Developing Scaling Relationships for Molecular Electrocatalysis through Studies of Fe-Porphyrin-Catalyzed O2 Reduction.

The oxygen reduction reaction (ORR) is a multiproton/multielectron transformation in which dioxygen (O2) is reduced to water or hydrogen peroxide and serves as the cathode reaction in most fuel cells. The ORR (O2 + 4e- + 4H+ → 2H2O) involves up to nine substrates and thus requires navigating a complicated reaction landscape, typically with several high-energy intermediates. Many catalysts can perform this reaction, though few operate with fast rates and at low overpotentials (close to the thermodynamic potential). Attempts to optimize these parameters, both in homogeneous and heterogeneous electrocatalytic systems, have focused on modifying catalyst design and understanding kinetic/thermodynamic relationships between catalytic intermediates. One such method for analyzing and predicting catalyst reactivity and efficiency has been the development of "molecular scaling relationships". Here, we share our experience deriving and utilizing molecular scaling relationships for soluble, iron-porphyrin-catalyzed O2 reduction in organic solvents. These relationships correlate turnover frequencies (TOFmax) and effective overpotentials (ηeff), properties uniquely defined for homogeneous catalysts. Following a general introduction of scaling relationships for both homogeneous and heterogeneous electrocatalysis, we describe the components of such scaling relationships: (i) the overall thermochemistry of the reaction and (ii) the rate and rate law of the catalyzed reaction. We then show how connecting these thermodynamic and kinetic parameters reveals multiple molecular scaling relationships for iron-porphyrin-catalyzed O2 reduction. For example, the log(TOFmax) responds steeply to changes in ηeff that result from different catalyst reduction potentials (18.5 decades in TOFmax/V in ηeff) but much less dramatically to changes in ηeff that arise from varying the pKa of the acid buffer (5.1 decades in TOFmax/V in ηeff). Thus, a single scaling relationship is not always sufficient for describing molecular electrocatalysis. This is particularly evident when the catalyst identity and reaction conditions are coupled. Using these multiple scaling relationships, we demonstrate that the metrics of turnover frequency and effective overpotential can be predictably tuned to achieve faster rates at lowered overpotentials. This Account uses a collection of related stories describing our research on soluble iron-porphyrin-catalyzed ORR to show how molecular scaling relationships can be derived and used for any electrocatalytic reaction. Such scaling relationships are powerful tools that connect the thermochemistry, mechanism, and rate law for a catalytic system. We hope that this collection shows the utility and simplicity of the molecular scaling approach for understanding catalysis, for enabling direct comparisons between catalyst systems, and for optimizing catalytic processes.

Interfacial Field-Driven Proton-Coupled Electron Transfer at Graphite-Conjugated Organic Acids.

Interfacial proton-coupled electron transfer (PCET) reactions are central to the operation of a wide array of energy conversion technologies, but molecular-level insights into interfacial PCET are limited. At carbon surfaces, designer sites for interfacial PCET can be incorporated by conjugating organic acid functional groups to graphite edges though aromatic phenazine linkages. At these graphite-conjugated catalysts (GCCs) bearing organic acid moieties, PCET is driven by complex interfacial electrostatic and field gradients that are difficult to probe experimentally. Herein, the spatially inhomogeneous interfacial electrostatic potentials and electric fields of GCC organic acids are computed as functions of applied potential. The calculated proton-coupled redox potentials for the PCET reactions at the GCC phenazine bridges and organic acid sites are in agreement with cyclic voltammetry measurements for a series of GCC acids. The trends in these redox potentials are explained in terms of the acidity of the molecular analogues and continuous conjugation between the acid and the graphite surface. The calculations illustrate that this conjugation is interrupted in a GCC acetic acid system, providing an explanation for the absence of a cyclic voltammetry peak corresponding to PCET at this acid site. This combined theoretical and experimental study demonstrates the critical role of continuous conjugation and strong electronic coupling between the GCC acid site and the graphite to enable interfacial field-driven PCET at the acid site. Understanding the connection between the atomic structure of the surface and the interfacial electrostatic potentials and fields that govern PCET thermochemistry may guide heterogeneous catalyst design.

Oxygen Reduction by Homogeneous Molecular Catalysts and Electrocatalysts.

The oxygen reduction reaction (ORR) is a key component of biological processes and energy technologies. This Review provides a comprehensive report of soluble molecular catalysts and electrocatalysts for the ORR. The precise synthetic control and relative ease of mechanistic study for homogeneous molecular catalysts, as compared to heterogeneous materials or surface-adsorbed species, enables a detailed understanding of the individual steps of ORR catalysis. Thus, the Review places particular emphasis on ORR mechanism and thermodynamics. First, the thermochemistry of oxygen reduction and the factors influencing ORR efficiency are described to contextualize the discussion of catalytic studies that follows. Reports of ORR catalysis are presented in terms of their mechanism, with separate sections for catalysis proceeding via initial outer- and inner-sphere electron transfer to O2. The rates and selectivities (for production of H2O2 vs H2O) of these catalysts are provided, along with suggested methods for accurately comparing catalysts of different metals and ligand scaffolds that were examined under different experimental conditions.

Mechanism of Catalytic O2 Reduction by Iron Tetraphenylporphyrin.

The catalytic reduction of O2 to H2O is important for energy transduction in both synthetic and natural systems. Herein, we report a kinetic and thermochemical study of the oxygen reduction reaction (ORR) catalyzed by iron tetraphenylporphyrin (Fe(TPP)) in N, N'-dimethylformamide using decamethylferrocene as a soluble reductant and para-toluenesulfonic acid ( pTsOH) as the proton source. This work identifies and characterizes catalytic intermediates and their thermochemistry, providing a detailed mechanistic understanding of the system. Specifically, reduction of the ferric porphyrin, [FeIII(TPP)]+, forms the ferrous porphyrin, FeII(TPP), which binds O2 reversibly to form the ferric-superoxide porphyrin complex, FeIII(TPP)(O2•-). The temperature dependence of both the electron transfer and O2 binding equilibrium constants has been determined. Kinetic studies over a range of concentrations and temperatures show that the catalyst resting state changes during the course of each catalytic run, necessitating the use of global kinetic modeling to extract rate constants and kinetic barriers. The rate-determining step in oxygen reduction is the protonation of FeIII(TPP)(O2•-) by pTsOH, which proceeds with a substantial kinetic barrier. Computational studies indicate that this barrier for proton transfer arises from an unfavorable preassociation of the proton donor with the superoxide adduct and a transition state that requires significant desolvation of the proton donor. Together, these results are the first example of oxygen reduction by iron tetraphenylporphyrin where the pre-equilibria among ferric, ferrous, and ferric-superoxide intermediates have been quantified under catalytic conditions. This work gives a generalizable model for the mechanism of iron porphyrin-catalyzed ORR and provides an unusually complete mechanistic study of an ORR reaction. More broadly, this study also highlights the kinetic challenges for proton transfer to catalytic intermediates in organic media.

Rational Design of Mononuclear Iron Porphyrins for Facile and Selective 4e-/4H+ O2 Reduction: Activation of O-O Bond by 2nd Sphere Hydrogen Bonding.

Facile and selective 4e-/4H+ electrochemical reduction of O2 to H2O in aqueous medium has been a sought-after goal for several decades. Elegant but synthetically demanding cytochrome c oxidase mimics have demonstrated selective 4e-/4H+ electrochemical O2 reduction to H2O is possible with rate constants as fast as 105 M-1 s-1 under heterogeneous conditions in aqueous media. Over the past few years, in situ mechanistic investigations on iron porphyrin complexes adsorbed on electrodes have revealed that the rate and selectivity of this multielectron and multiproton process is governed by the reactivity of a ferric hydroperoxide intermediate. The barrier of O-O bond cleavage determines the overall rate of O2 reduction and the site of protonation determines the selectivity. In this report, a series of mononuclear iron porphyrin complexes are rationally designed to achieve efficient O-O bond activation and site-selective proton transfer to effect facile and selective electrochemical reduction of O2 to water. Indeed, these crystallographically characterized complexes accomplish facile and selective reduction of O2 with rate constants >107 M-1 s-1 while retaining >95% selectivity when adsorbed on electrode surfaces (EPG) in water. These oxygen reduction reaction rate constants are 2 orders of magnitude faster than all known heme/Cu complexes and these complexes retain >90% selectivity even under rate determining electron transfer conditions that generally can only be achieved by installing additional redox active groups in the catalyst.

Highly Active NiO Photocathodes for H2O2 Production Enabled via Outer-Sphere Electron Transfer.

Tandem dye-sensitized photoelectrosynthesis cells are promising architectures for the production of solar fuels and commodity chemicals. A key bottleneck in the development of these architectures is the low efficiency of the photocathodes, leading to small current densities. Herein, we report a new design principle for highly active photocathodes that relies on the outer-sphere reduction of a substrate from the dye, generating an unstable radical that proceeds to the desired product. We show that the direct reduction of dioxygen from dye-sensitized nickel oxide (NiO) leads to the production of H2O2. In the presence of oxygen and visible light, NiO photocathodes sensitized with commercially available porphyrin, coumarin, and ruthenium dyes exhibit large photocurrents (up to 400 µA/cm2) near the thermodynamic potential for O2/H2O2 in near-neutral water. Bulk photoelectrolysis of porphyrin-sensitized NiO over 24 h results in millimolar concentrations of H2O2 with essentially 100% faradaic efficiency. To our knowledge, these are among the most active NiO photocathodes reported for multiproton/multielectron transformations. The photoelectrosynthesis proceeds by initial formation of superoxide, which disproportionates to H2O2. This disproportionation-driven charge separation circumvents the inherent challenges in separating electron-hole pairs for photocathodes tethered to inner sphere electrocatalysts and enables new applications for photoelectrosynthesis cells.

Identifying and Breaking Scaling Relations in Molecular Catalysis of Electrochemical Reactions.

Improving molecular catalysis for important electrochemical proton-coupled electron transfer (PCET) reactions, such as the interconversions of H+/H2, O2/H2O, CO2/CO, and N2/NH3, is an ongoing challenge. Synthetic modifications to the molecular catalysts are valuable but often show trade-offs between turnover frequency (TOF) and the effective overpotential required to initiate catalysis (ηeff). Herein, we derive a new approach for improving efficiencies-higher TOF at lower ηeff-by changing the concentrations and properties of the reactants and products, rather than by modifying the catalyst. The dependence of TOF on ηeff is shown to be quite different upon changing, for instance, the pKa of the acid HA versus the concentration or partial pressure of a reactant or product. Using the electrochemical reduction of dioxygen catalyzed by iron porphyrins in DMF as an example, decreasing [HA] 10-fold lowers ηeff by 59 mV and decreases the TOF by a factor of 10. Alternatively, a 10-fold decrease in Ka(HA) also lowers ηeff by 59 mV but only decreases the TOF by a factor of 2. This approach has been used to improve a catalytic TOF by 104 vs the previously reported scaling relationship developed via synthetic modifications to the catalyst. The analysis has the potential to predict improved efficiency and product selectivity of any molecular PCET catalyst, based on its mechanism and rate law.

Molecular Cobalt Catalysts for O2 Reduction: Low-Overpotential Production of H2O2 and Comparison with Iron-Based Catalysts.

A series of mononuclear pseudomacrocyclic cobalt complexes have been investigated as catalysts for O2 reduction. Each of these complexes, with CoIII/II reduction potentials that span nearly 400 mV, mediate highly selective two-electron reduction of O2 to H2O2 (93-99%) using decamethylferrocene (Fc*) as the reductant and acetic acid as the proton source. Kinetic studies reveal that the rate exhibits a first-order dependence on [Co] and [AcOH], but no dependence on [O2] or [Fc*]. A linear correlation is observed between log(TOF) vs E1/2(CoIII/II) for the different cobalt complexes (TOF = turnover frequency). The thermodynamic potential for O2 reduction to H2O2 was estimated by measuring the H+/H2 open-circuit potential under the reaction conditions. This value provides the basis for direct assessment of the thermodynamic efficiency of the different catalysts and shows that H2O2 is formed with overpotentials as low as 90 mV. These results are compared with a recently reported series of Fe-porphyrin complexes, which catalyze four-electron reduction of O2 to H2O. The data show that the TOFs of the Co complexes exhibit a shallower dependence on E1/2(MIII/II) than the Fe complexes. This behavior, which underlies the low overpotential, is rationalized on the basis of the catalytic rate law.

Medium effects are as important as catalyst design for selectivity in electrocatalytic oxygen reduction by iron-porphyrin complexes.

Several substituted iron-porphyrin complexes were evaluated for oxygen reduction reaction (ORR) electrocatalysis in different homogeneous and heterogeneous media. The selectivity for four-electron reduction to H2O versus two-electron reduction to H2O2 varies substantially from one medium to another for a given catalyst. In many cases, the influence of the medium in which the catalyst is evaluated has a larger effect on the observed selectivity than the factors attributable to chemical modification of the catalyst. For instance, introduction of potential proton relays has variable effects depending on the catalyst medium. Thus, comparisons of selectivity results from supported and soluble molecular ORR electrocatalysts must be interpreted with caution, as selectivity is a property not only of the catalyst, but also of the larger mesoscale environment beyond the catalyst. Still, in all the direct pairwise comparisons in the same medium, the catalysts with potential proton relays have similar or better selectivity for the preferred 4e(-) path.

Standard Reduction Potentials for Oxygen and Carbon Dioxide Couples in Acetonitrile and N,N-Dimethylformamide.

A variety of next-generation energy processes utilize the electrochemical interconversions of dioxygen and water as the oxygen reduction reaction (ORR) and the oxygen evolution reaction (OER). Reported here are the first estimates of the standard reduction potential of the O2 + 4e(-) + 4H(+) ⇋ 2H2O couple in organic solvents. The values are +1.21 V in acetonitrile (MeCN) and +0.60 V in N,N-dimethylformamide (DMF), each versus the ferrocenium/ferrocene couple (Fc(+/0)) in the respective solvent (as are all of the potentials reported here). The potentials have been determined using a thermochemical cycle that combines the free energy for transferring water from aqueous solution to organic solvent, -0.43 kcal mol(-1) for MeCN and -1.47 kcal mol(-1) for DMF, and the potential of the H(+)/H2 couple, - 0.028 V in MeCN and -0.662 V in DMF. The H(+)/H2 couple in DMF has been directly measured electrochemically using the previously reported procedure for the MeCN value. The thermochemical approach used for the O2/H2O couple has been extended to the CO2/CO and CO2/CH4 couples to give values of -0.12 and +0.15 V in MeCN and -0.73 and -0.48 V in DMF, respectively. Extensions to other reduction potentials are discussed. Additionally, the free energy for transfer of protons from water to organic solvent is estimated as +14 kcal mol(-1) for acetonitrile and +0.6 kcal mol(-1) for DMF.

Direct comparison of electrochemical and spectrochemical kinetics for catalytic oxygen reduction.

We describe here a direct comparison of electrochemical and spectrochemical experiments to determine rates and selectivity of oxygen reduction catalyzed by iron 5,10,15,20-meso-tetraphenylporphyrin chloride. Good agreement was found between the two methods, suggesting the same mechanism is occurring under both conditions, with the same third-order rate law, similar selectivity, and the derived rate constants agreeing within a factor of at most 4, with k(cat) ≅ 2 × 10(6) M(-2) s(-1). This Communication provides a rare example of a redox catalytic process characterized by two common but very different methods.

Synthesis and reactivity of tripodal complexes containing pendant bases.

The synthesis of a new tripodal ligand family that contains tertiary amine groups in the second-coordination sphere is reported. The ligands are tris(amido)amine derivatives, with the pendant amines attached via a peptide coupling strategy. They were designed to function as new molecular catalysts for the oxygen reduction reaction (ORR), in which the pendant acid/base group could improve the catalyst performance. Two members of the ligand family were each metalated with cobalt(II) and zinc(II) to afford trigonal-monopyramidal complexes. The reaction of the cobalt complexes [Co(L)](-) with dioxygen reversibly generates a small amount of a cobalt(III) superoxo species, which was characterized by electron paramagnetic resonance (EPR) spectroscopy. Protonation of the zinc complex Zn[N{CH2CH2NC(O)CH2N(CH2Ph)2}3)](-) ([Zn(TN(Bn))](-)) with 1 equiv of acid occurs at a primary-coordination-sphere amide moiety rather than at a pendant basic site. The addition of excess acid to any of the complexes [M(L)](-) results in complete proteolysis and formation of the ligands H3L. These undesired reactions limit the use of these complexes as catalysts for the ORR. An alternative ligand with two pyridyl arms was also prepared but could not be metalated. These studies highlight the importance of the stability of the primary-coordination sphere of ORR electrocatalysts to both oxidative and acidic conditions.

Molecular Magnetic Resonance Imaging of Nitric Oxide in Biological Systems.

Detection of nitric oxide (NO) in biological systems is challenging due to both physicochemical properties of NO and limitations of current imaging modalities and probes. Magnetic resonance imaging (MRI) could be applied for studying NO in living tissue with high spatiotemporal resolution, but there is still a need for chemical agents that effectively sensitize MRI to biological NO production. To develop a suitable probe, we studied the interactions between NO and a library of manganese complexes with various oxidation states and molecular structures. Among this set, the manganese(III) complex with N,N'-(1,2-phenylene)bis(5-fluoro-2-hydroxybenzamide) showed favorable changes in longitudinal relaxivity upon addition of NO-releasing chemicals in vitro while also maintaining selectivity against other biologically relevant reactive nitrogen and oxygen species, making it a suitable NO-responsive contrast agent for T1-weighted MRI. When loaded with this compound, cells ectopically expressing nitric oxide synthase (NOS) isoforms showed MRI signal decreases of over 20% compared to control cells and were also responsive to NOS inhibition or calcium-dependent activation. The sensor could also detect endogenous NOS activity in antigen-stimulated macrophages and in a rat model of neuroinflammation in vivo. Given the key role of NO and associated reactive nitrogen species in numerous physiological and pathological processes, MRI approaches based on the new probe could be broadly beneficial for studies of NO-related signaling in living subjects.

A pyridinic Fe-N4 macrocycle models the active sites in Fe/N-doped carbon electrocatalysts.

Iron- and nitrogen-doped carbon (Fe-N-C) materials are leading candidates to replace platinum catalysts for the oxygen reduction reaction (ORR) in fuel cells; however, their active site structures remain poorly understood. A leading postulate is that the iron-containing active sites exist primarily in a pyridinic Fe-N4 ligation environment, yet, molecular model catalysts generally feature pyrrolic coordination. Herein, we report a molecular pyridinic hexaazacyclophane macrocycle, (phen2N2)Fe, and compare its spectroscopic, electrochemical, and catalytic properties for ORR to a typical Fe-N-C material and prototypical pyrrolic iron macrocycles. N 1s XPS and XAS signatures for (phen2N2)Fe are remarkably similar to those of Fe-N-C. Electrochemical studies reveal that (phen2N2)Fe has a relatively high Fe(III/II) potential with a correlated ORR onset potential within 150 mV of Fe-N-C. Unlike the pyrrolic macrocycles, (phen2N2)Fe displays excellent selectivity for four-electron ORR, comparable to Fe-N-C materials. The aggregate spectroscopic and electrochemical data demonstrate that (phen2N2)Fe is a more effective model of Fe-N-C active sites relative to the pyrrolic iron macrocycles, thereby establishing a new molecular platform that can aid understanding of this important class of catalytic materials.

Graphite-Conjugated Acids Reveal a Molecular Framework for Proton-Coupled Electron Transfer at Electrode Surfaces.

Proton-coupled electron-transfer (PCET) steps play a key role in energy conversion reactions. Molecular PCET reactions are well-described by "square schemes" in which the overall thermochemistry of the reaction is broken into its constituent proton-transfer and electron-transfer components. Although this description has been essential for understanding molecular PCET, no such framework exists for PCET reactions that take place at electrode surfaces. Herein, we develop a molecular square scheme framework for interfacial PCET by investigating the electrochemistry of molecularly well-defined acid/base sites conjugated to graphitic electrodes. Using cyclic voltammetry, we first demonstrate that, irrespective of the redox properties of the corresponding molecular analogue, proton transfer to graphite-conjugated acid/base sites is coupled to electron transfer. We then show that the thermochemistry of surface PCET events can be described by the pK a of the molecular analogue and the potential of zero free charge (zero-field reduction potential) of the electrode. This work provides a general framework for analyzing and predicting the thermochemistry of interfacial PCET reactions.

Homogenous Electrocatalytic Oxygen Reduction Rates Correlate with Reaction Overpotential in Acidic Organic Solutions.

Improved electrocatalysts for the oxygen reduction reaction (ORR) are critical for the advancement of fuel cell technologies. Herein, we report a series of 11 soluble iron porphyrin ORR electrocatalysts that possess turnover frequencies (TOFs) from 3 s-1 to an unprecedented value of 2.2 × 106 s-1. These TOFs correlate with the ORR overpotential, which can be modulated by changing the E1/2 of the catalyst using different ancillary ligands, by changing the solvent and solution acidity, and by changing the catalyst's protonation state. The overpotential is well-defined for these homogeneous electrocatalysts by the E1/2 of the catalyst and the proton activity of the solution. This is the first such correlation for homogeneous ORR electrocatalysis, and it demonstrates that the remarkably fast TOFs are a consequence of high overpotential. The correlation with overpotential is surprising since the turnover limiting steps involve oxygen binding and protonation, as opposed to turnover limiting electron transfer commonly found in Tafel analysis of heterogeneous ORR materials. Computational studies show that the free energies for oxygen binding to the catalyst and for protonation of the superoxide complex are in general linearly related to the catalyst E1/2, and that this is the origin of the overpotential correlations. This analysis thus provides detailed understanding of the ORR barriers. The best catalysts involve partial decoupling of the influence of the second coordination sphere from the properties of the metal center, which is suggested as new molecular design strategy to avoid the limitations of the traditional scaling relationships for these catalysts.