Over the past decade, several metalloenzymes have been characterized which catalyze dioxygenase-type aliphatic carbon-carbon bond cleavage reactions. The substrates for these enzymes vary from species that are stable with respect to O2 under ambient conditions, to examples that in anionic form exhibit O2 reactivity in the absence of enzyme. Described herein are advances from studies of the enzymes themselves and model systems. These combined investigations provide insight into novel mechanistic pathways leading to aliphatic carbon-carbon bond cleavage and/or the factors that influence regioselectivity in the oxidative carbon-carbon bond cleavage reactions.
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The Fe(II)-ARD′ and Ni(II)-ARD-catalyzed reactions are of interest for several reasons. First, while several metalloenzymes exhibit varying degrees of activity as a function of the metal ion present, the ARD/ARD′ system is the only demonstrated example of different chemical reactions resulting from a change of the metal ion bound within the same protein component  . Second, the reaction catalyzed by Ni(II)-ARD results in the generation of CO, a biological signaling molecule. Third, the role of the divalent metal ion in these dioxygenases is proposed to be that of a Lewis acid which stabilizes a dianionic form of the acireductone substrate for reaction with O 2 . This notion is supported by the fact that Mg(II)-containing ARD′ catalyzes MTOB formation. For Fe(II)-ARD′, the role of the divalent iron center thus contrasts from that found in other Fe(II)-containing dioxygenases wherein the metal center is directly involved in oxygen activation via redox reactivity. Fourth, the observed regioselectivity of aliphatic carbon–carbon cleavage promoted by Fe(II)-ARD′ and Ni(II)-ARD is proposed to be the result of differing coordination modes for the acireductone dianion (an enediolate) in the ES complexes. This proposed coordination chemistry-driven regioselectivity for carbon–carbon cleavage is distinct from that proposed for the iron-containing catechol dioxygenases wherein the oxidation state of metal center (Fe(II) vs. Fe(III)) impacts substrate activation and the site of reactivity with O 2 .
- Bioinorganic chemistry
- Carbon monoxide
- Dioxygen activation
- Enzyme catalysis
- Structure-function relationships