Structure/function correlations over binuclear non-heme iron active sites

Abstract

Binuclear non-heme iron enzymes activate O2 to perform diverse chemistries. Three different structural mechanisms of O2 binding to a coupled binuclear iron site have been identified utilizing variable-temperature, variable-field magnetic circular dichroism spectroscopy (VTVH MCD). For the μ-OH-bridged Fe(II)2 site in hemerythrin, O2 binds terminally to a five-coordinate Fe(II) center as hydroperoxide with the proton deriving from the μ-OH bridge and the second electron transferring through the resulting μ-oxo superexchange pathway from the second coordinatively saturated Fe(II) center in a proton-coupled electron transfer process. For carboxylate-only-bridged Fe(II)2 sites, O2 binding as a bridged peroxide requires both Fe(II) centers to be coordinatively unsaturated and has good frontier orbital overlap with the two orthogonal O2 π* orbitals to form peroxo-bridged Fe(III)2 intermediates. Alternatively, carboxylate-only-bridged Fe(II)2 sites with only a single open coordination position on an Fe(II) enable the one-electron formation of Fe(III)-O2 (-) or Fe(III)-NO(-) species. Finally, for the peroxo-bridged Fe(III)2 intermediates, further activation is necessary for their reactivities in one-electron reduction and electrophilic aromatic substitution, and a strategy consistent with existing spectral data is discussed.

Keywords: Binuclear non-heme iron enzymes; Frontier molecular orbitals; O2 activation; Peroxide activation; Variable-temperature, variable-field magnetic circular dichroism.

Fig. 1

a LF splitting of a high-spin Fe(II) d⁶ system with variations in coordination number and geometry. Adapted with permission from [41]. Copyright 2005 Royal Society of Chemistry. b Variable field at low temperature, below 5 K, and c variable-temperature, variable-field MCD spectra of Fe(HB(3,5-iPr₂pz)₃)(S-C₆H₄-4-tBu). Reprinted with permission from [40]. Copyright 1998 American Chemical Society. d Ground-state energy-level diagram of a high-spin Fe(II) d⁶ system with the effects of axial and rhombic zero field, and Zeeman splittings. Left positive ZFS with H perpendicular to z; right negative ZFS with H parallel to z. Adapted with permission from [129]. Copyright 1992 American Chemical Society

Fig. 2

a Temperature-dependent MCD intensity of deoxyHr (top) and its associated J/D diagram (bottom). Adapted with permission from [50]. Copyright 1987 American Chemical Society. b VTVH MCD of T4MOH (top) [51] and its associated J/D diagram (bottom) [50]. Adapted with permission from [50] and [51]. Copyright 2008 and 1987 American Chemical Society

Fig. 3

CD spectra at 5 °C and MCD spectra at 7 T, 5 K (left) and VTVH MCD with fit energy-level diagram in insert (right) of Δ⁹D in the absence (a) and the presence (b) of stearoyl-ACP substrate Adapted with permission from [60]. Copyright 1999 American Chemical Society

Fig. 4

Energy diagram for the binding of O₂ to a biferrous site (a) terminal to Fe(2) as superoxide and (b) cis-μ-1,2-bridged to the two Fe centers as peroxide Reprinted with permission from [64]. Copyright 2005 American Chemical Society

Fig. 5

Orbital interactions for the O₂ reaction of Δ⁹D in the absence (left) and the presence (right) of stearoyl-ACP substrate. The β π* orbitals of O₂ are unoccupied, while the d_π orbitals shown contain the high-spin d⁶ β e^−. Adapted with permission from [60]. Copyright 1999 American Chemical Society

Fig. 6

Reversible O₂ binding to deoxyHr Reprinted with permission from [70]. Copyright 1999 American Chemical Society

Fig. 7

a Electronic absorption spectrum of oxyHr in solution. b Single crystal absorption spectra of oxyHr with parallel (solid) and perpendicular (dashed) polarization. Gaussian deconvolution of the perpendicular absorption (corrected for an oxo CT contribution to the perpendicular polarization due to the Fe–O–Fe angle of 125°) is given as dotted curves. c Single crystal absorption spectra of enH₂[(FeHEDTA)₂]·6H₂O, which has a linear Fe–O–Fe angle, with parallel (solid) and perpendicular (dashed) polarization Adapted with permission from [71, 130] and [70]. Copyright 1978, 1989, and 1999 American Chemical Society

Fig. 8

a oxyHr FMO variations involved in the PCET process induced by the elongation of Fe(1)–(OOH) bond. b Potential energy surface (PES) for the elongation of the Fe–(O₂) bond with the proton on the O₂ (red circles) and with the proton on the oxo bridge (blue squares). c Proton PES as a function of the peroxo-proton distance to the oxo bridge Adapted with permission from [75]. Copyright 1999 American Chemical Society

Fig. 9

rR excitation profiles of the P intermediate in W48F/D84E RNR (top) and the [Fe(III)₂(μ-1,2-O₂)(OBz)₂{HB(pz′)₃}₂] complex, where OBz is benzoate and HB(pz′)₃ is hydrotris(3,5-diisopropyl-1-pyrazolyl)borate Adapted with permission from [82] and [83]. Copyright 1998 and 2004 American Chemical Society

Fig. 10

μ-1,2-peroxo and μ-1,2-hydroperoxo structures for P (left) and P′ (right) and their peroxo-σ-antibonding LUMOs (bottom with relative energies)

Fig. 11

Calculated peroxy reaction coordinates for RNR. a 1-electron reduction of P′ (green) and P (red), b conversion of a μ-1,2-to a μ-1,1-hydroperoxo structure, and c F208 hydroxylation by peroxo (red) and hydroperoxo (green) intermediates