Fast Catalysis Research Articles

Fast Catalysis at Low Overpotential: Designing Efficient Dicationic Re(bpy2+)(CO)3I Electrocatalysts for CO2 Reduction.

We report a series of isomeric, dicationic Re(bpy2+)(CO)3I complexes with bpy (2,2'-bipyridine) modified by two phenyl-CH2-(NMe3)+ pendants with cations located at variable distances from the active site for electrocatalytic CO2 reduction in CH3CN/2.8 M H2O. The position of the cationic groups dramatically increases the rate of catalysis by ∼800-fold, from 1.2 to 950 s-1, with only a minor increase in overpotential. Acceleration is due to stabilization of the initial CO2 adduct and lowering of ΔG‡ for C-OH bond cleavage by Coulombic stabilization of anionic charges. Performance may be enhanced by accumulation in the electrochemical double layer. Transition state stabilization in the optimized isomer unlocks the low overpotential "protonation-first" pathway, highlighting the sizable effects of subtle structural optimization.

Nanoimpact Electrochemistry for Unraveling the Reactivity of Diffusion Limited Enzymes

The ultimate challenge of modern electroanalytical chemistry is to reach a single-molecule level of detection. In this framework, nanoimpact electrochemistry (NIE) has been recently developed. It allows studying at high throughput the reactivity of small entities such as nanoparticles, cells, or proteins, that collide on a biased ultramicroelectrode (UME) inside a solution or suspension.1 The collisions cause disturbances in the recorded chronoamperogram such as current spikes or current steps.2 Single enzyme electrochemistry (SEE) can contribute to uncovering effects of dynamics and non-equilibrium behavior of individual enzyme molecules on catalysis, which are hidden in measurements on ensembles due to averaging of the measured parameters over the entire molecular population. However, NIE of smaller entities such as enzymes, is very challenging due to the low sensitivity of the state-of-the-art electrochemical equipment, and most single enzyme techniques are currently based on fluorescence.3 One strategy to overcome this issue is the amplification of the current produced by a single enzyme molecule by fast catalysis: the single enzyme converts several substrate molecules per second consuming several electrons leading measurable current. Some of us reported the implementation of this strategy for the first time, designing a single-entity electrochemical experiment that allowed the detection of catalytic currents from single laccase molecules.4 Soon after the initial SEE report in 2016, a similar approach was applied for investigations of catalase,5 an enzyme that breaks down H2O2 to O2 and H2O with diffusion limited kinetics. However, the unequivocal attribution of current disturbances to the reduction of O2 (produced locally by enzyme) on the electrode during enzyme-electrode collisions remains a challenge. We will address this challenge based on the analysis of SEE experimental data under various conditions, on protein film voltammetry (PFV) studies on rotating disk electrode (RDE), and on simulations. The collected data from the SEE, that is the current spike characteristics in each set of conditions, are statistically analyzed and discussed. PFV studies are used to evaluate basic thermodynamic and kinetic parameters of the system. Finally, we have built a model using Comsol Multiphysics. To the best of our knowledge, this is the first model reported so far that can satisfactorily reproduce the experimental SEE data, using experimentally evaluated parameters as input. The developed methodology is the succesfully implemented to the study of superoxide dismutase.6

Stabilizer-free MnO2 nanozyme with singlet-oxygen conducted high oxidase-like activity and fast catalysis capability for improving alkaline phosphatase assay

Oxidase (OXD) nanozyme is a type of artificial enzyme that can directly oxidize reducible substrates. By virtue of enzyme catalysis, it is often designed as a sensor for alkaline phosphatase (ALP) assays. MnO2 nanozymes have received extensive attention due to their low cost and ease of preparation. To enhance its sensing capability, further development of MnO2-based OXD nanozyme with higher activity and faster catalysis is necessary. In this study, we synthesized Fe3O4 @polydopamine supported MnO2 (IOPM) nanoparticles, which exhibited excellent OXD activity with a Vmax of 19.67 × 10-8 M·s-1 and a catalysis balance period of less than 1 min. Further investigation confirms that IOPM's good performance is associated with its stabilizer-free interface, magnetic purification method, and singlet-oxygen-conducted catalysis mechanism. More importantly, IOPM is demonstrated to possess the ability of improving ALP assay, with lower limit of detection (0.045 U/L) and wider linear range (0.05 – 40 U/L). Finally, it is successfully used to evaluate ALP activity in clinical blood samples. This study aims to develop a more efficient MnO2-based OXD nanozyme. It emphasizes the positive impact of magnetic purification and a stabilizer-free interface in enhancing OXD activity and improving the ALP detection capability of the nanozyme.

Tailored hydrogel entrapped catalyst with highly active, controlled catalytic activity for the removal of 4-nitrophenol (4-NP)

In catalytic reactions, achieving large specific surface area immobilisation of the catalyst is an important factor affecting the catalytic effect, however, the primary challenges in utilizing hydrogels as catalyst carriers are to enhance the mechanical properties of the hydrogel to improve the activity and controllability of the catalyst. In this study, a new structure of P(AM-co-AA)/SMA/NH2-SiO2 hydrogels was synthesized via free radical polymerization, and the effects of the content of AA and NH2-SiO2 on the mechanical properties of the hydrogels were investigated. Without the use of additional cross-linking agents, both a chemical cross-linking network and a hydrophobic linkage network were established, which effectively reconstructed the structure of the hydrogels and dissipated energy. As a result, P(AM-co-AA-1.5 %)/SMA/NH2-SiO2-0.5 % hydrogel exhibited high mechanical properties, with tensile strength, elongation, and toughness reaching 1456 KPa, 4605 %, and 23.59 MJ/m3, respectively. This hydrogel can be utilized as a template for in situ and stable Ag NPs. Additionally, P(AM-co-AA)/SMA/NH2-SiO2@Ag composite hydrogels were prepared using cation exchange and in situ reduction methods for the catalytic reduction of 4-nitrophenol (4-NP). The composite hydrogel exhibited fast catalysis, high efficiency, stable cycling, recyclability and adjustable catalytic activity at 35 °C with Kapp = 0.811 min−1. Furthermore, using this composite hydrogel alleviated the need for separating metal nanoparticle catalysts from the reaction system, thereby enabling the development of robust hydrogel materials with controlled catalytic activity for the wastewater treatment industry.

Time-Resolved Vibrational and Electronic Spectroscopy for Understanding How Charges Drive Metal Oxide Catalysts for Water Oxidation.

Temporally resolved spectroscopy is a powerful approach for gaining detailed mechanistic understanding of water oxidation at robust Earth-abundant metal oxide catalysts for guiding efficiency improvement of solar fuel conversion systems. Beyond detecting and structurally identifying surface intermediates by vibrational and accompanying optical spectroscopy, knowledge of how charges, sequentially delivered to the metal oxide surface, drive the four-electron water oxidation cycle is critical for enhancing catalytic efficiency. Key issues addressed in this Perspective are the experimental requirements for establishing the kinetic relevancy of observed surface species and the discovery of the rate-boosting role of encounters of two or more one-electron surface hole charges, often in the form of randomly hopping metal oxo or oxyl moieties, for accessing very low-barrier O-O bond-forming pathways. Recent spectroscopic breakthroughs of metal oxide photo- and electrocatalysts inspire future research poised to take advantage of new highly sensitive spectroscopic tools and of methods for fast catalysis triggering.

Highly active Fenton-like catalyst derived from solid waste-iron ore tailings using wheat straw pyrolysis.

The pollutants degradation rate of iron ore tailings-based heterogeneous catalysts is the main factor limiting its application. Herein, an iron ore tailings-based Fenton-like catalyst (I/W(3:1)-900-60) with a relatively fast catalysis rate was constructed by co-pyrolysis (900°C, 60 min holding time) of iron ore tailings and wheat straw with a mass ratio of 3:1. With wheat straw blending, the generated I/W(3:1)-900-60 presented a larger surface area (24.53 m2/g), smaller pore size (3.76 nm), reduced iron species (Fe2+ from magnetic), and a higher catalytic activity (0.0229 min-1) than I-900-60 (1.32 m2/g, 12.87 nm, 0.012 min-1) pyrolyzed using single iron ore tailing under the same pyrolysis conditions. In addition, biochar and iron ore tailings in I/W(3:1)-900-60 were tightly combined through chemical bonding. The optimal catalyst remains active after three cycles, indicating its catalytic stability and recyclability. The good Fenton-like methylene blue degradation efficiency of I/W(3:1)-900-60 was ascribed to the sacrificial role of biochar, as well as the electron transfer between biochar and iron active sites or the redox cycles of ≡Fe3+/Fe2+. This finding provides a facile construction strategy for highly active iron ore tailings-based Fenton-like catalyst and thereby had a great potential application in wastewater treatment.

Reversible or Irreversible Catalysis of H+/H2 Conversion by FeFe Hydrogenases.

Studies of molecular catalysts traditionally aim at understanding how a certain mechanism allows the reaction to be fast. A distinct question, which has only recently received attention in the case of bidirectional molecular catalysts, is how much thermodynamic driving force is required to achieve fast catalysis in either direction of the reaction. "Reversible" catalysts are bidirectional catalysts that work either way in response to even a small departure from equilibrium and thus do not waste input free energy as heat; conversely, "irreversible" catalysts require a large driving force to proceed at an appreciable rate [Fourmond et al. Nat. Rev. Chem. 2021, 5, 348-360]. Numerous mechanistic rationales for these contrasting behaviors have been proposed. To understand the determinants of catalytic (ir)reversibility, we examined the steady-state, direct electron transfer voltammetry of a particular FeFe hydrogenase, from Thermoanaerobacter mathranii, which is very unusual in that it irreversibly catalyzes H2 oxidation and production: a large overpotential is required for the reaction to proceed in either direction [Land et al. Chem. Sci. 2020, 11, 12789-12801]. In contrast to previous hypotheses, we demonstrate that in this particular enzyme catalytic irreversibility can be explained without invoking slow interfacial electron transfer or variations in the mechanism: the observed kinetics is fully consistent with the same catalytic pathway being used in both directions of the reaction.

MOF-Derived Bimetal ZnPd Alloy as a Separator Coating with Fast Catalysis of Lithium Polysulfides for Li–S Batteries

MOF-Derived Bimetal ZnPd Alloy as a Separator Coating with Fast Catalysis of Lithium Polysulfides for Li–S Batteries

2D/2D FeNi-layered double hydroxide/bimetal-MOFs nanosheets for enhanced photo-Fenton degradation of antibiotics: Performance and synergetic degradation mechanism

The photo-Fenton system exhibits great potential in environmental remediation. However, photo-Fenton process suffers from slow reaction kinetics, which is caused by the low yield of available charge carriers and active radicals. In this work, the 2D/2D FeNi-layered double hydroxide/bimetal-organic frameworks nanosheets (FeNi-LDH/BMNSs) photocatalyst was fabricated via an in-situ semi-sacrificial template strategy. The optimized FeNi-LDH/BMNSs + H2O2+Vis system showed excellent tetracycline hydrochloride (TC-HCl) removal rate of 95.76% in 60 min. Besides, the high TC-HCl degradation rates (above 80%) are obtained in a wide pH range and the total organic carbon (TOC) removal rate of 48.98% was remained after four cycles. Experiments and characterizations identified the fast catalysis process were ascribed to the synergetic effect between 2D/2D heterojunctions and Lewis acid sites with mixed-valence (Fe (III)/Ni (II)) in FeNi-LDH/BMNSs. As a result, the catalysis of H2O2 and the reduction of O2 was accelerated by the continuous generation of Fe (II) and available photogenerated electrons, respectively, producing abundant active radicals including OH and O2−. Finally, this photo-Fenton system exhibited high removal rate to oxycycline, levofloxacin, norfloxacin and doxycycline and showed excellent performance for TC-HCl removal in different composed wastewater. The findings provide a new strategy towards creating 2D/2D active heterogeneous catalysts for photo-Fenton catalytic application.

Hydroxylamine enhanced treatment of highly salty wastewater in Fe0/H2O2 system: Efficiency and mechanism study

• Fe 0 -HA/H 2 O 2 enhanced 7.9 times for tartrazine removal in salty system than Fe 0 /H 2 O 2 . • Fe 0 -HA/H 2 O 2 could widen the application of pH to neutral pH. • Fe 0 -HA/H 2 O 2 could obtain remarkable performance at wide salt concentration levels. • Fe 0 -HA/H 2 O 2 have good suitability for treatment of various types of salty wastewater. This study demonstrated a fast and efficient treatment of highly salty wastewater in a hydroxylamine (HA) enhanced Fe 0 /H 2 O 2 system. The apparent rate constant ( k ) in Fe 0 -HA/H 2 O 2 system could achieve 7.9 times higher than that in Fe 0 /H 2 O 2 system using tartrazine as the target pollutant and Na 2 SO 4 as the model salt. The value of k for removing tartrazine in the salty system by Fe 0 -HA/H 2 O 2 process even 12.7 times higher than that in the conventional system which was attributed to the faster Fe 0 corrosion rate in the salty system. Meanwhile, Fe 0 -HA/H 2 O 2 process could obtain remarkable performance for highly salty wastewater treatment at wide salt concentration levels (0–0.2 M) and could also widen the application of pH to neutral pH. The characterizations by SEM and XPS, the intensity of DMPO–OH adduct signals and detection of Fe 2+ and Fe 3+ ions in different systems confirmed the good performance was owing to the faster Fe 0 corrosion rate in the salty system and acceleration of Fe 3+ /Fe 2+ recycle owing the addition of HA inducing fast catalysis of H 2 O 2 and generation of hydroxyl radicals. Moreover, the value of k for removing tartrazine in various types of salty system by Fe 0 -HA/H 2 O 2 process was 2.9–30.8 times larger than Fe 0 /H 2 O 2 process demonstrating the good suitability of Fe 0 -HA/H 2 O 2 process at various types of salty system. Therefore, this study will shed lights on the reactivity of the Fe 0 -HA/H 2 O 2 system and provide an alternative pathway for removal of salty wastewater.

Single-atom electrocatalysts templated by MOF for determination of levodopa

To overcome the problem of incorrect levodopa (LD) dosage in the treatment of Parkinson's disease, a new analytical tool is urgently needed for accurately determining the concentration of LD in human fluids. Herein, an effective and stable sensor based on a Co-single-atomic-site catalyst (Co-SASC)-modified glassy carbon electrode (Co-SASC/GCE) was developed for the determination of LD concentration. The physicochemical characterization of Co-SASC is systematically investigated. It has excellent thermal stability, graphitization degree, and a large specific surface area. Benefiting from its porous structure for kinetically fast catalysis and component advantages for fix a single cobalt atom to improve stability, Co-SASC/GCE exhibits a superior electrochemical response. Under optimal conditions (pH 2.0, coating amount is 10 μg), an ideal linear relationship is achieved between the logarithm of the peak current of the sensor and the logarithm of LD concentration. The linear range is 0.1–200 μM, and the limit of detection (LOD) is 0.033 μM. After a simple pretreatment, LD in human serum is detected by Co-SASC/GCE with excellent stability and selectivity. As such, this work enlarges the existing electrochemical sensor toolbox by offering a reasonable design and synthesis protocol for advanced materials to accurately determine LD in human fluids for the clinical treatment of Parkinson's disease.

Buffer Pk a Impacts the Mechanism of Hydrogen Evolution Catalyzed By a Cobalt Porphyrin-Peptide

The effect of buffer pK a on the mechanism of electrochemical hydrogen evolution catalyzed by a cobalt porphyrin peptide (CoMP11-Ac) at constant pH is presented. The addition of buffer to CoMP11-Ac in water and KCl leads to an enhancement of the catalytic current of up to 200-fold relative to its value in the absence of a buffer. Two distinct catalytic regimes are identified as a function of the buffer pK a. In the presence of buffers with pK a ≤ 7.4, a fast catalysis regime limited by diffusion of buffer is reached. The catalytic half-wave potential (E h ) shifts anodically (from −1.42 to −1.26 V vs Ag/AgCl/KCl(1M)) as the buffer pK a decreases from 7.4 to 5.6, proposed to result from fast Co(III)-H formation following the catalysis-initiating Co(II/I) reduction. With higher-pK a buffers (pK a > 7.7), an E h = −1.42 V, proposed to reflect the Co(II/I) couple, is maintained independent of the buffer pK a, consistent with rate-limiting Co(III)-H formation under these conditions. We conclude that the buffer species pK a impacts catalytic current and potential and the rate-determining step of the reaction.

Kinetic characterization of the oxidation of catecolamines and related compounds by laccase

The pathways of melanization and sclerotization of the cuticle in insects are carried out by the action of laccases on dopamine and related compounds. In this work, the laccase action of Trametes versicolor (TvL) on catecholamines and related compounds has been kinetically characterized. Among them, dopamine, l-dopa, l-epinephrine, l-norepinephrine, dl-isoprenaline, l-isoprenaline, dl-α-methyldopa, l-α-methyldopa and l-dopa methylester. A chronometric method has been used, which is based on measuring the lag period necessary to consume a small amount of ascorbic acid, added to the reaction medium.The use of TvL has allowed docking studies of these molecules to be carried out at the active site of this enzyme. The hydrogen bridge interaction between the hydroxyl oxygen at C-4 with His-458, and with the acid group of Asp-206, would make it possible to transfer the electron to the T1 Cu-(II) copper centre of the enzyme. Furthermore, Phe-265 would facilitate the adaptation of the substrate to the enzyme through Π-Π interactions.To kinetically characterize these compounds, we need to take into consideration that, excluding l-dopa, l-α-methyldopa and dl-α-methyldopa, all compounds are in hydrochloride form. Because of this, first we need to kinetically characterize the inhibition by chloride and, after that, calculate the kinetic parameters KM and VmaxS.From the kinetic data obtained, it appears that the best substrate is dopamine. The presence of an isopropyl group bound to nitrogen (isoprenaline) makes it especially difficult to catalyse. The formation of the ester (l-dopa methyl ester) practically does not affect catalysis. The addition of a methyl group (α-methyl dopa) increases the rate but decreases the affinity for catalysis. l-Epinephrine and l-norepinephrine have an affinity similar to isoprenaline, but faster catalysis, probably due to the greater nucleophilic power of their phenolic hydroxyl.

Buffer pKa Impacts the Mechanism of Hydrogen Evolution Catalyzed by a Cobalt Porphyrin-Peptide.

The effect of buffer pKa on the mechanism of electrochemical hydrogen evolution catalyzed by a cobalt porphyrin peptide (CoMP11-Ac) at constant pH is presented. The addition of buffer to CoMP11-Ac in water and KCl leads to an enhancement of the catalytic current of up to 200-fold relative to its value in the absence of a buffer. Two distinct catalytic regimes are identified as a function of the buffer pKa. In the presence of buffers with pKa ≤ 7.4, a fast catalysis regime limited by diffusion of buffer is reached. The catalytic half-wave potential (Eh) shifts anodically (from -1.42 to -1.26 V vs Ag/AgCl/KCl(1M)) as the buffer pKa decreases from 7.4 to 5.6, proposed to result from fast Co(III)-H formation following the catalysis-initiating Co(II/I) reduction. With higher-pKa buffers (pKa > 7.7), an Eh = -1.42 V, proposed to reflect the Co(II/I) couple, is maintained independent of the buffer pKa, consistent with rate-limiting Co(III)-H formation under these conditions. We conclude that the buffer species pKa impacts catalytic current and potential and the rate-determining step of the reaction.

Buffer Pka Impacts the Mechanism of Hydrogen Evolution in Water Catalyzed By a Cobalt Porphyrin-Peptide

A detailed study of the impact of buffer pKa (pKa 5.6 to 10.5) on electrochemical hydrogen evolution at constant pH catalyzed by CoMP11-Ac, a cobalt porphyrin peptide, is presented. The addition of buffer leads to a significant enhancement of the catalytic current of up to 20-fold relative to its value in absence of buffer. Two distinct catalytic regimes are identified based on the buffer pKa . In the presence of buffers with pKa ≤ 7.4 a fast catalysis regime limited by diffussion of buffer is reached. The catalytic half-wave potential (Eh ) shifts anodically (from -1.42 to -1.26 V vs Ag/AgCl/KCl(1M)) as the buffer pKa decreases from 7.4 to 5.6, proposed to result from fast Co(III)-H formation following the catalysis-initiating Co(II/I) reduction. With higher-pKa buffers (pKa > 7.7), an Eh = -1.42 V reflecting the potential of the Co(II/I) couple is maintained independent of the buffer pKa , consistent with a rate-limiting Co(III)-H formation under these conditions. We conclude that the buffer species pK a, even at constant pH, can have a large effect on both catalytic current and potential, as well as the rate-determining step of the reaction. Thus, buffer is a factor to consider in optimizing reaction conditions for hydrogen-evolving catalysis and for other proton-requiring reactions in water. Finally, buffer acids are shown to be a probe for studying hydrogen evolution mechanism in water.

Unraveling the High Activity of Ylide-Functionalized Phosphines in Palladium-Catalyzed Amination Reactions: A Comparative Study with CyJohnPhos and PtBu3.

Comprehensive mechanistic insights into the activity of different catalysts based on different ligands are important for further ligand design and catalyst improvement. Herein, we report a combined computational and experimental study on the mechanism and catalytic activity of the ylide-substituted phosphine Cy3P–C(Me)PCy2 (keYPhos, L1) in C–N coupling reactions including a comparison with the established and often-applied phosphines CyJohnPhos (L2) and P(tBu)3 (L3). Density functional theory (DFT) calculations together with the possible isolation of several intermediates within the catalytic cycle demonstrate that L1 readily forms low-coordinated palladium complexes [such as L1·Pd(dba)], which easily undergo oxidative addition and subsequent amine coordination as well as reductive elimination. Due to the possible opening and closing of the P–C–P angle in L1, the steric bulk can be adjusted to the metal environment so that L1 retains its conformation throughout the whole catalytic cycle, thus leading to fast catalysis at room temperature. Comparative studies of the three ligands with Pd2dba3 as a Pd source show that only L1 efficiently allows for the coupling of aryl chlorides at room temperature. DFT studies suggest that this is mainly due to the reluctance/inability of L2 and L3 to form the catalytically active species under these reaction conditions. In contrast, the YPhos ligand readily forms the prereactive complex and undergoes the first oxidative addition reaction. These observations are confirmed by kinetic studies, which indicate a short induction period for the formation of the catalytically active species of L1, followed by fast catalysis. This behavior of L1 is due to its unique electronic and steric properties, which support low activation barriers and fast catalyst generation.

Processive Chitinase is Burnt-Bridge Brownian Motor Operated by Fast Catalysis after Peeling Rail from Crystalline Chitin

Processive Chitinase is Burnt-Bridge Brownian Motor Operated by Fast Catalysis after Peeling Rail from Crystalline Chitin

Optimizing ligand structure for low-loading and fast catalysis for alkynyl-alcohol and -amine cyclization.

A series of [Ru(Cp/Cp*)(PR2NR'2)(MeCN)]PF6 complexes were prepared, in which the steric and electronic properties of the primary coordination sphere were varied (R = Ph, t-Bu, Bn; and Cp vs. Cp*). These complexes were catalytically active in the cyclization of alkyne substrates with an intramolecular nucleophile (amine or alcohol) to produce 5- and 6-membered heterocycles. The effect of the 1° coordination sphere structure on catalyst performance was evaluated. Steric bulk around the metal centre was a key feature to achieve rapid catalysis at low temperatures. The catalyst [Ru(Cp)(Pt-Bu2NPh2)(MeCN)]PF6 gave a turnover number that was >1 order of magnitude more active than previous catalysts in the cyclization of the benchmark substrate 2-ethynylaniline. This catalyst is tolerant of a diversity of functional groups and is competent at the formation of various substituted indoles.

Processive chitinase is Brownian monorail operated by fast catalysis after peeling rail from crystalline chitin

Processive chitinase is a linear molecular motor which moves on the surface of crystalline chitin driven by processive hydrolysis of single chitin chain. Here, we analyse the mechanism underlying unidirectional movement of Serratia marcescens chitinase A (SmChiA) using high-precision single-molecule imaging, X-ray crystallography, and all-atom molecular dynamics simulation. SmChiA shows fast unidirectional movement of ~50 nm s−1 with 1 nm forward and backward steps, consistent with the length of reaction product chitobiose. Analysis of the kinetic isotope effect reveals fast substrate-assisted catalysis with time constant of ~3 ms. Decrystallization of the single chitin chain from crystal surface is the rate-limiting step of movement with time constant of ~17 ms, achieved by binding free energy at the product-binding site of SmChiA. Our results demonstrate that SmChiA operates as a burnt-bridge Brownian ratchet wherein the Brownian motion along the single chitin chain is rectified forward by substrate-assisted catalysis.

O-O Radical Coupling: From Detailed Mechanistic Understanding to Enhanced Water Oxidation Catalysis.

A deeper mechanistic understanding of the key O-O bond formation step of water oxidation by the [Ru(bda)(L)2] (bdaH2 = 2,2'-bipyridine-6,6'-dicarboxylic acid; L is a pyridine or isoquinoline derivative) family of catalysts is reached through harmonious experimental and computational studies of two series of modified catalysts with systematic variations in the axial ligands. The introduction of halogen and electron-donating substituents in [Ru(bda)(4-X-py)2] and [Ru(bda)(6-X-isq)2] (X is H, Cl, Br, and I for the pyridine series and H, F, Cl, Br, and OMe for the isoquinoline series) enhances the noncovalent interactions between the axial ligands in the transition state for the bimolecular O-O coupling, resulting in a lower activation barrier and faster catalysis. From detailed transition state calculations in combination with experimental kinetic studies, we find that the main contributor to the free energy of activation is entropy due to the highly organized transition states, which is contrary to other reports. Previous work has considered only the electronic influence of the substituents, suggesting electron-withdrawing groups accelerate catalysis, but we show that a balance between polarizability and favorable π-π interactions is the key, leading to rationally devised improvements. Our calculations predict the catalysts with the lowest Δ G⧧ for the O-O coupling step to be [Ru(bda)(4-I-py)2] and [Ru(bda)(6,7-(OMe)2-isq)2] for the pyridine and isoquinoline families, respectively. Our experimental results corroborate these predictions: the turnover frequency for [Ru(bda)(4-I-py)2] (330 s-1) is a 10-fold enhancement with respect to that of [Ru(bda)(py)2], and the turnover frequency for [Ru(bda)(6-OMe-isq)2] reaches 1270 s-1, two times faster than [Ru(bda)(isq)2].