Functional Models for Vanadium Haloperoxidase: Reactivity and Mechanism of Halide Oxidation

A series of oxoperoxovanadium(V) complexes (ligands: 
H3nta = nitrilotriacetic acid,
H3heida = N-(2-hydroxyethyl)iminodiacetic acid, H2ada =
N-(2-amidomethyl)iminodiacetic acid, Hbpg =
N,N-bis(2-pyridylmethyl)glycine, and tpa =
N,N,N-tris(2-pyridylmethyl)amine)
were characterized as functional models for the vanadium
haloperoxidase enzymes. The crystal structures of
K[VO(O2)Hheida],
K[VO(O2)ada],
[VO(O2)bpg], and H[VO(O2)bpg]2(ClO4) were
obtained. These complexes all possess a distorted pentagonal
bipyramidal coordination sphere
containing a side-on bound peroxide. In the presence of sufficient
acid equivalents these complexes catalyze the
two-electron oxidation of bromide or iodide by peroxide.
Halogenation of an organic substrate was demonstrated
by following the visible conversion of Phenol Red to Bromophenol Blue.
In the absence of substrate, dioxygen can
be generated by the halide-assisted disproportionation of hydrogen
peroxide. In addition, some of these complexes
can efficiently catalyze the peroxidative halogenation reaction,
performing multiple turnovers in minutes. The kinetic
analysis of the halide oxidation reaction indicates a mechanism which
is first order in protonated peroxovanadium
complex and halide. The bimolecular rate constants for both
bromide and iodide oxidation were determined, with
the iodide rates being approximately 5−6 times faster than the
bromide rates. The rate constants obtained for
bromide
oxidation range from a maximum of 280 M-1
s-1 for the Hheida complex to a minimum of 21
M-1 s-1 for the
Hbpg
complex. The pKa of activation for each
complex in acetonitrile was determined to range from 5.4 to 6.0.
On the
basis of the chemistry observed for these model compounds, a mechanism
of halide oxidation and a detailed catalytic
cycle are proposed for the vanadium haloperoxidase enzyme.