Oxoiron(IV) Tetramethylcyclam Complexes with Axial Carboxylate Ligands: Effect of Tethering the Carboxylate on Reactivity

Abstract

Oxoiron(IV) species are implicated as reactive intermediates in nonheme monoiron oxygenases, often acting as the agent for hydrogen-atom transfer from substrate. A histidine is the most likely ligand trans to the oxo unit in most enzymes characterized thus far but is replaced by a carboxylate in the case of isopenicillin N synthase. As the effect of a trans carboxylate ligand on the properties of the oxoiron(IV) unit has not been systematically studied, we have synthesized and characterized four oxoiron(IV) complexes supported by the tetramethylcyclam (TMC) macrocycle and having a carboxylate ligand trans to the oxo unit. Two complexes have acetate or propionate axial ligands, while the other two have the carboxylate functionality tethered to the macrocyclic ligand framework by one or two methylene units. Interestingly, these four complexes exhibit substrate oxidation rates that differ by more than 100-fold, despite having E values for the reduction of the Fe═O unit that span a range of only 130 mV. Eyring parameters for 1,4-cyclohexadiene oxidation show that reactivity differences originate from differences in activation enthalpy between complexes with tethered carboxylates and those with untethered carboxylates, in agreement with computational results. As noted previously for the initial subset of four complexes, the logarithms of the oxygen atom transfer rates of 11 complexes of the Fe(O)TMC(X) series increase linearly with the observed E values, reflecting the electrophilicity of the Fe═O unit. In contrast, no correlation with E values is observed for the corresponding hydrogen atom transfer (HAT) reaction rates; instead, the HAT rates increase as the computed triplet-quintet spin state gap narrows, consistent with Shaik's two-state-reactivity model. In fact, the two complexes with untethered carboxylates are among the most reactive HAT agents in this series, demonstrating that the axial ligand can play a key role in tuning the HAT reactivity in a nonheme iron enzyme active site.

Engineering the Oxidative Potency of Non-Heme Iron(IV) Oxo Complexes in Water for C–H Oxidation by a cis Donor and Variation of the Second Coordination Sphere

“…82−84 We note that previous studies (in organic solvents) have found that a decreasing spin-state splitting ΔE Q−T (spanning −6 to +20 kJ/ mol with the B3LYP functional) for a series of 11 [Fe IV O(TMC)(X)] +/2+ complexes correlated with increasing k 2 (and decreasing free energy of activation ΔG*), in line with the two-state-reactivity (TSR) model. 77 We here focus on specific isomers of the iron(IV) oxo complexes of tpenOH/ HtpenO and tpenaH/tpena/Htpena (chosen on the basis of ligand conformations found in crystal structures of the vanadium(IV) oxo complexes and spectroscopic indications). For these complexes, calculations were performed for both S = 1 and S = 2 spin states; we only discuss B3LYP results here, but TPSS was also investigated.…”

Facile and Reversible Formation of Iron(III)–Oxo–Cerium(IV) Adducts from Nonheme Oxoiron(IV) Complexes and Cerium(III)

“…Assuming this comparison to be valid, little or no barrier may be expected for the S =1 Fe IV =O reactant to undergo spin‐crossover as it initiates HAT. We therefore conjecture that, for S =1 Fe IV =O centers, it is not the ability to undergo spin crossover that dictates which spin surface is relevant to its HAT reactivity, but rather the gap between the S =1 ground state and the S =2 excited state, as invoked in the Two‐State Reactivity model of Shaik and recently demonstrated by the correlation of HAT rates with spin state splitting energies for a series of eleven Fe IV =O complexes supported by the tetramethylcylam ligand …”

“…We therefore conjecture that, for S = 1Fe IV =Ocenters,itisnot the ability to undergo spin crossover that dictates which spin surface is relevant to its HATreactivity,but rather the gap between the S = 1g round state and the S = 2e xcited state,a si nvoked in the Tw o-State Reactivity model of Shaik [10] and recently demonstrated by the correlation of HATrates with spin state splitting energies for as eries of eleven Fe IV =Oc omplexes supported by the tetramethylcylam ligand. [26] Experimental Section Experimental Details.C aution!P erchlorate salts of metal complexes are potentially explosive.T hese compounds should be prepared in small quantities and handled with care. [27] See the Supporting Information for experimental details of synthesis and physical methods.…”

Beyond the classical thermodynamic contributions to hydrogen atom abstraction reactivity

“…5, which have essentially the same ΔG 0 , as candidates to test this observation. It is important to note that spin-transition probability of some (X)(TMC)Fe IV O complexes has been suggested to be rate determining for HAA reactions (12,25). While this effect might contribute to C−H activation by metal-oxo complexes, we consider that the thermodynamic bias, as introduced in the factor η, is a straightforward step toward a more general and unified description of the HAA process.…”