Seeking a quantum advantage with trapped-ion quantum simulations of condensed-phase chemical dynamics.

Simulating the quantum dynamics of molecules in the condensed phase represents a longstanding challenge in chemistry. Trapped-ion quantum systems may serve as a platform for the analog-quantum simulation of chemical dynamics that is beyond the reach of current classical-digital simulation. To identify a 'quantum advantage' for these simulations, performance analysis of both analog-quantum simulation on noisy hardware and classical-digital algorithms is needed. In this Review, we make a comparison between a noisy analog trapped-ion simulator and a few choice classical-digital methods on simulating the dynamics of a model molecular Hamiltonian with linear vibronic coupling. We describe several simple Hamiltonians that are commonly used to model molecular systems, which can be simulated with existing or emerging trapped-ion hardware. These Hamiltonians may serve as stepping stones towards the use of trapped-ion simulators for systems beyond the reach of classical-digital methods. Finally, we identify dynamical regimes in which classical-digital simulations seem to have the weakest performance with respect to analog-quantum simulations. These regimes may provide the lowest hanging fruit to make the most of potential quantum advantages.

Electron transfer rate modulation with mid-IR in butadiyne-bridged donor-bridge-acceptor compounds.

Controlling electron transfer (ET) processes in donor-bridge-acceptor (DBA) compounds by mid-IR excitation can enhance our understanding of the ET dynamics and may find practical applications in molecular sensing and molecular-scale electronics. Alkyne moieties are attractive to serve as ET bridges, as they offer the possibility of fast ET and present convenient vibrational modes to perturb the ET dynamics. Yet, these bridges introduce complexity because of the strong torsion angle dependence of the ET rates and transition dipoles among electronic states and a shallow torsion barrier. In this study, we implemented ultrafast 3-pulse laser spectroscopy to investigate how the ET from the dimethyl aniline (D) electron donor to the N-isopropyl-1,8-napthalimide (NAP) electron acceptor can be altered by exciting the CC stretching mode (νCC) of the butadiyne bridge linking the donor and acceptor. The electron transfer was initiated by electronically exciting the acceptor moiety at 400 nm, followed by vibrational excitation of the alkyne, νCC, and detecting the changes in the absorption spectrum in the visible spectral region. The experiments were performed at different delay times t1 and t2, which are the delays between UV-mid-IR and mid-IR-Vis pulses, respectively. Two sets of torsion-angle conformers were identified, one featuring a very fast mean ET time of 0.63 ps (group A) and another featuring a slower mean ET time of 4.3 ps (group B), in the absence of the mid-IR excitation. TD-DFT calculations were performed to determine key torsion angle dependent molecular parameters, including the electronic and vibrational transition dipoles, transition frequencies, and electronic couplings. To describe the 3-pulse data, we developed a kinetic model that includes a locally excited, acceptor-based S2 state, a charge separated S1 state, and their vibrationally excited counterparts, with either excited νCC (denoted as S1Atr, S1Btr, S2Atr, and S2Btr, where tr stands for the excited triplet bond, νCC) or excited daughter modes of the νCC relaxation (S1Ah, S1Bh, S2Ah, and S2Bh, where h stands for vibrationally hot species). The kinetic model was solved analytically, and the species-associated spectra (SAS) were determined numerically using a matrix approach, treating first the experiments with longer t1 delays and then using the already determined SAS for modeling the experiments with shorter t1 delays. Strong vibronic coupling of νCC and of vibrationally hot states makes the analysis complicated. Nevertheless, the SAS were identified and the ET rates of the vibrationally excited species, S2Atr, S2Btr and S2Bh, were determined. The results show that the ET rate for the S2A species is ca. 1.2-fold slower when the νCC mode is excited. The ET rate for species S2B is slower by ca. 1.3-fold if the compound is vibrationally hot and is essentially unchanged when the νCC mode is excited. The SAS determined for the tr and h species resemble the SAS for their respective precursor species in the 2-pulse transient absorption experiments, which validates the procedure used and the results.

Electron-donating functional groups strengthen ligand-induced chiral imprinting on CsPbBr3 quantum dots.

Chiral perovskite nanoparticles and films are promising for integration in emerging spintronic and optoelectronic technologies, yet few design rules exist to guide the development of chiral material properties. The chemical space of potential building blocks for these nanostructures is vast, and the mechanisms through which organic ligands can impart chirality to the inorganic perovskite lattice are not well understood. In this work, we investigate how the properties of chiral ammonium ligands, the most common organic ligand type used with perovskites, affect the circular dichroism of strongly quantum confined CsPbBr3 nanocrystals. We show that aromatic ammonium ligands with stronger electron-donating groups lead to higher-intensity circular dichroism associated with the lowest-energy excitonic transition of the perovskite nanocrystal. We argue that this behavior is best explained by a modulation of the exciton wavefunction overlap between the nanocrystal and the organic ligand, as the functional groups on the ligand can shift electron density toward the organic species-perovskite lattice interface to increase the imprinting.

Quantum Simulation of Polarized Light-Induced Electron Transfer with a Trapped-Ion Qutrit System.

Electron transfer within and between molecules is crucial in chemistry, biochemistry, and energy science. This study describes a quantum simulation method that explores the influence of light polarization on electron transfer between two molecules. By implementing precise and coherent control among the quantum states of trapped atomic ions, we can induce quantum dynamics that mimic the electron-transfer dynamics in molecules. We use three-level systems (qutrits), rather than traditional two-level systems (qubits), to enhance the simulation efficiency and realize high-fidelity simulations of electron-transfer dynamics. We treat the quantum interference between the electron coupling pathways from a donor with two degenerate excited states to an acceptor and analyze the transfer efficiency. We also examine the potential error sources that enter the quantum simulations. The trapped-ion systems have favorable scalings with system size compared to those of classical computers, promising access to richer electron-transfer simulations.

Correlated particle transport enables biological free energy transduction.

Studies of biological transport frequently neglect the explicit statistical correlations among particle site occupancies (i.e., they use a mean-field approximation). Neglecting correlations sometimes captures biological function, even for out-of-equilibrium and interacting systems. We show that neglecting correlations fails to describe free energy transduction, mistakenly predicting an abundance of slippage and energy dissipation, even for networks that are near reversible and lack interactions among particle sites. Interestingly, linear charge transport chains are well described without including correlations, even for networks that are driven and include site-site interactions typical of biological electron transfer chains. We examine three specific bioenergetic networks: a linear electron transfer chain (as found in bacterial nanowires), a near-reversible electron bifurcation network (as in complex III of respiration and other recently discovered structures), and a redox-coupled proton pump (as in complex IV of respiration).

Adenine Fine-Tunes DNA Photolyase's Repair Mechanism.

The comparative study of DNA repair by mesophilic and extremophilic photolyases helps us understand the evolution of these enzymes and their role in preserving life on our changing planet. The mechanism of repair of cyclobutane pyrimidine dimer lesions in DNA by electron transfer from the flavin adenine dinucleotide cofactor is the subject of intense interest. The role of adenine in mediating this process remains unresolved. Using microsecond molecular dynamics simulations, we find that adenine mediates the electron transfer in both mesophile and extremophile DNA photolyases through a similar mechanism. In fact, in all photolyases studied, the molecular conformations with the largest electronic couplings between the enzyme cofactor and DNA show the presence of adenine in 10-20% of the strongest-coupling tunneling pathways between the atoms of the electron donor and acceptor. Our theoretical analysis finds that adenine serves the critical role of fine-tuning rather than maximizing the donor-acceptor coupling within the range appropriate for the repair function.

Interference between Molecular and Photon Field-Mediated Electron Transfer Coupling Pathways in Cavities.

Cavity polaritonics creates novel opportunities to direct chemical reactions. Electron transfer (ET) reactions are among the simplest reactions, and they underpin energy conversion. New strategies to manipulate and direct electron flow at the nanoscale are of particular interest in biochemistry, energy science, bioinspired materials science, and chemistry. We show that optical cavities can modulate electron transfer pathway interferences and ET rates in donor-bridge-acceptor (DBA) systems. We derive the rate for DBA electron transfer when the molecules are coupled to cavity modes, emphasizing novel cavity-induced pathway interferences with the molecular electronic coupling pathways, as these interferences allow a new kind of ET rate tuning. The interference between the cavity-induced coupling pathways and the intrinsic molecular coupling pathway is dependent on the cavity properties. Thus, manipulating the interference between the cavity-induced DA coupling and the bridge-mediated coupling offers an approach to direct and manipulate charge flow at the nanoscale.

Mapping Simulated Two-Dimensional Spectra to Molecular Models Using Machine Learning.

Two-dimensional (2D) spectroscopy encodes molecular properties and dynamics into expansive spectral data sets. Translating these data into meaningful chemical insights is challenging because of the many ways chemical properties can influence the spectra. To address the task of extracting chemical information from 2D spectroscopy, we study the capacity of simple feedforward neural networks (NNs) to map simulated 2D electronic spectra to underlying physical Hamiltonians. We examined hundreds of simulated 2D spectra corresponding to monomers and dimers with varied Franck-Condon active vibrations and monomer-monomer electronic couplings. We find the NNs are able to correctly characterize most Hamiltonian parameters in this study with an accuracy above 90%. Our results demonstrate that NNs can aid in interpreting 2D spectra, leading from spectroscopic features to underlying effective Hamiltonians.

Regulating Singlet-Triplet Energy Gaps through Substituent-Driven Modulation of the Exchange and Coulomb Interactions.

Control of the singlet-triplet energy gap (ΔEST) is central to realizing productive energy conversion reactions, photochemical reaction trajectories, and emergent applications that exploit molecular spin physics. Despite this, no systematic methods have been defined to tune ΔEST in simple molecular frameworks, let alone by an approach that also holds chromophore size and electronic structural parameters (such as the HOMO-LUMO gap) constant. Using a combination of molecular design, photophysical and potentiometric experiments, and quantum chemical analyses, we show that the degree of electron-electron repulsion in excited singlet and triplet states may be finely controlled through the substitution pattern of a simple porphyrin absorber, enabling regulation of relative electronically excited singlet and triplet state energies by the designed restriction of the electron-electron Coulomb (J) and exchange (K) interaction magnitudes. This approach modulates the ΔEST magnitude by controlling the densities of state in the occupied and virtual molecular orbital manifolds, natural transition orbital polarization, and the relative contributions of one electron transitions involving select natural transition orbital pairs. This road map, which regulates electron density overlaps in the occupied and virtual states that define the singlet and triplet wave functions of these chromophores, enables new approaches to preserve excitation energy despite intersystem crossing.

Cofactor Dynamics Couples the Protein Surface to the Heme in Cytochrome c, Facilitating Electron Transfer.

Electron transport through biomolecules and in biological transport networks is of great importance to bioenergetics and biocatalysis. More generally, it is of crucial importance to understand how the pathways that connect buried metallocofactors to other cofactors, and to protein surfaces, affect the biological chemistry of metalloproteins. In terms of electron transfer (ET), the strongest coupling pathways usually comprise covalent and hydrogen bonded networks, with a limited number of through-space contacts. Herein, we set out to determine the relative roles of hydrogen bonds involved in ET via an established heme-to-surface tunneling pathway in cytochrome (cyt) c (i.e., heme-W59-D60-E61-N62). A series of cyt c variants were produced where a ruthenium tris(diimine) photooxidant was placed at position 62 via covalent modification of the N62C residue. Surprisingly, variants where the H-bonding residues W59 and D60 were replaced (i.e., W59F and D60A) showed no change in ET rate from the ferrous heme to Ru(III). In contrast, changing the composition of an alternative tunneling pathway (i.e., heme-M64-N63-C62) with the M64L substitution shows a factor of 2 decrease in the rate of heme-to-Ru ET. This pathway involves a through-space tunneling step between the heme and M64 residue, and such steps are usually disfavored. To rationalize why the heme-M64-N63-C62 is preferred, molecular dynamics (MD) simulations and Pathways analysis were employed. These simulations show that the change in heme-Ru ET rates is attributed to different conformations with compressed donor-acceptor distances, by ∼2 Å in pathway distance, in the M64-containing protein as compared to the M64L protein. The change in distance is correlated with changes in the electronic coupling that are in accord with the experimentally observed heme-Ru ET rates. Remarkably, the M64L variation at the core of the protein translates to changes in cofactor dynamics at the protein surface. The surface changes identified by MD simulations include dynamic anion-π and dipole-dipole interactions. These interactions influence the strength of tunneling pathways and ET rates by facilitating decreases in through-space tunneling distances in key coupling pathways.

A Chirality-Based Quantum Leap.

There is increasing interest in the study of chiral degrees of freedom occurring in matter and in electromagnetic fields. Opportunities in quantum sciences will likely exploit two main areas that are the focus of this Review: (1) recent observations of the chiral-induced spin selectivity (CISS) effect in chiral molecules and engineered nanomaterials and (2) rapidly evolving nanophotonic strategies designed to amplify chiral light-matter interactions. On the one hand, the CISS effect underpins the observation that charge transport through nanoscopic chiral structures favors a particular electronic spin orientation, resulting in large room-temperature spin polarizations. Observations of the CISS effect suggest opportunities for spin control and for the design and fabrication of room-temperature quantum devices from the bottom up, with atomic-scale precision and molecular modularity. On the other hand, chiral-optical effects that depend on both spin- and orbital-angular momentum of photons could offer key advantages in all-optical and quantum information technologies. In particular, amplification of these chiral light-matter interactions using rationally designed plasmonic and dielectric nanomaterials provide approaches to manipulate light intensity, polarization, and phase in confined nanoscale geometries. Any technology that relies on optimal charge transport, or optical control and readout, including quantum devices for logic, sensing, and storage, may benefit from chiral quantum properties. These properties can be theoretically and experimentally investigated from a quantum information perspective, which has not yet been fully developed. There are uncharted implications for the quantum sciences once chiral couplings can be engineered to control the storage, transduction, and manipulation of quantum information. This forward-looking Review provides a survey of the experimental and theoretical fundamentals of chiral-influenced quantum effects and presents a vision for their possible future roles in enabling room-temperature quantum technologies.

Synthetic Control of Exciton Dynamics in Bioinspired Cofacial Porphyrin Dimers.

Understanding how the complex interplay among excitonic interactions, vibronic couplings, and reorganization energy determines coherence-enabled transport mechanisms is a grand challenge with both foundational implications and potential payoffs for energy science. We use a combined experimental and theoretical approach to show how a modest change in structure may be used to modify the exciton delocalization, tune electronic and vibrational coherences, and alter the mechanism of exciton transfer in covalently linked cofacial Zn-porphyrin dimers (meso-beta linked ABm-ß and meso-meso linked AAm-m). While both ABm-ß and AAm-m feature zinc porphyrins linked by a 1,2-phenylene bridge, differences in the interporphyrin connectivity set the lateral shift between macrocycles, reducing electronic coupling in ABm-ß and resulting in a localized exciton. Pump-probe experiments show that the exciton dynamics is faster by almost an order of magnitude in the strongly coupled AAm-m dimer, and two-dimensional electronic spectroscopy (2DES) identifies a vibronic coherence that is absent in ABm-ß. Theoretical studies indicate how the interchromophore interactions in these structures, and their system-bath couplings, influence excitonic delocalization and vibronic coherence-enabled rapid exciton transport dynamics. Real-time path integral calculations reproduce the exciton transfer kinetics observed experimentally and find that the linking-modulated exciton delocalization strongly enhances the contribution of vibronic coherences to the exciton transfer mechanism, and that this coherence accelerates the exciton transfer dynamics. These benchmark molecular design, 2DES, and theoretical studies provide a foundation for directed explorations of nonclassical effects on exciton dynamics in multiporphyrin assemblies.

Twisted molecular wires polarize spin currents at room temperature.

A critical spintronics challenge is to develop molecular wires that render efficiently spin-polarized currents. Interplanar torsional twisting, driven by chiral binucleating ligands in highly conjugated molecular wires, gives rise to large near-infrared rotational strengths. The large scalar product of the electric and magnetic dipole transition moments ([Formula: see text]), which are evident in the low-energy absorptive manifolds of these wires, makes possible enhanced chirality-induced spin selectivity-derived spin polarization. Magnetic-conductive atomic force microscopy experiments and spin-Hall devices demonstrate that these designs point the way to achieve high spin selectivity and large-magnitude spin currents in chiral materials.

Discovery of the Xenon-Protein Interactome Using Large-Scale Measurements of Protein Folding and Stability.

The intermolecular interactions of noble gases in biological systems are associated with numerous biochemical responses, including apoptosis, inflammation, anesthesia, analgesia, and neuroprotection. The molecular modes of action underlying these responses are largely unknown. This is in large part due to the limited experimental techniques to study protein-gas interactions. The few techniques that are amenable to such studies are relatively low-throughput and require large amounts of purified proteins. Thus, they do not enable the large-scale analyses that are useful for protein target discovery. Here, we report the application of stability of proteins from rates of oxidation (SPROX) and limited proteolysis (LiP) methodologies to detect protein-xenon interactions on the proteomic scale using protein folding stability measurements. Over 5000 methionine-containing peptides and over 5000 semi-tryptic peptides, mapping to ∼1500 and ∼950 proteins, respectively, in the yeast proteome, were assayed for Xe-interacting activity using the SPROX and LiP techniques. The SPROX and LiP analyses identified 31 and 60 Xe-interacting proteins, respectively, none of which were previously known to bind Xe. A bioinformatics analysis of the proteomic results revealed that these Xe-interacting proteins were enriched in those involved in ATP-driven processes. A fraction of the protein targets that were identified are tied to previously established modes of action related to xenon's anesthetic and organoprotective properties. These results enrich our knowledge and understanding of biologically relevant xenon interactions. The sample preparation protocols and analytical methodologies developed here for xenon are also generally applicable to the discovery of a wide range of other protein-gas interactions in complex biological mixtures, such as cell lysates.

Mechanism of Side Chain-Controlled Proton Conductivity in Bioinspired Peptidic Nanostructures.

Bioinspired peptide assemblies are promising candidates for use as proton-conducting materials in electrochemical devices and other advanced technologies. Progress toward applications requires establishing foundational structure-function relationships for transport in these materials. This experimental-theoretical study sheds light on how the molecular structure and proton conduction are linked in three synthetic cyclic peptide nanotube assemblies that comprise the three canonical basic amino acids (lysine, arginine, and histidine). Experiments find an order of magnitude higher proton conductivity for lysine-containing peptide assemblies compared to histidine and arginine containing assemblies. The simulations indicate that, upon peptide assembly, the basic amino acid side chains are close enough to enable direct proton transfer. The proton transfer kinetics is determined in the simulations to be governed by the structure and flexibility of the side chains. Together, experiments and theory indicate that the proton mobility is the main determinant of proton conductivity, critical for the performance of peptide-based devices.

Excited-State Dynamics and Nonlinear Optical Properties of Hyperpolarizable Chromophores Based on Conjugated Bis(terpyridyl)Ru(II) and Palladium and Platinum Porphyrinic Components: Impact of Heavy Metals upon Supermolecular Electro-Optic Properties.

A new series of strongly coupled oscillators based upon (porphinato)Pd, (porphinato)Pt, and bis(terpyridyl)ruthenium(II) building blocks is described. These RuPPd, RuPPt, RuPPdRu, and RuPPtRu chromophores feature bis(terpyridyl)Ru(II) moieties connected to the (porphinato)metal unit via an ethyne linker that bridges the 4'-terpyridyl and porphyrin macrocycle meso-carbon positions. Pump-probe transient optical data demonstrate sub-picosecond excited singlet-to-triplet-state relaxation. The relaxed lowest-energy triplet (T1) excited states of these chromophores feature absorption manifolds that span the 800-1200 nm spectral region, microsecond triplet-state lifetimes, and large absorptive extinction coefficients [ε(T1 → Tn) > 4 × 104 M-1 cm-1]. Dynamic hyperpolarizability (ßλ) values were determined from hyper-Rayleigh light scattering (HRS) measurements carried out at several incident irradiation wavelengths over the 800-1500 nm spectral region. Relative to benchmark RuPZn and RuPZnRu chromophores which showed large ßHRS values over the 1200-1600 nm range, RuPPd, RuPPt, RuPPdRu, and RuPPtRu displayed large ßHRS values over the 850-1200 nm region. Generalized Thomas-Kuhn sum (TKS) rules and experimental hyperpolarizability values were utilized to determine excited state-to-excited state transition dipole terms from experimental electronic absorption data and thus assessed frequency-dependent ßλ values, including two- and three-level contributions for both ßzzz and ßxzx tensor components to the RuPPd, RuPPt, RuPPdRu, and RuPPtRu hyperpolarizability spectra. These analyses qualitatively rationalize how the ßzzz and ßxzx tensor elements influence the observed irradiation wavelength-dependent hyperpolarizability magnitudes. The TKS analysis suggests that supermolecules related to RuPPd, RuPPt, RuPPdRu, and RuPPtRu will likely feature intricate dependences of experimentally determined ßHRS values as a function of irradiation wavelength that derive from substantial singlet-triplet mixing, and complex interactions among multiple different ß tensor components that modulate the long wavelength regime of the nonlinear optical response.

Electron ratcheting in self-assembled soft matter.

Ratcheted multi-step hopping electron transfer systems can plausibly produce directional charge transport over very large distances without requiring a source-drain voltage bias. We examine molecular strategies to realize ratcheted charge transport based on multi-step charge hopping, and we illustrate two ratcheting mechanisms with examples based on DNA structures. The charge transport times and currents that may be generated in these assemblies are also estimated using kinetic simulations. The first ratcheting mechanism described for nanoscale systems requires local electric fields on the 109 V/m scale to realize nearly 100% population transport. The second ratcheting mechanism for even larger systems, based on electrochemical gating, is estimated to generate currents as large as 0.1 pA for DNA structures that are a few µm in length with a gate voltage of about 5 V, a magnitude comparable to currents measured in DNA wires at the nanoscale when a source-drain voltage bias of similar magnitude is applied, suggesting an approach to considerably extend the distance range over which DNA charge transport devices may operate.

Why Do Most Aromatics Fail to Support Hole Hopping in the Cytochrome c Peroxidase-Cytochrome c Complex?

Electron transport through aromatic species (especially tryptophan and tyrosine) plays a central role in water splitting, redox signaling, oxidative damage protection, and bioenergetics. The cytochrome c peroxidase (CcP)-cytochrome c (Cc) complex (CcP:Cc) is used widely to study interprotein electron transfer (ET) mechanisms. Tryptophan 191 (Trp191) of CcP supports hole hopping charge recombination in the CcP:Cc complex. Experimental studies find that when Trp191 is substituted by tyrosine, phenylalanine, or redox-active aniline derivatives bound in the W191G cavity, enzymatic activity and charge recombination rates both decrease. Theoretical analysis of these CcP:Cc complexes finds that the ET kinetics depend strongly on the chemistry of the modified Trp site. The computed electronic couplings in the W191F and W191G species are orders of magnitude smaller than in the native protein, due largely to the absence of a hopping intermediate and the large tunneling distance. Small molecules bound in the W191G cavity are weakly coupled electronically to the Cc heme, and the structural disorder of the guest molecule in the binding pocket may contribute further to the lack of enzymatic activity. The couplings in W191Y are not substantially weakened compared to the native species, but the redox potential difference for tyrosine vs tryptophan oxidation accounts for the slower rate in the Tyr mutant. Thus, theoretical analysis explains why only the native Trp supports rapid hole hopping in the CcP:Cc complex. Favorable free energies and electronic couplings are essential for establishing an efficient hole hopping relay in this protein-protein complex.

Oxalate decarboxylase uses electron hole hopping for catalysis.

The hexameric low-pH stress response enzyme oxalate decarboxylase catalyzes the decarboxylation of the oxalate mono-anion in the soil bacterium Bacillus subtilis. A single protein subunit contains two Mn-binding cupin domains, and catalysis depends on Mn(III) at the N-terminal site. The present study suggests a mechanistic function for the C-terminal Mn as an electron hole donor for the N-terminal Mn. The resulting spatial separation of the radical intermediates directs the chemistry toward decarboxylation of the substrate. A π-stacked tryptophan pair (W96/W274) links two neighboring protein subunits together, thus reducing the Mn-to-Mn distance from 25.9 Å (intrasubunit) to 21.5 Å (intersubunit). Here, we used theoretical analysis of electron hole-hopping paths through redox-active sites in the enzyme combined with site-directed mutagenesis and X-ray crystallography to demonstrate that this tryptophan pair supports effective electron hole hopping between the C-terminal Mn of one subunit and the N-terminal Mn of the other subunit through two short hops of ∼8.5 Å. Replacement of W96, W274, or both with phenylalanine led to a large reduction in catalytic efficiency, whereas replacement with tyrosine led to recovery of most of this activity. W96F and W96Y mutants share the wildtype tertiary structure. Two additional hole-hopping networks were identified leading from the Mn ions to the protein surface, potentially protecting the enzyme from high Mn oxidation states during turnover. Our findings strongly suggest that multistep hole-hopping transport between the two Mn ions is required for enzymatic function, adding to the growing examples of proteins that employ aromatic residues as hopping stations.