Dynamics Of Proton-coupled Electron Transfer Research Articles

Proton-coupled electron transfer dynamics in the alternative oxidase.

The alternative oxidase (AOX) is a membrane-bound di-iron enzyme that catalyzes O2-driven quinol oxidation in the respiratory chains of plants, fungi, and several pathogenic protists of biomedical and industrial interest. Yet, despite significant biochemical and structural efforts over the last decades, the catalytic principles of AOX remain poorly understood. We develop here multi-scale quantum and classical molecular simulations in combination with biochemical experiments to address the proton-coupled electron transfer (PCET) reactions responsible for catalysis in AOX from Trypanosoma brucei, the causative agent of sleeping sickness. We show that AOX activates and splits dioxygen via a water-mediated PCET reaction, resulting in a high-valent ferryl/ferric species and tyrosyl radical (Tyr220˙) that drives the oxidation of the quinol via electric field effects. We identify conserved carboxylates (Glu215, Asp100) within a buried cluster of ion-pairs that act as a transient proton-loading site in the quinol oxidation process, and validate their function experimentally with point mutations that result in drastic activity reduction and pK a-shifts. Our findings provide a key mechanistic understanding of the catalytic machinery of AOX, as well as a molecular basis for rational drug design against energy transduction chains of parasites. On a general level, our findings illustrate how redox-triggered conformational changes in ion-paired networks control the catalysis via electric field effects.

Proton-coupled electron transfer dynamics in the alternative oxidase

Proton-coupled electron transfer dynamics in the alternative oxidase

Proton-Coupled Electron Transfer Dynamics in the Obligate Mycobacterial Supercomplex III2IV2

Proton-Coupled Electron Transfer Dynamics in the Obligate Mycobacterial Supercomplex III2IV2

Water Oxidation and Hydrogen Evolution with Organic Photooxidants: A Theoretical Perspective.

In this Perspective, we discuss a novel water-splitting scenario, namely the direct oxidation of water molecules by organic photooxidants in hydrogen-bonded chromophore-water complexes. In comparison with the established scenario of semiconductor-based water splitting, the distance of electron transfer processes is thereby reduced from mesoscopic scales to the Ångström scale, and the time scale is reduced from milliseconds to femtoseconds, which suppresses competing loss processes. The concept is illustrated by computational studies for the heptazine-H2O complex. The excited-state landscape of this complex has been characterized with ab initio electronic-structure methods and the proton-coupled electron-transfer dynamics has been explored with nonadiabatic dynamics simulations. A unique feature of the heptazine chromophore is the existence of a low-lying and exceptionally long-lived 1ππ* state in which a substantial part of the photon energy can be stored for hundreds of nanoseconds and is available for the oxidation of water molecules. The calculations reveal that the absorption spectra and the photochemical functionalities of heptazine chromophores can be systematically tailored by chemical substitution. The options of harvesting hydrogen and the problems posed by the high reactivity of OH radicals are discussed.

Wavepacket propagations for the early time dynamics of proton-coupled electron transfer in the charge-transfer state of NH3Cl complex.

A charge-transfer (CT) excited state of NH3Cl, generated by photo-detachment of an electron from the anionic NH3Cl- precursor, can be represented as H2N+-H-Cl- and proceeds to two chemical reactions: one reaction generating NH2 and HCl resulting from a proton transfer (PT) and the other reaction producing NH3 and a Cl atom resulting from an electron transfer (ET); both are coupled to form a typical proton-coupled electron transfer (PCET) process. The early time dynamics of this CT were studied using time-dependent wavepacket propagation on three nonadiabatically coupled electronic states in a reduced three-dimensional space. The electronic states were treated using the XMS-CASPT2/aug-cc-pVTZ ab initio methodology. The population dynamics of the three coupled electronic states were analyzed in detail to reveal the initial stage of the PCET process up to ∼100 fs, while the branching ratio, χ = PT/(ET+PT), was determined after wavepacket propagations of up to 2000 fs. Another main result is the dependence of χ on the vibration levels of the initial precursor anion and the isotope substitution of the connecting H atom with deuterium and tritium. Our study reveals the detailed microscopic features of the PCET process embedded in the CT state of the NH3Cl complex and certain systematic dependences of the branching ratio χ on the above factors.

Nonequilibrium Dynamics of Proton-Coupled Electron Transfer in Proton Wires: Concerted but Asynchronous Mechanisms.

The coupling between electrons and protons and the long-range transport of protons play important roles throughout biology. Biomimetic systems derived from benzimidazole-phenol (BIP) constructs have been designed to undergo proton-coupled electron transfer (PCET) upon electrochemical or photochemical oxidation. Moreover, these systems can transport protons along hydrogen-bonded networks or proton wires through multiproton PCET. Herein, the nonequilibrium dynamics of both single and double proton transfer in BIP molecules initiated by oxidation are investigated with first-principles molecular dynamics simulations. Although these processes are concerted in that no thermodynamically stable intermediate is observed, the simulations predict that they are predominantly asynchronous on the ultrafast time scale. For both systems, the first proton transfer typically occurs ∼100 fs after electron transfer. For the double proton transfer system, typically the second proton transfer occurs hundreds of femtoseconds after the initial proton transfer. A machine learning algorithm was used to identify the key molecular vibrational modes essential for proton transfer: a slow, in-plane bending mode that dominates the overall inner-sphere reorganization, the proton donor–acceptor motion that leads to vibrational coherence, and the faster donor–hydrogen stretching mode. The asynchronous double proton transfer mechanism can be understood in terms of a significant mode corresponding to the two anticorrelated proton donor–acceptor motions, typically decreasing only one donor–acceptor distance at a time. Although these PCET processes appear concerted on the time scale of typical electrochemical experiments, attaching these BIP constructs to photosensitizers may enable the detection of the asynchronicity of the electron and multiple proton transfers with ultrafast two-dimensional spectroscopy. Understanding the fundamental PCET mechanisms at this level will guide the design of PCET systems for catalysis and energy conversion processes.

Energetics and Dynamics of Proton-Coupled Electron Transfer in the NADH/FMN Site of Respiratory Complex I.

Complex I functions as an initial electron acceptor in aerobic respiratory chains that reduces quinone and pumps protons across a biological membrane. This remarkable charge transfer process extends ca. 300 Å and it is initiated by a poorly understood proton-coupled electron transfer (PCET) reaction between nicotinamide adenine dinucleotide (NADH) and a protein-bound flavin (FMN) cofactor. We combine here large-scale density functional theory calculations and quantum/classical models with atomistic molecular dynamics simulations to probe the energetics and dynamics of the NADH-driven PCET reaction in complex I. We find that the reaction takes place by concerted hydrogen atom (H•) transfer that couples to an electron transfer (eT) between the aromatic ring systems of the cofactors and further triggers reduction of the nearby FeS centers. In bacterial, Escherichia coli-like complex I isoforms, reduction of the N1a FeS center increases the binding affinity of the oxidized NAD+ that prevents the nucleotide from leaving prematurely. This electrostatic trapping could provide a protective gating mechanism against reactive oxygen species formation. We also find that proton transfer from the transient FMNH• to a nearby conserved glutamate (Glu97) residue favors eT from N1a onward along the FeS chain and modulates the binding of a new NADH molecule. The PCET in complex I isoforms with low-potential N1a centers is also discussed. On the basis of our combined results, we propose a putative mechanistic model for the NADH-driven proton/electron-transfer reaction in complex I.

Proton-Coupled Electron-Transfer Processes in Ultrafast Time Domain: Evidence for Effects of Hydrogen-Bond Stabilization on Photoinduced Electron Transfer.

The proton-coupled electron-transfer (PCET) reaction is investigated for a newly synthesized imidazole-anthraquinone biomimetic model with a photoactive RuII -polypyridyl moiety that is covalently coupled to the imidazole fragment. Intramolecular H-bonding interactions between imidazole and anthraquinone moieties favor the PCET process; this can be correlated to an appreciable positive shift in the one-electron reduction potential of the coordinated anthraquinone moiety functionalized with the imidazole fragment. This can also be attributed to the low luminescence quantum yield of the RuII -polypyridyl complex used. The dynamics of the intramolecular electron-transfer (ET) and PCET processes are studied by using femtosecond transient absorption spectroscopy. The steady-state spectroscopic studies and the results of the time-resolved absorption studies confirm that H-bonded water molecules play a major role in both ET and PCET dynamics as a proton relay in the excited state. The electron-transfer process is followed by a change in the H-bonding equilibrium between AQ and imidazole in acetonitrile solvent, and protonation of AQ.- by water leads to PCET in the presence of water. A slower forward and backward electron-transfer rate is observed in the presence of D2 O compared with that in H2 O. These results provide further experimental support for a detailed understanding of the PCET process.

Reaction Dynamics of Proton-Coupled Electron Transfer from Reduced ZnO Nanocrystals.

The creation of systems that efficiently interconvert chemical and electrical energies will be aided by understanding proton-coupled electron transfers at solution-semiconductor interfaces. Steps in developing that understanding are described here through kinetic studies of reactions of photoreduced colloidal zinc oxide (ZnO) nanocrystals (NCs) with the nitroxyl radical TEMPO. These reactions proceed by proton-coupled electron transfer (PCET) to give the hydroxylamine TEMPOH. They occur on the submillisecond to seconds time scale, as monitored by stopped-flow optical spectroscopy. Under conditions of excess TEMPO, the reactions are multiexponential in character. One of the contributors to this multiexponential kinetics may be a distribution of reactive proton sites. A graphical overlay method shows the reaction to be first order in [TEMPO]. Different electron concentrations in otherwise identical NC samples were achieved by three different methods: differing photolysis times, premixing with an unphotolyzed sample, or prereaction with TEMPO. The reaction velocities were consistently higher for NCs with higher numbers of electrons. For instance, NCs with an average of 2.6 e(-)/NC reacted faster than otherwise identical samples containing ≤1 e(-)/NC. Surprisingly, NC samples with the same average number of electrons but prepared in different ways often had different reaction profiles. These results show that properties beyond electron content determine PCET reactivity of the particles.

Proton-coupled electron transfer dynamics in the catalytic mechanism of a [NiFe]-hydrogenase.

The movement of protons and electrons is common to the synthesis of all chemical fuels such as H2. Hydrogenases, which catalyze the reversible reduction of protons, necessitate transport and reactivity between protons and electrons, but a detailed mechanism has thus far been elusive. Here, we use a phototriggered chemical potential jump method to rapidly initiate the proton reduction activity of a [NiFe] hydrogenase. Coupling the photochemical initiation approach to nanosecond transient infrared and visible absorbance spectroscopy afforded direct observation of interfacial electron transfer and active site chemistry. Tuning of intramolecular proton transport by pH and isotopic substitution revealed distinct concerted and stepwise proton-coupled electron transfer mechanisms in catalysis. The observed heterogeneity in the two sequential proton-associated reduction processes suggests a highly engineered protein environment modulating catalysis and implicates three new reaction intermediates; Nia-I, Nia-D, and Nia-SR(-). The results establish an elementary mechanistic understanding of catalysis in a [NiFe] hydrogenase with implications in enzymatic proton-coupled electron transfer and biomimetic catalyst design.

Oxidation of Phenol by Tris(1,10-phenanthroline)osmium(III)

Outer-sphere oxidation of phenols is under intense scrutiny because of questions related to the dynamics of proton-coupled electron transfer (PCET). Oxidation by cationic transition-metal complexes in aqueous solution presents special challenges because of the potential participation of the solvent as a proton acceptor and of the buffers as general base catalysts. Here we report that oxidation of phenol by a deficiency of [Os(phen)(3)](3+), as determined by stopped-flow spectrophotometry, yields a unique rate law that is second order in [osmium(III)] and [phenol] and inverse second order in [osmium(II)] and [H(+)]. A mechanism is inferred in which the phenoxyl radical is produced through a rapid PCET preequilibrium, followed by rate-limiting phenoxyl radical coupling. Marcus theory predicts that the rate of electron transfer from phenoxide to osmium(III) is fast enough to account for the rapid PCET preequilibrium, but it does not rule out the intervention of other pathways such as concerted proton-electron transfer or general base catalysis.

Quantum dynamics of proton-coupled electron transfer in model systems

The quantum dynamics of model systems with strong coupling between the electron transfer (ET) and the proton transfer (PT) has been studied: the proton-coupled electron transfer (PCET) process. These reactions are very important in several chemical areas and in biochemistry above all, hence, in this study, the models have been built having in mind biochemical systems. The PCET process has been analyzed in terms of the two constituent phenomena (PT and ET) and we have studied both the situations where the two processes proceed together and where a process (PT or ET) is faster than the other. The risk of the adiabatic approximation for the proton has been underlined since there is the possibility of faster proton transfer despite of the mass disparity of proton and electron.

Quantum dynamics of proton-coupled electron transfer in model systems

The quantum dynamics of model systems with strong coupling between the electron transfer (ET) and the proton transfer (PT) has been studied: the proton-coupled electron transfer (PCET) process. These reactions are very important in several chemical areas and in biochemistry above all, hence, in this study, the models have been built having in mind biochemical systems. The PCET process has been analyzed in terms of the two constituent phenomena (PT and ET) and we have studied both the situations where the two processes proceed together and where a process (PT or ET) is faster than the other. The risk of the adiabatic approximation for the proton has been underlined since there is the possibility of faster proton transfer despite of the mass disparity of proton and electron.