Synthetic analogues of [Fe ₄ S ₄ (Cys) ₃ (His)] in hydrogenases and [Fe ₄ S ₄ (Cys) ₄ ] in HiPIP derived from all-ferric [Fe ₄ S ₄ {N(SiMe ₃ ) ₂ }

Abstract

The all-ferric ½Fe 4 S 4 4þ cluster ½Fe 4 S 4 fNðSiMe 3 Þ 2 g 4 1 and its oneelectron reduced form ½1 − serve as convenient precursors for the synthesis of 3∶1-site differentiated ½Fe 4 S 4 clusters and highpotential iron-sulfur protein (HiPIP) model clusters. The reaction of 1 with four equivalents (equiv) of the bulky thiol HSDmp (Dmp¼ 2,6-ðmesitylÞ 2 C 6 H 3 , mesityl ¼2,4,6-Me 3 C 6 H 2 ) followed by treatment with tetrahydrofuran (THF) resulted in the isolation of ½Fe 4 S 4 ðSDmpÞ 3 ðTHFÞ 3 2. Cluster 2 contains an octahedral iron atom with three THF ligands, and its FeðSÞ 3 ðOÞ 3 coordination environment is relevant to that in the active site of substrate-bound aconitase. An analogous reaction of ½1 − with four equiv of HSDmp gave ½Fe 4 S 4 ðSDmpÞ 4 − 3, which models the oxidized form of HiPIP. The THF ligands in 2 can be replaced by tetramethyl-imidazole (Me 4 Im) to give ½Fe 4 S 4 ðSDmpÞ 3 ðMe 4 ImÞ 4 modeling the ½Fe 4 S 4 ðCysÞ 3 ðHisÞ cluster in hydrogenases, and its one-electron reduced form ½4 − was synthesized from the reaction of 3 with Me 4 Im. The reversible redox couple between 3 and ½3 − was observed at E 1∕2 ¼−820 mV vs. Ag∕Ag þ , and the corresponding reversible couple for 4 and ½4 − is positively shifted by þ440 mV. The cyclic voltammogram of 3 also exhibited a reversible oxidation couple, which indicates generation of the all-ferric ½Fe 4 S 4 4þ cluster, ½Fe 4 S 4 ðSDmpÞ 4 .Fe4S4 cluster | thiolates C uboidal ½Fe 4 S 4 clusters are ubiquitous metal-centers in proteins, expediting electron transfer and enzymatic reactions. These ½Fe 4 S 4 cores are usually bound to four cysteinyl thiolates (Cys) as found in the high-potential iron-sulfur proteins (HiPIP) and widely distributed ferredoxins (Fd). Some ½Fe 4 S 4 clusters carrying an N-or O-donor ligand and three Cys ligands are also known, for example the ½Fe 4 S 4 ðCysÞ 3 ðHisÞ cluster (His ¼ histidinyl imidazole) in [NiFe] and [FeFe] hydrogenases ( Fig. 1) (1-6), and the ½Fe 4 S 4 ðCysÞ 3 ðO-donorÞ cluster in aconitase (7-9) and protochlorophyllide reductase (10). All of these ½Fe 4 S 4 clusters are present in three oxidation states, ½Fe 4 S 4 3þ (HiPIP ox ), ½Fe 4 S 4 2þ (HiPIP red ∕Fd ox ), and ½Fe 4 S 4 þ (Fd red ), while the ½Fe 4 S 4 0 state has been suggested for the cluster in the Fe-protein of nitrogenase (11,12). To date, no ½Fe 4 S 4 4þ cluster has been found in proteins.

Developments in the Biomimetic Chemistry of Cubane-Type and Higher Nuclearity Iron–Sulfur Clusters

“…Scheme [7] of Figure 7 demonstrates a particularly interesting approach based on bis(trimethylsilyl)amido clusters 13 and 26 . 66 Treatment of 13 with highly hindered 2,6-bis(mesityl)benzene-1-thiol results in elimination of (Me 3 Si) 2 NH, core reduction, and thiolate binding. Addition of THF affords the tris(THF) cluster 24 which undergoes substitution at the unique site with tetramethylimidazole to form 25 .…”

“…Analogue 3:1 clusters have been employed in a number of biologically relevant investigations, including ligand binding affinities at the unique site, 11 formation of sulfide-bridged double cubanes, 66,69 , binding of cluster and iron porphyrins through an Fe-S-Fe bridge, 69,70 construction of the H-cluster framework of [FeFe]-hydrogenases, 71 and reaction of thiolate at the unique site with sulfonium cations in relation to the reductive cleavage of 71 S- adenosyl -L- methionine by biotin synthase. 64 Other applications dependent upon regioselective reactivity will doubtless follow, particularly because of the availability of a succeeding generation of trithiols ( 23 ) more convenient synthetically than the first ( 21 ) and the emergence of clusters ( 24–28 ) not requiring multi-step ligand synthesis.…”

“…66). Three [Fe 4 S 4 ] n oxidation states are represented: n = 4+ ( 13 ), 3+ ( 24 – 27 ), 2+ ( 28 ).…”

Tridentate Thiolate Ligands: Application to the Synthesis of the Site‐Differentiated [4Fe‐4S] Cluster having a Hydrosulfide Ligand at the Unique Iron Center

“…[10,11] Pohl and co-workers also reported a few clusters coordinated by the tridentate ligand TriS 3À (TriSH 3 = 1,3,5-triethyl-2,4,6-tris(3-sulfanylindolyl [1]methyl)benzene). [12] As a part of our efforts to synthesize models of metalloenzyme active sites containing metal sulfide/thiolate complexes, [14] we have been interested in these site-differentiated [15] Along with the above approach, we extended the scope of the synthesis of site-differentiated [4Fe-4S] clusters by designing the new tripodal trithiols Temp(SH) 3 (1 a) and Tefp(SH) 3 (1 b; Scheme 1). Although the use of tripodal trithiol is the same as the Holm groups strategy, the new ligands are advantageous in that they can be prepared easily in short steps and tend to give crystalline [4Fe-4S] clusters suitable for X-ray structural analysis.…”

Ligandenumlagerungen an Fe/S‐Cofaktoren: langsame Isomerisierung eines biomimetischen [2Fe‐2S]‐Clusters

“…[8][9][10] Diese Ergebnisse lassen die Frage offen, wie Ligandenaustausch-und Ligandenumlagerungsprozesse in Eisen-Schwefel-Clustern auf molekularer Ebene mechanistisch ablaufen. Aufd em Gebiet der präparativen Eisen-Schwefel-Chemie werden Ligandenaustauschreaktionen regelmäßig zur Synthese neuer [2Fe-2S]und [4Fe-4S]-Modellverbindungen mit O-, N-und S-Donoren [11][12][13][14] (beispielsweise dem fünffach-koordinierten Cluster 2, [15] verschiedener asymmetrischer [4Fe-4S]-Cluster als Modelle fürH iPIP-Eisen-Schwefel-Cluster [16][17][18] oder dem Rieske-Modell [19,20] 1;A bbildung 1) genutzt. Die kinetischen und mechanistischen Details derartiger Ligandenaustauschund Isomerisierungsprozesse sind bisher allerdings kaum untersucht.…”