Utilizing the Trispyrazolyl Borate Ligand for the Mimicking of O₂-Activating Mononuclear Nonheme Iron Enzymes

Abstract

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.

Synthesis, X-ray Structures, Electronic Properties, and O2/NO Reactivities of Thiol Dioxygenase Active-Site Models

“…34–35 Recently, Limberg and coworkers have prepared structural and functional CDO and ADO mimics supported by the hydrotris(3-phenyl-5-methylpyrazolyl)borate ( Ph,Me Tp − ) ligand and featuring bidentate L -cysteine ethyl ester (CysOEt) or cysteamine (CysAm) anions, respectively. 36–38 These 5C Fe(II) complexes react with O 2 to give the S -dioxygenated products, as confirmed by experiments involving isotopically-labeled O 2 . De Visser and others have explored the O 2 -activation mechanisms of CDO and select TDO models using computational methods.…”

Aliphatic C−C Bond Cleavage in α‐Hydroxy Ketones by a Dioxygen‐Derived Nucleophilic Iron–Oxygen Oxidant

“…Synthetic model complexes provideu seful insights into the mechanistic aspects of aliphatic CÀCb ond cleavage reactions. [2,24] We recentlyr eported the CÀCb ond cleavage of ahydroxy ketones containing a-H atoms by iron(II) complexes of nitrogen-donor polydentate ligands. [25,26] However,t he iron(II) complexes were unable to cleave the CÀCb ond of the a-hydroxy ketones without a-CÀHb onds.…”

Synthetic Bioinorganic Chemistry: Scorpionates Turn 50

“…6) was prepared as a structural and functional model of catechol dehydrogenase, and its reactivity towards O 2 was investigated [67]. Nonheme iron oxygenases [68] catalyze a variety of complex oxidation processes such as the oxidative cleavage of carbon-carbon bonds and several monohydroxylation and dihydroxylation reactions [69][70][71][72][73] [74]. Significantly, mechanistic studies suggest that iron(III)-superoxo and iron(IV)-oxo species are implicated as key oxidants in these reactions.…”