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Mechanistic Investigations of Hydrogen and Oxygen Atom Transfer Reactions by Manganese-Oxygen Species
Singh, Priya
Singh, Priya
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Abstract
Metalloenzymes, such as cytochrome P450 and manganese lipoxygenase (Mn-LOX), act as oxidants to perform essentially challenging reactions by activating dioxygen. These reactions commonly feature high-valent metal-oxygen species as key intermediates responsible for the transfer of a hydrogen or oxygen atom from the metal-center to the substrate under favourable conditions. For example, the iron(IV)-oxo intermediate, in cytochrome P450 enzyme, is invoked as the reactive species that oxidizes the inert C‒H bonds of hydrocarbon through an initial concerted proton electron transfer process (CPET). Likewise, a manganese(III)-hydroxo intermediate in the active site of the Mn-LOX enzyme is proposed to oxidize polyunsaturated fatty acids into hydroperoxides via CPET process. The oxidation of C‒H bonds by high-valent iron(IV)-oxo intermediates is quite common in biological enzymes, however, it is rare for Mn(III)-hydroxo species to perform CPET reactions with C‒H bonds. Understanding how these enzymes achieve their reactivity is of ongoing interest, and relevant model complexes can be used to explore how changing the electronic structure can modulate reactivity of the metal-oxygen species. A substantial number of synthetic iron(IV)-oxo intermediates bearing porphyrin and non-porphyrin ligands have been successfully investigated as the models of iron enzymes. However, synthetic manganese(IV)-oxo species are also proposed to be the reactive species catalyzing the oxidation reactions of C‒H bonds but the factors influencing their reactivity and reaction mechanisms are poorly understood. This work aims to address the factors affecting the reactivity of manganese-oxygen species in CPET reaction by exploring a series of structurally tuned manganese(IV)-oxo and manganese(III)-hydroxo complexes.A series of manganese(IV)-oxo complexes supported by neutral, pentadentate ligands with varied equatorial ligand-field strength were synthesized and characterized using structural and spectroscopic methods. The reactivity of these complexes has been explored with several substrates. Interestingly, a substantial rate enhancement (~4000-fold) is seen among these manganese(IV)-oxo complexes in the OAT reactions with thioanisole. We examined the basis for this rate variation by performing variable-temperature kinetic studies which reveals that the activation barriers is predominantly controlled by the activation enthalpy. We also compared the reactivity of these manganese(IV)-oxo complexes through Hammett analysis, using para-substituted thioanisole derivatives. The results suggest a common sulfoxidation mechanism for these complexes. Additionally, the rates of oxidation of the para-substituted thioanisole derivatives by the manganese(IV)-oxo complexes are much faster than expected from the Marcus theory of outer-sphere electron-transfer. Therefore, we conclude that these reactions proceed by a single-step OAT mechanism. Thus, large variations in sulfoxidation reactions by this series of manganese(IV)-oxo complexes occur without a change in reaction mechanism.We also explore the role of equatorial ligand field perturbations in manganese(IV)-oxo complexes on the chemoselectivity in olefin oxidation reactions. Within this series, the product distribution in olefin oxidation is highly dependent on the coordination environment of the manganese(IV)-oxo unit. While manganese(IV)-oxo complexes with sterically encumbered Mn=O units favor C=C epoxidation products in cyclohexene oxidation, a less encumbered analogue prefers to cleave allylic C–H bonds, resulting in cyclohexenol and cyclohexenone formation. DFT computations successfully established a trend in thermodynamic properties of the manganese(IV)-oxo complexes and their reactivity towards olefin oxidation on the basis of the Mn=O bond dissociation free energy (BDFE). Collectively, these results suggest that the chemoselectivity obtained in oxidation of olefins is controlled by both the coordination environment around the Mn=O unit, which modulates the Mn=O BDFE, and the BDFEs of the allylic C–H bond of the olefins.Further, we examined the reactivity of these complexes with C‒H bonds of various BDEs ranging from 74 kcal mol-1 to 98 kcal mol-1. The manganese(IV)-oxo complexes with weak equatorial ligand field were found to be better oxidants compared to the one with electron rich manganese(IV) center. However, a more details study by including new manganese(IV)-oxo complexes revealed that while thermodynamic driving force remains a robust predictor of reactivity for manganese(IV)-oxo centers, other factors such as substrate–complex interactions and, potentially, tunneling effects, can lead to deviations in linear free energy relationships. We also determined the activation parameters for the oxidation reactions of these set of complexes. Interestingly, the Eyring analysis exhibited similar activation enthalpy for the fastest and slowest complexes in the series which is unusual as a 65-fold rate enhancement is observed for the oxidation reactions involving the fastest oxidant. A temperature dependent analysis of these reactions also revealed large H/D kinetic isotope effects for some manganese(IV)-oxo complexes suggests hydrogen atom tunneling. Therefore, a more rigorous approach was employed in which these reactions were evaluated by Arrhenius analysis. The results obtained implied contributions from hydrogen atom tunnelling which likely complicates the results obtained Eyring analysis.Lastly, the influence of the hydrogen bonding interactions on the redox activity of the manganese(III)-hydroxo complexes was explored. Such interactions are believed to play a crucial role in modulating the thermodynamic properties of the manganese(III)-hydroxo complexes, especially by increasing the basicity of the MnIII-OH unit. A detailed thermodynamic analysis for the CPET reaction of manganese(III)-hydroxo complexes with several phenol substrates, especially the acidic phenol substrates have been discussed. This analysis highlights that the more basic manganese(III)-hydroxo complex might have a preference for a stepwise proton electron transfer in the oxidation reactions with acidic phenols rather than a concerted proton-electron transfer process.
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2023-12-31
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University of Kansas
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Inorganic chemistry, chemoselectivity, cytochrome P450, hydrogen atom transfer, manganese hydroxo, oxomanganese, oxygen atom transfer