Characterization of a monocyanide model of FeFe hydrogenases - highlighting the importance of the bridgehead nitrogen for catalysis

An azadithiolate bridged monocyanide derivative [Fe-2(adt)(CO)(5)(CN)](-) of [Fe-2(adt)(CO)(4)(CN)(2)](2-) has been prepared and extensively characterized as a model of the [FeFe]-hydrogenase active site, using a combination of FTIR spectroscopy, electrochemical methods and catalytic assays with chemical reductants. The presence of two basic nitrogen sites opens up multiple protonation pathways, enabling catalytic proton reduction. To our knowledge [Fe-2(adt)(CO)(5)(CN)](-) represents the first example of a cyanide containing [FeFe]-hydrogenase active site mimic capable of catalytic H-2 formation in aqueous media

From protein engineering to artificial enzymes - biological and biomimetic approaches towards sustainable hydrogen production

Hydrogen gas is used extensively in industry today and is often put forward as a suitable energy carrier due its high energy density. Currently, the main source of molecular hydrogen is fossil fuels via steam reforming. Consequently, novel production methods are required to improve the sustainability of hydrogen gas for industrial processes, as well as paving the way for its implementation as a future solar fuel. Nature has already developed an elaborate hydrogen economy, where the production and consumption of hydrogen gas is catalysed by hydrogenase enzymes. In this review we summarize efforts on engineering and optimizing these enzymes for biological hydrogen gas production, with an emphasis on their inorganic cofactors. Moreover, we will describe how our understanding of these enzymes has been applied for the preparation of bio-inspired/-mimetic systems for efficient and sustainable hydrogen production

Influence of the copper coordination spheres on the N2Or activity of a mixed-valent copper complex containing a {Cu2S} core

International audienceA new mixed-valent dicopper complex [5] was generated from ligand exchange by dissolving a bis(CH3CN) precursor [3] in acetone. Introduction of a water molecule in place of an acetonitrile ligand was evidenced by base titration and the presence of a remaining coordinated CH3CN by IR, 19F NMR, and theoretical methods. The proposed structure (CH3CN–Cu–(SR)–Cu–OH2) was successfully DFT-optimized and the calculated parameters are in agreement with the experimental data. [5] has a unique temperature-dependence EPR behavior, with a localized valence from 10 to 120 K that undergoes delocalized at room temperature. The electrochemical signatures are in the line of the other aquo parent [2] and sensibly different from the rest of the series. Similar to the case of [2], [5] was finally capable of single turnover N2O reduction at room temperature. N2 was detected by GC-MS, and the redox character was confirmed by EPR and ESI-MS. Kinetic data indicate a reaction rate order close to 1 and a rate 10 times faster compared to [2]. [5] is thus the second example of that kind and highlights not only the main role of the Cu–OH2 motif, but also that the adjacent Cu-X partner (X = OTf– in [2] and CH3CN in [5]) is a new actor in the casting to establish structure/activity correlations

Hybrid Bis-Histidine Phenanthroline-Based Ligands to Lessen Aβ-Bound Cu ROS Production: An Illustration of Cu(I) Significance

International audienceWe here report the synthesis of three new hybrid ligands built around the phenanthroline scaffold and encompassing two histidine-like moieties: phenHH, phenHGH and H’phenH’, where H correspond to histidine and H’ to histamine. These ligands were designed to capture Cu(I/II) from the amyloid-β peptide and to prevent the formation of reactive oxygen species produced by amyloid-β bound copper in presence of physiological reductant (e.g., ascorbate) and dioxygen. The amyloid-β peptide is a well-known key player in Alzheimer’s disease, a debilitating and devasting neurological disorder the mankind has to fight against. The Cu-Aβ complex does participate in the oxidative stress observed in the disease, due to the redox ability of the Cu(I/II) ions. The complete characterization of the copper complexes made with phenHH, phenHGH and H’phenH’ is reported, along with the ability of ligands to remove Cu from Aβ, and to prevent the formation of reactive oxygen species catalyzed by Cu and Cu-Aβ, including in presence of zinc, the second metal ions important in the etiology of Alzheimer’s disease. The importance of the reduced state of copper, Cu(I), in the prevention and arrest of ROS is mechanistically described with the help of cyclic voltammetry experiments

Sequence–Activity Relationship of ATCUN Peptides in the Context of Alzheimer’s Disease

International audienceAmino-terminal CuII and NiII (ATCUN) binding sequences are widespread in the biological world. Here, we report on the study of eight ATCUN peptides aimed at targeting copper ions and stopping the associated formation of reactive oxygen species (ROS). This study was actually more focused on Cu(Aβ)-induced ROS production in which the Aβ peptide is the “villain” linked to Alzheimer’s disease. The full characterization of CuII binding to the ATCUN peptides, the CuII extraction from CuII(Aβ), and the ability of the peptides to prevent and/or stop ROS formation are described in the relevant biological conditions. We highlighted in this research that all the ATCUN motifs studied formed the same thermodynamic complex but that the addition of a second histidine in position 1 or 2 allowed for an improvement in the CuII uptake kinetics. This kinetic rate was directly related to the ability of the peptide to stop the CuII(Aβ)-induced production of ROS, with the most efficient motifs being HWHG and HGHW

Impact of N‐Truncated Aβ Peptides on Cu‐ and Cu(Aβ)‐Generated ROS: Cu I Matters!

International audienceIn vitro Cu(Aβ1–x)-induced ROS production has been extensively studied. Conversely, the ability of N-truncated isoforms of Aβ to alter the Cu-induced ROS production has been overlooked, even though they are main constituents of amyloid plaques found in the human brain. N-Truncated peptides at the positions 4 and 11 (Aβ4–x and Aβ11–x) contain an amino-terminal copper and nickel (ATCUN) binding motif (H2N-Xxx-Zzz-His) that confer them different coordination sites and higher affinities for CuII compared to the Aβ1–x peptide. It has further been proposed that the role of Aβ4–x peptide is to quench CuII toxicity in the brain. However, the role of CuI coordination has not been investigated to date. In contrast to CuII, CuI coordination is expected to be the same for N-truncated and N-intact peptides. Herein, we report in-depth characterizations and ROS production studies of Cu (CuI and CuII) complexes of the Aβ4–16 and Aβ11–16 N-truncated peptides. Our findings show that the N-truncated peptides do produce ROS when CuI is present in the medium, albeit to a lesser extent than the unmodified counterpart. In addition, when used as competitor ligands (i.e., in the presence of Aβ1–16), the N-truncated peptides are not able to fully preclude Cu(Aβ1–16)-induced ROS production

Solid-state and solution characterizations of [(TMPA)Cu(II)(SO3)] and [(TMPA)Cu(II)(S2O3)] complexes: Application to sulfite and thiosulfate fast detection

International audienceSulfite (SO32−) and thiosulfate (S2O32−) ions are used as food preservative and antichlor agent respectively. To detect low levels of such anions we used Cu(II) complex of the Tris-Methyl Pyridine Amine (TMPA) ligand, denoted L. Formation of [LCu(SO3)] (1) and [LCu(S2O3)] (2) in solution were monitored using UV–Vis, EPR and cyclic voltammetry, while the solid-state X-ray structures of both complexes were solved. In addition, we also evaluated the pH range in which the complexes are stable, and the anions binding affinity values for the [LCu(solvent)]2+ (3) parent complex. As a matter of illustration, we determined the sulfite content in a commercial crystal sugar

In vivo activation of an [FeFe] hydrogenase using synthetic cofactors

[FeFe] hydrogenases catalyze the reduction of protons, and oxidation of hydrogen gas, with remarkable efficiency. The reaction occurs at the H-cluster, which contains an organometallic [2Fe] subsite. The unique nature of the [2Fe] subsite makes it dependent on a specific set of maturation enzymes for its biosynthesis and incorporation into the apo-enzyme. Herein we report on how this can be circumvented, and the apo-enzyme activated in vivo by synthetic active site analogues taken up by the living cell.<p>Correction in: ENERGY &amp; ENVIRONMENTAL SCIENCE, Volume: 11, Issue: 11, Pages: 3321-3321, DOI: 10.1039/c8ee90054j</p

The reactivity of molecular oxygen and reactive oxygen species with [FeFe] hydrogenase biomimetics : reversibility and the role of the second coordination sphere

The development of oxygen-tolerant H-2-evolving catalysts plays a vital role for a future H-2 economy. For example, the [FeFe] hydrogenase enzymes are excellent catalyst for H-2 evolution but rapidly become inactivated in the presence of O-2. The mechanistic details of the enzyme's inactivation by molecular oxygen still remain unclear. Here, two H-2-evolving diiron complexes [Fe-2(mu-SCH2NHCH2S)(CO)(6)] (1(adt)) and [Fe-2(mu-SCH2CH2CH2S)(CO)(6)] (2(pdt)), inspired by the active site of [FeFe] hydrogenase, were investigated for their reactivity with molecular oxygen and reactive oxygen species. A one-electron reduced and oxygenated 1(adt) species was identified and characterized spectroscopically, which can be directly generated by reacting with molecular oxygen and chemical reductants at room temperature but it is unstable and gradually decomposes. Interestingly, the whole process is reversible and the addition of protons can facilitate the deoxygenation process and prevent further degradation at room temperature. This new identification of intermediate species serves as a model for studying the reversible inactivation and degradation of oxygen-sensitive [FeFe] hydrogenases by O-2, and provides chemical precedence for such processes. In comparison, the complex lacking the nitrogen bridgehead, 2(pdt), exhibits reduced reactivity towards O-2 in the presence of reductants, highlighting that the importance of the second coordination sphere on modulating the oxygenation processes. These results provide new directions to design molecular electrocatalysts for proton reduction operated at ambient conditions and the re-engineering of [FeFe] hydrogenases for improving oxygen tolerance