Mechanism of aromatic hydroxylation by an activated FeIV=O core in tetrahydrobiopterin-dependent hydroxylases

The chemical pathways leading to the hydroxylated aromatic amino acids in phenylalanine and tryptophan hydroxylases have been investigated by means of hybrid density functional theory. In the catalytic core of these non-heme iron enzymes, dioxygen reacts with the pterin cofactor and is likely to be activated by forming an iron(IV)=O complex. The capability of this species to act as a hydroxylating intermediate has been explored. Depending on the protonation state of the ligands of the metal, two different mechanisms are found to be energetically possible for the hydroxylation of phenylalanine and tryptophan by the high-valent iron-oxo species. With a hydroxo ligand the two-electron oxidation of the aromatic ring passes through a radical, while an arenium cation is involved when a water replaces the hydroxide. After the attack of the activated oxygen on the substrate, it is also found that a 1,2-hydride shift (known as an NIH shift) generates a keto intermediate, which can decay to the true product through an intermolecular keto-enol tautomerization. The benzylic hydroxylation of 4-methylphenylalanine by the Fe(IV)=O species has also been investigated according to the rebound mechanism. The computed energetics lead to the conclusion that Fe(IV)=O is capable not only of aromatic hydroxylation, but also of benzylic hydroxylation.     

Mechanism of dioxygen cleavage in tetrahydrobiopterin-dependent amino acid hydroxylases

The reaction mechanism for the formation of the hydroxylating intermediate in aromatic amino acid hydroxylases (i.e., phenylalanine hydroxylase, tyrosine hydroxylase, tryptophan hydroxylase) was investigated by means of hybrid density functional theory. These enzymes use molecular oxygen to hydroxylate both the tetrahydrobiopterin cofactor and the aromatic amino acid. A mechanism is proposed in which dioxygen forms a bridging bond between the cofactor and iron. The product is an iron(II)-peroxy-pterin intermediate, and iron was found to be essential for the catalysis of this step. No stable intermediates involving a pterin radical cation and a superoxide ion O(2)(-) were found on the reaction pathway. Heterolysis of the O-O bond in the iron(II)-peroxy-pterin intermediate is promoted by one of the water molecules coordinated to iron and releases hydroxypterin and the high-valent iron oxo species Fe(IV)=O, which can carry out subsequent hydroxylation of aromatic rings. In the proposed mechanism, the formation of the bridging C-O bond is rate-limiting in the formation of Fe(IV)=O.     

The Spin Equilibrium 5T2—1A1 in the Mixed-ligand Complex [Fe(II)py2phen(NCS)2] and the MÖSSBAUER-Parameters

The MÖSSBAUER parameters (isomer shift δ and quadrupole splitting ΔE_Q) were determined for [Fe(II)py₂phen(NCS)₂] at 298° and 77°K, their values being compared with those for [Fe(II)phen₂(NCS)₂]. The existence of a spin equilibrium ⁵T₂ — ¹A₁ already put in evidence by the magnetic measurements for the mixed-ligand complex [Fe(II)py₂phen(NCS)₂] has been ckecked up using the γ-resonance spectroscopy.     

The ammonia-ammonium equilibrium in seawater at temperatures between 5 and 25°C

The stability constantK ₁of the equilibrium NH ₃ +H⁺NH ₄ ⁺ was determined by potentiometric titration in synthetic seawaters of 5 to 40 (per mille) salinity and sodium chloride solutions between 0.2 and 0.7M ionic strength at temperatures of 5, 15 and 25°C. Moreover,K ₁was determined in sulfate-free seawater of 35 salinity and 25°C. The dependence of logK ₁on salinity (or ionic strength) and temperature can be reasonably well described by linear relations. TheK ₁obtained for sulfate-free seawater agrees very well with earlier experimental results and theoretical predictions. From the measuredK ₁and literature data on the equilibrium NH ₃ (atm)NH ₃ (aq., NaCl), the atmospheric concentration of ammonia at equilibrium with seawater was estimated.     

Synthesis and Crystal Structure of meso-Δ,Λ-μ-Peroxo-μ-hydroxobis[bis(ethylenediamine)rhodium(III)]trifluoromethane Sulfonate

The reaction of the meso-diol, Δ,Λ-[(en)₂Rh(OH)₂Rh(en)₂]⁴⁺, with aqueous H₂O₂ and 1 equiv. of NaOH at 90° forms the μ-peroxo-μ-hydroxo-bridged species Δ,Λ-[(en)₂Rh(O₂,OH)Rh(en)₂]³⁺ in a yield of ca. 50%. The compound was crystallized as perchlorate and trifluoromethanesulfonate salts. The structure of the latter salt was determined by single-crystal X-ray diffraction. The crystals are triclinic with space group P1 and lattice constants a = 11.895(5), b = 12.491(4), c = 13.053(5) Å, α = 103.98(3), β = 92.59(3), γ = 119.52(6)°. The distances of the metal centres to the bridging peroxo ligand are 1.999(8) and 1.983(6) Å. The O? O distance in the peroxo group is 1.521(14) Å, and the dihedral angle of the Rh? O? O? Rh unit deviates 65° from planarity. The peroxo complex reacts reversibly with acid, and spectrophotometric studies suggest that the reaction involves protonation of the peroxo bridge, with pK_a = 2.70(2) at 25° in 1M NaClO₄.     

Über Reaktionen oxygenierter Kobalt(II)-Chelate. II. Konfigurationsisomere Oxygenierungsprodukte von Tetraäthylenpentaminkobalt(II)

On oxygenation of alcoholic solutions of tetraethylenepentamine cobalt(II) two isomeric forms of [(tetren)CoO₂Co(tetren)]⁴⁺ are obtained in which the configuration of the pentadentate ligand is either α or β. The binuclear complex can be crystallized as thiocyanate or as perchlorate. Oxygenation at 35° produces the pure α isomer. At lower temperature a mixture of α and β is obtained. The isomers differ slightly in their absorption spectra and their reactivity. The ligand configuration has been elucidated by transforming the perchlorates into the [ZnCl₄]^2? salts of the corresponding mononuclear chelates [Co(tetren)Cl]²⁺. The latter have also been prepared starting from a compound of known configuration according to the literature. The IR. spectra of the α and β forms differ characteristically in the NH stretch bands.     

A formal [3 + 3] cycloaddition reaction. Improved reactivity using alpha,beta-unsaturated iminium salts and evidence for reversibility of 6pi-electron electrocyclic ring closure of 1-oxatrienes

A detailed account regarding a formal [3 + 3] cycloaddition method using 4-hydroxy-2-pyrones and 1,3-diketones is described here. This formal cycloaddition reaction or annulation reaction is synthetically useful for constructing 2H-pyranyl heterocycles. The usage of alpha,beta-unsaturated iminium salts is significant in controlling competing reaction pathways to give exclusively 2H-pyrans. Most significantly, experimental evidence is provided to support the mechanism of this reaction that involves a sequential Knoevenagel condensation and a reversible 6pi-electron electrocyclic ring-closure of 1-oxatrienes.     

Reactions of oxygenated cobalt (II) complexes. XIII. Diastereoisomeric forms of μ-peroxo-μ-hydroxo-bis[bis(ethylenediamine) cobalt(III)]. Preparation,X-ray structure determination and reactivity

Oxygenation of solutions containing bis(ethylenediamine) cobalt(II) ions leads to a mixture of diastereomeric forms of μ-peroxo-μ-hydroxo-bis[bis(ethylenediamine) cobalt(III)] cations. The existence of a meso-isomer has now been proved by its isolation as perchlorate and by an X-ray structure determination. The crystals are monoclinic with space group P2₁/n and lattice constants: a = 19.280, b = 11.984, c = 11.654 Å, β = 99.190°. The UV./VIS. spectra of the isomers are practically identical but show different kinetic behaviour. In acidic solution the meso-isomer decomposes 4 times faster than the racemic form. In alkaline solution the meso-isomer isomerizes to the racemic form. A mechanism which explains all the kinetic observations has been devised.     

Über Reaktionen Oxygenierter Kobalt (II)-Komplexe. X. 1,4,7,10-Tetraazadecan-kobalt (II) und 4, 7-dimethyl-1,4,7,10-tetraazadecan-kobalt (II) als sauerstoffträger

Reactions of oxygenated cobalt (II) complexes. X. 1,4,7,10-tetraazadecanecobalt (II) and 4,7-dimethyl-1,4,7,10-tetraazadecanecobalt (II) as dioxygen carriers

1 IX: siehe [1].

Oxygenation of cobalt (II) chelates with fourdentate amines such as 1,4,7,10-tetraazadecane (= tad) in aqueous solution yields μ-peroxo-μ-hydroxo-dicobalt (III) complexes. Due to facultative ligand disposition of the amine, 8 different diastereoisomers are possible. Introducing methyl groups in positions 4 and 7 of tad destabilizes the isomers with β-configuration. A crystallized perchlorate, obtained by oxygenation of 4, 7-dimethyl-1,4,7,10-tetraazadecanecobalt (II) (= dmtad) in alcaline solution, proved to be of the expected μ-peroxo-μ-hydroxo type. The ligand configuration is and lattice constants a (ΔΔ/ΛΛ). The X-ray structure was solved by Patterson's method and refined to R = 0.093. The crystals are orthorhombic with space group Pna2₁ and lattice constants a = 14.632 (4), b = 17.525 (5), c = 12.888 (5) Å. In its UV./VIS. absorption spectrum and its solution reactivity the binuclear cation is closely related to oxygenation products obtained with the chelate of unsubstituted tad. The kinetic parameters of the decomposition reaction of the μ-peroxo complexes in acidic solution are compared. The binuclear cations with 4, 7-dimethyl-1,4,7,10-tetraazadecane as ligand are generally more reactive. In slightly alcaline solution isomerization of the μ-peroxo-μ-hydroxo complexes has been observed.