Deciphering the origin of million-fold reactivity observed for the open core diiron [HO-FeIII-O-FeIV[double bond, length as m-dash]O]2+ species towards C-H bond activation: role of spin-states, spin-coupling, and spin-cooperation

Abstract

High-valent metal-oxo species have been characterised as key intermediates in both heme and non-heme enzymes that are found to perform efficient aliphatic hydroxylation, epoxidation, halogenation, and dehydrogenation reactions. Several biomimetic model complexes have been synthesised over the years to mimic both the structure and function of metalloenzymes. The diamond-core [Fe₂(μ-O)₂] is one of the celebrated models in this context as this has been proposed as the catalytically active species in soluble methane monooxygenase enzymes (sMMO), which perform the challenging chemical conversion of methane to methanol at ease. In this context, a report of open core [HO(L)Fe^III-O-Fe^IV(O)(L)]²⁺ (1) gains attention as this activates C-H bonds a million-fold faster compared to the diamond-core structure and has the dual catalytic ability to perform hydroxylation as well as desaturation with organic substrates. In this study, we have employed density functional methods to probe the origin of the very high reactivity observed for this complex and also to shed light on how this complex performs efficient hydroxylation and desaturation of alkanes. By modelling fifteen possible spin-states for 1 that could potentially participate in the reaction mechanism, our calculations reveal a doublet ground state for 1 arising from antiferromagnetic coupling between the quartet Fe^IV centre and the sextet Fe^III centre, which regulates the reactivity of this species. The unusual stabilisation of the high-spin ground state for Fe^IV[double bond, length as m-dash]O is due to the strong overlap of with the orbital, reducing the antibonding interactions via spin-cooperation. The electronic structure features computed for 1 are consistent with experiments offering confidence in the methodology chosen. Further, we have probed various mechanistic pathways for the C-H bond activation as well as -OH rebound/desaturation of alkanes. An extremely small barrier height computed for the first hydrogen atom abstraction by the terminal Fe^IV[double bond, length as m-dash]O unit was found to be responsible for the million-fold activation observed in the experiments. The barrier height computed for -OH rebound by the Fe^III-OH unit is also smaller suggesting a facile hydroxylation of organic substrates by 1. A strong spin-cooperation between the two iron centres also reduces the barrier for second hydrogen atom abstraction, thus making the desaturation pathway competitive. Both the spin-state as well as spin-coupling between the two metal centres play a crucial role in dictating the reactivity for species 1. By exploring various mechanistic pathways, our study unveils the fact that the bridged μ-oxo group is a poor electrophile for both C-H activation as well for -OH rebound. As more and more evidence is gathered in recent years for the open core geometry of sMMO enzymes, the idea of enhancing the reactivity via an open-core motif has far-reaching consequences.

Scheme 1. Generic mechanism for hydroxylation vs. desaturation by using sMMO (soluble methane monooxygenase) and Δ9D (stearoyl-ACP Δ⁹-desaturase).

Scheme 2. The schematic mechanism of oxidation of cyclopentane by complex 1 [HO(L)Fe^III–O–Fe^IV(O)(L)]²⁺.

Fig. 1. (a and b) The optimized structure of ²1_hs–hs and its corresponding spin density plot, (c and d) optimized structure of ¹⁰1_hs–hs and its corresponding spin density plot, (e and f) optimized structure of ²RC_hs–hs and its corresponding spin density plot and (g and h) optimized structure of ²TS_Hhs–hs and its corresponding spin density plot. Some important structural parameters computed for the spin states and spin density values are given below for species 1, RC and I-TS_H. For spin state ²1_hs–hs, Fe^IV–O1 = 1.641, Fe^III–O2 = 1.828, Fe^IV–μO = 1.757, Fe^III–μO1 = 1.865, O2–H = 0.984, and O1–H = 1.856 and spin density Fe^IV = –3.04, Fe^III = 3.99, O1 = –0.48, O2 = 0.38, and μO = 0.05. For spin state ¹⁰1_hs–hs, Fe^IV–O1 = 1.642, Fe^III–O2 = 1.834, Fe^IV–μO = 1.778, Fe^III–μO1 = 1.901, O2–H = 0.981, and O1–H = 1.901 and spin density Fe^IV = 3.04, Fe^III = 4.04, O1 = 0.56, and O2 = 0.39, μO = 0.42. For spin state ²RC_hs–hs, Fe^IV–O1 = 1.639, Fe^III–O2 = 1.825, Fe^IV–μO = 1.757, Fe^III–μO1 = 1.866, O1–H1 = 2.575, H1–C1 = 1.097, ∠Fe^IV–O1–H1 = 112°, and ∠O1–H1–C1 = 120° and spin density Fe^IV = –3.04, Fe^III = 3.99, O1 = –0.48, O2 = 0.38, μO = 0.05, and C1 = 0.00. For spin state I-²TS_Hhs–hs, Fe^IV–O1 = 1.752, Fe^III–O2 = 1.835, Fe^IV–μO = 1.805, Fe^III–μO1 = 1.826, O1–H1 = 1.303, H1–C1 = 1.230, ∠Fe^IV–O1–H1 = 157°, and ∠O1–H1–C1 = 170° and spin density Fe^IV = –3.87, Fe^III = 3.97, O1 = 0.02, O2 = 0.38, μO = 0.00, and C1 = 0.39. All bond lengths are given in Å and angles are given in °. All hydrogen atoms (except O2–H, C1–H1, and C2–H2) are omitted for clarity.

Fig. 2. B3LYP-D3 computed energy for the C–H bond hydroxylation of cyclopentane (CP) by species 1 (energies are in kJ mol^–1).

Fig. 3. Electron shift diagrams of I-TS_H for both (a) I-²TS_Hhs–hs, (b) I-¹⁰TS_Hhs–hs, (c) Ia-²TS_rebhs–hs and (d) Ib-²TS_2Hhs–hs with SNOs and their occupation (noted in parentheses).

Fig. 4. (a) Relative thermodynamic free energies between the Fe^IVO unit and its hydroxo complexes (all energies are in kJ mol^–1) and (b) the relationship between the barrier (ΔE^‡), the deformation energy of reactant (ΔE_def) and the interaction energy ΔE_int at the transition state: ΔE_int > 0.

Fig. 5. (a and b) The optimised structure of I-²Int_hs–hs and its corresponding spin density plot. Some important structural parameters computed for the spin states and spin density values are given below for species I-Int. For spin state ²Int1_hs–hs, Fe^III–O1 = 1.854, Fe^III–O2 = 1.835, Fe^III–μO = 1.806, Fe^III–μO1 = 1.825, O1–H1 = 0.981, H1–C1 = 2.012, ∠Fe^III–O1–H1 = 129°, and ∠O1–H1–C1 = 167° and spin density Fe^III = –3.97, Fe^III = 3.96, O1 = –0.25, O2 = 0.38, μO = –0.07, and C1 = 0.93. All the distances are given in Å and angles in °. All hydrogen atoms (except O2–H, C1–H1, and C2–H2) are omitted for clarity.

Fig. 6. Potential energy surface computed (energies are in kJ mol^–1) for C–H activation of cyclopentane by species ²1_hs–hs comparing the lowest estimate of barrier heights obtained from various pathways computed in Scheme 2.

Fig. 7. B3LYP-D3 computed PES for the formation of C₅H₁₁OH/C₅H₁₀ through intermediates leading to desaturation and hydroxylation (energies are in kJ mol^–1).

Fig. 8. (a and b) The optimized structure of Ia-²TS_rebhs–hs and its corresponding spin density plot, (c and d) optimized structure of Ib-²TS_2Hhs–hs and its corresponding spin density plot, (e and f) the optimized structure of Ia-²P_rebhs–hs and its corresponding spin density plot, and (g and h) the optimized structure of Ib-²P_2Hhs–hs and its corresponding spin density plot. Some important structural parameters computed for the spin states and spin density values are given below for species Ia-TS_reb, Ib-TS_2H, Ia-²P_rebhs–hs and Ib-²P_2Hhs–hs. For spin state Ia-²TS_rebhs–hs, Fe^III–O1 = 1.851, Fe^III–O2 = 1.889, Fe^III–μO = 1.852, Fe^III–μO1 = 1.784, O1–H1 = 0.986, O1–C1 = 2.649, ∠Fe^III–O1–C1 = 139°, and ∠H1–O1–C1 = 82° and spin density Fe^III = –3.92, Fe^III = 3.96, O1 = –0.37, O2 = 0.23, μO = 0.21, C1 = 0.85. For spin state Ib-²TS_2Hhs–hs, Fe^III–O1 = 2.111, Fe^III–O2 = 1.940, Fe^III–μO = 1.899, Fe^III–μO1 = 1.770, O2–H2 = 1.336, H2–C2 = 1.291, ∠Fe^III–O1–H1 = 157°, and ∠O1–H1–C1 = 166° and spin density Fe^III = –3.64, Fe^III = 3.94, O1 = –0.02, O2 = 0.14, μO = 0.42, and C2 = –0.02. For spin state Ia-²P_rebhs–hs, Fe^II–O1 = 2.158, Fe^III–O2 = 1.923, Fe^II–μO = 1.876, Fe^III–μO = 1.769, O1–H1 = 1.010, O1–C1 = 1.444, ∠Fe^II–O1–C1 = 101°, and ∠H1–O1–C1 = 110° and spin density Fe^II = –3.66, Fe^III = 3.96, O1 = –0.02, O2 = 0.18, μO = 0.41, and C1 = 0.00. For spin state Ib-²P_2Hhs–hs, Fe^III–O1 = 1.928, Fe^II–O2 = 2.163, Fe^III–μO = 1.769, Fe^II–μO = 1.879, O2–H2 = 0.977, H2–C2 = 3.059, ∠Fe^II–O2–H2 = 114°, and ∠O2–H2–C2 = 147° and spin density Fe^III = 3.95, Fe^II = –3.64, O1 = –0.03, O2 = 0.18, μO = 0.41, and C2 = 0.00. All bond lengths are given in Å and angles are given in °. All hydrogen atoms (except O2–H, C1–H1 and C2–H2) are omitted for clarity.

Fig. 9. Computed orbital diagram corresponding to the (a) LUMO of the ²1_hs–hs and (b) HOMO of the I-²TS_Hhs–hs.

Fig. 10. Structural overlay of ²RC_hs–hs (blue), I-²TS_Hhs–hs (red), II-²TS_Hhs–hs (dark green), and III-²TS_Hhs–hs (magenta) and their corresponding cyclopentane ring (right) shown separately. H atoms are omitted for clarity.

Fig. 11. Valence bond curve crossing diagram for the rebound transition state (²TS_rebhs–hs (a)) and second hydrogen abstraction transition state (²TS_2Hhs–hs (b)) from ²Int_hs–hs. Dots represent valence electrons, and lines implicate chemical bonds.