Group Transfer to an Aliphatic Bond: A Biomimetic Study Inspired by Nonheme Iron Halogenases

Abstract

In this work, we predict a group-transfer reaction to an aliphatic substrate on a biomimetic nonheme iron center based on the structural and functional properties of nonheme iron halogenases. Transferring groups other than halogens to C–H bonds on the same catalytic center would improve the versatility and applicability of nonheme iron halogenases and enhance their use in biotechnology; however, few studies have been reported on this matter. Furthermore, very few biomimetic models are known that are able to transfer halogens or other groups to aliphatic C–H bonds. To gain insight into group transfer to an aliphatic C–H bond, we performed a detailed computational study on a biomimetic nonheme iron complex and studied the reactivity patterns with a model substrate (ethylbenzene). In particular, we investigated the reaction mechanisms of [FeIV(O)­(TPA)­X]+, TPA = tris­(2-pyridylmethy1)­amine, and X = Cl, NO2, N3 with ethylbenzene leading to 1-phenylethanol and 1-phenyl-1-X-ethane products. Interestingly, we find that the product distributions vary with the nature of the equatorial X-substituent on the metal center. Thus, [FeIV(O)­(TPA)­NO2]+ reacts with ethylbenzene by dominant hydroxylation of the substrate, whereas with halide/azide in the cis-position a group transfer is more likely. As such, we predict a catalytic mechanism of azidation of aliphatic groups using a biomimetic nonheme iron oxidant. The results have been analyzed with thermochemical cycles, valence bond schemes and electronic assignments of reactants and products, which put our results in a broad perspective and predict the effect of other substituents. Finally, predictions are given on how these systems could be utilized in vivo.

Computational Study on the Catalytic Reaction Mechanism of Heme Haloperoxidase Enzymes

“…[27] As seen in nonheme iron halogenase calculations, halide transfer is easier when the halide group is neutral rather than anionic. [28] It may very well be that haloperoxidases operate by a similar mechanism, whereby the halide loses electron density prior to a covalent bond formation step. Moreover, the oxygen atom transfer to halide may be sensitive to environmental factors and the polarity of the protein pocket.…”

Mechanism of Oxidative Activation of Fluorinated Aromatic Compounds by N‐Bridged Diiron‐Phthalocyanine: What Determines the Reactivity?

“…[23] Furthermore, these VB diagrams helped to explain regioselectivity patterns and reaction mechanisms by giving detailso ft he electronic configuration and electron migration steps. [24] In Figure 6, the reactant species has an umber of p-type orbitals along the O-Fe1-N-Fe2 axis through interactions of the 2p x /2p y on O/N with the 3d xz / 3d yz on Fe1/Fe2. The full set of bonding combinations are the almostd egenerate p 1,x /p 1,y orbitals that are both doubly occupied.…”

Investigating the Effect of NO on the Capture of CO2 Using Superbase Ionic Liquids for Flue Gas Applications

“…24,25 This methodology has been used extensively for calculating kinetic and thermodynamic properties of group transfer reactions. [26][27][28] Additional benchmarking and verification was done using the pure density functional UBP86, and is available in the SI (Tables S11 S16). 24,29 All major trends obtained with the UB3LYP functional were replicated with the pure UBP86 functional.…”