More Like this

1. Single‐Step Sulfur Insertions into Iron Carbide Carbonyl Clusters: Unlocking the Synthetic Door to FeMoco Analogues

   https://doi.org/10.1002/anie.202011517  

   Joseph, Chris ; Cobb, Caitlyn R. ; Rose, Michael J. ( December 2020 , Angewandte Chemie International Edition)

   The one‐step syntheses, X‐ray structures, and spectroscopic characterization of synthetic iron clusters, bearing either inorganic sulfides or thiolate with interstitial carbide motifs, are reported. Treatment of iron carbide carbonyl clusters [Fe_n(μ_n‐C)(CO)_m]^x(n=5,6;m=15,16;x=0,−2) with electrophilic sulfur sources (S₂Cl₂, S₈) results in the formation of several μ₄‐S dimers of clusters, and moreover, iron‐sulfide‐(sulfocarbide) clusters. The core sulfocarbide unit {C−S}⁴⁻serves as a structural model for a proposed intermediate in the radicalS‐adenosyl‐L‐methionine biogenesis of the M‐cluster. Furthermore, the electrophilic sulfur strategy has been extended to provide the first ever thiolato‐iron‐carbide complex: an analogous reaction with toluylsulfenyl chloride affords the cluster [Fe₅(μ₅‐C)(SC₇H₇)(CO)₁₃]⁻. The strategy described herein provides a breakthrough towards developing syntheses of biomimetic iron‐sulfur‐carbide clusters like FeMoco.

    

   more » « less
2. Single‐Step Sulfur Insertions into Iron Carbide Carbonyl Clusters: Unlocking the Synthetic Door to FeMoco Analogues

   https://doi.org/10.1002/ange.202011517  

   Joseph, Chris ; Cobb, Caitlyn R. ; Rose, Michael J. ( December 2020 , Angewandte Chemie)

   The one‐step syntheses, X‐ray structures, and spectroscopic characterization of synthetic iron clusters, bearing either inorganic sulfides or thiolate with interstitial carbide motifs, are reported. Treatment of iron carbide carbonyl clusters [Fe_n(μ_n‐C)(CO)_m]^x(n=5,6;m=15,16;x=0,−2) with electrophilic sulfur sources (S₂Cl₂, S₈) results in the formation of several μ₄‐S dimers of clusters, and moreover, iron‐sulfide‐(sulfocarbide) clusters. The core sulfocarbide unit {C−S}⁴⁻serves as a structural model for a proposed intermediate in the radicalS‐adenosyl‐L‐methionine biogenesis of the M‐cluster. Furthermore, the electrophilic sulfur strategy has been extended to provide the first ever thiolato‐iron‐carbide complex: an analogous reaction with toluylsulfenyl chloride affords the cluster [Fe₅(μ₅‐C)(SC₇H₇)(CO)₁₃]⁻. The strategy described herein provides a breakthrough towards developing syntheses of biomimetic iron‐sulfur‐carbide clusters like FeMoco.

    

   more » « less
3. Secondary structure analysis of peptides with relevance to iron–sulfur cluster nesting

   https://doi.org/10.1002/jcc.25741  

   Hanscam, Rebecca ; Shepard, Eric M. ; Broderick, Joan B. ; Copié, Valérie ; Szilagyi, Robert K. ( December 2018 , Journal of Computational Chemistry)

   Peptides coordinated to iron–sulfur clusters, referred to as maquettes, represent a synthetic strategy for constructing biomimetic models of iron–sulfur metalloproteins. These maquettes have been successfully employed as building blocks of engineered heme‐containing proteins with electron‐transfer functionality; however, they have yet to be explored in reactivity studies. The concept of iron–sulfur nesting in peptides is a leading hypothesis in Origins‐of‐Life research as a plausible path to bridge the discontinuity between prebiotic chemical transformations and extant enzyme catalysis. Based on past biomimetic and biochemical research, we put forward a mechanism of maquette reconstitution that guides our development of computational tools and methodologies. In this study, we examined a key feature of the first stage of maquette formation, which is the secondary structure of aqueous peptide models using molecular dynamics simulations based on the AMBER99SB empirical force field. We compared and contrasted S…S distances, [2Fe‐2S] and [4Fe‐4S] nests, and peptide conformations via Ramachandran plots for dissolved Cys and Gly amino acids, the CGGCGGC 7‐mer, and the GGCGGGCGGCGGW 16‐mer peptide. Analytical tools were developed for following the evolution of secondary structural features related to [Fe‐S] cluster nesting along 100 ns trajectories. Simulations demonstrated the omnipresence of peptide nests for preformed [2Fe‐2S] clusters; however, [4Fe‐4S] cluster nests were observed only for the 16‐mer peptide with lifetimes of a few nanoseconds. The origin of the [4Fe‐4S] nest and its stability was linked to a “kinked‐ribbon” peptide conformation. Our computational approach lays the foundation for transitioning into subsequent stages of maquette reconstitution, those being the formation of iron ion/iron–sulfur coordinated peptides. © 2018 Wiley Periodicals, Inc.

    

   more » « less
4. Structure of the respiratory MBS complex reveals iron-sulfur cluster catalyzed sulfane sulfur reduction in ancient life

   https://doi.org/10.1038/s41467-020-19697-7  

   Yu, Hongjun ; Haja, Dominik K. ; Schut, Gerrit J. ; Wu, Chang-Hao ; Meng, Xing ; Zhao, Gongpu ; Li, Huilin ; Adams, Michael W. ( December 2020 , Nature Communications)

   Abstract Modern day aerobic respiration in mitochondria involving complex I converts redox energy into chemical energy and likely evolved from a simple anaerobic system now represented by hydrogen gas-evolving hydrogenase (MBH) where protons are the terminal electron acceptor. Here we present the cryo-EM structure of an early ancestor in the evolution of complex I, the elemental sulfur (S 0 )-reducing reductase MBS. Three highly conserved protein loops linking cytoplasmic and membrane domains enable scalable energy conversion in all three complexes. MBS contains two proton pumps compared to one in MBH and likely conserves twice the energy. The structure also reveals evolutionary adaptations of MBH that enabled S 0 reduction by MBS catalyzed by a site-differentiated iron-sulfur cluster without participation of protons or amino acid residues. This is the simplest mechanism proposed for reduction of inorganic or organic disulfides. It is of fundamental significance in the iron and sulfur-rich volcanic environments of early earth and possibly the origin of life. MBS provides a new perspective on the evolution of modern-day respiratory complexes and of catalysis by biological iron-sulfur clusters. 

   more » « less
5. Facile hydrogen atom abstraction and sulfide formation in a methyl-thiolate capped iron–sulfur–carbonyl cluster

   https://doi.org/10.1039/C9DT04098F  

   Shupp, J. Patrick ; Rose, Michael J. ( January 2020 , Dalton Transactions)

   The interest in methyl group C–H bond activation near or bound to iron-containing clusters is of key biological importance, due to the broad relevance of radical SAM reactions. Specifically, such processes are implicated in the biogenesis of the interstitial carbide found in the nitrogenase FeMoco active site. In this work, we find that the diamagnetic, methyl-thiolate capped iron–carbonyl cluster anion [(CH 3 S)Fe 3 (CO) 9 ] − (1) undergoes facile C–H hydrogen atom abstraction upon treatment with TEMPO. The process leads to (i) eradication of the CH 3 moiety, (ii) formation of a sulfide bridge, and (iii) cluster dimerization—thereby generating the ‘dimer of trimers’ cluster [K(benzo-15-crown-5) 2 ] 2 [(SFe 2 (CO) 12 ) 2 Fe(CO) 2 ] (2). In contrast, the corresponding isopropyl variant [Fe 3 (S i Pr)(CO) 9 ] − (3) does not react with TEMPO . Mass spectrometry confirmed the presence of TEMPOH, as well as CO oxidation vis a vis CO 2 and 2,2,6,6-tetramethylpiperidine. GC-MS measurements of the headspace reveal that the ultimate fate of the methyl carbon is likely incorporation into multiple products—one of which may be a volatile low mass hydrocarbon—rather than carbon/carbide incorporation. 

   more » « less