Oxoiron(V) Complexes of Relevance in Oxidation Catalysis of Organic Substrates

The selective oxidation of alkane and olefin moieties are reactions of fundamental importance in both chemical synthesis and biology. Nature efficiently catalyzes the oxidation of hydrocarbons using iron-dependent enzymes, which operate through the mediation of oxoiron(IV) or oxoiron(V) species. In the quest for chemo, regio and stereoselective transformations akin to those taking place in nature, bioinspired iron catalysts have been developed and understanding their mechanism of action has become a particularly relevant area of research. While a prominent advance in the preparation and characterization of oxoiron(IV) species has been accomplished, oxoiron(V) species remain exceedingly rare, presumably because the high reactivity that makes them particularly interesting also makes them difficult to observe. This review summarizes the advances in the field, focusing in synthetic systems for which the oxoiron(V) species relevant in these transformations have been directly detected and spetroscopically characterized.     

Parallel enzymatic and non-enzymatic formation of zinc protoporphyrin IX in pork

Zinc protoporphyrin is formed in pork homogenates in both enzymatic and non-enzymatic reactions. Ferrochelatase is active in formation of the highly fluorescent pigment known from Parma ham as demonstrated by inhibition with N-methylmesoporphyrin and by thermal inactivation. A non-enzymatic transmetallisation reaction, exchange of iron in myoglobin by zinc(II), is demonstrated by Pb(II) inhibition of zinc protoporphyrin formation at low Pb(II) concentrations, but promoted at higher Pb(II) concentrations. The non-enzymatic reaction is characterised as a slow bimolecular reaction between protoporphyrin IX and zinc(II) with a second-order rate constant of 0.63 l mol⁻¹ s⁻¹ at 35 °C and a high energy of activation of 98 kJ mol⁻¹ for acetone:water (3:1, v/v) as solvent. Zinc protoporphyrin formation is concluded to be thermodynamically controlled with a formation constant of 4 × 10⁵ M (35 °C, acetone:water (3:1)). An efficient inhibition of formation of zinc protoporphyrin by nitrite is related to myoglobin as substrate and involves both enzymatic and non-enzymatic reactions.     

An Enantioselective Recyclable Polystyrene‐Supported Threonine‐Derived Organocatalyst for Aldol Reactions

A series of primary amino acids covalently supported onto polystyrene through alkyne–azide cycloaddition reactions has been synthesized and evaluated as catalysts in asymmetric aldol reactions. A polymer‐supported threonine behaves as an easily recyclable, highly reactive and stereoselective (up to 99% ee) catalyst in the aldol reaction of both cyclic and acyclic ketone donors with aromatic aldehydes in aqueous environments. While cyclic ketones react with anti diastereoselectivity, syn adducts are predominantly obtained with acyclic substrates. The heterogenized threonine catalyst has been used for the sequential synthesis of a small library of enantiopure aldol products.

     

Copper Transfer from Cu–Aβ to Human Serum Albumin Inhibits Aggregation,Radical Production and Reduces Aβ Toxicity

Amyloid‐β peptides (Aβ) and the protein human serum albumin (HSA) interact in vivo. They are both localised in the blood plasma and in the cerebrospinal fluid. Among other functions, HSA is involved in the transport of the essential metal copper. Complexes between Aβ and copper ions have been proposed to be an aberrant interaction implicated in the development of Alzheimer's disease, where Cu is involved in Aβ aggregation and production of reactive oxygen species (ROS). In the present work, we studied copper‐exchange reaction between Aβ and HSA or the tetrapeptide DAHK (N‐terminal Cu‐binding domain of HSA) and the consequence of this exchange on Aβ‐induced ROS production and cell toxicity. The following results were obtained: 1) HSA and DAHK removed Cu^II from Aβ rapidly and stoichiometrically, 2) HSA and DAHK were able to decrease Cu‐induced aggregation of Aβ, 3) HSA and DAHK suppressed the catalytic HO^. production in vitro and ROS production in neuroblastoma cells generated by Cu–Aβ and ascorbate, 4) HSA and DAHK were able to rescue these cells from the toxicity of Cu–Aβ with ascorbate, 5) DAHK was more potent in ROS suppression and restoration of neuroblastoma cell viability than HSA, in correlation with an easier reduction of Cu^II–HSA than Cu–DAHK by ascorbate, in vitro. Our data suggest that HSA is able to decrease aberrant Cu^II–Aβ interaction. The repercussion of the competition between HSA and Aβ to bind Cu in the blood and brain and its relation to Alzheimer's disease are discussed.