is an avenue worth pursuing. Development of novel main group element systems for the potential use of small molecule activation is the aim of many synthetic chemists.Many basic chemical processes such as catalysis rely on the bond cleavage of ubiquitous small molecules as the initial step for further transformations. For several decades, the activation of small molecules has been dominated by transition‐metal systems. Over the last two decades, the chemistry of low‐valent main group species has become more mature and as main group compounds that mimic the behavior of transition‐metal complexes have developed significantly, remarkable progress has been made in the field of activating small molecules.3Si)2Si=C(OSiMe3)Ad] (Ad=1‐adamantyl).S)‐BINOL  was chosen as a chiral precursor as it is commercially available, cheap, and easy to doubly deprotonate with n‐BuLi.Heavier group 14 alkene analogues have unique properties and reactivities distinguishing them from their parent organic species. The synthesis and characterization of compounds comprising silicon‐carbon double bonds was first realized in 1981 when Brook isolated the first stable silene [(MetBu)2(Ph)C=Si(LPh)] (1) (LPh=PhC(NtBu)2) comprising a chiral (S)‐BINOL backbone. Compound 1 features an excellent combination of high thermal stability and high reactivity towards S8, CO2 and HCl. Due to the presence of the chiral (S)‐BINOL moiety, the reactions with the corresponding molecules occurred in highly stereoselective pathways and thus, exclusively produced a single activation product.Herein, we report the synthesis of the cyclic silene Ph=PhC(NtBu)2) led to the formation of a dark brown solution (Scheme tBu)2(Ph)C=Si(LPh)] (1) could be obtained in 69 % yield as orange crystalline solid. The molecular structure of 1 was established by multinuclear  NMR spectroscopy and single crystal X‐ray diffraction analysis. Compound 1 crystallized in the non‐centrosymmetric space group P21 with a low Flack parameter,# which indicated the expected retention of the chiral axis.Deprotonation of (n Scheme . After e1 is formed via a bis(silylene) intermediate 1’ and subsequent insertion of one silylene unit into the C−NtBu bond of the other silylene. Two crystallographically independent molecules were found in the asymmetric unit with similar metric parameters, therefore, the following discussion is restricted to only one of them. The central motif of 1 is composed of a slightly puckered five‐membered Si2N2C heterocycle ‐BINOL ligand. In turn, Si1 is coordinated by the amidinato moiety, one amide nitrogen (N2) and the carbon atom C1 with a Si−C distance of 1.759(3) Å. The Si1−C1 bond distance in 1 is much shorter than typical Si−C single bonds (1.86‐1.93 Å),3Si)2Si=C(OSiMe3)Ad] (1.764(3) Å),∑C1=356.8°), indicating a sp2‐hybridized carbon atom. In addition, the Si=C double bond length in compound 1 is only marginally longer to that of another P‐containing heterocyclic silene (1.7536(3) Å),1 in which the Si=C double bond is incorporated in a five‐membered ring, is the first structurally characterized chiral cyclic silene.The molecular structure confirmed the formation of a cyclic silene Figure , a. Even1H NMR spectrum of 1 shows four singlets at δ 1.11, 1.20, 1.36 and 1.52 ppm for the four non‐equivalent tBu substituents. The 29Si{1H} NMR spectrum displays two singlets at δ −27.5 (Si=C) and −61.3 ppm (OSiO). The silene silicon signal is comparable to that of the disilapentalene (δ −18.9 ppm)δ −18.7 ppm),2 silicon signals found in most of the 1,1‐disilyl‐substituted silenes (Me3Si)2Si=CR2 (δ 41–54 ppm).13C resonance of the unsaturated carbon nucleus appeared at δ 58.2 ppm, considerably upfield‐shifted compared to Brook's silene (δ 214.2 ppm).The 6D6 solution of 1 was heated at 80 °C for one week, no decomposition occurred. Although the silene 1 is very stable in the solid state as well as in solution under inert atmosphere, it was found to be highly reactive. Due to the polarization of the Siδ+=Cδ− bond, silenes are highly unstable species and have ambiphilic reactivity. Previous work has shown that typical reactions are cycloadditions with π‐bonded species or insertion reactions with polarized compounds., very complex mixtures were obtained. Only in one instance when a silyl group on the silicon atom was exchanged by a mesityl group, the simple addition product, a three‐membered silathiirane (SiCS‐ring), could be isolated.1 with S8, the NMR‐scale reaction between the two compounds (1 : 0.14 molar ratio) was carried out in C6D6 . And indeed, an unexpected and rather complicated reaction occurred.In an early report in 1994, Brook described that when they attempted to add sulfur across the double bonds of silenes of the type [StBu] (1.984(8) Å),PhSi(=S)Si(SiMe3)3] (1.9996(6) Å)PhSi(=S)N(SiMe3)3] (1.984(8) Å),1 with sulfur provided a novel route for the preparation of a chiral compound, which comprises two newly generated functional groups (imine and silanethione).Of the mixture, compound 2 clearly suggests the co‐existence of two closely related isomers in solution. In C6D6, the two sets of tBu protons  are found in 4 : 3 molar ratio. This is in accordance with its 29Si{1H} NMR spectrum in which four signals were detected due to the presence of two species . Changing the solvent from the aromatic C6D6 to the non‐aromatic but more polar CDCl3, the molar ratio of the two isomers varied from 4 : 3 to 9 : 4. The corresponding 29Si signals are only marginally shifted compared with those in C6D6. The signal for the major isomer was obtained at δ −13.1 and −56.6 ppm and those for the minor isomer at δ −20.0 and −64.8 ppm. The assignment of the conformation obtained by XRD being the major species in solution was corroborated by DFT calculations (Gaussian16/PBE0/def2‐SVP), as the calculated NMR parameters of 2 obtained by XRD are in good agreement with the experimental values of the major isomer (see Supporting Information). For the minor signals, we considered several isomers until assigning 2’ as a rotamer of 2, where the imine moiety is rotated around the Si−C bond by 180°. It is reasonable to assume the rotation around this bond to be hindered, as all involved tBu and Ph substituents are in close proximity. The characteristic upfield‐shifted 1H NMR resonances for two of the aromatic protons are accurately reproduced by the computation and result from the orientation of the imine‐phenyl group, which causes one ortho and one meta H to point into the aromatically shielded region of the BINOL moiety. High temperature 1H NMR studies indicate free rotation of the imine‐phenyl group but no interconversion of the two isomers .The NMR data of the isolated single crystals of 2 was monitored by 29Si NMR spectroscopy and the results were interpreted by using DFT methods. Details are outlined in the Supporting Information and only briefly summarized here. Complete consumption of the starting materials occurred after 10 min reaction. Four new singlet signals  appeared in the 29Si{1H} NMR spectrum, indicative of the formation of two new compounds. We suggested that sulfur was added in the first step to the Si=C bond forming two silaazirane isomers. These signals slowly disappear and a new transient intermediate, which is the result of the silaazirane ring opening, was seen. Thermally driving the reaction to completion resulted finally in 2 and 2’ as stable products.The reaction leading to 2 has been a great scientific challenge over the years. Synthetic chemists have developed different strategies to utilize this greenhouse gas as useful C1 building blocks. Compared to transition‐metal‐based systems, the reaction and conversion of CO2 with main group species are underexplored. Prominent examples in main group chemistry are FLPs, which combine nucleophilic and electrophilic centers and thus can form the corresponding CO2 insertion products. cycloaddition of the phosphine‐oxide‐stabilized silene with CO2.2 insertion and fixation by a disilapentalene.2. Stirring a toluene solution of silene 1 under CO2 atmosphere at room temperature led to the decoloration of the solution , which hinted the quantitative and selective formation of only a sole reaction product 3 and there was spectroscopic evidence for neither an intermediate nor for the formation of a second diasteromer. Thus, 3 is the result of a stereoselective activation of CO2 with quantitative ee.The efficient capture and utilization of COproducts.3c, 183 was structurally characterized by X‐ray diffraction analysis. It crystallizes in the non‐centrosymmetric monoclinic space group P21 with a flack parameter showing the formation of just one enantiomer.# The molecular structure depicted in Figure 3 consists of two fused rings (CNSi2O and C2NSi), which are twisted by 46.1°. During the reaction, one of the C=O bonds of CO2 was completely cleaved and the isolated oxygen atom O3 is now bridging the two silicon atoms Si1 and Si2. The remaining carbonyl (C=O) moiety is coordinated to C1 and N2, giving rise to a new amide functional group. The carbonyl C=O distance (1.213(3) Å) is well comparable with the usual carbonyl C=O bond distances in organic amides (1.22–1.23 Å).R)‐configuration).# We were able to show by NMR spectroscopy and XRD, that indeed only one of the two possible diastereomers  or ) was formed. In the 13C{1H} NMR spectrum, the signal for the carbonyl carbon atom was observed at δ 179.4 ppm and the one for the chiral quaternary carbon nucleus at δ 78.2 ppm, the assignment of signals were based on 13C‐DEPT, 1H‐13C‐HMBC NMR experiments and DFT calculations. The 29Si{1H} NMR spectrum displays two sharp singlets at δ −59.9 and −97.7 ppm, assignable to the resonances for the SiC and SiO2 silicon nuclei, respectively. In the IR spectrum, the C=O stretching band appears at 1645 cm−1. The formation of 3 provided an elegant pathway to access an enantiopure heterocycle featuring a carbonylated quaternary stereocenter through reductive cleavage of CO2.The reaction product 3 and C=O double bond cleavage, DFT calculations were performed to shed light on the reaction mechanism. On a model compound with small substituents , the whole sequence was calculated including activation barriers, while with the full molecule 1, the transition states eluded localization and hence, only the intermediates are considered . Then, the rotation of the CO2 moiety towards amidinate‐Si completes the [2+2] cycloaddition (#I2/I2). This bicylic species undergoes a cycloreversion reaction into a ketene and a silanone moiety (#I3/I3). The silanone‐O then attacks the BINOL−Si to give a Si2NO heterocycle (#I4/I4). This cycle opens up to the silaimine (#I5/I5), that then undergoes [2+2] cycloaddition with the ketene moiety again to give the final product #3/3. As no intermediates were observed spectroscopically, the reaction pathway solely rests on the plausibility of intermediates and activation barriers. With the model compound, the initial [2+2] addition product #I2 is very stable and its cycloreversion reaction has a very high activation barrier, which would render this reaction impossible. However, when considering the whole molecule, I2 is less stable due to steric strain resulting from the interaction of the NtBu group with adjacent substituents. This steric strain can be relieved by the rearrangement reaction, that leaves the NtBu group as an exocyclic moiety.Given the unusual structure of compound 1 with the polar HCl molecule. The addition of equimolar amount of HCl to silene 1 in toluene resulted in the completely regio‐ and stereoselective formation of the simple 1,2‐addition product 4 , indicating only one diastereomer was formed. Thus, again the reaction proceeds with quantitative stereoselectivity. However, in this case even two new stereocenters were formed.After adding a non‐polar molecule, we intended to further explore the reactivity of silene 1H, 13C, 29Si) and 2D NMR (1H‐13C‐HMQC/HMBC) spectroscopic methods as primary diagnostic tools. The 1H NMR signal at δ 4.50 ppm showed HMQC correlations to the 13C atom at 54.6 ppm. The latter signal could be assigned to the newly generated stereogenic carbon nucleus. In the 29Si{1H} NMR spectrum, two signals were detected at δ −21.8 and −49.7 ppm, slightly upfield shifted with respect to those of silene 1. Using NMR spectroscopic methods, the regioselectivity of the reaction could be confirmed, but computations indicate that upon reaction with HCl, the amidinate acts only as monodentate substituent. For this species, excellent agreement of all NMR data with the predictions was found .4 suitable for X‐ray diffraction analysis could be obtained. However, we found that the reaction between 1 and two equivalents of HCl in toluene resulted in the clean formation of the amidinium chloride salt 5 as colorless precipitate  and features the two newly generated proton signals at δ 13.26 (NH) and 6.10 (CH) ppm. The molecular structure of the diastereoisomer was confirmed by X‐ray analysis on the single crystals of 5. As shown in Figure S) and Si1 (R), while the amidinato functional group was protonated by the second equivalent of HCl molecule, forming the cationic amidinium moiety. The correct assignment of the absolute configurations around the stereogenic centers were supported by a low flack parameter and a non‐centrosymmetric space group (P21).# With 4 and 5 in hand, we expected that 5 could be formed directly from 4. Indeed, treatment of 4 with 1 molar equiv. of HCl in toluene at ambient temperature furnished 5. This gave us more detailed information of the molecular structure of the diastereoisomer 4.The structure of the adduct was established by using a combination of 1D (1 comprising an (S)‐BINOL ligand scaffold under mild reaction conditions was provided. The unique bonding feature and ring structure in 1 was used to demonstrate further reactivity with elemental sulfur, CO2 and HCl. The reaction with S8 led to the ring‐opening product 2 with imine and silanethione functional groups. Moreover, 1 is capable of cleaving the CO2 molecule into a carbonyl group and an isolated O atom, thus a new stereocenter was formed in a highly selective manner. The stepwise reaction with HCl molecule to the saturated silane 4 and the cationic compound 5 further shows the high reactivity of the double bond in 1. In this case even two new stereocenters are formed fully selectively. The chiral (S)‐BINOL scaffold in the silene 1 enabled unprecedented complete control over the diastereoselectivity in the reactions with the respective small molecules.In summary, a facile method of generating the first example of a chiral cyclic silene species 2164389, 2164390, 2164391, 2164392 contain the supplementary crystallographic data for this paper. These data are provided free of charge by the joint Cambridge Crystallographic Data Centre and Fachinformationszentrum Karlsruhe Access Structures service.Deposition Numbers S)‐BINOL should be present.# Single crystal X‐ray diffraction is not a method of bulk analysis. In principle, both enantiomers could be formed. However, presuming the configurational stability of the BINOL backbone, only  should be addressed to the authors.Supporting InformationClick here for additional data file.


H2O2 oxidizes free iodide and regenerated I2 returns back to the catalytic cycle. Addition of a reductant to the reaction mixture precipitates gold quantitatively and partially regenerates the ligand. We anticipate our work will open a new pathway to more sustainable metal recycling with the utilization of just catalytic amounts of reagents and green solvents.Gold is a scarce element in the Earth's crust but indispensable in modern electronic devices. New, sustainable methods of gold recycling are essential to meet the growing eco‐social demand of gold. Here, we describe a simple, inexpensive, and environmentally benign dissolution of gold under mild conditions. Gold dissolves quantitatively in ethanol using 2‐mercaptobenzimidazole as a ligand in the presence of a catalytic amount of iodine. Mechanistically, the dissolution of gold begins when I Gold can be dissolved in a sustainable manner with common household chemicals: iodine solution in ethanol, resembling diluted iodine tincture, green oxidant hydrogen peroxide and 2‐mercaptobenzimidazole, a compound used in medicinal applications. Catalytic reactions and green solvents are the basis for sustainable development and recycling of precious metals like gold. Noble metals have attractive chemical and physical properties, including good electrical and thermal conductivity, combined with resistance to oxidative stress. In particular, gold plays an invaluable role in modern microelectronics, including ubiquitous cell phones and computers.7, 8 D0 to AuI or AuIII cations and stabilize the formed Au cations in the solution as Lewis bases.− species  identified from the ESI‐HRMS spectra . 1, a labile complex, readily undergoes a ligand exchange reaction, and one iodide ligand is substituted with a S‐bonding 2‐MBI molecule in its dominant thione tautomeric form.[2) is a fingerprint of ligand exchange reaction and observed by ESI‐HRMS as [M−H]− . After the second iodide is replaced with yet another 2‐MBI molecule, relatively stable complex 3[3) is formed and detected by ESI‐HRMS in positive and negative mode as [M]+  and [M−2 H]− , respectively. Both, OH− or SO42− that are produced by redox reactions between H2O2 and I− or 2‐MBI, could serve as a counterion for 3.2O2, and newly formed I2 returns to the catalytic cycle  are predominant at different time periods during the 24 h reaction. In the beginning, I2 concentration is the highest, causing the steepest reaction slope of rate k1 , which is also resembled in the brownish colour of the ethanol solution . Even though H2O2 is already re‐oxidizing iodide to I2, it's being consumed by a presumably faster reaction, Au oxidation. This makes I2 regeneration the rate limiting factor for Au dissolution. It manifests itself as flatter slope for reaction rate k2  and discoloration of the reaction mixture . From 2 h onwards, I2 exists in low, yet sufficient, concentration for the catalytic cycle to proceed. However, after approximately 13 h, concentration of the 2‐MBI ligand is depleted due to the redox reaction with H2O2 (see below) and some precipitation of Au occurs. This is revealed as reaction rate with a flat and negative slope, k3 . As seen from the dissolution curve  than in previous examples with marked excess of 4‐PS−1) but only slightly lower than in the recently reported bi‐ligand systems−1).Dissolution progress was monitored by flame atomic absorption spectroscopy (FAAS) for 24 h and a graph of total dissolved Au vs. time was plotted Figure . Three m1, 2, and 3 in the first three hours of the reaction. The intensities of different reaction species were plotted against time using the data acquired from ESI‐HRMS negative mode. The total amount of dissolved Au measured with FAAS was added for comparison /7.7(2)/100.0(3) even at 3 h.Since the main change in the reaction speed, as well as the discolouration, occurs after 2 h, we monitored the concentrations of Au species n Figure . The intG) for substitution reactions from 1 to 2 and from 2 to 3 were determined as the difference between Gibbs energies of products and reactants . When I− and I2 are both present in the solution, I3− is readily formed with a large stability constant in ethanol,G. The first substitution reaction, in which either iodide of complex 1 is replaced by 2‐MBI, is a thermodynamically favourable reaction regardless of I2 concentration; At high concentrations resembling the initial state of the reaction, ΔG is −65.4 kJ mol−1 and at low I2 concentrations resembling the end state of the reaction, −19.5 kJ mol−1, respectively. The spontaneity for substitution of the second iodide relies on I2 concentration. With higher concentrations of I2, formation of 3 is spontaneous (−24.3 kJ mol−1) but becomes thermodynamically less favourable when I2 concentrations are depleted (+21.6 kJ mol−1) as in the end of the reaction. This is in correlation with the observed lower reaction rate after 3 h and the disappearance of the brownish iodine colour. Small positive ΔG for overall substitution (+2.1 kJ mol−1) therefore explains why 20 equivalents of 2‐MBI are still needed to push the equilibrium towards 3 and free iodide ions after I2 concentrations are depleted.We performed DFT calculations related to the geometry and stability of the above‐described intermediates to gain further insight into the process at the TPSS‐D3/def2‐TZVP/CPCM (ethanol) level. The change of Gibbs free energy  containing 6 and one 2‐MBI molecule. Its peak emerged with low intensity compared to 3, having a ratio of 0.2(4)/100.0(3) at 13 h. Desulfurization product 8 was also confirmed by ESI‐HRMS, but its concentration in the reaction is likely low since it was not observed by 1H NMR. Similarly, Au complexes 2 and 4, as well as a main Au species 3, were not confirmed by 1H NMR likely due to their low concentrations, similar proton shifts compared to the free ligands,[I centre and with this reducing amount of iodine needed for complete dissolution of gold.During the reaction, 2‐MBI reacts with H ligands,54, 594 was chosen as an example of the reducing agent capable in transforming disulphides to thiols4 directly into the scaled‐up reaction mixture with 20 mg of dissolved Au, resulting in formation of a black precipitate which was collected, thoroughly washed, and dried. A sample was taken and analysed using scanning electron microscopy (SEM) and energy‐dispersive X‐ray spectroscopy (EDS) to conclude that it was in fact elemental Au with a particle size of 10–20 nm, acquired as a quantitative precipitate with 92 % yield. By evaporation of reaction solvent and subsequent quenching of the residual NaBH4 with diluted aqueous HCl, pure 2‐MBI in 41 % yield was collected as precipitate. Reduction of disulphide 5 and trisulfide 7 to 2‐MBI is evident from crude 1H NMR spectra of the reaction mixture before and after reduction . Quantitative precipitation of Au and partial reduction of side reaction products back to 2‐MBI increases the sustainability of the recycling process.Next, we investigated ways to close the Au recycling loop. NaBH2 and ethanol as green solvent. Au was successfully dissolved with mild heating (60 °C) using 20 equivalents of inexpensive, safe, and partially recyclable ligand, 2‐MBI, and 20 equivalents of environmentally benign oxidant, aqueous H2O2. 100 % dissolution was reached after 13 h with 3 being the main Au species as proven by ESI‐HRMS. The I2 regenerative cycle for Au dissolution proceeds through four mechanistic steps: oxidations of Au with elemental I2 and dissolution of formed 1, subsequent substitution of both iodides on AuI centre with two 2‐MBI molecules producing 2 and then 3. This is followed by re‐oxidation of free iodide ions by H2O2 to form I2, which returns back to the catalytic cycle. The mechanism was supported by detecting important species with ESI‐HRMS and measuring ratios between their intensities through time and by DFT calculations. To close the recycling loop, we demonstrated the quantitative precipitation of Au and recycling of 2‐MBI in a one‐step procedure using NaBH4 as a reductant. With their high demand and limited sources, recycling of precious metals like Au will become unavoidable in the foreseeable future. Since environmental impact is often ignored, solving this issue by employment of established methods creates another troubling problem of polluting Earth's crust with large quantities of toxic waste. With this in mind, dissolving Au under very mild conditions with a safe, inexpensive, and environmentally benign mixture of now daily used disinfectants like ethanol, hydrogen peroxide, and iodine tincture seems very promising. The astonishing fact is that gold can be dissolved in ethanol with just catalytic amounts of iodine. To further improve the sustainability of this system a logical future direction is to find a ligand with high complex constant and oxidative stress resistance allowing its stoichiometric use in atom‐economic dissolution. We also anticipate that a similar process can be applied in the dissolution of other precious metals by appropriate choice of ligand.In conclusion, we developed a new strategy for the sustainable gold dissolution using catalytic amounts (10 mol %) of IThe authors declare no conflict of interest.1As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re‐organized for online delivery, but are not copy‐edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors.Supporting InformationClick here for additional data file.


Here, we review the physiological functions and pathophysiological alterations of Cl−/HCO3− exchangers belonging to the solute carriers SLC4 and SLC26 superfamilies in relation to oxidative stress. Particularly well studied is the impact of oxidative stress on the red blood cell SLC4A1/AE1 (Band 3 protein), of which the function seems to be directly affected by oxidative stress and possibly involves oxidation of the transporter itself or its interacting proteins, with detrimental consequences in oxidative stress‐related diseases including inflammation, metabolic dysfunctions and ageing. The effect of oxidative stress on SLC26 members was less extensively explored. Indirect evidence suggests that SLC26 transporters can be target as well as determinants of oxidative stress, especially when their expression is abolished or dysregulated.Bicarbonate is one of the major anions in mammalian tissues and fluids, is utilized by various exchangers to transport other ions and organic substrates across cell membranes and plays a critical role in cell and systemic pH homoeostasis. Chloride/bicarbonate (Cl Specifically, cells can generate ROS with function of second messengers, use them for intracellular signalling and for stimulating redox‐sensitive pathways in order to modify the cellular levels of cytoprotective regulatory proteins.By representing the boundary between the cell interior and the extracellular environment, the cell membrane is most vulnerable to free radical attack.+/K+‐ATPase can cause OS with mechanisms distinct from its well‐understood function of ion pump but rather dependent on the scaffolding properties of the alpha1 subunit, which is targeted by OS and post‐translationally modified, thus leading to the activation of a downstream signalling cascade eventually amplifying ROS production.The modulation of the activity of membrane transport systems is part of the cellular response to OS.−/HCO3−) exchangers, which are essential for maintaining crucial homoeostatic functions, such as the regulation of systemic and intracellular pH and ion composition, and the regulation of cell and extracellular fluid volume.In this review, we will focus on the impact of OS on plasma membrane SLC transporters, and specifically on the members of SLC4 and SLC26 families of chloride/bicarbonate Cl−/HCO3− exchang23−) and other electrolytes (Na+ and Cl−) across the plasma membrane. These proteins play a critical role in the acid‐base homoeostasis of the body by acting as either acid loaders or acid extruders, thus regulating both intra‐ and extracellular pH.+‐independent Cl−/HCO3− exchangers, which include SLC4A1, SLC4A2, and SLC4A3; (2) Na+‐dependent HCO3− transporters, comprising electrogenic Na+/HCO3− cotransporters , electroneutral Na+/HCO3− cotransporters (SLC4A7 – formerly SLC4A6 – and SLC4A10), and an electroneutral Na+‐driven Cl−/HCO3− exchanger (SLC4A8); (3) Na+‐coupled borate transporter that do not transport bicarbonate, which is represented by the unique member SLC4A11.The SLC4 transporters, also known as the bicarbonate‐transporter family, are integral membrane proteins that carry bicarbonate HCO3− and oth+‐independent Cl−/HCO3− exchangers, and particularly SLC4A1 and SLC4A2, have been well characterized in the context of OS and will be reviewed in the following. For the other SLC4 family members, there is no information available  or band 3 protein (B3p), is encoded by the In 2015, the crystal structure of B3p revealed two domains: an N‐terminal cytosolic domain that anchors the cytoskeleton at the membrane and interacts with different erythrocyte proteins and a C‐terminal membrane domain that mediates the anion exchange−/HCO3− exchange across the plasma membrane, a fundamental process for an efficient respiration.3− enters the erythrocytes via B3p in exchange for Cl− and is converted by CAII to carbon dioxide, which then diffuses across the plasma membrane to be excreted by the lungs.3−. Each B3p molecule exchanges 105 pairs of monovalent anions per second. The Cl−/HCO3− exchange is the largest ion‐specific flux of a secondary active transporter known in the body,In physiological conditions, B3p mediates electroneutral Cl−/HCO3− exchange is so fast that it cannot be easily monitored without the confounding factor of the cellular metabolism,42−, even if at different rates. The use of SO42− transport to monitor B3p activity offers the advantage that the exchange time is slow enough to employ relatively simple experimental protocols.42− within the erythrocyte ensures that intracellular SO42− determinations are essentially indicative of the anion uptake. This experimental approach has been recognized as an effective tool to monitor erythrocyte homoeostasis in several experimental conditions in vitro and ex vivo.42− transport can be measured by using a turbidimetric method aimed at quantifying the amount of SO42− internalized through B3p as a function of time . This compound, which is commonly used in in vitro assays to model oxidant conditions, easily permeates the plasma membrane. In this regard, it has been demonstrated that not haemolytic concentrations of H2O2 induce OS and reduce B3p transport efficiency  at the cytoplasmic domain of B3p, thus leading to erythrocyte membrane destabilization.via B3p. Thus, these studies suggest a link between inflammation and B3p functional and/or structural alterations.A large number of inflammatory mediators, including the C‐reactive protein (CRP), have been proposed as potential markers of inflammatory response.Among inflammatory conditions, Canine leishmaniasis is also associated with ROS generation and a reduction of erythrocyte survival. The leishmaniasis parasite, even though not directly invading red blood cells, causes a decrease in cell membrane fluidity, as well as an increase in cell rigidity, which may account for the reduced B3p transport efficiency observed in erythrocytes from infected dogs.2.1.3Diabetes mellitus is a chronic metabolic disorder characterized by insulin deficiency, insulin insensitivity, or both, as well as by hyperglycemia and vascular complications. Oxidative stress is a major participant in the pathophysiology of diabetes and not only promotes the onset of diabetes but also exacerbates its associated complications.via B3p was accelerated in both conditions.To investigate the possible influence of diabetes on B3p transport efficiency, two different conditions have been considered: erythrocytes from diabetic patients and from healthy volunteers exposed to increasing concentrations of glucose for 24 hours in vitro, according to.42− uptake via B3p is significantly reduced in erythrocytes treated for 1 hour with 0.1‐10 mmol/L D‐Galactose . This effect was accompanied by the formation of glycated haemoglobin rather than OS, which was mitigated by the endogenous catalase. These findings suggest that B3p dysfunction might contribute to the pathophysiology of galactosemia and further underscore the sensitivity of B3p function for the formation of glycated haemoglobin.Galactosemia is a group of disorders of galactose metabolism characterized by erythrocyte galactose‐1‐phosphate levels usually >10 mg/dL. If undiagnosed or left untreated, galactosemia can result in life‐threatening complications including failure to thrive, hepatocellular damage, bleeding, sepsis, and neonatal death. Despite adequate treatment, children with galactosemia remain at increased risk for developmental delays, apraxia of speech, abnormalities of motor function, and hypergonadotropic hypogonadism or premature ovarian insufficiency in females.2.1.4Oxidative stress has also been postulated to play an important role in pathophysiological pathways involved in ageing as well as several age‐related diseases. The plasma membrane of red blood cells plays a crucial role in regulating cellular homoeostasis, and proteins and lipids involved in this function are very susceptible to oxidative modifications during ageing.via increased production of ROS and changes in antioxidant enzyme activities in the cell.42− uptake via B3p was increased; however, the total amount of SO42− trapped by the cell was significantly reduced. These changes in the transport properties were paralleled by and increased formation of glycated haemoglobin, as well as a marked OS.Unfortunately, no studies exploring possible functional changes of B3p in aged individuals are reported in the literature. Chronic administration of D‐Gal has been widely used as a model to mimic a process very similar to the natural ageing, provoking OS 2.1.52+) deficiency has been associated with an increased production of ROS, increased levels of inflammation, and several age‐related diseases.via B3p. Magnesium pre‐treatment ameliorated the efficiency of anion exchange in these cells.2+, the phosphorylation grade of B3p and tyrosine kinase Syk expression have been assayed in normal erythrocytes after OS induced by exposure to NEM.2+ is not mediated by phosphorylation pathways, but is rather linked to an improvement of the endogenous antioxidant system and protection of SH groups. In fact, pre‐exposure to Mg2+ restored B3p ion transport following an increase of intracellular glutathione levels.2O2) could be prevented or attenuated by a short‐time pre‐incubation of red blood cells with low (10 μmol/L) H2O2 concentrations.Both the enzymatic and non‐enzymatic antioxidant system are essential for the cellular response in order to deal with OS injuries. Also, antioxidants provided by the diet help the activity of endogenous antioxidants and contribute to the maintaining of redox homoeostasis.42− uptake via B3p, as well as the reduction in B3p expression levels was observed following treatment with H2O2.42− uptake observed in a cell‐based model of hyperglycaemia represented by red blood cells treated with high glucose concentrations (15‐35 mmol/L) for 24 hours.In a recent study, a correlation between melatonin effect, OS injury and B3p anion exchange capability was shown. In particular, the authors reported that pre‐treatment of human erythrocytes with melatonin ameliorated the reduction in rate constant for SOApart from haemolysis, exposure of red blood cells to low pH values can evoke alterations of cell membranes.via B3p.B3p is expressed in all cells and tissue of the body, including brain and lymphocytes, and represents an excellent marker protein for post‐translational modifications during ageing. In this respect, the anion transport ability of B3p decreased in brains and erythrocytes from old mice and, in addition, this functional reduction was associated to obvious structural changes.2.2−/HCO3− exchanger that in humans is encoded by the SLC4A2 gene. This transporter is expressed in many tissues, including blood vessels, airways epithelia, proximal colon, and salivary glands cells and regulates the intracellular pH and Cl− concentration.4+ in several cell types. All AE anion exchangers have a large N‐terminal cytoplasmic domain, which is about 700 amino acid long for AE2, followed by a 500 amino acid polytopic transmembrane domain and a short C‐terminal cytoplasmic tail.SLC4A2, or anion exchanger 2 (AE2), is an electroneutral Cl2.2.1− concentration. Pharmacological inhibition or silencing of the expression of AE2 protected cells from apoptosis.Diabetes mellitus causes a wide variety of vascular complications that are closely related to the degree of glycaemic control, suggesting that abnormal blood glucose levels are a critical risk factor for the damage of endothelial cells.2O2.via AE2 raises interesting questions with regard to the regulation of AE2 in the lung. Since superoxide radicals can contribute to oxidant lung injury, the increase of expression of AE2 following OS exposure should provide increased transport of O2·− out of the cell, thus limiting the oxidative damage. Accordingly, AE2 has been demonstrated to protect cell viability in a model of lung reperfusion injury.Turi and collaborators have reported that the expression of AE2 in rat airway epithelial cells is regulated by OS, and this regulation seems to be mediated by transcription factor AP‐1, a specific protein able to respond to elevated intracellular concentrations of ROS, including H3SLC26A1‐11) of which 10 are protein coding and one (SLC26A10) is a pseudogene. With the exception of SLC26A5, which encodes for the outer hair cells motor protein prestin, these genes encode multifunctional anion exchangers, of which SLC26A7, A9 and A11 can also operate as uncoupled ion transporters in a channel‐like mode. The anion exchangers of this family can accept divalent as well as monovalent anions and generally show versatile substrate selectivity, being able to exchange chloride for inorganic anions such as bicarbonate, hydroxyl, sulphate and iodide, or small organic anions such as formate and oxalate. SLC26A3, A4, A6, A7, A9, and A11 can operate in Cl−/HCO3− exchange mode, while SLC26A1 and A2 are selective sulphate transporters.The SLC26 family of multifunctional ion transporters and channels comprises 11 genes ,+/SO4Arabidopsis thalianaArabidopsis thaliana SULTR4;1Synechocystis sp,The SLC26 family was discovered more recently and is less well characterized compared with SLC4. SLC26 members are highly hydrophobic, large  proteins sharing relatively low (21%‐43%) amino acid identity with the members of the same family. The structure of mammalian SLC26 transporters has long been elusive. Structures of the murine Slc26a9,SLC26 genes cause inherited diseases, including diastrophic dysplasia (phenotype MIM number 222600) and other osteochondrodysplastic syndromes (SLC26A2), secretory chloride diarrhoea , Pendred syndrome  and non‐syndromic deafness , calcium oxalate nephrolithiasis , and spermatogenic failure . SLC26A3, A4, A6, A8 and A9 physically and/or functionally interact with the CFTR chloride channel and regulate the CFTR activity or are regulated by CFTR.Some of the members of the SLC26 family show restricted tissue distribution, whereas other isoforms are more broadly expressed and orchestrate the ion transport across epithelia such as the intestine and kidney.The information regarding the impact of OS on SLC26 function is sparse, and will be reviewed in the following and in Table 3.1−/HCO3− exchanger in tandem with NHE3, which mediates a Na+/H+ exchange, to generate an electroneutral NaCl reabsorption across the intestinal mucosa, or gives rise to HCO3− secretion in the absence of NHE3.SLC26A3/DRA was initially identified as a candidate tumour suppressor gene that was downregulated in adenoma .3.1.12O2 inhibited the SLC26A3 and SLC26A6‐mediated Cl−/OH−(HCO3−) exchange activity in Caco‐2 cells independently of the prostaglandin/COX‐dependent pathway, but occurring via a signalling cascade that involved the activation of the Src kinase Fyn, PI3K, PLCγ 1 and the Ca2+‐dependent PKCα.Oxidative stress plays an essential role in the pathogenesis and progression of inflammatory bowel disease (IBD).−/OH−HCO3− exchang3− secretion.In a recent study, the gene expression of SLC26A3 was decreased in the colonic mucosa from patients with active UC compared with patient in remission and non‐inflamed donors. In parallel, SOD2 was significantly upregulated in the colonic mucosa from patients with active UC compared with controls, thus denoting an increased OS, and SOD2 levels correlated with severe histological activity in the inflamed mucosa.3.2−/anion exchanger abundantly expressed on the apical membrane of distinct epithelial cells of the stria vascularis and endolymphatic duct and sac of the inner ear, as well as in the thyroid and kidney. In the inner ear, pendrin drives HCO3− secretion and Cl− reabsorption and controls the endolymphatic pH and volume. In the thyroid, pendrin participates in the iodide flux into the thyroid follicle, possibly via its I−/Cl− exchange activity. In addition, pendrin expression is upregulated in the airways and oesophageal mucosa by the pro‐inflammatory cytokines IL‐4/IL‐13 via a STAT6‐mediated pathway.− reabsorption and HCO3− excretion and controls the systemic electrolyte, vascular volume and acid‐base homoeostasis by working in concert with other ion absorbing transport systems, including the sodium chloride cotransporter NCC and the epithelial sodium channel ENaC.SLC26A4/pendrin is an electroneutral Cl3.2.1stria vascularis in pendrin‐knockout mice. Hyperpigmentation of the stria vascularis was linked to an increased melanin production in the strial intermediate cells, which are in charge of detoxification of free radicals produced by the metabolically active strial marginal cells. The authors proposed a model where lack of bicarbonate secretion in the endolymph due to the absence of pendrin, with consequent increase of bicarbonate concentration and pH in the intra‐strial fluid, may have led to inhibition of cysteine uptake and glutathione synthesis in the intermediate cells and free radical damage of these cells. Oxidative stress in the intermediate cells was proposed to be responsible for the reduced protein expression of KCNJ10/Kir4.1, an inwardly rectifying K+ channel essential for the generation and maintenance of the endochoclear potential and proper hearing function.stria vascularis of pendrin‐knockout mice, and OS reduced Kcnj10 expression in a heterologous system.A possible link between OS and pendrin expression and function in the inner ear was firstly reported by Wangemann and collaborators, who described hyperpigmentation of the A recent study has evidenced a significant increase in the Slc26a4 transcript levels in the cochlea of three distinct mouse models of age‐related hearing loss linked to chronic OS, represented by mice subjected to intermitted hypoxia alone, high‐fat diet plus galactose injection and intermitted hypoxia combined with high‐fat diet and galactose injection for 12 weeks, respectively. These changes were paralleled by an increase in the hearing threshold and morphological damage of cochlear hair cells.via pendrin and is subsequently incorporated (organified) into thyroglobulin (Tg) by the thyroid peroxidase (TPO), which requires H2O2 as cofactor. H2O2 is generated by dual oxidases (DUOXs). In a normal thyroid, TPO and DUOX expression is restricted to the apical membrane of thyrocytes or confined within Caveolin‐1‐positive intracellular vesicles. Similar to what was observed in the inner ear of pendrin‐knockout mice, OS was augmented in the thyroid of a patient with Pendred syndrome, as evidenced by greatly increased lipid peroxidation as well as catalase and peroxiredoxin PRDX5 expression. In parallel, TPO and DUOX showed greatly enhanced expression, lost their normal apical distribution and were mislocalized within the cytosol, while the expression of Caveolin‐1 was absent. These authors linked the increased OS in the thyroid tissue with aberrant, intracellular thyroid hormone biosynthesis, a process that would require H2O2 production within the cytosol.In the thyroid, iodide reaches the follicular lumen Pendrin transcript was found downregulated  in the kidney from F344 male rats exposed to 400 ppm (high) potassium bromate in drinking water. Potassium bromate is a nephrotoxic compound and a kidney and thyroid carcinogen, can induce deafness and promotes OS, as evidenced by de‐regulation of OS‐related genes.2O2 at the apical membrane through DUOX1 and DUOX2. H2O2 serves to oxidize luminal SCN− to OSCN− (hypothiocyanite) in a reaction catalyzed by lactoperoxidase and other peroxidases. Both anions are pro‐oxidant species, have an antimicrobial role and play an important function in the innate mucosal defense. Pendrin is a major determinant of the IL‐4/IL‐13‐stimulated SCN− secretion at the luminal surface of human bronchial epithelial cells and lung.− secretion may lead to increased OSCN− production. OSCN− in low doses can be sensed by the OS‐sensitive PKA, which dimerizes and activates NF‐κB, a transcription factor critical for inflammatory responses. High doses of OSCN− can induce necrosis of epithelial cells, further triggering inflammation.− secretion via pendrin might be linked to increased bacterial colonization of the airway epithelium− to OSCN−Similarly to thyroid, the airway and lung epithelium has the ability to generate H3.3SLC26A5 mutations has been identified in patients with hearing loss; one of these mutations was linked to autosomal recessive deafness DFNB61 but later was found non‐pathogenic.SLC26A5/prestin is the transmembrane sensor‐motor protein of the outer air cells (OHC) of the mammalian organ of Corti and enables changes in length of these cells depending on the frequency of a sound stimulus, which is the basis of the mechanism of cochlear amplification of sounds.3.3.1Katbamna et al have shown that prenatal smoke exposure (≥10 cigarettes/d) leads to significant reductions in the cochlear response amplitudes and auditory brainstem recording (ABR) wave latencies in newborns. These alterations in the auditory function were paralleled by a dysregulation of the expression of placental genes, including SLC26A5, which was upregulated 8.95 fold, again suggesting an adaptive change. Also, several OS pathway genes were found dysregulated. The authors suggested that placental gene expression might be a good surrogate of foetal gene expression.Oxidative stress following production of ROS is a hallmark of noise‐induced hearing loss and mainly targets OHC.3.4−/HCO3−, Cl−/OH−, chloride/oxalate and chloride/formate exchange modes.3− secretion by acting synergistically with CFTR; in addition, SLC26A6 mediates oxalate excretion in the intestine and kidney proximal tubule and Cl−/HCO3− exchange in the myocardium. These findings imply a role of SLC26A6 in the development of intestinal and pancreatic diseases, nephrolithiasis and arrhythmia.SLC26A6 putative anion transporter 1 (PAT1) and chloride‐formate exchanger (CFEX) was cloned based on the homology to the genes encoding SLC26A3 and SLC26A4, was found most abundantly expressed in the kidney and pancreas,3.4.1In normal rat proximal tubular epithelial (NRK‐52E) cells, SLC26A6 expression correlated with oxalate‐induced cell injury, apoptosis, crystal adhesion, ROS formation and lipid peroxidation. Accordingly, selective attenuation of SLC26A6 expression in the kidney of rats with lentivirus‐transfected siRNAs decreased SOD generation, cell apoptosis and crystal formation.4Several studies have investigated in detail the impact of OS on some transporters of the SLC4 family in different experimental conditions Table . In partThe potential impact of OS on the expression and activity of SLC26 family members was less extensively studied compared with SLC4A1. For several SLC26 members, there is no information available in this context. The current knowledge denotes a dual role of these transporters in being potential targets as well as determinants of OS Figure . For exaFurther research should establish whether and how members of the SLC4 and SLC26 family of proteins can be safely and effectively targeted by antioxidants in the prevention and treatment of OS‐related conditions, including inflammation, metabolic dysfunctions, hearing loss and ageing.The authors declare no conflict of interest.All authors contributed to performing the literature search and writing the manuscript. All authors have read and agreed to the final version of the manuscript.


The bead is then formally a [1014] rotaxane. The number of complexes attached is counted by EPR spectroscopy after including TEMPO radicals within the thread of the hybrid [2]rotaxanes.Polymer beads have been used as the core of magnetic particles for around twenty years. Here we report studies to attach polymetallic complexes to polymer beads for the first time, producing beads of around 115 microns diameter that are attached to 10 14 [2]rotaxanes containing paramagnetic {Cr7Ni} rings.Polymer beads are used in the core of magnetic particles, and beads functionalised with paramagnetic molecules are promising as agents for dynamic nuclear polarization. Here, the authors use conventional click chemistry to decorate a polymer bead with 10 This hugely influential work involved use of a polyelectrolyte attached to the polystyrene core before attachment of Fe3O4 nanoparticles. Similar approaches have been used to make core-shell structures with other inorganic materials. ZnS has been grown around polystyrene as a route to photonic crystals2 and metal-organic framework shells have been grown as a route to particles that can be used to adsorb pollutants4.Since 1999 polymer beads have been used as the core of magnetic particles, with Caruso et al. showing that magnetite could be grown on the exterior of polystyrene5 and studied as agents for dynamic nuclear polarisation (DNP)6. Further functionality has been introduced by blending these properties on or in polymer hosts, and such magnetic polymer beads have been exploited in many areas, including sensing, imaging and separations7. Radical-bead functionalisation has been used to probe the macromolecular structures of the beads and their swelling on solvation8.Beads functionalised with paramagnetic molecules have been used in catalysisWe wondered if it was possible to attach polymetallic compounds to a polystyrene bead. This could then be developed in two distinct directions: the attached compound could be decomposed to give a core-shell particle with great control of the metal shell, and perhaps allow formation of different metal-shells than are accessible from synthesis from simple precursors. Secondly, decorating a bead with a very large number of highly paramagnetic molecules could lead to a use in DNP or as a contrast agent or even as a ferrofluid. However, before speculating on possible applications we needed to establish that the chemistry itself is possible. This is purpose of this report.9. To enable this to work we functionalised commercially available polystyrene microspheres with pendant azides  click chemistrydes Fig. . As the 13.We note that the first reported [2]rotaxane was prepared by repetitive statistical threading-and-capping of a polymer-supported macrocycle7Ni} rings forming around a secondary ammonium cation template, while the exterior of the ring is covered by sixteen pivalate groups, giving [(R2NH2)Cr7NiF8(tBuCO2)16]. Full details are given in the Methods Section and the Supplementary methods sections The approach is summarised in Fig. 6H4CH2CH2)2NH 1 is formed from a primary amine and an alkyl bromide, each bearing a terminal phenolic group, and is the neutral precursor to the ammonium template. Choice of the distance between the ammonium and phenol unit is important. If the distance is too short, the phenol will be too sterically hindered for further functionalisation. If the distance is too long, the phenol is esterified by reaction with the pivalic acid used during the formation of the ring12. Here, we aimed for an intermediate distance, but a small amount of esterified product is always obtained when 1 is used to form [2]rotaxanes. This ability to control the reactivity of the phenol is important as it allows difunctionalisation of the thread.The thread (HOC2 was prepared by reacting 1 with hydrated chromium(III) fluoride and basic nickel carbonate in pivalic acid (See Methods section for preparative details) and was purified by column chromatography. X-ray quality single crystals of 2 were grown from acetone by slow evaporation. The crystal structure of 2 shows the inorganic–organic [2]rotaxane with the axle terminated by phenols.Rotaxane 2 was reacted with 4-pentynoic acid under Steglich esterification conditions to yield 3. A second esterification reaction with 4-carboxy-TEMPO gave 4. Formation of rotaxane 4 was confirmed by electrospray mass spectrometry (ESI-MS), elemental analysis and single-crystal X-ray crystallography.To introduce a terminal alkyne for CuAAC click chemistry, rotaxane 4 was reacted with azide-functionalised polymer beads 5 or 6 . We attribute the small, residual azide band in the IR spectrum to azide functionalities present in inner, inaccessible regions of the bead15.Product formation was monitored by FT-IR spectroscopy. The IR absorption peak for an azide group around 2090 cmhttps://www.sigmaaldrich.com/GB/en/product/mm/855011, http://www.rapp-polymere.com/index.php?id=893&currency=968, http://www.rapp-polymere.com/index.php?id=1219&currency=498), and that the polymer bead is spherical. Secondly, that the density of accessible sites is uniform across the polymer bead, and that the number of accessible surface sites is not limited to the surface of the bead as there is a degree of swelling and ‘depth’ in which molecules can react at sites further inside the sphere. We then have to estimate a lower bound depth and we chose 0.5 µm. Thirdly, that the surface volume can be determined from the volume of two spheres of different diameters and that the density of polymer sites is uniform at the surface. Given these assumptions and assuming that all azide sites within 0.5 μm of the surface react, the number of rotaxanes on a single bead of diameter 115 µm, 5, was estimated to be at least 2 × 1013 and for the smaller beads, 6, we estimate that 8 × 1010rotaxanes could be attached  Q-Band ca. 34 GHz) EPR spectra of 4 GHz EPRing Fig. 18. This 4 and beads 7 and 8 contain TEMPO radicals terminating the thread, and the EPR spectra show resonances for the nitroxides that are observed at all temperatures  with a single (or a few) beads, positioning of the sample in the EPR tube becomes more crucial, and (ii) there is a distribution of bead sizes with bead diameters between 80 and 150 μm. Hence, we consider the average number of nitroxide spins per bead from the larger numbers of beads to be the most meaningful. The conclusion is that there are ~1014 spins per bead, which is within an order of magnitude of the lowest estimate of the number of rotaxanes that could be bound (ca. 2 × 1013), calculated from the number of solvent-accessible surface sites .The number of nitroxide spins per bead was found to be of the order 1014 Table . Althoug6 were decorated with 4 giving 8, and these beads were also studied , calculated from the number of solvent-accessible surface sites . The nitroxide resonance in 4 and 8 is slightly broader than in 7.In addition, 10 µm diameter beads ied Fig. . The mas5, 7 and a bead decorated with crystallographically characterised (see Table 10 [{(HC≡CCH2CH2C(O)O-Ph-CH2)2NH2}][Cr7NiF8(O2CtBu)16], forming 11 that does not contain the nitroxide radical on the thread (See Methods section for preparative details). The results are shown in Fig. 11.Measuring the magnetic properties of samples containing polystyrene beads presents significant challenges, particularly as there is considerable static between the beads within samples. Nonetheless we have attempted to measure the magnetic properties of three samples of beads: an azide-decorated bead 7 and 11 are similar, especially given the limitations of the experiment, and higher than that of the beads alone. As the temperature is lowered the behaviour diverges , which is found in pure samples of the {Cr7Ni} rings10. This indicates that the predominant paramagnetic species present are intact {Cr7Ni} rings. This led us to compare 7 and 11 with the magnetic behaviour of [Pr2NH2][Cr7NiF8(O2CtBu)16] 12. In Fig. 12, scaled by both 1014/NA and 3 × 1014/NA giving the value for 1014 and 3 × 1014 molecules.At room temperature the susceptibility of ges Fig. . Both sh7 and 11 match the scaled value for 1014 molecules of 12 well. At low T both the temperature and field dependence of the moment for 7 match that for 1014 molecules of 12; this is unexpected as 7 contains an additional s = ½ centre per rotaxane due to the radical. When comparing with 11, the moment in both variable T and H fits with 3 × 1014 molecules of 12. The susceptibility of 11 diverges after the maximum at 25 K.At the highest temperatures the magnetic susceptibilities of both 14 rotaxanes per bead; this is close to the lowest estimate of 2 × 1013 we calculate based on solvent-accessible sites . Full characterisation details of all compounds are given in the section All chemicals were of reagent grade quality, and they were purchased from commercial sources and used as received. The azide functionalized polystyrene beads were prepared by literature procedures1H NMR spectra were recorded on a Bruker AVIII HD 400 MHz at 298 K. Chemical shifts are reported in parts per million (ppm) from high to low frequency using the residual solvent peak as the internal reference (DMSO-d6 = 2.50 ppm). All 1H resonances are reported to the nearest 0.01 ppm. Infrared spectra were recorded neat on a Bruker FT-IR Alpha II Platinum ATR spectrometer. Fully characterised compounds were chromatographically homogeneous. Flash column chromatography was carried out using Silica 60 Å  as the stationary phase. Analytical TLC was performed on precoated silica gel plates  and visualised using both short and longwave ultraviolet light in combination with standard laboratory stains . Low-resolution ESI mass spectrometry and high-resolution mass spectrometry was carried out by staff at the Mass Spectrometry Service, Department of Chemistry, The University of Manchester. Elemental analysis was carried out by the Analytical Service of the University of Manchester; metals analysis by Thermo iCap 6300 inductively coupled plasma optical emission spectroscopy (ICP-OES).N-ethyldiisopropylamine . The reaction mixture was heated at 75 °C for 16 h. When the reaction was complete, the mixture was cooled to room temperature, diluted with EtOAc and washed with brine. The organic phase was dried (MgSO4), filtered, and the solvent removed under reduced pressure. The solid residue was dissolved in hot CH3OH (100 mL) and precipitated by addition of water (20 mL). The product was filtered and washed repeatedly with CHCl3 to yield the title compound as brown solid .To a solution of 2-(4-hydroxyphenyl)−1-bromoethane  in anhydrous DMF (45 mL) was added 2-(4-hydroxyphenyl)ethylamine  and 1 . The reaction mixture was stirred at 100 °C for 10 min then [CrF3·4H2O]  and [2NiCO3·3Ni(OH)2·4H2O]  were added. The reaction mixture was stirred at 140 °C for 24 h. The reaction mixture was cooled to room temperature and the crude product was extracted with CHCl3. The solvent was removed under reduced pressure and the crude residue was purified by column chromatography  to yield rotaxane 2 .To pivalic acid  at 100 °C in a Teflon™ flask was added 4, a two-step esterification was performed. Firstly, to a solution of rotaxane 2 , in THF (100 mL) was added pentynoic acid , DCC  and DMAP . The reaction mixture was stirred at 50 °C for 16 h. The solvent was removed under reduced pressure and the crude residue was purified by column chromatography  to yield mono-esterified rotaxane 3 .To prepare molecule 3  in CH2Cl2 (50 mL) was added 4-carboxy-TEMPO , DCC  and DMAP . The reaction mixture was stirred at room temperature for 16 h. The solvent was removed under reduced pressure and the crude residue was purified by column chromatography  to yield rotaxane 4 .To a solution of rotaxane 5  were added to [(C31H40N2O5)Cr7NiF8(C5H9O2)16] 4  and Cu(MeCN)4PF6  under argon. A CH2Cl2:DMF mixture  was added and the reaction was stirred for 72 h at room temperature. The reaction mixture was then filtered and washed with CH3CN (3 × 10 mL), CH3OH (3 × 10 mL), and CH2Cl2 (3 × 10 mL) to afford [2]rotaxane–polystyrene beads 7 .Azide polystyrene beads 6  were added to [(C31H40N2O5)Cr7NiF8(C5H9O2)16] 4  and Cu(MeCN)4PF6  under argon. A CH2Cl2:DMF mixture  was added and the reaction was stirred for 72 h at room temperature. The reaction mixture was then filtered and washed with CH3CN (3 × 10 mL), CH3OH (3 × 10 mL), and CH2Cl2 (3 × 10 mL) to afford [2]rotaxane–polystyrene beads 8 .Azide polystyrene beads 1  and 5.0 mL of 1,2-dichlorobenzene and heated to 140 °C for 10 min. To this solution [CrF3·4H2O]  and [2NiCO3·3Ni(OH)2·4H2O]  were added and stirred at 140 °C for 24 h. The reaction mixture was cooled to room temperature, transferred in to a 500 mL flask and 300 mL of hexane was added. The crude product was extracted with diethyl ether and purified by column chromatography  to yield rotaxane 9 (2.5 g). Single-crystal X-ray quality crystals were grown from acetone by slow evaporation method.To 3,3-dimethylacrylic acid  in a Teflon™ flask was added 10, to a solution of rotaxane 9 , in THF (100 mL) was added pentynoic acid , DCC  and DMAP . The reaction mixture was stirred at 50 °C for 16 h. The solvent was removed under reduced pressure and the crude residue was purified by column chromatography  to yield 10. Single-crystal X-ray quality crystals were grown from acetone by slow evaporation method.To prepare rotaxane 5  were added to [(C26H28NO4)Cr7NiF8(C5H7O2)16] 10  and Cu(MeCN)4PF6  under argon. A CH2Cl2:DMF mixture  was added and the reaction was stirred for 72 h at room temperature. The reaction mixture was then filtered and washed with CH3CN (3 × 10 mL), CH3OH (3 × 10 mL), and CH2Cl2 (3 × 10 mL) to afford [2]rotaxane–polystyrene beads 11 .Azide polystyrene beads 2, 4 and 9 were collected at a temperature of 100 K using a dual wavelengh Rigaku FR-X with Cu-Kα radiation equipped with a HypixHE6000 detector and an Oxford Cryosystems nitrogen flow gas system. X-ray data for compound 10 was collected at a temperature of 100 K using synchrotron radiation at beamline I19 in Diamond Light Source equipped with a Pilatus 2 M detector and an Oxford Cryosystems nitrogen flow gas system. Data were measured using GDA and CrysAlisPro suite of programmes.X-Ray data for compounds 23. The crystal structure was solved and refined against all F2 values using the SHELXL24 and Olex 2 suite of programmes25.X-Ray data were processed and reduced using CrysAlisPro suite of programmes. Absorption correction was performed using empirical methods (SCALE3 ABSPACK) based upon symmetry-equivalent reflections combined with measurements at different azimuthal anglesAll atoms in crystal structures were refined anisotropically with the exception of the hydrogen atoms, that were placed in the calculated idealised positions for all crystal structures. The pivalate ligands, and threads in crystal structures were disordered and modelled over two positions, using structural same distance (SADI) and distance fix (DFIX) Shelxl restraints commands. The atomic displacement parameters (adp) of the ligands have been restrained using similar Ueq and rigid bond (SIMU) and Similar Ueq (SIMU) restraints.EasySpin 4.5.5 simulation software26.Q-band (ca. 34 GHz) EPR spectra were recorded with a Bruker EMX580 spectrometer at the EPRSC UK National EPR Research Facility at The University of Manchester. The data were collected on polycrystalline powders and on solid polymeric beads at 280 K, and 5 K using liquid helium cooling. Spectral simulations were performed using the 5, 21.83 mg; 7, 7.04 mg; 11, 14.28 mg; 12. 15.01 mg. No diamagnetic correction has been applied to data. For 7, beads were counted and weighed and this leads to an estimate of 831 beads per mg, which we have used in calculations.Magnetic properties were measured on a Quantum Design MPMS3. Susceptibility was measured from 300 to 2 K in a 1000 Oe magnetic field. Magnetisation was measured at 2 K to a maximum field of 7 T. Samples were mounted in gelatine capsules. The mass of samples measured were: Supplemental MaterialDescription of Additional Supplementary FilesSupplementary Data 1


Electrochemically the Fe(mnt)2 is reduced twice to the trianionic Fe(mnt)23− state, which is correspondingly found to be active towards CO2. Interestingly, the first reduction event appears to comprise overlapping reversible couples, attributed to the presence of both a dimeric and monomeric form of the dithiolene complex. In acetonitrile Fe(mnt)2 demonstrates a catalytic response to CO2 yielding typical two‐electron reduction products: H2, CO and CHOOH. The product distribution and yield were governed by the proton source. Operating with H2O as the proton source gave only H2 and CO as products, whereas using 2,2,2‐trifluoroethanol gave 38 % CHOOH faradaic efficiency with H2 and CO as minor products.In this work, the dithiolene complex iron(III) bis‐maleonitriledithiolene [Fe(mnt) The first iron‐based dithiolene complex, iron(III) bis‐maleonitriledithiolene, is characterised for carbon dioxide reduction activity and stability. Operating with 2,2,2‐trifluoroethanol proton source in acetonitrile electrolyte, the homogeneous catalyst gave 38 % CHOOH faradaic efficiency with H2 and CO minor products. The catalyst performance is presently limited by parasitic side‐reactions with the electrolyte and catalyst decomposition. In the present work, yields of 31, 21 and 66 % were obtained for the cyanodithioformate intermediate, maleonitriledithiolate ligand and (TEA)[Fe(mnt)2] complex, respectively. In comparison, higher yields have been demonstrated in the literature giving 71, 97 and 54 %,[2] ⋅ 2H2O, as determined by elemental analysis . The presence of two stoichiometric quantities of water is inconsequential in the current study as proton source concentrations of at least 0.1 M 2,2,2‐trifluoroethanol (TFE) or 1 M H2O were used which far exceeds the 0.002 M water originating from the catalyst material.The preparation of the iron(III) bis‐maleonitriledithiolene catalyst proceeds via a simple three step method starting from low toxicity and inexpensive starting materials. Initially, the ligand was prepared by reaction of chloroacetonitrile with sulfur and then subsequent dimerisation of the cyanodithioformate intermediate. The complexation of iron(III) chloride with excess ligand at room temperature yields (TEA)2− in the solid phase whereby each Fe centre adopts a square pyramidal coordination with five sulfur donors, giving a biologically relevant Fe2S8 core, shown in Figure Crystals suitable for powder and single‐crystal X‐ray diffraction (XRD) analysis were grown by slow recrystallisation from EtOH to give black anhydrous needles (SI). Single‐crystal XRD analysis shows that the Fe(mnt)21−, Co(mnt)22−, Ni(mnt)22− and Cu(mnt)22− as molecular catalysts for HER and CO2R due to accessible redox states at suitably negative potentials . The Ni and Cu complexes showed no response to the presence of CO2, with the voltammetric trace overlaying that of N2 and a proton source. Co(mnt)22− showed a slight increase in cathodic current when in the presence of CO2, but the response was considered catalytically negligible . The onset of HER is also not tied to the reduction of the complex, indicating no catalytic activity. The Fe complex stood out as possessing a high catalytic response towards CO2R as shown in Figure 21− for full characterisation. Herein the electrochemical properties of Fe(mnt)2 are discussed as a redox material in aprotic electrolyte and as a catalyst for HER and CO2R in protic media.Building on our previous work employing metal dithiolenes in redox flow batteries,21− complex was first prepared and studied over 50 years ago, its electrochemistry has been essentially unreported. Indeed, the complex was only briefly characterised in the work of Yamaguchi et al. in 2009 and by us in 2019.Although the Fe(mnt)21− species undergoes two sequential one‐electron reductions to the trianionic Fe(mnt)23− oxidation state at −0.69 and −2.11 V vs ferrocene (Fc) as shown in Figure Under inert conditions and in the absence of a proton source, the as synthesised anionic Fe(mnt)22−/3− redox couple gave a high peak current ratio close to unity (0.89) and a peak‐to‐peak separation of 77 mV (at a scan rate of 100 mV s−1) and a modest increase in peak separation at higher scan rates confirms quasi‐reversible kinetics. In contrast, the Fe(mnt)21−/2− couple shows more complicated voltammetry, illustrated in Figure 21−/2− process gives a passed charge comparable to the Fe(mnt)22−/3− couple  suggesting that the redox events are stoichiometrically one‐electron processes.Peak analysis of the Fe(mnt)2 catalyst exists as the binuclear dimer Fe2(mnt)42− in the solid phase due to more favourable square pyramidal coordination. Yet, in solution phase it was thought that the dimer is dissociated into monomer unitset al.3/2 (quartet) and in the solid state as S=1/2 (doublet), however the cause of this disparity was not formally identified and may result from a change in electronic structure. Considering that the Fe−S bond length between Fe(mnt)2 units is only 0.2 Å longer than Fe−S bond lengths within each Fe(mnt)2 unit, the dimer binding is evidently strong. Therefore, we hypothesise that the Fe2(mnt)42− dimer formally exists in solution or dominates a fast‐exchanging equilibrium with the monomeric form:To account for the observed two diffusion‐limited redox couples which are identified in the peak deconvolution we postulate that the dimer and monomer forms of the dithiolene complex are both present in solution. As shown in Figure similar diffusion coefficients and electrode kinetics (parameters could not obtained in the present work). The electronic stoichiometry is preserved because the integrated charge of the Fe(mnt)21−/2− and Fe(mnt)22−/3− redox couples are both dependent on the total quantity of Fe(mnt)2 units at the electrode interface, irrespective of monomeric or dimeric form. Based on the similar peak currents of the deconvoluted peaks, we propose that the redox processes are sequential, and each constitute half of the total Fe(mnt)2 units in the diffusion layer. As such, the reduction of Fe2(mnt)42− proceeds to the trianionic Fe2(mnt)43− dimer. This rapidly dissociates to give Fe(mnt)22− and the Fe(mnt)21− monomer, which is then further reduced at the lower redox potential. Here we hypothesise that the Fe2(mnt)43− dissociation is a dynamic equilibrium driven by unfavourable Fe−S bond lengthening between Fe(mnt)2 units due to addition of electron density in the Fe−S core upon reduction. Overall, the proposed reactions are:The co‐existence of the dimer and monomer species in solution of other Fe‐dithiolene complexes has been previously reported,39, 40Redox couple Dimerisation/dissociation:Redox couple Overall:2O), we do not observe the two‐peak waveforms exhibited in Figure −1). To account for this behaviour, we hypothesise that the Fe(mnt)21− species coordinates with water to give a pseudo‐octahedral geometry which causes more favourable dissociation of the Fe2(mnt)42− dimer. Thus, the reduction of Fe(mnt)21− proceeds in a single step one‐electron process. In stark contrast, voltammetry performed in an electrolyte containing 5 M TFE caused further separation of the superimposed redox couples as shown in Figure 21−/2− redox couple is heavily dependent on the solvation and electrolyte composition. To investigate this further, voltammetry using different supporting electrolytes was conducted in the absence of proton source and under N2 . The use of highly coordinating halide anions caused the Fe(mnt)21−/2− waveform to revert to a classical fully reversible redox couple exhibiting a small peak separation of 72 mV and accompanied negative shift of ∼100 mV. This result indicates a shift of the equilibrium towards full dissociation of the dimer due to coordination of halide ligands.Interestingly, when dissolved in a concentrated hydrous electrolyte 3 M H M H2O, w2 in these solvation environments was then probed using UV/vis spectroscopy. It was found that in all electrolytes examined the iron dithiolene solution showed high intensity bands in the UV region corresponding to spin‐allowed intraligand (π-π*)transitions . A lower energy peak at 450 nm was also observed for the anhydrous MeCN and in the presence of 5 M TFE, the latter being more intense. However, in the presence of 3 M H2O or with highly coordinating halide ions present, the peak at 450 nm splits into two broader peaks either side of 450 nm with much lower intensity. Evidently, there is significant change in the electronic structure associated with dissociation of the dimer in solution.The electronic structure of the Fe(mnt)2 the Fe(mnt)23− catalyst displays a loss of reversibility due to a coupled homogeneous chemical reaction with CO2 as shown in Figure S13. This promising behaviour indicated likely catalytic activity, facilitated by the trace water in the electrolyte originating from the synthesised catalyst dihydrate (proton source diffusion limitation). However, upon addition of an excess of a suitable proton source, the Fe(mnt)23− catalytic activity towards CO2R is evident, as shown in Figure 2 towards CO2R and HER with H2O as the proton source. Also shown is the electrochemical response in the absence of catalyst recorded at a GC electrode which indicated no significant heterogenous catalysis at the carbon electrode. In the presence of 3 M H2O under CO2 23− at the same potential 23− species is rapidly chemically oxidised by dissolved CO2 and reduced again within the interface, hence the peak displays CO2 diffusion limitation rather than Fe(mnt)2 diffusion limitation. The solubility of CO2 in the MeCN‐based electrolyte is approximately 0.3 M2, the onset of HER is observed beyond −2.25 V vs. Fc. Therefore, a favourably high HER overpotential of approximately 300 mV exists under these conditions. This suggests that electrolysis conducted between −1.9 and −2.2 V vs. Fc should display high selectivity towards CO2R products and produce minimal quantities of H2.In the presence of CO2 Figure a a large23− oxidation peak by ∼30 mV when under N2 21−/2− voltammogram coalesces into a single redox couple, whereas at high concentrations (>5 M H2O) the redox chemistry significantly changes to yield multiple new oxidation and reduction peaks . The deterioration of the voltammetry response is exacerbated when the electrode is swept to lower vertex potentials. These effects indicate that the catalyst is decomposed somewhat by the HER reaction. Despite this, long‐term scanning  of the catalyst HER and CO2R reactions with 3 M H2O  indicated good stability of the catalyst over the applied potential range. The catalytic CO2R peak increases with the concentration of proton donor until CO2 diffusion limitation is established at ∼5 M H2O content, however the HER overpotential continually decreases with increasing water content. We therefore conclude that a water content of ≤3 M provides a suitable balance between CO2R current response, HER overpotential and catalyst stability.Close inspection of the HER voltammogram Figure a highlig2 was also studied using TFE which possesses a relatively low pKa of 12.46 compared to water and other alcohols. As a result, the acidic proton of TFE is significantly dissociated and therefore more labile for protonation of catalytic intermediates. Figure 2R catalysis in the presence of 0.1 M TFE recorded under otherwise identical conditions. Here we observe comparable behaviour to Figure 2R peak current at −2.20 V vs. Fc. In TFE the onset of HER occurs at less negative potentials such that the waveform differs in Figure 2R peak merges with the HER. Approximately only 200 mV of HER overpotential exists and HER begins to dominate the catalysis beyond −2.5 V vs. Fc. By varying the TFE content , the competing HER reaction was found to become very problematic beyond concentrations of 1 M. As such, TFE concentrations of ≤0.5 M appear most suitable for mitigating the HER. Under N2, the HER voltammogram shows a significant negative shift of the Fe(mnt)21−/2− redox couple on the second scan onwards . This new redox couple displays only one cathodic and anodic peak with a significantly smaller peak separation of 72 mV. Evidently, a new species is generated during the HER mechanism which displays a long lifetime and is fully reversible.The catalytic activity of Fe(mnt)2 complex, cyclic voltammetry of the system was analysed using the approach outlined by Costentin and Savéant.) such that the gradient of this line can be used to determine k, which is equal to the TOFmax under these conditions. As with Tafel analysis, only the gradient of the initial linear portion of the line should be used to estimate the TOFmax, where side phenomena including mass transport limitation are assumed to be negligible. Using this value, it is then possible to determine the TOF at zero overpotential (TOF0) so that the performance of the catalyst can be compared fairly with other catalysts. However, this requires determining the standard potential for the specific reaction taking place, and as a transient method cyclic voltammetry offers no insight into the product(s) of the reduction and so does not entirely avoid the need for bulk electrolysis.FOWA is done using Equation 1 by plotting the diffusion normalised current against 1/ yields a TOFmax of 21.7 s−1. This value is of course specific to the exact reaction conditions. The rate constant k is the overall rate constant for the reduction reaction(s) and cannot be deconvoluted from the substrate concentration without knowing its involvement in the rate limiting step. This is compounded when multiple products are created, each with their own rate limiting step. A relatively low turnover frequency would explain why diffusion character dominates the cyclic voltammogram at fast scan rates, as on these timescales only a small portion of the current is provided by catalytic cycling. A catalyst with a high turnover frequency, such as the widely reported Fe‐porphyrin complexes, would possess a TOFmax of magnitude 104 s−1.Applying this methodology to data from cyclic voltammetry performed on a solution of 1 mM Fe(mnt)2 catalysed CO2R reaction, bulk electrolysis experiments were conducted to quantify the gaseous and liquid products as a function of proton source. Representative results and analysis are shown in Figure S36 and Figure S37 for H2O and TFE electrolytes respectively. Here, electrolysis was conducted to a total charge threshold of 100 C and the working electrode area was adjusted as needed to produce comparable currents (∼15 mA) and total electrolysis time of approximately 1.5 to 2 h. These measures ensured that the moles of product and associated concentrations were comparable between experiments so detection and quantification would be unbiased as peaks would reside above instrument‐associated detection limits. As a further consequence, the catalyst utilisation was approximately 3.5 in each experiment; assuming no parasitic loses and two‐electron reduction in each instance . Therefore, the imposed charge limit ensured that the entire quantity of catalyst was reduced at least threefold to assess stability. Critically, the catalyst persisted to completion of 100 C in each instance which proves that the catalyst is not consumed during reaction with dissolved CO2.To identify the products from the Fe(mnt)2 can provide two‐electrons per molecule for driving catalytic reactions which suggests that the two‐electron products H2, CO and CHOOH will be generated. However, the possibility of further‐reduced products being generated should not be immediately ruled out. This is because cyclical regeneration of the catalyst at the electrode interface is plausible, thus resulting in further reductions of intermediates. Despite this, only H2, CO and CHOOH were detected in our analysis, whereas other hydrocarbons were not observed . The yields of these products are shown in Figure 2O and TFE proton sources. In both cases, electrolysis experiments gave low yields such that the total quantified faradaic efficiency was only 24±5% and 47±4% for H2O and TFE respectively. Evidently, the majority of charge passed is unaccounted for in our analysis which is in part attributed to uncompensated cell resistance and product loss. Indeed, achieving a gas‐tight electrolysis cell proved challenging over long‐duration experiments causing losses of gaseous products. To estimate the degree of product loss, we conducted comparable water splitting electrolysis experiments using 1 M sulfuric acid electrolyte. Here, 100 C was passed galvanostatically at 13.8 mA (corresponding to a 2 h electrolysis) giving a H2 faradaic yield of 67±2%. This suggests that approximately one‐third of the generated H2 gas was lost or remained dissolved in the electrolyte. Consequently, we speculate that gaseous yields in our catalysis experiments were higher than those measured, however this only hypothetically increases total yields to 32 and 50 % for H2O and TFE proton sources, respectively.As shown by voltammetry, reduction of Fe(mnt)2 production is more favoured than CO production for both proton sources. This result is surprising because the applied potentials resided before the onset of HER for both proton sources as indicated in Figure 2 is an effective catalyst for HER, as noted by others.2, we quantify higher H2 yields of 31 and 23 % for H2O and TFE proton sources, respectively.Considering the product yields in Figure 2O as the proton source. Instead, the Fe(mnt)2 catalyst favours H2 and CO production with average yields of 19±3 and 5±2% and TONs of 0.7 and 0.2 respectively. This preference towards CHOOH when using TFE was also observed by Fogeron et al. for the analogous nickel molybdopterin‐like dithiolene complex.2O, methanol, and phenol, respectively. Their work showed that the product distribution was very dependent on the electrolyte acidity with too weakly or too strongly acidic solutions giving lower CHOOH yield than their most optimum 2 M TFE electrolyte. This therefore suggests that careful manipulation of the electrolyte acidity in the present study could in theory tune the product distribution towards higher CHOOH selectivity.A more striking result shown in Figure 2 may be a suitable CO2R catalyst given that it is protected from oxygen and that the CO2R reaction regenerates the Fe(mnt)1− species. Indeed, long term cyclic voltammetry experiments  showed minimal changes in current response under various conditions; without proton source under N2 , and with 3 M H2O  and 100 mM TFE  under N2 and CO2. These results suggested good electrochemical stability, at least under transient voltammetry conditions.A catalyst solution stored within a nitrogen glovebox for six months gave near‐identical electrochemical response to that of a freshly prepared solution . In contrast, comparable solutions stored under ambient conditions gave completely unrecognisable voltammetry after only two weeks. This observation suggested that Fe(mnt)2 in CO2R electrolysis experiments unfortunately highlighted additional stability issues. During the course of our studies, we noted that Fe(mnt)2 degrades during storage via a tendency to react with the electrolyte. This was most evident for electrolytes containing H2O proton source, whereby gradual discolouration of the catalyst solution  was accompanied by precipitation of a yellow‐orange solid and brown staining of the glassware that required strong acid to clean. We attribute this to oxidative decomposition of the complex that produces an insoluble iron oxide. The rate of this degradation was found to accelerate with increasing H2O concentration such that 7 M H2O solutions completely decomposed in under one day of ambient storage. In comparison, solutions containing the TFE proton source appeared to degrade no faster than those containing only supporting TBAPF6 electrolyte, which suggested that water‐reactivity is problematic. Despite this, electrolyte degradation during CO2R electrolysis was evident for both proton sources after only 2 h experiments. Electrolyte discolouration was observed for solutions containing 3 M H2O or 100 mM TFE, with precipitated solid observed in the post‐electrolysis H2O solution. In addition, the electrolysis current response typically decreased with time in all experiments, and cyclic voltammetry performed afterwards showed slightly diminished CO2R current response . These observations indicated only short‐term viability of the catalyst, which limited the duration of our electrolysis experiments to ∼2 h for reliable product quantification. Interestingly, electrolysis experiments with 3 M H2O proton source performed under Ar gas caused the most rapid decomposition observed, with entire decomposition occurring in ∼1 h, which implies electrochemically induced decomposition via reactivity with H2O. Considering the high reactivity of the Fe(mnt)2 catalyst towards the electrolyte, H2O and O2, we speculate that the low faradaic yields of H2, CO and CHOOH measured are likely due to competing parasitic reactions of the catalyst. This is most likely a combination of self‐discharge; whereby the reduced catalyst is oxidised by the electrolyte solvent or supporting salt, and to a lesser extent, decomposition reactions. Here we note that cyclic voltammetry performed post‐CO2R electrolysis showed minimal decrease in current response which indicates that only a small portion of catalyst decomposition occurred .Employing Fe(mnt)2 catalyst to form the trianionic state. This activated state then binds a proton to initiate H2 or CHOOH production, or CO2 to initiate CO production. Despite the poor ability of DFT to provide a reliable, quantitative description of the Fe(mnt)3− state, qualitative analysis of this state along with quantitative analysis of the other structures proposed, allowed for the derivation of a plausible mechanistic route that reflects the product distribution in relation to proton source. Here we assume that reductions occur before bindings, however we acknowledge that these bindings may plausibly form prior to catalyst reduction. Close examination of the first voltammetry scans shown in Figure S19 and Figure S20 shows that the catalyst behaves essentially as unbound in the initial conditions, which suggests that bindings with the monoanionic state do not occur. Despite the possibility of substrate binding to the dianionic species, no catalytic current is observed until a second reduction of the catalyst has taken place; as such, pathways involving dianionic binding were not considered during this work. Though it has been recognised in other photochemical systems that the dianionic species of several other Fe‐dithiolene complexes are catalytic towards HER.Based on the experimental observations and computational studies, we propose reaction mechanisms as illustrated in Figure 2 must proceed by the binding of two protons to the catalyst within sufficient proximity to form a H2 molecule, as characterised by its short bond length of 0.74 Å. Therefore, the only plausible pathway proceeds by protonation of the Fe centre and one adjacent S donor. Here, the first protonation most likely proceeds at the Fe centre because the [FeH(mnt)2]2− geometry lies 14.7 kcal mol−1 lower in energy compared to the [Fe(mnt)(mnt‐H)]2− alternative. In addition, we compute a small intramolecular rearrangement barrier of only 2.7 kcal mol−1 from the [Fe(mnt)(mnt‐H)]2− state which suggests facile interconversion. In both cases, the protonation induces minimal change in coordination geometry with near‐planarity maintained. Sequential protonation at a S donor then occurs in the cis conformation which lies at a negligibly higher energy compared to the trans conformation. Investigation of cis‐trans interconversion showed a significant barrier, coupled to a large geometric rearrangement, suggesting the need for dissociation, and rebinding in order to convert from a trans confirmation to a catalytically active cis geometry. We therefore speculate that trans‐deprotonation and subsequent cis‐protonation is likely more facile. Regardless, electrochemical results show that the H2 mechanism is facile at high overpotential which suggests that formation of the trans conformation imposes little kinetic limitation. Finally, release of H2 proceeds with a small barrier of 20 kcal mol−1.Production of H2 to the trianionic catalyst state. In examining possible CO2 binding modes, we obtain and identify η1‐CO2 as the lowest energy conformation. Indeed, the η2‐CO2 and η1‐OCO modes could not be obtained because these structures tended to relax in energy to the η1‐CO2 geometry during optimisation. The [Fe(mnt)2(η1‐CO2)]3− geometry is characterised by a O−C−O angle of 126° and C−O bond elongation from 1.17 to 1.26 Å indicating CO2 activation and resemblance with the radical anion CO2⋅− (133° bond angle and 1.25 Å bond length). This state is then protonated to give the carboxylate intermediate [Fe(mnt)2(C(O)OH)]2− which, in the presence of another proton, undergoes heterolytic C−O bond cleavage releasing water. This then yields [Fe(mnt)2(CO)]1− which consequently dissociates CO with a transition state barrier of 11 kcal mol−1.Production of CO proceeds by direct coordination of CO2(η1‐OCO)]3− and subsequent protonation to [Fe(mnt)2(OCHO)]2− followed by CHOO− release as in Ni(cyclam);2]2− hydride by CO2 as in molybdpterin‐like Ni(dithiolene);2 yielding [Fe(mnt)2(OCHO)]2− followed by CHOO− release. Considering that the η1‐OCO adduct is energetically disfavoured compared to the η1‐CO2 mode, we conclude that pathway (1) is unlikely. Pathway (2) was investigated; however, a suitable concerted transition state was not obtained, and instead the hydride insertion transition state invoked in (3) was found to be more plausible. Therefore, while we cannot discount the plausibility of (1) and (2), we are able to note the apparent favourability of (3) in our simulations. This conclusion is consistent with our voltammetry results whereby a change of the catalyst structure is evident in the N2 voltammograms with H2O and, to a greater extent, TFE proton sources 21−/2− redox couple is reminiscent of the catalyst response in the absence of proton source or CO2 2]2− does not poison the catalyst towards CO2R but is rather the initiating reaction step for CHOOH production. Evidently, the formation of the initial [FeH(mnt)2]2− hydride is crucial in the CHOOH mechanism. Therefore, the observed CHOOH production when using TFE is likely explained by the higher acidity of the electrolyte, which facilitates the formation of a longer‐lifetime hydride.Production of CHOOH may occur by one of three plausible pathways: (1) formation of the intermediate 2− species in solution. The prevalence of this dimer appears suppressed during catalysis, however, due to catalyst protonation and CO2‐adduct formation.The dithiolene complex Fe(mnt)2, CO and CHOOH. Comparing water and TFE as proton sources, the selectivity and performance was markedly different, with the catalyst displaying a comparatively higher selectivity towards CHOOH production when using TFE, whereas none was observed in the presence of water. DFT was used to investigate the catalytic mechanism, wherein the formation of an initial hydride species was identified as critical in the production of CHOOH. This is typical of the mechanism associated with the formation of CHOOH with other homogeneous complexes. Further tuning of solution pH may therefore lead to a further increase in selectivity towards formate. This work represents a promising starting point for Fe‐based dithiolene CO2R catalysis, and further study of analogous derivatives.During electrolysis, the complex typically produced two‐electron reduction products; namely HAll chemicals and reagents were used without further purification, with the exception of tetrabutylammonium hexafluorophosphate which was recrystallised from hot ethanol. Chloroacetonitrile (98 %), sodium hydroxide , N,N‐dimethylformamide , isobutanol (99 %) and 2,2,2‐tiflouroethanol (99+%) were purchased from Alfa Aesar. Sulfur , acetonitrile  and tetraethylammonium chloride hydrate (99 %) were purchased from Acros Organics. Isopropanol , ethanol  and iron(III) chloride  were purchased from Fisher Scientific. Tetrabutylammonium hexafluorophosphate (>98 %) was purchased from Tokyo Chemical Industry UK Ltd. Ferrocene (98 %) was purchased from Sigma Aldrich.2] was prepared by use of the method published in ref(TEA)[Fe(mnt)3+, Autolab PGSTAT204 or Bio‐Logic SP‐300 potentiostat. Voltammetry investigations were performed using a standard three‐electrode cell (BASI®) with an electrolyte volume of 20 mL. A glassy‐carbon (GC) macro electrode with a 7.05 mm2 electroactive area was employed as a working electrode (WE) whereas a platinum wire served as the counter electrode (CE). A silver wire housed in a glass‐fritted tube containing supporting electrolyte was employed as a quasi‐reference electrode (RE). Before use, a layer of AgPF6 was deposited on the Ag wire by oxidation in TBAPF6/MeCN electrolyte. The quasi‐reference was calibrated against the Ferrocene/Ferrocenium ion (Fc/Fc+) redox couple after voltammetry investigations by addition of Fc to the test solution. Prior to conducting voltammetry, saturation of the test solution was ensured by bubbling with either N2 or CO2 gas for 10 mins, whereas during scans, the headspace was continuously flushed. The GC WE was polished before use using two grades of diamond slurry (3 and 0.25 μM) and alumina slurry (0.05 μM) purchased from Büehler. Electrodes were then sonicated in 50 % v/v iPrOH/H2O solution for 5 mins before rinsing with deionised water then iPrOH and finally being air dried with compressed air.Electrochemical investigations were performed using either a Palmsens EmStat6 supporting salt in MeCN solvent with either 100 mM TFE or 3 M H2O as the proton source. Prior to electrolysis, the cathode compartment was saturated with CO2 by bubbling through the electrolyte for 20 mins. In contrast, the anode chamber was continuously bubbled with Ar gas during electrolysis to protect the Fc+ ion from decomposition due to air sensitivity.Bulk electrolysis experiments were conducted by use of a custom H‐type glass cell comprised of two electrolyte chambers separated by a Nafion® 117 membrane. High‐purity graphite rods (Goodfellows 99.997 %) served as both the WE and CE, whereas the previously described Ag electrode served as the RE which was placed within close proximity to the WE (∼2 mm separation). The cathode compartment was filled with a 150 mL catalyst solution at 1 mM concentration which was paired with a sacrificial 100 mL Fc electrolyte at 25 mM concentration within the anode compartment. Each electrolyte contained 100 mM TBAPF2R electrolysis experiments were analysed by use of a gas chromatograph equipped with a ResTek Sin Carbon ST 80/100 column and barrier ionisation detector (Shimadzu GC‐BID 2030). The instrument was calibrated in the 0–1000 ppm range for gaseous products H2, CO, CH4 and C2H4 by use of calibration gas supplied by BOC Ltd. Calibration curves and limits of detection are given in the supporting information. Calibration samples were prepared and introduced into the GC‐BID by use of a sealed pressure vessel assembled from stainless steel fittings . For product analysis, a gas‐tight syringe  was used to sample the electrochemical headspace and dilute the sample concentration into the calibration range  using CO2 gas.Gaseous products from CO1 NMR spectroscopy (Bruker 400 Hz) with a solvent suppression method to account for the non‐deuterated MeCN electrolyte used in electrolysis experiments. Quantification of products was achieved by use of non‐deuterated DMSO as an internal standard at 10 mM concentration; NMR samples were prepared by diluting 2 mL of a 100 mM DMSO solution in MeCN with 18 mL of post‐electrolysis Fe(mnt)2 catalyst solution in a 20 mL volumetric flask. The concentration of liquid phase products was then calculated on a proton basis.Liquid phase products were analysed using Hϵ=35.688) was chosen as the solvent, consistent with the experiment. Minima and transition state geometries where determined through vibrational frequency analysis such that minima possess solely positive curvature and transition states showed a single vibration of negative curvature.To aid mechanistic understanding, a DFT study was conducted to obtain key reaction intermediates and transition states. Simulations were performed using the Gaussian 09 (Revision E.01) programThe authors declare no conflict of interest.1As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re‐organized for online delivery, but are not copy‐edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors.Supporting InformationClick here for additional data file.