Two-electron shuttle

The reaction serves as an illustrative example of the synthetic utilization of the Te(II)—>Te(IV) two-electron shuttle. Another promising application is seen in photodynamic therapy in which tellurapyrylium dyes 119 can function as photosensitizers to produce either singlet oxygen or superoxide radical-anions (via electron transfer), thereby serving as cytotoxic agents. An important useful property of tellurapyrylium dyes is their absorbance in the near-infrared region where biological tissues are most important. 

Here we report the generation and the chemical properties of oxidized forms by two (II) and four (III) electrons (see Scheme 3) of the me o-octaethylporphyrinogen tetraanion bonded to transition metals. " The redox chemistry of such systems is based on the formation and cleavage of cyclopropane units which function as two electron shuttles. Important inter- and intra-molecular electron transfer between the metal and the cyclopropane unit has been synthetically detected. In addition we have discovered that those oxidations are stepwise processes which have been clarified by the isolation of a number of intermediates. ... 

The final step of the reaction involves the transfer of two electrons from iron-sulfur clusters to coenzyme Q. Coenzyme Q is a mobile electron carrier. Its isoprenoid tail makes it highly hydrophobic, and it diffuses freely in the hydrophobic core of the inner mitochondrial membrane. As a result, it shuttles electrons from Complexes I and II to Complex III. The redox cycle of UQ is shown in Figure 21.5, and the overall scheme is shown schematically in Figure 21.6. 

In mitochondria (Fig. lb), the electron acceptor protein is also a flavoprotein termed NADPH-adrenodoxin reductase (MW 50 kDa) because it was discovered in the adrenal cortex and because it donates its electrons not directly to the P450 but to the smaller redox protein adrenodoxin (MW 12.5 kDa). The two iron-sulphur clusters of this protein serve as electron shuttle between the flavoprotein and the mitochondrial P450. 

The high catalytic activity of enzymes has a number of sources. Every enzyme has a particular active site configured so as to secure intimate contact with the substrate molecule (a strictly defined mutual orientation in space, a coordination of the electronic states, etc.). This results in the formation of highly reactive substrate-enzyme complexes. The influence of tfie individual enzymes also rests on the fact that they act as electron shuttles between adjacent redox systems. In biological systems one often sees multienzyme systems for chains of consecutive steps. These systems are usually built into the membranes, which secures geometric proximity of any two neighboring active sites and transfer of the product of one step to the enzyme catalyzing the next step. 

During the last two decades, more studies have been conducted to explore the catalytic effects of different redox mediators on the bio-transformation processes. Redox mediators, also referred to as electron shuttles, have been shown to play an important role not only as final electron acceptor for many recalcitrant organic compounds, but also facilitating electron transfer from an electron donor to an electron acceptor, for example, azo dyes [8, 11, 12], Redox mediators accelerate reactions by lowering the activation energy of the total reaction, and are organic molecules that can reversibly be oxidized and reduced, thereby conferring the capacity to serve as an electron carrier in multiple redox reactions. 

Immobilizing the catalyst on the electrode surface is useful for both synthetic and sensors applications. Monomolecular coatings do not allow redox catalysis, but multilayered coatings do. The catalytic responses are then functions of three main factors in addition to transport of the reactant from the bulk of the solution to the film surface transport of electrons through the film, transport of the reactant in the reverse direction, and catalytic reaction. The interplay of these factors is described with the help of characteristic currents and kinetic zone diagrams. In several systems the mediator plays the role of an electron shuttle and of a catalyst. More interesting are the systems in which the two roles are assigned to two different molecules chosen to fulfill these two different functions, as illustrated by a typical experimental example. 

Transition metal complexes with o-dioxolene ligands constitute one of the most intriguing classes of complexes as far as their electrochemical behaviour is concerned, in that, as already mentioned in Chapter 5, Section 1, such ligands are able to shuttle through the oxidation states o-benzoquinone)o-benzosemiquinone/catecholate illustrated in Scheme 250 (a process carried out in nature by the dicopper (I I)-based enzyme catechol oxidase through a single two-electron step see Chapter 9, Section 1.2). 

In the malate-aspartate shuttle, two electrons are transferred to form NADH in the inner mitochondrial matrix (Figure 6-2A). 

In addition to NAD and flavoproteins, three other types of electron-carrying molecules function in the respiratory chain a hydrophobic quinone (ubiquinone) and two different types of iron-containing proteins (cytochromes and iron-sulfur proteins). Ubiquinone (also called coenzyme Q, or simply Q) is a lipid-soluble ben-zoquinone with a long isoprenoid side chain (Fig. 19-2). The closely related compounds plastoquinone (of plant chloroplasts) and menaquinone (of bacteria) play roles analogous to that of ubiquinone, carrying electrons in membrane-associated electron-transfer chains. Ubiquinone can accept one electron to become the semi-quinone radical ( QH) or two electrons to form ubiquinol (QH2) (Fig. 19-2) and, like flavoprotein carriers, it can act at the junction between a two-electron donor and a one-electron acceptor. Because ubiquinone is both small and hydrophobic, it is freely diffusible within the lipid bilayer of the inner mitochondrial membrane and can shuttle reducing equivalents between other, less mobile electron carriers in the membrane. And because it carries both electrons and protons, it plays a central role in coupling electron flow to proton movement. 

As ascribed, the EPR spectrum with g = 2.10 can be low-spin Fec(III). When the isolated enzyme is reductively titrated this signal disappears at a potential Emj -0.3 V [65]. This would seem to indicate that the putative Fec(III) form is not relevant, at least not to hydrogen-production activity. The cubane is a one-electron acceptor as it can shuttle between the 2+ and 1 + oxidation states. Therefore, if the active center were to take up a total of two electrons, then the oxidation state of the Fec would, as least formally, shuttle between II and I. Recently, a redox transition in Fe hydrogenase with an Em below the H2/H+ potential has been observed in direct electrochemistry [89]. This superreduced state has not been studied by spectroscopy. It might well correspond to the formal Fec(I) state. For NiFe hydrogenases Fec(I) has recently been proposed as a key intermediate in the catalytic cycle [90] (cf. Chapter 9). 

Another superfamily is formed by bacterial di-heme CCP (with over 110 entries in PeroxiBase) that are periplasmic enzymes providing protection from oxidative stress. These homodimeric enzymes have a conserved tertiary structure containing two type-c hemes covalently attached to two predominantly a-helical domains via a characteristic binding motif. One heme acts as a low redox-potential center where H2O2 is reduced, and the other as a high redox-potential center that feeds electrons to the peroxidatic site from soluble electron-shuttle proteins such as cytochrome c [24]. In the crystal structure of the Geobacter sulfurreducens enzyme shown in Fig. 3.1g, the first heme appears as a bis-histidinyl-coordinated form (and... 

Electrons in the iron-sulfur clusters of NADH-Q oxidoreduetase are shuttled to coenzyme Q. The flow of two electrons from NADH to coenzyme Q through NADH-Q oxidoreduetase leads to the pumping offour hydrogen ions out of the matrix of the mitochondrion. The details of this process remain the subject of active investigation. However, the coupled electron- proton transfer reactions of Q are crucial. NADH binds to a site on the vertical arm and transfers its electrons to FMN. These electrons flow within the vertical unit to three 4Fe-4S centers and then to a bound Q. The reduction of Q to... 

Anabaena, is a 36 kDa basic protein having a noncovalently bound flavin (FAD) cofactor. Fd is a smaller (11 kDa) acidic [2Fe-2S] protein that is present in all photosynthetic organisms, and acts as a shuttle between larger proteins (in this case the iron-sulfur subunit of photosystem I and FNR), which are often anchored in membranes and have restricted mobility. Note that Fd is a one-electron carrier and NADP" " requires the simultaneous addition of two electrons for its reduction. 

Most of the electrons removed from fuels during energy metabolism are transferred via nicotinamide adenine dmucleotide (NAD). NAD collects electrons from many different energy fuels in reactions catalyzed by specific enzymes. These enzymes are dehydrogenases. Reduced NAD, in turn, shuttles the electrons to the respiratory chain. Flavin adenine dinudeohde (FAD) also acts as an electron shuttle. In each reaction involving NAD (or FAD), two electrons are transferred that is, two electrons are carried or shuttled. NAD and PAID are small molecules with molecular weights of 663 and 7S5 and a re manufactured in the body from the vitamins niacin and riboflavin, respectively. These molecules are called N.A.D. and F.A.D., not nad" o r "fad."... 

Two structural abnormahties in the mitochondria are considered important pathogenetic factors during ischemia. One is characterized by pore formation in the itmer mitochondrial membrane and high amplitude swelling (mitochondrial permeability transition or MPT) [30, 31]. The second involves leakage of cytochrome C from the inter-membrane space into the cytosol [32]. Because of its role as an electron shuttle, dislocation of cytochrome c compromises respiration [33, 34], and as a cytosolic cofactor cytochrome C activates caspase 9, and triggers apoptosis [33-35] (see below). 

The overall effect of the malate-aspartate shuttle is to transfer the equivalent of two electrons from the cytoplasm to the mitochondrion. The cycle is thought to be driven by cytoplasmic acid (H ). The concentration of protons in the cytoplasm is greater than that in the mitochondrion, which has an alkaline interior. This concentration gradient is thought to drive the membrane-bound glutamate/aspartate exchanger. 

---