Browse
Submit Data
Databases
API
Help

Dataset Information

24 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Protonation and Proton-Coupled Electron Transfer at S-Ligated [4Fe-4S] Clusters.

ABSTRACT: Biological [Fe-S] clusters are increasingly recognized to undergo proton-coupled electron transfer (PCET), but the site of protonation, mechanism, and role for PCET remains largely unknown. Here we explore this reactivity with synthetic model clusters. Protonation of the arylthiolate-ligated [4Fe-4S] cluster [Fe4 S4 (SAr)4 ](2-) (1, SAr=S-2,4-6-(iPr)3 C6 H2 ) leads to thiol dissociation, reversibly forming [Fe4 S4 (SAr)3 L](1-) (2) and ArSH (L=solvent, and/or conjugate base). Solutions of 2+ArSH react with the nitroxyl radical TEMPO to give [Fe4 S4 (SAr)4 ](1-) (1ox ) and TEMPOH. This reaction involves PCET coupled to thiolate association and may proceed via the unobserved protonated cluster [Fe4 S4 (SAr)3 (HSAr)](1-) (1-H). Similar reactions with this and related clusters proceed comparably. An understanding of the PCET thermochemistry of this cluster system has been developed, encompassing three different redox levels and two protonation states.

SUBMITTER: Saouma CT

PROVIDER: S-EPMC4646712 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Protonation and Proton-Coupled Electron Transfer at S-Ligated [4Fe-4S] Clusters.

Saouma Caroline T CT Morris Wesley D WD Darcy Julia W JW Mayer James M JM

Chemistry (Weinheim an der Bergstrasse, Germany) 20150512 25

Biological [Fe-S] clusters are increasingly recognized to undergo proton-coupled electron transfer (PCET), but the site of protonation, mechanism, and role for PCET remains largely unknown. Here we explore this reactivity with synthetic model clusters. Protonation of the arylthiolate-ligated [4Fe-4S] cluster [Fe4 S4 (SAr)4 ](2-) (1, SAr=S-2,4-6-(iPr)3 C6 H2 ) leads to thiol dissociation, reversibly forming [Fe4 S4 (SAr)3 L](1-) (2) and ArSH (L=solvent, and/or conjugate base). Solutions of 2+ArSH ...[more]

PMID: 25965413

Similar Datasets

Protonation and concerted proton-electron transfer reactivity of a bis-benzimidazolate ligated [2Fe-2S] model for Rieske clusters.

Project description:A model system for biological Rieske clusters that incorporates bis-benzimidazolate ligands ((Pr)bbim)(2-) has been developed ((Pr)bbimH(2) = 4,4-bis(benzimidazol-2-yl)heptane). The diferric and mixed-valence clusters have been prepared and characterized in both their protonated and deprotonated states. The thermochemistry of interconversions of these species has been measured, and the effect of protonation on the reduction potential is in good agreement to that observed in the biological systems. The mixed-valence and protonated congener [Fe(2)S(2)((Pr)bbim)((Pr)bbimH)](Et(4)N)(2) (4) reacts rapidly with TEMPO or p-benzoquinones to generate diferric and deprotonated [Fe(2)S(2)((Pr)bbim)(2)](Et(4)N)(2) (1) and 1 equiv of TEMPOH or 0.5 equiv of p-benzohydroquinones, respectively. The reaction with TEMPO is the first well-defined example of concerted proton-electron transfer (CPET) at a synthetic ferric/ferrous [Fe-S] cluster.

| S-EPMC3342399 | biostudies-literature

Reversible cycling between cysteine persulfide-ligated [2Fe-2S] and cysteine-ligated [4Fe-4S] clusters in the FNR regulatory protein.

Project description:Fumarate and nitrate reduction (FNR) regulatory proteins are O(2)-sensing bacterial transcription factors that control the switch between aerobic and anaerobic metabolism. Under anaerobic conditions [4Fe-4S](2+)-FNR exists as a DNA-binding homodimer. In response to elevated oxygen levels, the [4Fe-4S](2+) cluster undergoes a rapid conversion to a [2Fe-2S](2+) cluster, resulting in a dimer-to-monomer transition and loss of site-specific DNA binding. In this work, resonance Raman and UV-visible absorption/CD spectroscopies and MS were used to characterize the interconversion between [4Fe-4S](2+) and [2Fe-2S](2+) clusters in Escherichia coli FNR. Selective (34)S labeling of the bridging sulfides in the [4Fe-4S](2+) cluster-bound form of FNR facilitated identification of resonantly enhanced Cys(32)S-(34)S stretching modes in the resonance Raman spectrum of the O(2)-exposed [2Fe-2S](2+) cluster-bound form of FNR. This result indicates O(2)-induced oxidation and retention of bridging sulfides in the form of [2Fe-2S](2+) cluster-bound cysteine persulfides. MS also demonstrates that multiple cysteine persulfides are formed on O(2) exposure of [4Fe-4S](2+)-FNR. The [4Fe-4S](2+) cluster in FNR can also be regenerated from the cysteine persulfide-coordinated [2Fe-2S](2+) cluster by anaerobic incubation with DTT and Fe(2+) ion in the absence of exogenous sulfide. Resonance Raman data indicate that this type of cluster conversion involving sulfide oxidation is not unique to FNR, because it also occurs in O(2)-exposed forms of O(2)-sensitive [4Fe-4S] clusters in radical S-adenosylmethionine enzymes. The results provide fresh insight into the molecular mechanism of O(2) sensing by FNR and iron-sulfur cluster conversion reactions in general, and suggest unique mechanisms for the assembly or repair of biological [4Fe-4S] clusters.

| S-EPMC3465412 | biostudies-literature

Proton-coupled electron transfer.

Project description: Not available

| S-EPMC3449329 | biostudies-literature

Minimal Heterochiral de Novo Designed 4Fe-4S Binding Peptide Capable of Robust Electron Transfer.

Project description:Ambidoxin is a designed, minimal dodecapeptide consisting of alternating L and D amino acids that binds a 4Fe-4S cluster through ligand-metal interactions and an extensive network of second-shell hydrogen bonds. The peptide can withstand hundreds of oxidation-reduction cycles at room temperature. Ambidoxin suggests how simple, prebiotic peptides may have achieved robust redox catalysis on the early Earth.

| S-EPMC7050467 | biostudies-literature

Cleavage of [4Fe-4S]-type clusters: breaking the symmetry.

Project description:The cleavage of [4Fe-4S]-type clusters is thought to be important in proteins such as Fe-S scaffold proteins and nitrogenase. However, most [4Fe-4S](2+) clusters in proteins have two antiferromagnetically coupled high-spin layers in which a minority spin is delocalized in each layer, thus forming a symmetric Fe(2.5+)-Fe(2.5+) pair, and how cleavage occurs between the irons is puzzling because of the shared electron. Previously, we proposed a novel mechanism for the fission of a [4Fe-4S] core into two [2Fe-2S] cores in which the minority spin localizes on one iron, thus breaking the symmetry and creating a transition state with two Fe(3+)-Fe(2+) pairs. Cleavage first through the weak Fe(2+)-S bonds lowers the activation energy. Here, we propose a test of this mechanism: break the symmetry of the cluster by changing the ligands to promote spin localization, which should enhance reactivity. The cleavage reactions for the homoligand [Fe(4)S(4)L(4)](2-) (L = SCH(3), Cl, H) and heteroligand [Fe(4)S(4)(SCH(3))(2)L(2)](2-) (L = Cl, H) clusters in the gas phase were examined via broken-symmetry density functional theory calculations. In the heteroligand clusters, the minority spin localized on the iron coordinated by the weaker electron-donor ligand, and the reaction energy and activation barrier of the cleavage were lowered, which is in accord with our proposed mechanism and consistent with photoelectron spectroscopy and collision-induced dissociation experiments. These studies suggest that proteins requiring facile fission of their [4Fe-4S] cluster in their biological function might have spin-localized [4Fe-4S] clusters.

| S-EPMC2754062 | biostudies-literature

Separating Proton and Electron Transfer Effects in Three-Component Concerted Proton-Coupled Electron Transfer Reactions.

Project description:Multiple-site concerted proton-electron transfer (MS-CPET) reactions were studied in a three-component system. 1-Hydroxy-2,2,6,6-tetramethylpiperidine (TEMPOH) was oxidized to the stable radical TEMPO by electron transfer to ferrocenium oxidants coupled to proton transfer to various pyridine bases. These MS-CPET reactions contrast with the usual reactivity of TEMPOH by hydrogen atom transfer (HAT) to a single e-/H+ acceptor. The three-component reactions proceed by pre-equilibrium formation of a hydrogen-bonded adduct between TEMPOH and the pyridine base, and the adduct is then oxidized by the ferrocenium in a bimolecular MS-CPET step. The second-order rate constants, measured using stopped-flow kinetic techniques, spanned 4 orders of magnitude. An advantage of this system is that the MS-CPET driving force could be independently varied by changing either the pKa of the base or the reduction potential (E°) of the oxidant. Changes in ?G°MS-CPET from either source had the same effect on the MS-CPET rate constants, and a combined Brønsted plot of ln(kMS-CPET) vs ln(Keq) was linear with a slope of 0.46. These results imply a synchronous concerted mechanism, in which the proton and electron transfer components of the CPET process make equal contributions to the rate constants. The only outliers to the Brønsted correlation are the reactions with sterically hindered pyridines, which apparently hinder the close approach of proton donor and acceptor that facilitates MS-CPET. These three-component reactions are compared with a related HAT reaction of TEMPOH, with the 2,4,6-tri-tert-butylphenoxyl radical. The MS-CPET and HAT oxidations of TEMPOH at the same driving force occurred with similar rate constants. While this is an imperfect comparison, the data suggest that the separation of the proton and electron to different reagents does not significantly inhibit the proton-coupled electron transfer process.

| S-EPMC5812448 | biostudies-literature

Electron transfer and proton-coupled electron transfer reactivity and self-exchange of synthetic [2Fe-2S] complexes: models for Rieske and mitoNEET clusters.

Project description:This report describes the thermochemistry, proton-coupled electron transfer (PCET) reactions and self-exchange rate constants for a set of bis-benzimidazolate-ligated [2Fe-2S] clusters. These clusters serve as a model for the chemistry of biological Rieske and mitoNEET clusters. PCET from [Fe2S2((Pr)bbim)((Pr)bbimH)](2-) (4) and [Fe2S2((Pr)bbim)((Pr)bbimH2)](1-) (5) to TEMPO occurs via concerted proton-electron transfer (CPET) mechanisms ((Pr)bbimH2 = 4,4-bis-(benzimidazol-2-yl)heptane). Intermolecular electron transfer (ET) self-exchange between [Fe2S2((Pr)bbim)2](2-) (1) and [Fe2S2((Pr)bbim)2](3-) (2) occurs with a rate constant of (1.20 ± 0.06) × 10(5) M(-1) s(-1) at 26 °C. A similar self-exchange rate constant is found for the related [2Fe-2S] cluster [Fe2S2(SArO)2](2-/3-), SArO(2-) = thiosalicylate. These are roughly an order of magnitude slower than that reported for larger [4Fe-4S] clusters and 1 order of magnitude faster than that reported for N-ligated high-spin iron complexes. These results suggest that the rate of intermolecular ET to/from [Fe-S] clusters is modulated by cluster size. The measured PCET self-exchange rate constant for 1 and 4 at -30 °C is (3.8 ± 0.7) × 10(4) M(-1) s(-1). Analysis of rate constants using the Marcus cross-relation suggests that this process likely occurs via a concerted proton-electron transfer (CPET) mechanism. The implications of these findings to biological systems are also discussed, including the conclusion that histidine-ligated [2Fe-2S] clusters should not have a strong bias to undergo concerted e(-)/H(+) transfers.

| S-EPMC3993882 | biostudies-literature

Theoretical study of DNA damage recognition via electron transfer from the [4Fe-4S] complex of MutY.

Project description:The mechanism of site-specific recognition of DNA by proteins has been a long-standing issue. The DNA glycosylase MutY, for instance, must find the rare 8-oxoguanine-adenine mismatches among the large number of basepairs in the DNA. This protein has a [4Fe-4S] cluster, which is highly conserved in species as diverse as Escherichia Coli and Homo sapiens. The mixed-valent nature of this cluster suggests that charge transfer may play a role in MutY's function. We have studied the energetics of the charge transfer in Bacillus stearothermophilus MutY-DNA complex using multiscale calculation including density functional theory and molecular dynamics. The [4Fe-4S] cluster in MutY is found to undergo 2+ to 3+ oxidation when coupling to DNA through hole transfer, especially when MutY is near an oxoguanine modified base (oxoG). Employing the Marcus theory for electron transfer, we find near optimal Frank-Condon factors for electron transfer from MutY to oxoguanine modified base. MutY has modest selectivity for oxoguanine over guanine due to the difference in oxidation potential. The tunneling matrix element is significantly reduced with the mutation R149W, whereas the mutation L154F reduces the tunneling matrix element as well as the Frank-Condon factor. Both L154F and R149W mutations are known to dramatically reduce or eliminate repair efficiency. We suggest a scenario where the charge transfer leads to a stabilization of the specific binding conformation, which is likely the recognition mode, thus enabling it to find the damaged site efficiently.

| S-EPMC2547449 | biostudies-literature

Proton-Coupled Electron Transfer Guidelines, Fair and Square.

Project description:Proton-coupled electron transfer (PCET) reactions are fundamental to energy transformation reactions in natural and artificial systems and are increasingly recognized in areas such as catalysis and synthetic chemistry. The interdependence of proton and electron transfer brings a mechanistic richness of reactivity, including various sequential and concerted mechanisms. Delineating between different PCET mechanisms and understanding why a particular mechanism dominates are crucial for the design and optimization of reactions that use PCET. This Perspective provides practical guidelines for how to discern between sequential and concerted mechanisms based on interpretations of thermodynamic data with temperature-, pressure-, and isotope-dependent kinetics. We present new PCET-zone diagrams that show how a mechanism can switch or even be eliminated by varying the thermodynamic (ΔGPT° and ΔGET°) and coupling strengths for a PCET system. We discuss the appropriateness of asynchronous concerted PCET to rationalize observations in organic reactions, and the distinction between hydrogen atom transfer and other concerted PCET reactions. Contemporary issues and future prospects in PCET research are discussed.

| S-EPMC7880575 | biostudies-literature

Biochemistry and theory of proton-coupled electron transfer.

Project description: Not available

| S-EPMC4317057 | biostudies-literature