X-ray Absorption and Emission Spectroscopic Studies of [L2Fe2S2](n) Model Complexes: Implications for the Experimental Evaluation of Redox States in Iron-Sulfur Clusters.

Herein, a systematic study of [L2Fe2S2](n) model complexes (where L = bis(benzimidazolato) and n = 2-, 3-, 4-) has been carried out using iron and sulfur K-edge X-ray absorption (XAS) and iron Kß and valence-to-core X-ray emission spectroscopies (XES). These data are used as a test set to evaluate the relative strengths and weaknesses of X-ray core level spectroscopies in assessing redox changes in iron-sulfur clusters. The results are correlated to density functional theory (DFT) calculations of the spectra in order to further support the quantitative information that can be extracted from the experimental data. It is demonstrated that due to canceling effects of covalency and spin state, the information that can be extracted from Fe Kß XES mainlines is limited. However, a careful analysis of the Fe K-edge XAS data shows that localized valence vs delocalized valence species may be differentiated on the basis of the pre-edge and K-edge energies. These findings are then applied to existing literature Fe K-edge XAS data on the iron protein, P-cluster, and FeMoco sites of nitrogenase. The ability to assess the extent of delocalization in the iron protein vs the P-cluster is highlighted. In addition, possible charge states for FeMoco on the basis of Fe K-edge XAS data are discussed. This study provides an important reference for future X-ray spectroscopic studies of iron-sulfur clusters.

Fast proton-coupled electron transfer observed for a high-fidelity structural and functional [2Fe-2S] Rieske model.

Rieske cofactors have a [2Fe-2S] cluster with unique {His2Cys2} ligation and distinct Fe subsites. The histidine ligands are functionally relevant, since they allow for coupling of electron and proton transfer (PCET) during quinol oxidation in respiratory and photosynthetic ET chains. Here we present the highest fidelity synthetic analogue for the Rieske [2Fe-2S] cluster reported so far. This synthetic analogue 5(x-) emulates the heteroleptic {His2Cys2} ligation of the [2Fe-2S] core, and it also serves as a functional model that undergoes fast concerted proton and electron transfer (CPET) upon reaction of the mixed-valent (ferrous/ferric) protonated 5H(2-) with TEMPO. The thermodynamics of the PCET square scheme for 5(x-) have been determined, and three species (diferric 5(2-), protonated diferric 5H(-), and mixed-valent 5(3-)) have been characterized by X-ray diffraction. pKa values for 5H(-) and 5H(2-) differ by about 4 units, and the reduction potential of 5H(-) is shifted anodically by about +230 mV compared to that of 5(2-). While the N-H bond dissociation free energy of 5H(2-) (60.2 ± 0.5 kcal mol(-1)) and the free energy, ΔG°CPET, of its reaction with TEMPO (-6.3 kcal mol(-1)) are similar to values recently reported for a homoleptic {N2/N2}-coordinated [2Fe-2S] cluster, CPET is significantly faster for 5H(2-) with biomimetic {N2/S2} ligation (k = (9.5 ± 1.2) × 10(4) M(-1) s(-1), ΔH(‡) = 8.7 ± 1.0 kJ mol(-1), ΔS(‡) = -120 ± 40 J mol(-1) K(-1), and ΔG(‡) = 43.8 ± 0.3 kJ mol(-1) at 293 K). These parameters, and the comparison with homoleptic analogues, provide important information and new perspectives for the mechanistic understanding of the biological Rieske cofactor.

A functional model for the Rieske center: full characterization of a biomimetic N-ligated [2Fe-2S] cluster in different protonation states.

Give and take both: A bis(benzimidazolate)-capped biomimetic [2Fe-2S] cluster has been characterized in different protonation states, both in the diferric and mixed-valent forms. Protonation does not lead to structural changes of the [2Fe-2S] core, but facilitates its reduction and causes pronounced valence localization in the mixed-valent state. Concerted proton and electron transfer back to the diferric cluster emulates a key step in the function of mitochondrial Rieske proteins (see scheme).

A super-reduced diferrous [2Fe-2S] cluster.

A biomimetic [2Fe-2S] cluster has been isolated in the fully reduced diferrous form and characterized by X-ray diffraction. This completes a consistent series of synthetic analogues of protein-bound [2Fe-2S](z) redox centers (z = 2+, 1+, 0) with identical capping ligands. (57)Fe Mössbauer data of the extremely oxidation-sensitive complex compare well with those of the very few reports of all-ferrous ferredoxins and Rieske centers; they confirm the S(T) = 0 ground state and establish a lower limit for the exchange coupling, -J ≥ 30 cm(-1).

Tandem driven dynamic self-inhibition of acetylcholinesterase.

A concept of tandem driven dynamic self-inhibition is demonstrated through dynamic inhibitors of acetylcholinesterase (AChE) using reversible transthiolesterification.