Effect of pressure on electron transfer reactions in inorganic and bioinorganic chemistry

Kinetic and thermodynamic studies involving the application of different high-pressure techniques, are very useful in gaining mechanistic information on the basis of volume changes that occur during inorganic and bioinorganic electron transfer reactions. The most fundamental type of electron transfer reaction concerns self-exchange reactions, for which the overall reaction volume is zero, and activation volumes can be measured and discussed. In the case of non-symmetrical electron transfer reactions, intra- and intermolecular processes can be studied and volume profiles can be constructed. Precursor complex formation can in some cases be recognized kinetically in such systems. Typical values of activation and reaction volumes are reviewed for various reversible and irreversible electron transfer reactions. Mechanistic conclusions reached on the basis of these parameters are presented. Volume profiles for electron transfer reactions enable a simplistic presentation of the reaction mechanism on the basis of intrinsic and solvational volume changes along the reaction coordinate.     

Activation of electron transfer reactions of the blue proteins.

Thermal activation of electron transfer reactions of the blue proteins is considered in terms of vibronic coupling. Use of the electron paramagnetic resonance spectral distribution to obtain an estimate of the force constant for the relevant protein mode is proposed and demonstrated. This analysis leads to a model in which the configurations of the cupric and cuprous sites are displaced only a few degrees from each other, both being close to the configuration midway between planar and tetrahedral.     

Coupled electron and proton transfer reactions during the O→E transition in bovine cytochrome c oxidase

A combined DFT/electrostatic approach is employed to study the coupling of proton and electron transfer reactions in cytochrome c oxidase (CcO) and its proton pumping mechanism. The coupling of the chemical proton to the internal electron transfer within the binuclear center is examined for the O→E transition. The novel features of the His291 pumping model are proposed, which involve timely well-synchronized sequence of the proton-coupled electron transfer reactions. The obtained pK(a)s and E(m)s of the key ionizable and redox-active groups at the different stages of the O→E transition are consistent with available experimental data. The PT step from E242 to H291 is examined in detail for various redox states of the hemes and various conformations of E242 side-chain. Redox potential calculations of the successive steps in the reaction cycle during the O→E transition are able to explain a cascade of equilibria between the different intermediate states and electron redistribution between the metal centers during the course of the catalytic activity. All four electrometric phases are discussed in the light of the obtained results, providing a robust support for the His291 model of proton pumping in CcO.     

On the rates of enzymatic, protein and model compound reactions: the importance of diffusion control

A meaningful method of comparison is suggested for saturation kinetics, typical of enzyme-catalyzed reactions, and nonsaturation kinetics, often typical of model compound reactions. True diffusion-controlled reactions do not give saturation behavior; but enzymes may need saturation behavior to attain selectivity and stereospecificity for complicated substrates or for reactions beyond the complexity of electron transfer. However, the diffusion controlled limit provides a better reference point for rate comparisons than does the rate of uncatalyzed reaction. The failure of the Stokes-Einstein equation for small substrates is documented, as are ways of circumventing the problem. Advantages and pitfalls in the use of viscosogens to test for diffusion control are delineated. Finally, the possible advantages of surface diffusion for an enzyme, but lack of experimental evidence, is discussed.     

Lipid radicals--possible mediators of charge transfer and energy transformation (a hypothesis)

A number of enzymatic reactions with the participation of lipid radicals is discussed in the article. It is supposed that NADPH- and NADH-dependent formation of the lipid radicals has a functional importance. The uptake of oxygen by free radicals is considered as one of the reactions of radicals utilization. It is proposed that other reactions with participation of lipid radicals can take place in the membranes of microsomes and mitochondria: the reaction of electron transfer from flavoprotein to cytochrome P448 and the reaction of energy transfer which provide the coupling of oxidation and phosphorylation.     

Dynamics of electron transfer pathways in cytochrome C oxidase

Cytochrome c oxidase mediates the final step of electron transfer reactions in the respiratory chain, catalyzing the transfer between cytochrome c and the molecular oxygen and concomitantly pumping protons across the inner mitochondrial membrane. We investigate the electron transfer reactions in cytochrome c oxidase, particularly the control of the effective electronic coupling by the nuclear thermal motion. The effective coupling is calculated using the Green's function technique with an extended Huckel level electronic Hamiltonian, combined with all-atom molecular dynamics of the protein in a native (membrane and solvent) environment. The effective coupling between Cu(A) and heme a is found to be dominated by the pathway that starts from His(B204). The coupling between heme a and heme a(3) is dominated by a through-space jump between the two heme rings rather than by covalent pathways. In the both steps, the effective electronic coupling is robust to the thermal nuclear vibrations, thereby providing fast and efficient electron transfer.     

Quantum and classical dynamics in biochemical reactions

The classic experiment of deVault and Chance touched off a long series of theoretical and experimental studies of the interplay between quantum and classical dynamics in photosynthetic electron transfer. More recently these issues have also been addressed in experiments on ligand binding reactions in heme proteins and through the study of kinetic isotope effects in enzymatic proton transfer. Theoretical effort has focused on a class of relatively simple models which display a surprisingly rich spectrum of dynamical behavior. Much less attention has been paid to a very important issue: Why are we allowed to use such simple models to describe such obviously complex molecules? Here we provide some tentative answers to this question, contrasting the cases of electron and proton transfer. We suggest that ideas based on simple models can inspire novel strategies for ‘realistic’ simulations, and that we can begin to think about the general problems of enzymatic catalysis in terms of dynamical pictures that previously have been applied only to the simpler case of electron transfer.     

Electromagnetic acceleration of electron transfer reactions

The Moving Charge Interaction (MCI) model proposes that low frequency electromagnetic (EM) fields affect biochemical reactions through interaction with moving electrons. Thus, EM field activation of genes, and the synthesis of stress proteins, are initiated through EM field interaction with moving electrons in DNA. This idea is supported by studies showing that EM fields increase electron transfer rates in cytochrome oxidase. Also, in studies of the Na,K-ATPase reaction, estimates of the speed of the charges accelerated by EM fields suggest that they too are electrons. To demonstrate EM field effects on electron transfer in a simpler system, we have studied the classic oscillating Belousov--Zhabotinski (BZ) reaction. Under conditions where the BZ reaction oscillates at about 0.03 cycles/sec, a 60 Hz, 28 microT (280 mG) field accelerates the overall reaction. As observed in earlier studies, an increase in temperature accelerates the reaction and decreases the effect of EM fields on electron transfer. In all three reactions studied, EM fields accelerate electron transfer, and appear to compete with the intrinsic chemical forces driving the reactions. The MCI model provides a reasonable explanation of these observations.     

Problems of the theory of electron transfer in biological systems

Based on comparative analysis, it is shown that the electron transfer theory traditionally used in biophysics is often unable to explain the electron transfer regularities observed in biological molecular systems. The data for seven electron transfer reactions (direct and reverse) that occur in bacterial photosynthetic reaction centers (mainly, purple bacteria Rhodobacter sphaeroides) have been analyzed. Conceivable reasons for the discrepancy between the theoretical and experimental data are discussed and some approaches to overcoming this contradiction are offered.     

Theory and simulation of proton-coupled electron transfer, hydrogen-atom transfer, and proton translocation in proteins

A theory of proton coupled electron transfer (PCET) is reviewed with application to charge transfer steps in the photosystem II oxygen-evolving complex (PSII/OEC). The relation between PCET when it is a concerted electron proton transfer (ETPT) process and hydrogen-atom transfer (HAT) reactions is discussed. Signatures expected for HAT reactions in terms of the size of the kinetic isotope effect and overall magnitude of the rate constant are discussed in the context of PSII/OEC. The formal similarity of ETPT to proton transfer and translocation is used to introduce a combined quantum mechanical (for the transferring protons) and molecular dynamics for the heavy-atom degrees of freedom approach. The method is used to examine double proton transfer in cytochrome c oxidase where two waters and a glutamate (Glu286) that is implicated in the proton translocation mechanism form a cyclic hydrogen bonded structure. Protonation of the glutamate is found to occur in agreement with experimental results.     

Photo-induced charge transfer. A critical test of the mechanism and range of biological electron transfer processes.

The vibronic coupling theory of electron tunneling between biomolecules requires that all such tunnelings involve vibronic coupling, finds temperature dependence to tunneling at finite temperatures, and predicts relatively short tunneling distances. This theory might be expected to apply to most electron transfers involved in the membrane-bound electron transfer reactions of photosynthesis and oxidative phosphorylation. This paper calculates the properties of a weak charge-transfer optical absorption band, whose predicted characteristics are a direct and simple consequence of the model that describes vibronically coupled tunneling. The new absorption band provides the basis for a critical experimental test of the constructs and parameters of the tunneling theory. If the tunneling theory is valid, the oscillator strength of such bands will be the most reliable measure of the tunneling matrix element and of the distance between the sites exchanging an electron.     

Membrane catalysis: synchronous multielectron reactions at the interface between two liquid phases. Bioenergetic mechanisms

Kinetics of multi-electron reactions at the interface between two immiscible liquids are considered. Calculations of the energy of solvent reorganization, of the work required to bring reactants and reaction products together, and of the electrostatic contributions to the Gibbs free energy of the reaction during electron transfer between reactants which are in different dielectric media are reported. Conditions under which the free energy of activation of the interfacial reaction of electron transfer decreases are established. The influence of the distance between reactants and of the dielectric permittivity of the non-aqueous phase on the solvent reorganization energy value is studied. Conditions under which multielectron reactions at the interface proceed are discussed. The biophysics and biochemistry of photosynthesis and respiration are considered as examples of multielectron processes.     

Application of high pressure laser flash photolysis in studies on selected hemoprotein reactions

This article focuses on the application of high pressure laser flash photolysis for studies on selected hemoprotein reactions with the objective to establish details of the underlying reaction mechanisms. In this context, particular attention is given to the reactions of small molecules such as dioxygen, carbon monoxide, and nitric oxide with selected hemoproteins (hemoglobin, myoglobin, neuroglobin and cytochrome P450(cam)), as well as to photo-induced electron transfer reactions occurring in hemoproteins (particularly in various types of cytochromes). Mechanistic conclusions based on the interpretation of the obtained activation volumes are discussed in this account.     

Iron-sulfur flavoenzymes: the added value of making the most ancient redox cofactors and the versatile flavins work together

Iron-sulfur (Fe-S) flavoproteins form a broad and growing class of complex, multi-domain and often multi-subunit proteins coupling the most ancient cofactors (the Fe-S clusters) and the most versatile coenzymes (the flavin coenzymes, FMN and FAD). These enzymes catalyse oxidoreduction reactions usually acting as switches between donors of electron pairs and acceptors of single electrons, and vice versa. Through selected examples, the enzymes'' structure−function relationships with respect to rate and directionality of the electron transfer steps, the role of the apoprotein and its dynamics in modulating the electron transfer process will be discussed.     

The roles of cytochrome b5 in cytochrome P450 reactions

Cytochrome b(5), a 17-kDa hemeprotein associated primarily with the endoplasmic reticulum of eukaryotic cells, has long been known to augment some cytochrome P450 monooxygenase reactions, but the mechanism of stimulation has remained controversial. Studies in recent years have clarified this issue by delineating three pathways by which cytochrome b(5) augments P450 reactions: direct electron transfer of both required electrons from NADH-cytochrome b(5) reductase to P450, in a pathway separate and independent of NADPH-cytochrome P450 reductase; transfer of the second electron to oxyferrous P450 from either cytochrome b(5) reductase or cytochrome P450 reductase; and allosteric stimulation of P450 without electron transfer. Evidence now indicates that each of these pathways is likely to operate in vivo.     

Radical reactions of thiamin pyrophosphate in 2-oxoacid oxidoreductases

Thiamin pyrophosphate (TPP) is essential in carbohydrate metabolism in all forms of life. TPP-dependent decarboxylation reactions of 2-oxo-acid substrates result in enamine adducts between the thiazolium moiety of the coenzyme and decarboxylated substrate. These central enamine intermediates experience different fates from protonation in pyruvate decarboxylase to oxidation by the 2-oxoacid dehydrogenase complexes, the pyruvate oxidases, and 2-oxoacid oxidoreductases. Virtually all of the TPP-dependent enzymes, including pyruvate decarboxylase, can be assayed by 1-electron redox reactions linked to ferricyanide. Oxidation of the enamines is thought to occur via a 2-electron process in the 2-oxoacid dehydrogenase complexes, wherein acyl group transfer is associated with reduction of the disulfide of the lipoamide moiety. However, discrete 1-electron steps occur in the oxidoreductases, where one or more [4Fe-4S] clusters mediate the electron transfer reactions to external electron acceptors. These radical intermediates can be detected in the absence of the acyl-group acceptor, coenzyme A (CoASH). The π-electron system of the thiazolium ring stabilizes the radical. The extensively delocalized character of the radical is evidenced by quantitative analysis of nuclear hyperfine splitting tensors as detected by electron paramagnetic resonance (EPR) spectroscopy and by electronic structure calculations. The second electron transfer step is markedly accelerated by the presence of CoASH. While details of the second electron transfer step and its facilitation by CoASH remain elusive, expected redox properties of potential intermediates limit possible scenarios. This article is part of a Special Issue entitled: Radical SAM enzymes and Radical Enzymology.     

Direct electron transfer reactions of cytochrome c553 from Desulfovibrio vulgaris Hildenborough at indium oxide electrodes

The direct, heterogeneous, electron transfer reactions of cytochrome c553 from Desulfovibrio vulgaris Hildenborough have been studied at indium oxide optically transparent electrodes. These reactions have been studied using cyclic voltammetry and derivative cyclic voltabsorptometry and the kinetics of heterogeneous electron transfer is quasi-reversible. The thermodynamics and kinetics of electron transfer by this molecule can be studied at this electrode surface without the need for surface modification or the addition of surface promoters or mediators.