The natural paragon taken seriously: A trispyrazolylborato cysteinato iron complex not only excellently mimics the active site structure of cysteine dioxygenase (see picture: both structures superimposed): a dioxygenation of cysteinate occurs on treatment with O2, and hence, the system represents the hitherto most realistic model for cysteine dioxygenase.

Cysteine dioxygenase is a unique nonheme iron enzyme that is involved in the metabolism of cysteine in the body. It contains an iron active site with an unusual 3-His ligation to the protein, which contrasts with the structural features of common nonheme iron dioxygenases. Recently, some of us reported a truly biomimetic model for this enzyme, namely a trispyrazolylborato iron(II) cysteinato complex, which not only has a structure very similar to the enzyme-substrate complex but also represents a functional model: Treatment of the model with dioxygen leads to cysteine dioxygenation, as shown by isolating the cysteine part of the product in the course of the work-up. However, little is known on the conversion mechanism and, so far, not even the structure of the actual product complex had been characterised, which is also unknown in case of the enzyme. In a multidisciplinary approach including density functional theory calculations and X-ray absorption spectroscopy, we have now determined the structure of the actual sulfinato complex for the first time. The Cys-SO2 (-) functional group was found to be bound in an η(2) -O,O-coordination mode, which, based on the excellent resemblance between model and enzyme, also provides the first support for a corresponding binding mode within the enzymatic product complex. Indeed, this is again confirmed by theory, which had predicted a η(2) -O,O-binding mode for synthetic as well as the natural enzyme.

Mononuclear, O2-activating nonheme iron enzymes are a fascinating class of metalloproteines, capable of realizing the most different reactions, ranging from C-H activation, via O atom transfer to C-C bond cleavage, in the course of O2 activation. They can lead us the way to achieve similar reactions with comparable efficiency and selectivity in chemical laboratories, which would be highly desirable aiming at accessing value-added products or to achieve degradation of unwanted compounds. Hence, these enyzmes motivate attempts to construct artificial low-molecular weight analogues, mimicking structural or functional characteristics. Such models can, for instance, provide insights about which of the features inherent to an active site are essential and guarantee the enzyme function, and from this kind of information the minimal requirements for a biomimetic or bioinspired complex that may be applied in catalysis can be derived. On the other hand, they can contribute to an understanding of the enzyme functioning. In order to create such replicates, it is important to faithfully mimic the surroundings of the iron centers in their active sites. Most of them feature two histidine residues and one carboxylate donor, while a few exhibit a deceptively simple (His)3Fe active site. For the simulation of these, the trispyrazolyl borate ligand (Tp) particularly offers itself, as the facial arrangement of three pyrazole donors is reminiscent of the three histidine-derived imidazole donors. The focus of this Account will be on bioinorganic/biomimetic research from our laboratory utilizing Tp ligands to develop molecular models for (i) two representatives of the (His)3Fe-enzyme family, namely, the cysteine dioxygenase (CDO) and acetyl acetone dioxygenase (Dke1), (ii) a related but less well-explored variant of the CDO-the 2-aminoethanethiol dioxygenase-as well as (iii) the 2-His-1-carboxylate representative 1-aminocyclopropane-1-carboxylic acid oxidase (ACCO). The CDO catalyzes the dioxygenation of cysteine with O2 to give cysteine sulfinic acid, which could be mimicked at TpFe units in a realistic manner. Furthermore, the successful dioxygenation of 2-aminoethanethiol at the same complex metal fragments lends further support to the hypothesis that the active sites of CDO and the one of 2-aminoethanethiol dioxygenase, whose structure is unknown, are quite similar. Dke1 is capable of cleaving diketones and ketoesters to give the corresponding carboxylic acids and α-keto aldehydes, and Tp-based models have achieved comparable C-C bond cleavage reactions. The ACCO develops ethylene from ACC in the course of oxidation, and recently this has been achieved the first time for a TpFe model, too.

A novel complex Tp(Me,Ph)Fe(SCH2CH2NH2) has been synthesized as a speculative model for ADO. Indeed its reaction with O2 led to the dioxygenation of the S atom and thus to hypotaurine. This finding may allow us to draw conclusions on the constitution of the ADO active site, whose structure is still unknown.

The hitherto most realistic low-molecular-weight analogue for the 1-aminocyclopropane-1-carboxylic acid oxidase (ACCO) is reported. The ACCOs 2-His-1-carboxylate iron(II) active site was mimicked by a TpFe moiety, to which the natural substrate ACC could be bound. The resulting complex [Tp(Me,Ph) FeACC] (1), according to X-ray diffraction analysis performed for the nickel analogue, represents an excellent structural model, featuring ACC coordinated in a bidentate fashion-as proposed for the enzymatic substrate complex-as well as a vacant coordination site that forms the basis for the first successful replication also of the ACCO function: 1 is the first known ACC complex that reacts with O2 to produce ethylene. As a FeOOH species had been suggested as intermediate in the catalytic cycle, H2 O2 was tested as the oxidant, too, and indeed evolution of ethylene proceeded even more rapidly to give 65 % yield.

Das bislang realistischste niedermolekulare Analogon für die 1-Aminocyclopropan-1-carbonsäure-Oxidase (ACCO) wird beschrieben. Das aktive Zentrum der ACCO, bestehend aus einer 2-His-1-Carboxylateisen(II)-Spezies, wurde durch eine Tp-Eisen-Einheit nachgeahmt, welche in der Lage ist, ACCz ub inden. Der resultierende Komplex [Tp Me,Ph FeACC] (1) [7] Nach wie vor bleiben also viele Fragen zur Substratwechselwirkung,z ur Rolle verschiedener Kofaktoren/Kosubstrate (Ascorbinsäure,D isauerstoff und Kohlendioxid) und zum Katalysemechanismus unbeantwortet.Bioanorganische Modellstudien kçnnen wertvolle Informationen über strukturelle Parameter sowie auch über Voraussetzungen für die enzymatische Reaktivität liefern. Dennoch sind bislang kaum Verbindungen bekannt, die manunter der Minimalvoraussetzung,dass sie ACCenthalten und eine nennenswerte ACCO-ähnliche Reaktivität besitzen -als ACCO-Modelle betrachten kçnnte. [8,9] Ein Eisen-Komplex ist bekannt, der jedoch zweikernig ist, Eisen(III)-Ionen enthält und zwei verbrückende ACC-Liganden aufweist.[

To support mechanistic inferences made for an iron-based dioxygenase model, a nickel analogue, i.e. a TpNi-malonate (1) was prepared. 1 proved to represent a rare case of a nickel complex reacting with O in a controlled manner - mechanistically different from the iron case - and leads to hydroxylation of the malonate.

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