Protonation first electron transfer

The structure of the products is determined by the site of protonation of the radical anion intermediate formed after the first electron transfer step. In general, ERG substituents favor protonation at the ortho position, whereas EWGs favor protonation at the para position.215 Addition of a second electron gives a pentadienyl anion, which is protonated at the center carbon. As a result, 2,5-dihydro products are formed with alkyl or alkoxy substituents and 1,4-products are formed from EWG substituents. The preference for protonation of the central carbon of the pentadienyl anion is believed to be the result of the greater 1,2 and 4,5 bond order and a higher concentration of negative charge at C(3).216 The reduction of methoxybenzenes is of importance in the synthesis of cyclohexenones via hydrolysis of the intermediate enol ethers. 

Of more intrinsic interest are processes involving two electrons, since these constitute the great bulk of organic reductive processes, especially in protonic solvents. The reason for this is that the first electron transfer will generate an unstable radical species, whereas the second can regenerate a stable closed-shell product. One example that we have already encountered is C02 reduction but a case that has been well studied is that of quinone reduction as ... 

Under the advisement of PhD mentor Professor Joseph T. Hupp, the PI successfully used spectroelectrochemical quartz crystal microgravimetry to elucidate the mechanism of charge transport... for both aqueous and nonaqueous sytems. This was the first demonstration of proton-coupled electron transfer at oxide semiconductor interfaces. These findings were then successfully applied to a new interpretation of photoinduced electron transfer at similar interfaces, which are of importance in the field of solar energy conversion. ... 

Since the products of the second electron transfers are typically more basic or more acidic than those of the first electron transfer, it is possible to add a guest that is only capable of proton transfer with the product of the second electron transfer. It is important to note that in this case the result of proton transfer may be very similar to that of H-bonding, with simply a positive Ey2 shift for the second wave in a reduction or a negative shift for an oxidation. In this case, information about p values is very helpful for trying to sort out whether it is H-bonding or proton transfer that causes the shift. 

Jinnouchi and Okazaki performed AIMD studies of the first-electron transfer reaction with 1 hydronium ion, 9 water molecules, and 12 Pt atoms at 350 K as shown in Fig. 13.108 The adsorbed water molecules and the hydronium ion hydrated the adsorbed oxygen atoms, and proton transfer through the constructed hydrogen bonds frequently occurred. When the conformation of these species satisfied certain conditions, the oxygen dissociation with the proton transfer reaction was induced and three OH were generated on the platinum surface (Fig. 14). The authors concluded that the oxygen dissociation tendency is one of the dominant factors for the reactivity of the cathode catalyst. This work demonstrates the power of AIMD that does not require specific assumption in order to describe charge transfer. 

For the first proton and electron transfers, the substitution is not expected to have any significant effects and these processes were therefore not studied. For the second electron transfer there is a small effect of 1.3 kcal/mol, with the lower redox potential in the selenium case. The effect on the second proton transfer is larger with 4.1 kcal/ mol, which is the most significant effect that can be noted in the table. It is thus much easier to remove the proton from selenium than from sulfur, which is expected since selenium is more acidic. 

Fig. 17.85. Mechanistic analysis of the second part of the reaction process where the treatment of the acetoxy sul-fones syn- and anti-A with sodium amalgam completes the Julia-Lythgoe olefination. Series of a first electron transfer (—> alkenyl phenylsulfone radical anion E), homolysis (—> alkenyl radical G + sodium benzene sulfinate), second electron transfer (—> alkenyl anion trans"-D) and in-situ protonation.

The pathway for proton transfer to QB is studied in the reaction center (RC) from Rb. sphaeroides using two approaches (Adelroth et al., 2001) 1) the binding of Zn2+ or Cd2+ to the RC surface at His-H126, His-H128, and Asp-H124 and 2) the replacement of the histidines for Ala. In the double mutant RC at pH 8.5, the observed rates of proton uptake associated with both the first and the second proton-coupled electron-transfer... 

Nabedryk, E., Breton, J., Okamura, M.Y., and Paddock, M. L. (2001) Simultaneous replacement of Asp-L210 and Asp-M17 with Asn increases proton uptake by Glu-L212 upon first electron transfer to Qb in reaction centers from Rhodobacter sphaeroides, Biochemistry 40, 13826-13832. 

The two one-electron transfer events exhibit the two basic roles for proton uptake and redistribution—weakly coupled charge stabilization for the first electron (m w r s l), and strongly coupled bond formation for the second (net uptake of 2H+ per QH2). However, it is now evident that the two are functionally related, and part of the charge-compensating H+ uptake, e.g., on the first electron transfer, is destined for delivery to the quinone head group in the second reduction step. 

Although the acid cluster plays a distinct and identifiable role in the relaxation response of the protein on the first electron transfer, electrostatic calculations indicate that the full energetic contribution is quite widely distributed, with small ionization state changes of a number of residues. On the other hand, proton delivery to the quinone head group during the second reduction step is a targeted function, with discrete termini at the quinol oxygens. 

It seems reasonable to think that the H-bonded connection between Qb-, SerL22S, and AspHL21s, established after the first electron transfer, provides the terminal path for delivery of the first proton to the quinone, ahead of the second electron. From the X-ray structures, a water molecule is positioned between AspL21s and AspM17 and a complete pathway could comprise... 

The charge compensation role of intraprotein proton transfer is an essentially dielectric response and is not structurally specific. Transfer of a proton requires specificity of contact, but a variety of geometries and protein motifs can fulfill the underlying requirement of charge redistribution. Thus, many second site mutations can recover significant function of the first electron transfer in bacterial RCs. On the other... 

Figure 10 shows the proposed ubiquinol oxidation and electron bifurcation mechanism at Qp site. (A) In the absence of the ubiquinone, the side chain of Glu-271 is connected to the solvent in the mitochondrial intermembrane space via a water chain. (B) As a reduced ubiquinol molecule binds to the site, the side chain of Glu-271 flips to form a hydrogen bond to the bound ubiquinone. (C) Now, the ISP, which is moving around the intermediate position by thermal motion is trapped at the b" position by a hydrogen bond to the bound ubiquinone. (D,E) Coupled to deprotonation, the first electron transfer occurs. Since the Rieske FeS cluster has a much higher redox potential (ca. +300 mV) than heme bl (ca. 0 mV), the first electron is favorably transferred to ISP. This yields ubisemiquinone, (F,G). After ubisemiquinone formation, the hydrogen bond to the His-161 of ISP is destabilized. The ISP moves to the c position, where the electron is transferred from the Rieske FeS cluster to heme c. Now unstable ubisemiquinone is left in the Qp pocket. The redox potential of the deprotonated ubisemiquinone is assumed to be several hundred millivolts. Now the electron transfer to the heme bl is a downhill reaction. (H) Coupled to the second electron transfer, the second proton is transferred to Glu-271 and subsequently to the mitochondrial intermembrane space. The fully oxidized ubiquinone is released to the membrane. 

At high pH values, the first electron transfer process occurs without protonation so that a single irreversible one-electron process is initially observed. The resulting catechol violet radical anion is then reduced (66) at a more negative potential in an EC reaction (67) (resulting in the observation of a second reduction wave), in which the dianion is doubly protonated ... 

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