Advancing hydrogen energy through enzyme-mimetic electrocatalysis

Graphical abstract

The structure of natural enzymes involved in essential bioenergetic processes on Earth offers a blueprint for designing efficient, durable, and affordable electrocatalysts for hydrogen energy applications. Due to significant differences in operating conditions, unlocking the full potential of these enzyme-mimetic electrocatalysts necessitates integrating their advantages with the demands of practical technological systems.

The evolution of energy carriers has played a pivotal role in accelerating human civilization. From the primitive use of wood for fire, to the coal-powered agricultural age, and the oil and natural gas-dominated industrial era, a clear trend emerges: a decreasing carbon content and an increasing hydrogen content, progressively reducing the carbon-to-hydrogen ratio. As a zero-carbon energy carrier, hydrogen (H₂) is now an essential component of a clean energy future [1,2].

The transition to hydrogen civilization hinges on the discovery of efficient and stable catalytic materials composed of abundant elements [3]. These materials are crucial for storing renewable energy as H₂ and subsequently reconverting it back into electricity. Such energy conversion processes typically involve multiple electron and proton transfer reactions that are inherently slow without the aid of electrocatalysts. Proton exchange membrane (PEM) fuel cells and water electrolyzers, for instance, currently rely exclusively on platinum (Pt) and iridium oxide (IrO_x) electrocatalysts for H⁺/H₂ and O₂/H₂O interconversion [4]. The global adoption of these technologies is severely limited by the scarce availability of these precious metals. While alkaline electrolysis offers a precious-group metal (PGM)-free alternative, its practical application is hindered by the intermittent nature of renewable energy sources [5]. Although a burgeoning subfield of materials science is dedicated to addressing these challenges through advancements in nanoscience and catalysis, current efforts are heavily dependent on a trial-and-error approach, lacking high-level design principles and strategies.

Nature, however, offers a blueprint for overcoming these limitations [6–8]. Over the course of evolution, organisms developed sophisticated catalytic systems to manage energy and fuel metabolism. These systems employ specific cofactors, metallic ions or chemical compounds embedded within proteins and enzymes, to perform essential functions like redox reactions, electron and hydrogen transfer, and light harvesting—exactly the capabilities required for sustainable energy technologies.

Therefore, enzyme mimicry holds significant promise for advancing hydrogen energy-related electrocatalysts. First, natural enzymes exclusively employ earth-abundant elements, which were the only substances available to primordial organisms for developing metabolic abilities and complex regulatory systems. This feature aligns well with the availability of electrocatalyst materials required to expand the opportunity for large-scale deployment of hydrogen energy technologies. Second, enzymes maximize metal-atom utilization efficiency to achieve their function. In contrast, conventional metal nanoparticle catalysts can only utilize the surface metal atoms. For example, a nanoparticle with a diameter of approximately 5 nm uses only 10% of its atoms for catalytic reactions, with the remaining 90% not being used. Third, natural enzymes demonstrate exceptional activity and selectivity. Lastly, their operation in aqueous media under mild conditions is consistent with sustainability requirements, making enzyme-mimetic electrocatalysts promising candidates for green, safe, and efficient technologies.

While enzymes exhibit remarkable catalytic efficiency, directly translating these systems into real-world technological applications often proves challenging due to significant differences in operating conditions [6]. Enzymatic processes function within a narrow range of physiologic conditions conducive to life, whereas industrial processes often demand harsher environments to optimize mass transport. Additionally, natural enzymes regulate nearly all metabolic processes by exclusively exploiting a limited set of building blocks while avoiding the precursors of potential toxicity. These constraints, however, are less relevant in abiotic systems and can be overlooked when designing electrocatalysts or electrochemical devices. Finally, the intricate interplay between an enzyme’s active site and its polypeptide backbone governs its reactivity, which presents a challenge for translating these systems into economically viable electrocatalytic technologies.

To more effectively learn from nature, a functional approach to enzyme mimicry—focusing on replicating their catalytic behavior rather than their structure—is essential. By selectively incorporating nature’s design principles and combining them with the versatility of synthetic chemistry and materials science, high-performance and economically feasible electrocatalysts can be developed. In the following sections, specific examples of enzyme-mimetic electrocatalysts will be explored for key reactions, including the hydrogen evolution reaction (HER), hydrogen oxidation reaction (HOR), oxygen reduction reaction (ORR), and oxygen evolution reaction (OER), highlighting their limitations and demonstrating how a functional approach can address critical technological challenges.

1 Hydrogen evolution and oxidation reactions

Overpotential, a critical performance metric for electrocatalysts, quantifies the thermodynamic driving force required for electrocatalysis and directly affects power-to-chemical conversion efficiency. In the case of hydrogen electrode reactions, specifically anodic HOR in hydrogen fuel cells and cathodic HER in water electrolyzers, achieving reversibility, or catalysis at the thermodynamic equilibrium potential (0 V versus RHE), remains a significant challenge for catalysts beyond Pt [9]. Currently, Pt is the only reversible electrocatalyst in abiotic systems under acidic and neutral conditions.

Few enzymes demonstrate reversible behavior in H⁺/H₂ interconversion, with hydrogenase being a notable exception (Fig. 1(a)) [10]. Hydrogenases catalyze both HER and HOR, but even their most precise synthetic mimics still do not operate near zero overpotential. Intriguingly, integrating amine functions from the 2-aza-1,3-propanedithiolate cofactor of the [FeFe]-hydrogenase active site into the diphosphine ligands of nickel complexes has enabled these complexes to exhibit reversible hydrogen electrocatalysis [11]. The amine group, mechanistically, functions as a proton relay adjacent to the metal-bound hydride, facilitating the formation of H₂, or the polarization of H–H bond, which promotes bond cleavage [12].

When supported on electrically conductive carbon materials, these enzyme-mimetic complexes exhibited active and stable electrocatalysts for HER [13]. Notably, they showed reversible behavior in acidic conditions, and proved operational at the device level when coupled with PEMs. Further structuring the electrode materials in three dimensions significantly improved their performances under technologically relevant operational conditions, even comparable to commercial Pt/C. These electrocatalysts were successfully integrated into the first PGM-free hydrogen fuel cell [14].

2 Oxygen reduction reaction

The ORR is a primary bottleneck in fuel cell technologies, requiring four times more Pt loading compared to the anode for the HOR [15]. Analogously, in aerobic organisms, cytochrome c oxidase (CcO) catalyzes the ORR via a four-electron process, which is the essential final step of respiration. The CcO’s active site features a ferrous protoporphyrin IX (heme) coupled with a proximal (~ 4.4–5.3 Å) copper (Cu) ion (Fig. 1(b)).

While synthetic mimics of heme–Cu binuclear center exhibit promising ORR activity and stability at neutral pH, the Cu center’s role diminishes under technologically relevant conditions with abundant electron supply [16]. In actuality, hemes alone are highly effective ORR electrocatalysts, and substantial efforts have been devoted to designing and synthesizing advanced metalloporphyrins for enhanced ORR performance [17]. However, hemes exhibit stability and considerable activity only in neutral and alkaline electrolytes, which presents a challenge, as PEM hydrogen fuel cells operate only in strongly acidic environments. In comparison, cobalt (Co) porphyrins, while more stable under acidic conditions, preferentially catalyze the ORR via a two-electron pathway, producing hydrogen peroxide instead of water [18].

Intriguingly, a breakthrough emerged with a covalently linked Co porphyrin array on carbon nanotubes, demonstrating improved selectivity for the four-electron ORR [19]. This example highlights how enzyme mimicry, retaining the porphyrin motif while substituting the metal center, coupled with nanoscience, specifically the covalent integration of the catalyst with carbon nanotubes, can generate new materials capable of operating effectively under demanding, technologically relevant conditions.

More recently, compellingly studies have indicated that porphyrin motifs serve as the active sites for ORR in metal- and nitrogen-doped carbon (M–N–C) materials, which are currently among the most promising PGM-free ORR electrocatalysts for acidic environments [20,21]. These M–N–C materials originate from decades of research involving the pyrolysis of Fe and Co porphyrins sublimated onto the surface of carbon black, a process once believed to completely degrade molecular structures. Recent studies, however, have confirmed that the preservation of the porphyrin motif, specifically the MN₄ moiety, survives even after pyrolysis at temperatures up to 1000 °C in an inert atmosphere [21]. The exceptional stability of these porphyrin motifs is crucial for their survival and incorporation into M–N–C materials, mirroring their historical role as cofactors in early life forms exposed to harsh environmental conditions [22].

3 Oxygen evolution reaction

In water electrolysis, the anodic OER remains the primary bottleneck, limiting the overall efficiency and hindering broader industrial applications [23]. Corresponding enzymatic systems, such as the oxygen-evolving complex (OEC) in photosystem II of oxygenic photosynthetic organisms, typically feature polynuclear clusters at their active sites [24]. The Mn₄CaO_x cluster, identified within the OEC [25], as depicted in Fig. 1(c), undergoes proton-coupled electron transfers (PCETs) to store multiple redox equivalents delocalized across the multi-metal architecture, while providing specific binding sites to stabilize reaction intermediates during the successive four-electron forward steps [24].

A synthetic analogous to the Mn₄CaO_x cluster, in an amorphous MnO_x phase with calcium incorporation, has demonstrated high activity [26]. Since Mn₄CaO_x clusters perform optimally under physiologic conditions, such as room temperature and neutral pH, their design could play a crucial role in developing anode catalysts for anion exchange membrane (AEM) water electrolyzers, particularly as AEM performance continues to improve.

Another example of high OER activity was observed in Co–phosphate-based materials, which also features a molecular motif within an amorphous structure [27]. The enhancement in catalytic performance primarily stems from the presence of the molecular motif, rather than just an increased active surface area. These polynuclear molecular motifs offer three-dimensional active sites where substrates can bind and undergo activation through controlled interactions and controlled PCET processes.

4 Toward system innovation

These examples not only demonstrate how enzyme mimicry can inspire electrocatalyst design but also emphasize the importance of a functional approach to developing electrocatalysts that combine both high activity and stability in acidic environments. For instance, embedding the molecular motif within a carbonaceous matrix enhances the electrocatalyst’s stability in acidic environments and within the technologically relevant electrochemical potential range. In PEM fuel cells and water electrolyzers, conductive carbon facilitates electron transfer, while Nafion membranes and ionomers mediate proton transport, both to and from the electrocatalyst. In natural enzymes, analogous functions are performed by iron–sulfur clusters and hydrogen-bonded amino acid networks (Fig. 2) [28].

Therefore, transferring insights from enzymes to hydrogen energy technologies, such as improving the triple-phase boundary of catalyst layers of fuel cells and water electrolyzers and building interpenetrating networks, could significantly enhance system performance. Another promising direction for enzyme mimicry involves replicating specific regulatory and maintenance mechanisms that enable optimal and continuous operation in biological systems. While biological repair processes involving sophisticated machinery remain elusive, recent advancements have led to self-healing systems that utilize self-assembly [29] and supramolecular architectures, often incorporating bioinspired molecular switches to regulate PCET reactions [30].

The application of the principles of enzyme mimicry to design high-performance electrocatalysts still remains in its preliminary stage. To fully realize the potential of enzyme-mimetic electrocatalysts, significant time and close collaboration between fundamental research and engineering design will be required. This process involves integrating technological specifications and traditional electrocatalysis concepts with the core advantages of enzyme mimicry, while also acknowledging the limitations of such innovations. The overall system performance, rather than merely individual components, ultimately determines efficacy of the final device. This requires re-engineering and optimization for each new material, as unique conditions are needed for their best performance [31–34]. For relatively mature PEM technologies, this includes developing new polymer electrolyte membranes and electrode ionomers to interface effectively with enzyme-mimetic electrocatalysts, much like Nafion was selected for its optimal compatibility with Pt/C.

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