CYTOCHROME c OX IDASE 443
spectroscopy and density functional theory.^153 Figure 2 of reference 153 illus-
trates a consensus O 2 reduction mechanism involving heme a 3 and Cu B. The
scheme involves the Cu B histidine ligand and its covalently attached tyrosine
side chain whose hydroxyl group successively becomes a radical (statePM ) and
is protonated (stateF ), deprotonated (state O ), and then protonated (states
R and A ) as the cycle resumes. Proton pumping (from matrix to the cytosol)
occurs in transitions from statesPM to F, F to O , and O to R. State A has also
been formulated as an FeIII−O− 2 (superoxo) intermediate.^154 (See Figures 7.40
and 7.42 .)
In CcO enzyme X - ray crystallographic structures, the heme a 3 – Cu B centers
are separated by 4.4 – 5.3 Å , depending on the protein derivative and its oxida-
tion state. This distance would preclude strong antiferromagnetic coupling
between the high - spin iron and copper ion centers. However, structures that
include a peroxide bridge (PDB: 2OCC and the model compounds being dis-
cussed here and others) do report strong antiferromagnetic coupling between
the two metal centers. One model compound containing a peroxo bridge has
had its crystal structure determined.^155 The binuclear heme a 3 – Cu B peroxo -
bridged center of a tethered [( ) III−−( 22 −+) II( 5 )] TMP Fe shows a O Cu MeTPA
μη η-FeOCu^12 :()III−−^22 − II coordination mode. The all - in - one ligand TMP -
5MeTMPA (TMP - 5MeTMPA = 6 - {[ bis - (5 - methylpyridin - 2 - ylmethyl)amino]methyl} - N -
{2 - [ tris (2,4,6 - trimethylphenyl)porphyrinate]phenyl}nicotinamide) forms the
tethered complex with the iron and copper ions. The peroxo anion is bound
end - on to the copper ion ( η^1 ) and side - on to the high - spin iron ion ( η^2 ). The
high - spin heme a 3 Fe III center sits 0.534 Å above the plane formed by the por-
phyrinate nitrogen ligands. (See Figure 7.46 .)
In reference 153 , for the untethered complex [( 82 ) III−−(^2 −) F TPP FeII O Cu
()]TMPA+, the authors use density functional theory (DFT) to involve the
peroxo ligand in the observed metal center antiferromagnetic coupling —
for theSTOT = 2 system, − J > 200 cm − 1. The spin - unrestricted DFT calculations
for theSTOT = 2 spin state, performed on a [( ) III−−( 22 −) II( )] PFe+ O Cu TMPA
model, P = porphyrinate, indicate that the peroxide π σ orbital donates
electron density into the half - occupied dz^2 Cu II orbital forming an η^1 bond.
For the Fe III ion – peroxide η^2 bond, there are two major interaction compo-
nents: (1) The peroxide π σ orbital donates electron density into the dxz Fe III
Figure 7.45 Electron confi gurations for high - spin Cu(II), d^9 , and Fe(III), d^5.CuII d^9 FeIII d^5