Redox-active Molecules Research Articles

Recent Advances in NIR-Switchable Multi-Redox Systems Based on Organic Molecules.

In recent years, near-infrared (NIR) dyes, exhibiting absorption in the NIR region (750-2500 nm), have been applied to various optical applications such as security marking, photovoltaic cells and chemotherapy of deep tissues in vivo. Electrochromic systems capable of switching NIR absorption are attractive from the viewpoint of applications for material and life science, and thus several examples have been reported to date. The development of organic-based materials is needed to reduce the environmental impact and improve biocompatibility, however, the switching of NIR absorption based on redox interconversion is still a challenging issue regarding reversibility and durability during interconversion. To overcome this potential instability, several studies on organic electrochromic systems that allow ON/OFF switching of NIR absorption have been developed in recent years. In this review, we focus on redox-active well-defined small molecules that enable ON/OFF switching of NIR absorption, and present recent studies on their intrinsic electrochemical and spectroscopic properties and/or structural characterization of their charged states. We also address more sophisticated electrochromic systems that can modulate their properties in response to external stimuli such as light, heat, and electric potential.

Redox-active molecules in bacterial cultivation media produce photocurrent.

Renewable energy concepts such as microbial fuel cells (MFCs) present a promising, yet intrinsically complex electrochemical approach for utilizing bacteria as an electron source. In this work, we show that just the cultivation media for bacterial growth, which is based on yeast extract, is sufficient for generating electrical current in a bio-electrochemical cell (BEC). We apply cyclic voltammetry and 2-dimensional fluorescence spectroscopy to identify redox active molecules such as NADH, NAD+, and flavines that may play key roles in electron donation. Finally, we show that upon illumination, current production is enhanced 2-fold. This photocurrent is generated by a variety of metabolites capable of photochemical reduction, enabling them to donate electrons at the anode of the BEC.

Polymerization of redox-active alizarin in biomass porous carbon with enhanced cycling stability for supercapacitor

Redox-active organic molecules have optimistic application prospects in energy storage due to their high theoretical capacitance, designable electrochemical activity and environmental friendliness. However, low conductivity and solubility in electrolyte severely hinder their redox activity. Here, alizarin molecules containing carbonyl and phenolic hydroxyl are encapsulated in biomass-derived porous carbon, and stable alizarin polymers are further grown on porous carbon substrate by electrochemical polymerization. Porous carbon as conductive network can improve electron transport properties, and provide suitable accommodation environment for confinement and polymerization of alizarin. The electrochemical polymerization strategy on carbon substrate allows alizarin to be connected by rigid C-O-C bond, which inhibits the dissolution of organic monomers while maintaining redox activity. The optimized polyalizarin/porous carbon composite (PAZ/PC-0.5) exhibits superior charge storage performance, with a specific capacitance of 355.8 F g−1 at 1 A g−1 and 220.8 F g−1 at high current density of 30 A g−1. Moreover, PAZ/PC electrode has more durable long-term charge-discharge stability (capacitance retention is 98 % after 10,000 charge and discharge cycles). The assembled symmetrical supercapacitor exhibits excellent energy-power characteristics (21.4 Wh kg−1 at 700 W kg−1) and durable cycle stability. This work sheds light on the design of stable organic electrode towards high-performance supercapacitor.

A highly water-soluble phenoxazine quaternary ammonium compound catholyte for pH-neutral aqueous organic redox flow batteries

The pH-neutral aqueous redox flow battery (ARFB) is one of the most attractive flow batteries due to its non-corrosiveness, low-cost, and wider electrochemical stability window compared to those with acidic or alkaline electrolytes. However, there are few families of organic redox-active molecules available as catholyte materials for pH-neutral ARFBs. Herein, through incorporation of quaternary ammonium moiety into the redox-active phenoxazine nucleus, an organic catholyte material, N, N, N-trimethyl-2-(10H-phenoxazin-10-yl) ethan-1-aminium chloride (NEt-POZ) is achieved for pH-neutral ARFBs. The NEt-POZ has a high redox potential of 0.79 V versus SHE and rapid redox kinetics (0.23 cm s−1) as well as high water-solubility (∼2.6 M in H2O). Paired with a methyl viologen (MV) anolyte in the pH-neutral aqueous electrolyte, a viologen-phenoxazine ARFB full cell is assembled, which shows an open circuit voltage of ∼1.23 V. However, the results of long-term cycling experiments indicate low Coulomb efficiency and rapid declining capacity of the NEt-POZ catholyte. The mechanism analysis unveils that the unstable doubly oxidized tri-cations (NEt-POZ3+) formed via the disproportionation of radical di-cations (NEt-POZ2+) in solution readily react with chloride anions to form poly-chlorinated derivatives, which precipitate from the catholyte due to their poor water solubility, leading to a rapid decrease in capacity. When there is no chloride present in the electrolyte solution, highly reactive NEt-POZ3+ cations can interact with other counter-anions (such as sulfate and carbonate ions) and even water to form complex adducts.

In Situ Molecular Reconfiguration of Pyrene Redox-Active Molecules for High-Performance Aqueous Organic Flow Batteries.

Aqueous organic flow batteries (AOFBs) hold great potential for large-scale energy storage, however, scalable, green, and economical synthetic methods for stable organic redox-active molecules (ORAMs) are still required for their practical applications. Herein, pyrene-based ORAMs are obtained via an in situ organic electrolysis strategy in a flow cell. It is revealed that the water attacking pyrenes restructured molecules to produce a variety of isomers and dimers during the electrolysis, which can be modulated by regulating the local electron cloud density and steric hindrance of pyrene precursors. As a result, the molecularly reconfigured pyrene-based catholytes, even without any further purification, achieved a high electrolyte utilization of ≈96% and volumetric capacity above 50AhL-1. Inspiringly, remarkable cell stability with almost no capacity decay for ≈70 days is achieved, benefiting from the robust aromatic structure of the pyrene cores. The insights into the in situ electrosynthesis of pyrene-based ORAMs provided in the work will provide guidance for designing ultra-stable ORAMs for AOFB applications.

Redox-Induced Aromatic Substitution: A Study on Guanidino-Functionalized Aromatics.

Aromatic substitution of redox-active aromatic compounds could be initiated by a preceding redox step. We report on the different reaction pathways of such redox-induced substitution (RIAS) reactions between a redox-active guanidino-functionalized aromatic molecule (GFA) and an amine or guanidine. Oxidation of the GFA leads to an umpolung of the guanidine from a nucleophile to an electrophile and thereby enables addition of the amine or guanidine. Several examples are given, demonstrating the use of redox substitution in synthetic chemistry, e.g. for the convenient synthesis of novel N-heteropolycyclic molecules and unsymmetrically-substituted aromatics.

Dehydrogenative Coupling Reactions with Guanidino-Functionalized Aromatics.

Dehydrogenative coupling (DC) reactions are of importance for the construction of new carbon-element bonds in synthetic organic chemistry. In this work, we report on the synthesis and characterization of several redox-active guanidino-functionalized aromatic molecules (GFAs) for use in DC (C-C and C-O) reactions. In a systematic approach, we first characterize the new DC reagents in all relevant redox and protonation states, and compare their performance in competitive test proton-coupled electron transfer (PCET) reactions. Then, their use in four different DC reactions with different mechanisms is evaluated.

Bio-inspired 3D-Printed supercapacitors for sustainable energy storage

This study presents a significant enhancement of the electrochemical properties of commercially available high-surface-area bare activated carbon (BAC) through the grafting of catechin hydrate (CH) redox active molecules. The grafting of CH onto the BAC was confirmed by the results from the Thermogravimetric analysis, X-ray photoelectron spectroscopy and Brunauer-Emmett-Teller. Moreover, this study introduces 3D printed deep eutectic solvent electrolytes, composed of choline chloride and urea, highlighting the potential of sustainable and greener materials in energy storage. A 3D-printed fully bio-inspired supercapacitor achieved a maximum specific capacitance of 75 F g−1 at a scan rate of 1 mV s−1 (37 F g−1 at a current density of 0.2 A g−1), demonstrating performance comparable to that of previously reported state-of-the-art fully 3D-printed and disposable paper supercapacitors (25.6 F g−1 at a scan rate of 1 mV s−1 for 1.2 V). Furthermore, the device exhibited electrochemical performance within an extended potential window of 2.0 V, coupled with cycling stability of approximately 90.2 % after 10,000 cycles, offering a specific energy of 20.6 W h kg−1 at a specific power of 560 W kg−1. The developed bio-inspired, eco-friendly, sustainable, 3D-printed supercapacitors can replace the harmful Li-ion batteries currently used in low-power wireless sensor applications.

Opening the Hysteresis Loop in Ferromagnetic Fe3GeTe2 Nanosheets Through Functionalization with TCNQ Molecules.

Ferromagnetic metal Fe3GeTe2 (FGT), whose structure exhibits weak van-der-Waals interactions between 5-atom thick layers, was subjected to liquid-phase exfoliation (LPE) in N-methyl pyrrolidone (NMP) to yield a suspension of nanosheets that were separated into several fractions by successive centrifugation at different speeds. Electron microscopy confirmed successful exfoliation of bulk FGT to nanosheets as thin as 6 nm. The ferromagnetic ordering temperature for the nanosheets gradually decreased with the increase in the centrifugation speed used to isolate the 2D material. These nanosheets were resuspended in NMP and treated with an organic acceptor, 7,7,8,8-tetracyano-quinodimethane (TCNQ), which led to precipitation of FGT-TCNQ composite. The formation of the composite material is accompanied by charge transfer from the FGT nanosheets to TCNQ molecules, generating TCNQ•- radical anions, as revealed by experimental vibrational spectra and supported by first principles calculations. Remarkably, a substantial increase in magnetic anisotropy was observed, as manifested by the increase in the coercive field from nearly zero in bulk FGT to 1.0 kOe in the exfoliated nanosheets and then to 5.4kOe in the FGT-TCNQ composite. The dramatic increase in coercivity of the composite suggests that functionalization with redox-active molecules provides an appealing pathway to enhancing magnetic properties of 2D materials.

Continuous Monitoring of Monochloramine in Water, and Its Distinction from Free Chlorine and Dichloramine Using a Functionalized Graphene-Based Array of Chemiresistors.

Monochloramine (MCA) is commonly added to drinking water as a disinfectant to prevent pathogen growth. The generation of MCA at the treatment plant requires tight control over both pH and the ratio of free chlorine (FC) to ammonia to avoid forming undesirable byproducts such as dichloramine (DCA) and trichloramine (TCA), which can impart odor and toxicity to the water. Therefore, continuous monitoring of MCA is essential to ensuring drinking water quality. Currently, standard colorimetric methods to measure MCA rely on the use of reagents and are unsuitable for online monitoring. In addition, other oxidants can interfere with MCA measurement. Here, we present a solid-state, reagent-free MCA sensing method using an array of few-layer graphene (FLG) chemiresistors. The array consists of exfoliated FLG chemiresistors functionalized with specific redox-active molecules that have differential responses to MCA, FC, and DCA over a range of concentrations. Chemometric methods were employed to separate the analytes' responses and to generate multivariate calibration for quantification. A minimum of three sensors are required in the array to maintain full functionality. The array has been demonstrated to quantify MCA in buffered and tap water as a low-cost, reagent-free approach to continuous monitoring.

Correlating the structure of quinone-functionalized carbons with electrochemical CO2 capture performance

Electrochemical carbon dioxide capture is emerging as an energy-efficient alternative to traditional carbon capture technology. In particular, redox-active molecules that can capture carbon dioxide when electrochemically reduced and release carbon dioxide when electrochemically re-oxidized are under active development. To prepare a carbon capture device, these molecules can be incorporated into a solid electrode in a battery-like cell. In this work, we explore the scope of a recently developed method where anthraquinones are covalently attached to porous carbon supports to obtain electrodes for electrochemical carbon dioxide capture. We functionalize four different porous carbon materials with varying porosities and surface chemistries, and use gas sorption analysis and solid-state NMR spectroscopy to probe the location of the grafted anthraquinones. All four functionalized materials show electrochemically mediated capture and release of carbon dioxide, and we explore the factors that determine their performance. While the anthraquinone-functionalized mesoporous carbon, f-CMK-3, showed the highest quinone loading, it showed poor quinone utilization for CO2 capture and poor long-term cycling stability. In contrast, the predominantly microporous functionalized carbon, f-YP-80F, showed a higher quinone utilization and improved cycling stability. This work can guide the design of functionalized carbon electrodes for electrochemical carbon dioxide capture.

Nonfunctional coq10 mutants maintain the ERMES complex and reveal true phenotypes associated with the loss of the coenzyme Q chaperone protein Coq10

Coenzyme Q (CoQ) is a redox-active lipid molecule that acts as an electron carrier in the mitochondrial electron transport chain. In Saccharomyces cerevisiae, CoQ is synthesized in the mitochondrial matrix by a multi-subunit protein-lipid complex termed the CoQ synthome, the spatial positioning of which is coordinated by the Endoplasmic Reticulum-Mitochondria Encounter Structure (ERMES). The MDM12 gene encoding the cytosolic subunit of ERMES, is co-expressed with COQ10, which encodes the putative CoQ chaperone Coq10, via a shared bidirectional promoter. Deletion of COQ10 results in respiratory deficiency, impaired CoQ biosynthesis, and reduced spatial coordination between ERMES and the CoQ Synthome. While Coq10 protein content is maintained upon deletion of MDM12, we show that deletion of COQ10 by replacement with a HIS3 marker results in diminished Mdm12 protein content. Since deletion of individual ERMES subunits prevents ERMES formation, we asked whether some or all of the phenotypes associated with COQ10 deletion result from ERMES dysfunction. To identify the phenotypes resulting solely due to the loss of Coq10, we constructed strains expressing a functionally impaired (coq10-L96S) or truncated (coq10-R147*) Coq10 isoform using CRISPR-Cas9. We show that both coq10 mutants preserve Mdm12 protein content and exhibit impaired respiratory capacity like the coq10Δ mutant, indicating that Coq10's function is vital for respiration regardless of ERMES integrity. Moreover, the maintenance of CoQ synthome stability and efficient CoQ biosynthesis observed for the coq10-R147* mutant suggests these deleterious phenotypes in the coq10Δ mutant result from ERMES disruption. Overall, this study clarifies the role of Coq10 in modulating CoQ biosynthesis.

High-Performance p-type organic electrode materials with oxygen atoms as active centers enabled by molecular design and in situ electropolymerization

Redox-active organic molecules are considered to be one type of promising electrode materials for next generation lithium-ion batteries (LIBs), among which p-type electrode materials with higher voltage and outstanding reaction kinetics receive much attention. However, it is a great challenge to develop p-type materials with oxygen atom as the active center and the electrochemical performance of the few reported examples needs significant improvement. Herein, 1,3,5-tri(benzofuran-2-yl)benzene (TBFB) was elaborately designed and facilely synthesized through one-step Suzuki coupling reaction from commercially available raw reagents. When used as p-type electrode material for LIBs, it was found that TBFB with poor solubility can be effectively in situ electropolymerized during the charging process, forming more insoluble polymers. Experimental results demonstrate that TBFB electrode achieves a high specific capacity of 179.1 mAh g−1 and an ultralong cycle life of 8000 cycles. This work manifests the electrochemical performance of p-type organic electrode materials with oxygen atom as active center can be effectively enhanced by rational molecular design and in situ electropolymerization method.

Characterizing Mediated Extracellular Electron Transfer in Lactic Acid Bacteria with a Three-Electrode, Two-Chamber Bioelectrochemical System.

Many bacteria perform extracellular electron transfer (EET), whereby electrons are transferred from the cell to an extracellular terminal electron acceptor. This electron acceptor can be an electrode and electrons can be delivered indirectly via a redox-active mediator molecule. Here, we present a protocol to study mediated EET in Lactiplantibacillus plantarum, a probiotic lactic acid bacterium widely used in the food industry, using a bioelectrochemical system. We detail how to assemble a three-electrode, two-chambered bioelectrochemical system and provide guidance on characterizing EET in the presence of a soluble mediator using chronoamperometry and cyclic voltammetry techniques. We use representative data from 1,4-dihydroxy-2-naphthoic acid (DHNA)-mediated EET experiments with L. plantarum to demonstrate data analysis and interpretation. The techniques described in this protocol can open new opportunities for electro-fermentation and bioelectrocatalysis. Recent applications of this electrochemical technique with L. plantarum demonstrated an acceleration of metabolic flux towards producing fermentation end-products, which are critical flavor components in food fermentation. As such, this system has the potential to be further developed to alter flavors in food production or produce valuable chemicals.

Perspectives on aqueous organic redox flow batteries

Aqueous organic redox flow batteries (AORFBs) have pioneered new routes for large-scale energy storage. The tunable nature of redox-active organic molecules provides a robust foundation for creating innovative AORFBs with exceptional performance. Molecular engineering endows various organic molecules with considerable advantages in solubility, stability, and redox potential. Advanced characterizations have enabled a comprehensive understanding of the redox reaction and degradation mechanisms of these organic molecules. Computational chemistry and machine learning have guided the development of new organic molecules. The practical application of AORFBs will depend on the complementary efforts of multiple parties. This paper consolidates the current design principles of molecular engineering, degradation mechanisms, characterization techniques, and the utilization of computational chemistry. It also offers perspectives and forecasts the necessary attributes and strategic efforts for the next-generation AORFBs, aiming to provide the research community with a deeper understanding.

(Invited) Designing Photocatalytic Membrane to Direct Electron and Hole Transport

Surface interaction of chromophore or redox active molecule which dictate the efficiency of energy/electron transfer, plays an important role in realizing photocatalytic and optoelectronic applications. Metal halide perovskite nanocrystals are interesting in the sense that they can either transfer energy or selectively transfer electrons or holes to the adsorbed molecules.1,2 The presentation will focus on two specific scenarios of the flow of energy and electron processes in CsPbX3 (X= Br, I) nanocrystal-molecular hybrids. The energy transfer is probed through three moleculr acceptors – rhodamine B (RhB), rhodamine isothiocyanate (RhB-NCS), and rose Bengal (RoseB), which contain an increasing degree of heavy atom pendant groups. Electron and/or hole transfer from excited CsPbX3 nanocrystals to a molecular relay present near the interface offers another avenue to directly convert light energy into chemical energy. Such interfacial electron transfer of semiconductor nanocrystals has been widely explored in photocatalytic processes. A basic understanding of the fundamental differences between the two excited deactivation processes (energy and charge transfer) and ways to modulate them should enable design of more efficient light harvesting assemblies with semiconductor and molecular systems.

Molecular Engineering for Organic Redox-Flow Batteries

Recent advances in organic redox-flow batteries have made them a viable option for grid scale energy storage as they can increase energy density through molecular engineering. Here, we present the importance of molecular engineering as a key factor in the development of novel redox-active organic molecules (ROMs). Importantly, this presentation will highlight the design and synthesis of these molecules and how they are tuned to obtain optimal properties necessary for ROMs that will improve key performance needed in organic-based redox-flow batteries. This talk will feature two distinct classes of compounds as ROMs and will systematically describe their development and application to redox-flow batteries.

Exploring the Role of Redox-Shuttle Mediators in Lithium-Sulfur Batteries

The lithium-ion battery (LIB) is widely acknowledged as the state-of-the-art battery technology today and is used in consumer electronics, stationary storage, and electrified transportation1,2. However, there is a drive towards developing technologies with higher energy densities. The lithium-sulfur battery is one of the most promising next-generation batteries for high-energy applications, due to its high theoretical gravimetric energy density of 2567 W h kg-1, low raw material costs, and reduced environmental impact3. Despite these potential advantages, lithium-sulfur batteries are still beset with difficulties, one of the most significant is the so-called “polysulfide shuttle effect.” Operation of the battery involves the conversion of sulfur to polysulfide species, which dissolve into the electrolyte and diffuse to the lithium metal electrode, leading to loss of active material. This results in poor cycle life, rapid capacity fading and low coulombic efficiencies4.The use of dissolved, electrochemically active redox mediators could mitigate these effects by catalysing sulfur redox reactions during cell cycling. While it is generally agreed that the redox potential of the mediators is a key factor in their operation, no report to date has conclusively demonstrated how mediators of varying potentials can target specific sulfur redox reactions. Herein, we report a study of the mediators 9-fluorenone (9-FO), duroquinone (DQ), 2,6-di-tert-butyl-1,4-benzoquinone (TBBQ) and 1,5-bis(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)anthra-9,10-quinone (AQT) to understand their interactions with sulfur, lithium polysulfides, lithium sulfide and lithium metal5. We use liquid-chromatography mass spectrometry (LC-MS) to isolate various polysulfide chain lengths after reaction with mediators. It is observed that high potential redox mediators, such as TBBQ, are better able to drive Li2S oxidation to higher polysulfide chain lengths, and low potential redox mediators such as 9-FO push sulfur towards lower chain polysulfides. This offers a novel and effective approach to screening suitable redox-active molecules. Galvanostatic cycling is employed to relate these chemical interactions to enhanced cell performance. Developing a fundamental understanding of how redox mediators operate in a cell will aid in the molecular design of novel redox-active compounds.[1] J. Vetter, P. et al: Ageing mechanisms in lithium-ion batteries, J. Power Sources, 2005, 147, 269–281.[2] D. Castelvecchi: Electric cars: the battery challenge, Nature, 2021, 596, 336–339.[3] P. G. Bruce et al: Li-O2 and Li-S batteries with high energy storage, Nat. Mater., 2012, 11, 19–29.[4] S. Zhang et al: Recent advances in electrolytes for lithium-sulfur batteries, Adv. Energy Mater., 2015, 5, 1–28.[5] Y. Tsao et al: Designing a quinone-based redox mediator to facilitate Li2S oxidation in Li-S batteries, Joule, 2019, 3, 872–884.

Square Wave Electrogravimetry Monitors Transient Submonolayer Adsorption of Redox-Active Molecules with a Precision of Less Than 1% of a Monolayer

Square wave voltammetry on electrolytes containing the reversible redox pairs flavin adenine dinucleotide (FAD) and methyl viologen (MV) was complemented by a new form of acoustic microgravimetry. The analytes FAD and MV have promising applications in bacterial fuel cells and redox flow batteries. The instrument operates similarly to a quartz crystal microbalance with dissipation monitoring (EQCM-D). It reports shifts in resonance frequency and half bandwidth on several overtones. Compared to the existing instruments, the time resolution was improved by a factor of 40 down to 2.5 ms by multifrequency lockin amplification, which is important for the analysis of the transients in electrochemistry. The frequency noise after accumulation was reduced below 10 mHz ≙ 0.12 ng/cm2 ≙ 1.2 pm (assuming ρ = 1 g/cm3) by employing modulation and averaging. Square wave modulation of the electrode potential is superior to linear ramps (cyclic voltammetry) because it reduces the contribution of non-Faraday currents and, also, improves sensitivity. The shifts of frequency,Δf, and half bandwidth, ΔΓ, are in line with the Sauerbrey prediction (Δf/n ≈const. and ΔΓ/n < -Δf/nwith n the overtone order). Small deviations (Figure B and D) presumably are caused by the layer’s softness. The apparent shear modulus, G app, of this layer is in the GPa range. The frequency difference, Δf/n|CT (Figure E), amounts to an apparent mass transfer rate. Plots of Δf/n|CT versus potential sometimes show curves similar to the electric current as observed for e. g. MV. For FAD, the results obtained depended on pH and the apparent mass transfer rates are much different from the current (Figure C and E). This difference is most likely caused by adsorbed molecules that are intermediates of the underlying two-electron process. The explanation is further corroborated by the response time of the QCM signals being much larger than the RC time of double layer recharging as determined with EIS. An interpretation in terms of adsorption/desorption is more plausible than an interpretation in terms of changed viscosity in the diffuse double layer.[1] Caption: Currents and frequency shifts obtained on a solution containing FAD. Df/n|av evidences the preferred adsorption of the intermediate state (FADH).

Design of Cr-Based Molecular Electrocatalyst Systems for the CO2 Reduction Reaction.

ConspectusHuman influence on the climate system was recently summarized by the sixth Intergovernmental Panel on Climate Change (IPCC) Assessment Report, which noted that global surface temperatures have increased more rapidly in the last 50 years than in any other 50-year period in the last 2000 years. Elevated global surface temperatures have had detrimental impacts, including more frequent and intense extreme weather patterns like flooding, wildfires, and droughts. In order to limit greenhouse gas emissions, various climate change policies, like emissions trading schemes and carbon taxes, have been implemented in many countries. The most prevalent anthropogenic greenhouse gas emitted is carbon dioxide (CO2), which accounted for 80% of all U.S. greenhouse gas emissions in 2022. The reduction of CO2 through the use of homogeneous electrocatalysts generally follows a two-electron/two-proton pathway to produce either carbon monoxide (CO) with water (H2O) as a coproduct or formic acid (HCOOH). These reduced carbon species are relevant to industrial applications: the Fischer-Tropsch process uses CO and H2 to produce fuels and commodity chemicals, while HCOOH is an energy dense carrier for fuel cells and useful synthetic reagent. Electrochemically reducing CO2 to value-added products is a potential way to address its steadily increasing atmospheric concentrations while supplanting the use of nonrenewable petrochemical reserves through the generation of new carbon-based resources. The selective electrochemical reduction of CO2 (CO2RR) by homogeneous catalyst systems was initially achieved with late (and sometimes costly) transition metal active sites, leading the field to conclude that transition metal complexes based on metals earlier in the periodic table, like chromium (Cr), were nonprivileged for the CO2RR. However, metals early in the table have sufficient reducing power to mediate the CO2RR and therefore could be selective in the correct coordination environment. This Account describes our efforts to develop and optimize novel Cr-based CO2RR catalyst systems through redox-active ligand modification strategies and the use of redox mediators (RMs). RMs are redox-active molecules which can participate cocatalytically during an electrochemical reaction, transferring electrons─often accompanied by protons─to a catalytic active site. Through mechanistic and computational work, we have found that ligand-based redox activity is key to controlling the intrinsic selectivity of these Cr compounds for CO2 activation. Ligand-based redox activity is also essential for developing cocatalytic systems, since it enables through-space interactions with reduced RMs containing redox-active planar aromatic groups, allowing charge transfer to occur within the catalyst assembly. Following a summary of our work, we offer a perspective on the possibilities for future development of catalytic and cocatalytic systems with early transition metals for small molecule activation.