A highly reactive functional model for catechol 1,2-dioxygenase: reactivity
studies of iron(iii) catecholate complexes of
bis[(2-pyridyl)methyl][(1-methylimidazol-2-yl)methyl]amine
Mark Duda, Matthias Pascaly and Bernt Krebs*
Anorganisch-Chemisches Institut der Westfa¨lischen Wilhelms-Universita¨t, Wilhelm-Klemm-Str. 8, D-48149 Mu¨nster, Germany
The system consisting of an iron(III) salt and bis[(2-pyridyl)-
methyl][(1-methylimidazol-2-yl)methyl]amine (bpia) in
methanol reacts with various catechols with insertion of
dioxygen; in the case of 3,5-di-tert-butylcatechol the efficient
catalytic activity of the system is shown.
with the shorter bond is in the trans position to the much weaker
amine ligand.
All catecholate complexes of Table 1 react with dioxygen to
yield products due to the oxidative cleavage of the catechol
ring.‡ The immediate product appears to be the cis,cis-muconic
anhydride, although only in the case of 3,5-di-tert-butylcatechol
was this cleavage product isolated as 3,5-di-tert-butyl-1-oxa-
cyclohepta-3,5-diene-2,7-dione. With 4-bc, 4-mc, and cat
furanones derived from nucleophilic attack on one carbonyl of
the anhydride, followed by cyclisation, were identified.
The kinetics of the reaction with dioxygen was followed by
monitoring the disappearance of the lower energy charge-
transfer band (Fig. 2). The reactions all exhibit pseudo-first-
order kinetics under conditions where dioxygen is in excess
after complex formation. The pseudo-first-order rate constants
show a dependence on the nature of the substrate. The rates of
the reactions increase in the order tcc << cat < 4-bc ≈ 4-mc <
dbc (Table 1). While [Fe(bpia)(tcc)]+ is rather stable against
dioxygen attack, the reaction rate of the [Fe(bpia)(dbc)]+
complex with O2 is rather high. This order of activity correlates
with the energy of the lower energy LMCT band of the
complexes: electron-donating substituents on the catechol result
in a higher dioxygenase reactivity.
Intradiol dioxygenases are non-haem iron enzymes and take
part in biological mechanisms for metabolising aromatic
compounds.1 The enzymes catalyse the intradiol cleavage of
catechols to cis,cis-muconic acids. Spectroscopic investigations
indicate that the active site iron remains in the iron(iii) oxidation
state during the whole catalytic cycle. A variety of studies have
tried to understand the mechanism in its enzymatic and model
chemistry aspects and a number of functional models have been
synthesised with various ligand systems.2–4 Especially tetra-
dentate ligands (L) have shown a great ability to influence the
physical properties of the metal complexes and therefore the
dioxygenase activity as the ligand sets are varied. Que and
coworkers have found a correlation between the Lewis acidity
of the iron centre in a series of iron(iii) complexes of tripodal
ligands, the product yield, and the reactivity.2 According to
these investigations a substrate activation rather than oxygen
activation mechanism has been proposed. In this mechanism the
substrate loses both of its protons upon coordination to the iron
centre followed by partial oxidation of the catecholate due to
ligand-to-metal charge transfer, resulting in a substrate with
semiquinone character. The attack of O2 on the activated
substrate yields a transient alkylperoxy radical which combines
with the equally short-lived iron(ii) centre to generate an
alkylperoxoiron(iii) species. The peroxy adduct decomposes by
a Criegee-type rearrangement to muconic anhydride. In most
cases 3,5-di-tert-butylcatechol (dbc) has been used as a
substrate in functional investigations, but little work has been
devoted to the oxygenation of other catechols.3
Accordingly the reactivity grows with increasing Lewis
acidity of the iron centre within the series of [Fe(bpia)(catechol-
Table 1 Properties of the [Fe(bpia)(catecholate)]+ complexes
Catechol
lmax/nm
ka/dm3 mol21 s21
dbc
4-mc
4-bc
cat
558, 865
515, 842
519, 836
510, 800
528, 729
4.3
2.6
2.3
0.083
> 1025
tcc
We have prepared iron(iii) catecholate complexes in situ
under an argon atmosphere with bis[(2-pyridyl)methyl][(1-
methylimidazol-2-yl)methyl]amine (bpia)5 as a tetradentate
ligand and a series of catechols (dbc, 4-mc, 4-bc, cat, tcc).†
Their UV–VIS spectra in methanol solution are dominated by
two moderately intense absorption bands. These bands are
assigned as catcholate-to-FeIII charge-transfer transitions sim-
ilar to those observed in the spectra of other iron catecholate
complexes with tripodal ligands,6 suggesting that a complex of
the form [Fe(bpia)(catecholate)]+ has been prepared. The
positions of the lower energy band are dependent on the nature
of the catecholate, with the LMCT bands observed to shift to
lower energies by varying the substituents on the catecholate
from electron-withdrawing to -donating (Table 1). The com-
plexes have been isolated, and with tetrachlorocatecholate (tcc)
as substrate we have obtained crystals to solve the structure of
[Fe(bpia)(tcc)]ClO4.7 The crystal structure exhibits an asym-
metrical chelated tetrachlorocatecholate ligand (Fig. 1). The
Fe–O bond trans to the aliphatic N [Fe–O(1) 1.919(3) Å] is
about 0.03 Å shorter than the corresponding bond trans to the
heterocyclic N [Fe–O(2) 1.948(3) Å]. The difference in bond
lengths is due to a trans effect where the catecholate oxygen
a Reactions run in methanol under air, 25 °C, c = 5 3 1024 mol dm23, 2
equiv. of piperidine as base, k = kobs/[O2].
C(5)
C(4)
C(6)
C(16)
C(3)
C(15)
C(17)
C(2)
N(4)
N(5)
N(2)
C(14)
Cl(4)
O(1)
C(1)
C(13)
C(18)
N(1)
Fe
C(23)
C(22)
C(7)
C(8)
N(3)
O(2)
C(19)
Cl(3)
Cl(2)
C(9)
C(20)
C(21)
C(12)
C(10)
Cl(1)
C(11)
Fig. 1 Structure of [Fe(bpia(tcc)]+
Chem. Commun., 1997
835
Duda, Mark
