Tuning the Reactivity of Fe(O) toward C−H Bonds at Room Temperature: Effect of Water

The presence of an Fe(O) species has been postulated as the active intermediate for the oxidation of both C−H and CC bonds in the Rieske dioxygenase family of enzymes. Understanding the reactivity of these high valent iron−oxo intermediates, especially in an aqueous medium, would provide a better understanding of these enzymatic reaction mechanisms. The formation of an Fe(O) complex at room temperature in an aqueous CH3CN mixture that contains up to 90% water using NaOCl as the oxidant is reported here. The stability of Fe(O) decreases with increasing water concentration. We show that the reactivity of Fe(O) toward the oxidation of C−H bonds, such as those in toluene, can be tuned by varying the amount of water in the H2O/CH3CN mixture. Rate acceleration of up to 60 times is observed for the oxidation of toluene upon increasing the water concentration. The role of water in accelerating the rate of the reaction has been studied using kinetic measurements, isotope labeling experiments, and density functional theory (DFT) calculations. A kinetic isotope effect of ∼13 was observed for the oxidation of toluene and d8-toluene showing that C−H abstraction was involved in the rate-determining step. Activation parameters determined for toluene oxidation in H2O/CH3CN mixtures on the basis of Eyring plots for the rate constants show a gain in enthalpy with a concomitant loss in entropy. This points to the formation of a more-ordered transition state involving water molecules. To further understand the role of water, we performed a careful DFT study, concentrating mostly on the rate-determining hydrogen abstraction step. The DFT-optimized structure of the starting Fe(O) and the transition state indicates that the rate enhancement is due to the transition state’s favored stabilization over the reactant due to enhanced hydrogen bonding with water. ■ INTRODUCTION Metalloenzymes use oxidants like O2 and H2O2 to catalyze oxidation reactions that exhibit exquisite substrate specificity and selectivity and operate under mild conditions through inherently “green” processes. Examples of such catalysts include cytochrome P450 and peroxidases, enzymes that use an iron(IV) oxoporphyrin radical cation intermediate to catalyze the oxidation of various organic substrates selectively and efficiently. Other non-heme-based monooxygenases, such as α-KG dioxygenase, catalyze the oxidation of C−H bonds by an Fe(O) intermediate. In the Rieske dioxygenase family of enzymes, Fe(O) has been postulated to be the active intermediate reactive species for carrying out oxidation of both C−H and CC bonds. Although several models of Fe(O) intermediates have been synthesized, and their reactivity for oxidizing C−H bonds has been studied in detail, very few studies have explored the reactivity of Fe(O) toward the oxidation of C−H bonds. Recently, we reported for the first time the quantitative formation of a well-defined Fe(O) complex at room temperature using biuret-modified Fe−TAML and mCPBA in CH3CN. 8 Fe(O) was characterized by UV−vis, X-band electron paramagnetic resonance (EPR), Mössbauer, and high resolution mass spectrometry (HR-MS). It has also been shown to catalyze the oxidation of C−H bonds with abstraction of the hydrogen atom being the rate-determining step. Because the iron monooxygenase reactions occur in water, it is important to understand the effect of water on the rate of reaction for the oxidation of C−H bonds by Fe(O). Water has been shown to play a critical role during oxidation of organic substrates in heme-containing enzymes such as cytochrome P450. The formation of Fe(O) by Fe−TAML in water has been previously reported. In this Article, we verify the stability of Fe(O) in H2O/CH3CN mixtures containing up to 90% water. The effect of water on the reactivity of Fe(O) during C−H activation has also been studied both experimentally and theoretically. We also report that the rate of oxidation of Received: October 17, 2014 Published: January 16, 2015 Article