The systematic influence of tripodal ligands on the catechol cleaving activity of iron(III) containing model compounds for catechol 1,2-dioxygenases

Article abstract of DOI:10.1039/b008511l

A series of mononuclear iron(III) complexes as functional and structural model compounds for intradiol cleaving catechol dioxygenases were synthesized. For all model compounds the iron(III) cores are in a distorted octahedral environment derived from tripodal tetradentate N₄-donor ligands and a catechol. Model complexes for enzyme-substrate adducts were characterized by spectroscopic and electrochemical methods, and in four cases by single-crystal X-ray crystallography. The systematic variation of one ligand arm in the structurally characterized complexes yields a different steric shielding of the iron(III) center, significantly influencing the bonding of the catechol substrate and the subsequent reaction with dioxygen. The spectroscopic features and catechol cleaving activities of in situ generated complexes with the above ligands were probed. All complexes are highly reactive towards intradiol cleavage of various catechols in the presence of air. The catechol 1,2-dioxygenase reaction depends on the redox potential of both the iron(III) complex and the catechol derivative as well as the steric demand of the tripodal ligand. Some complexes show high catalytic activities with yields up to 84% with respect to aerial cleavage of catechols. The Royal Society of Chemistry 2001.

Full text of DOI:10.1039/b008511l

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The systematic influence of tripodal ligands on the catechol
cleaving activity of iron(III) containing model compounds for
catechol 1,2-dioxygenases†
Matthias Pascaly, Mark Duda, Florian Schweppe, Kristin Zurlinden, Felizitas K. Müller and
Bernt Krebs*
Anorganisch-Chemisches Institut der Westfälischen Wilhelms-Universität Münster,
Wilhelm-Klemm-Straße 8, D-48149 Münster, Germany. Fax: (ϩ49) 251-833 8366;
E-mail: krebs@uni-muenster.de
Received 23rd October 2000, Accepted 25th January 2001
First published as an Advance Article on the web 26th February 2001
A series of mononuclear iron() complexes as functional and structural model compounds for intradiol cleaving
catechol dioxygenases were synthesized. For all model compounds the iron() cores are in a distorted octahedral
environment derived from tripodal tetradentate N4-donor ligands and a catechol. Model complexes for enzyme–
substrate adducts were characterized by spectroscopic and electrochemical methods, and in four cases by single-
crystal X-ray crystallography. The systematic variation of one ligand arm in the structurally characterized complexes
yields a different steric shielding of the iron() center, significantly influencing the bonding of the catechol substrate
and the subsequent reaction with dioxygen. The spectroscopic features and catechol cleaving activities of in situ
generated complexes with the above ligands were probed. All complexes are highly reactive towards intradiol cleavage
of various catechols in the presence of air. The catechol 1,2-dioxygenase reaction depends on the redox potential of
both the iron() complex and the catechol derivative as well as the steric demand of the tripodal ligand. Some
complexes show high catalytic activities with yields up to 84% with respect to aerial cleavage of catechols.
electron accepting character of the iron() core. An increased
Introduction
semiquinone character of the intermediate leads to a more
Catechol dioxygenases are mononuclear non-heme iron
favorable attack of dioxygen at the enzyme–substrate complex.
enzymes that can be isolated from bacteria.1 These enzymes
have attracted considerable attention due to their key role in the
In the next step oxygen binds end-on to the semiquinone and,
upon ring closure, an iron()–peroxo species is formed. In a
metabolism of aromatic compounds. The catalytic cleavage of
Criegee-type rearrangement the peroxo adduct yields deriv-
catechols yields aliphatic products by insertion of both atoms
atives of muconic acid anhydride.1,6 This mechanism describes
of dioxygen into the aromatic ring.1–3 Traditionally, catechol
dioxygenases are subdivided into intradiol and extradiol
a substrate activation due to electron transfer from the
catecholate to iron().6,7 Very recent quantum chemical calcu-
cleaving enzymes according to their catalysis of the ring cleav-
lations support the initial binding of molecular oxygen to the
age between or outside the two ortho-hydroxo groups (Fig. 1).4
iron center forming an epoxide-like structure upon oxygen
The intradiol cleaving enzymes (catechol 1,2-dioxygenases)
contain iron() in their active site whereas extradiol cleaving
insertion into the C–C bond.8
In previous studies several functional models have been syn-
thesized in order to gain insight into the mechanism of catechol
dioxygenases (catechol 2,3-dioxygenases) possess an iron()
center.5
In the first step of the proposed mechanism (Fig. 2) of
catechol 1,2-dioxygenases the substrate binds to the metal site.
An equilibrium is suggested between an iron() catecholate
complex and an iron() semiquinone tautomer due to the
Fig. 1 Modes of catechol cleavage catalyzed by catechol 1,2-dioxygen-
ases (intradiol cleavage) and catechol 2,3-dioxygenases (extradiol
cleavage).
† This paper is dedicated to Professor Dieter Sellmann on the occasion
of his 60th birthday.
Fig. 2 Proposed substrate activation mechanism of catechol 1,2-
dioxygenases.
828
J. Chem. Soc., Dalton Trans., 2001, 828–837
This journal is © The Royal Society of Chemistry 2001
DOI: 10.1039/b008511l

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Fig. 3 Structures of the tripodal tetradentate ligands and catechol derivatives used in this work.
cleavage.9–12 Especially tetradentate tripodal ligands have shown
Results and discussion
considerable abilities to regulate the properties of model
complexes,6,9,13–16 indicating that the dioxygenase activity
strongly depends on the nature of the ligand set. With such
tripodal ligands distorted coordination spheres are formed
similar to the steric situation in the metalloproteins. Two cis
coordination sites, essential for substrate binding, remain
unoccupied. Model compounds synthesized by Que and Pal-
aniandavar and co-workers consist of tripodal ligands with
pyridine, carboxylate, benzimidazole, or phenolate moieties and
3,5-di-tert-butylcatechol (H2dbc) as substrate analogue.6,9,16
The advantages of this substrate are the relatively high stability
of the main cleavage product (3,5-di-tert-butyl-1-oxacyclo-
hepta-3,5-diene-2,7-dione) and the fast reaction of the
catecholate complexes with dioxygen.6,9,17,18 Little work has
been devoted to the oxygenation of other catechols and their
structural modeling.19,20
There are only a few reports on structural and functional
model complexes for catechol 1,2-dioxygenase enzyme–
substrate complexes.6,9,10,12,19,21 These iron() catecholate com-
plexes are of considerable interest as such species are formed in
the first step of the reaction mechanism (Fig. 2).
Here we describe the first model compounds for catechol 1,2-
dioxygenases with the inhibitor substrate tetrachlorocatechol
(H2tcc; yielding air stable complexes) and various tripodal
ligands (Fig. 3) that exclusively provide nitrogen donors.
In this series of tripodal ligands one donor moiety was changed
systematically. The steric and electronic influence of the
nitrogen-donor ligand set and of various catechols (Fig. 3) on
the biomimetic and catalytic catechol 1,2-dioxygenase activity
is probed with spectroscopic and functional investigations on
in situ prepared iron() complexes.
Syntheses
The synthesized ligands are derivatives of the exclusively
pyridine containing tripodal ligand tpa (tris[(2-pyridyl)methyl]-
amine). They selectively leave two cis oriented coordination
sites at the iron() center unoccupied. A systematic ligand
variation (Fig. 3) of one donor arm was achieved with
methylimidazole (bpia: [(1-methylimidazol-2-yl)methyl]bis-
[(2-pyridyl)methyl]amine), benzimidazole (bpba: [(benzimid-
azol-2-yl)methyl]bis[(2-pyridyl)methyl]amine), quinoline (bpqa:
bis[(2-pyridyl)methyl][(2-quinolyl)methyl]amine), and methyl-
pyridine (me1tpa: [(6-methyl-2-pyridyl)methyl]bis[(2-pyridyl)-
methyl]amine). For reactivity studies complexes of the ligand
bipa
(bis[(1-methylimidazol-2-yl)methyl][(2-pyridyl)methyl]-
amine) were also synthesized (Fig. 3). In this ligand one
pyridine and two methylimidazole moieties are attached to the
central tertiary amine. All ligands synthesized provide N4-
donor sets. Such donor groups mimic the metal coordinating
side chains of amino acids (histidine) in many enzymes.
The tripodal ligands bpia, me1tpa, bpqa and bipa were
prepared by slightly modified procedures described in the
literature.13,22–24 The novel benzimidazole containing ligand
bpba was prepared via [(2-benzimidazolyl)methyl]amine and
subsequent reaction with two equivalents of 2-pyridylmethyl
chloride hydrochloride. The novel iron() catecholate com-
plexes [Fe(bpia)(tcc)]ClO4 1, [Fe(bpba)(tcc)]ClO4ؒ(CH3)2CO 2,
[Fe(bpqa)(tcc)]ClO4ؒCH3CH2OH 3, and [Fe(me1tpa)(tcc)]NO3
4 were synthesized and crystallized by similar synthetic routes
from iron() perchlorate and nitrate, respectively, and the
corresponding tetradentate ligand. Upon addition of tetra-
chlorocatechol and treatment with two equivalents of piper-
J. Chem. Soc., Dalton Trans., 2001, 828–837
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Table 1 Selected bond lengths [Å] and angles [Њ] in complexes 1–4
1
2
3
4
Fe(1)–O(1)
Fe(1)–O(2)
Fe(1)–N(1)
Fe(1)–N(2)
Fe(1)–N(3)
Fe(1)–N(4)
O(1)–C
1.948(3)
1.919(3)
2.120(4)
2.246(4)
2.126(4)
2.081(4)
1.333(5)
1.330(5)
1.9612(17)
1.8970(18)
2.117(2)
2.208(2)
2.139(2)
2.083(2)
1.325(3)
1.334(3)
1.950(5)
1.911(6)
2.190(6)
2.160(6)
2.128(5)
2.153(6)
1.371(8)
1.326(8)
1.938(5)
1.917(7)
2.146(6)
2.180(7)
2.132(6)
2.171(7)
1.304(9)
1.340(9)
O(2)–C
O(1)–Fe(1)–O(2)
O(1)–Fe(1)–N(1)
O(1)–Fe(1)–N(2)
O(1)–Fe(1)–N(3)
O(1)–Fe(1)–N(4)
O(2)–Fe(1)–N(1)
O(2)–Fe(1)–N(2)
O(2)–Fe(1)–N(3)
O(2)–Fe(1)–N(4)
N(1)–Fe(1)–N(2)
N(1)–Fe(1)–N(3)
N(1)–Fe(1)–N(4)
N(2)–Fe(1)–N(3)
N(2)–Fe(1)–N(4)
N(3)–Fe(1)–N(4)
84.7(1)
89.8(1)
102.5(1)
93.3(1)
176.0(1)
104.8(2)
172.8(1)
102.8(2)
92.8(1)
76.2(2)
152.4(2)
87.9(1)
76.3(1)
80.2(1)
90.2(1)
85.19(8)
92.81(8)
92.92(8)
91.02(8)
173.42(7)
99.62(8)
176.04(7)
106.47(8)
101.15(8)
76.97(8)
153.86(8)
87.89(8)
77.01(8)
80.86(8)
85.52(8)
85.1(2)
91.8(2)
98.4(2)
177.0(2)
92.6(2)
98.2(2)
173.3(2)
95.3(2)
106.8(3)
76.0(2)
91.1(2)
154.9(2)
81.5(2)
78.9(3)
84.4(2)
83.9(2)
95.0(2)
106.4(2)
171.3(3)
91.2(2)
94.4(3)
166.6(2)
89.8(2)
111.7(3)
76.4(3)
91.6(2)
153.7(3)
80.8(2)
77.4(3)
85.4(2)
Fig. 4 Structure of the complex cation in [Fe(bpia)(tcc)]ClO4 1 with
thermal ellipsoids (50% probability); hydrogen atoms omitted for
clarity.
Fig. 5 Structure of the complex cation in [Fe(bpba)(tcc)]ClO4ؒ(CH3)2-
CO 2. Details as in Fig. 4.
Fig. 7 Structure of the complex cation in [Fe(me1tpa)(tcc)]NO3 4.
Details as in Fig. 4.
Crystal structures of complexes 1–4
The structure analyses of the four complexes show very similar
features. The iron() cores are in distorted octahedral coordin-
ation spheres involving the N4O2-donor sets of the ligands and
tetrachlorocatecholate.
The Fe–N bond lengths to the aromatic heterocycles pyrid-
ine, imidazole, and quinoline (Fe(1)–N(1)/N(3)/N(4)) are
smaller than to the tertiary amine donors (Fe(1)–N(2)) due
to their different π-donating properties. As a result of
the extended π-molecular orbitals and electrostatic effects the
coordinated catecholate units form the shortest bond lengths
(Fe(1)–O(1)/O(2)). The trans effect of the weakly bound tertiary
amine nitrogen donor causes slightly decreased bond lengths of
the oxygen donors in trans position (O(2)). However, the very
small differences in the C–O (∆max = 0.045 Å) and Fe–O
(∆max = 0.064 Å) bond lengths within each complex clearly indi-
cate that the ligand coordinates with its two phenolate donors
(tetrachlorocatecholate) rather than with a phenolate and a
quinone donor (tetrachlorosemiquinone). The slightly differ-
ing Fe–O bond lengths are caused by the asymmetry of the
[Fe(L)]3ϩ complex. The use of complexes with a higher sym-
metry will lead to identical Fe–O bond lengths (Table 2).12 This
is also supported by the more or less equal C–C lengths within
Fig. 6 Structure of the complex cation in [Fe(bpqa)(tcc)]ClO4ؒCH3-
CH2OH 3. Details as in Fig. 4.
idine the complex solutions change from yellow-red to dark
purple due to the formation of catecholate to iron() charge
transfer transitions between 500 and 1000 nm. Single crystals
suitable for X-ray crystallography were obtained upon slow
cooling and standing of the reaction mixtures. The structures
of the complex cations in 1–4 are shown as ellipsoid plots
in Figs. 4–7. Table 1 gives a comparison of selected bond
lengths and angles for the four structures. In Table 2 a com-
parison of selected bond lengths and angles for the determined
structures and other well documented six-coordinate iron()
catecholate complexes with N4-donor ligands is listed.
830
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Table 2 Comparison of selected structural and spectroscopic data
Fe–O/Å
O(2)–Fe(1)–N(4)/Њ
λ/nm (ε/MϪ1 cmϪ1
)
E1/2 a/mV
ϩ345
References
[Fe(bpia)(tcc)]ClO4 1
1.948(3)
1.919(3)
1.961(2)
1.897(2)
1.950(5)
1.911(6)
1.938(5)
1.917(7)
—
1.917(3)
1.898(2)
1.915(3)
1.903(3)
1.914(2)
1.914(4)
92.8
101.2
106.8
111.7
—
529 (2080), 729 (3100)
532 (1817), 678 (2041)
590 (1989)
This work
This work
This work
This work
[Fe(bpba)(tcc)]ClO4ؒ(CH3)2CO 2
[Fe(bpqa)(tcc)]ClO4ؒCH3CH2OH 3
[Fe(me1tpa)(tcc)]NO3 4
ϩ425
ϩ466
ϩ464
577 (2746), 743 (3199)
[Fe(bipa)]3ϩ
[Fe(tpa)(dbc)]BPh4ؒCH3CN
—
568, 883
ϩ315
—
This work
9
—
[Fe(N4Me2)(cat)]BPh4
501, 734
—
—
10
12
—
[Fe(bispicme2en)(dbc)]BPh4
550 (1250), 925 (1850)
—
Abbreviations: bispicme2en = N,NЈ-dimethyl-N,NЈ-bis(2-pyridylmethyl)ethane-1,2-diamine; H2cat = pyrocatechol; N4Me2 = N,NЈ-dimethyl-2,11-
diaza[3.3](2,6)-pyridinophane. a Values reported for the in situ prepared [Fe(L)Cl2]ϩ complexes.
Fig. 8 The influence of the third ligand arm on the angle O(2)–Fe(1)–N(4) displaying the shielding of the iron center.
the tetrachlorocatecholate ligands of 1 – 4 which are consistent
with an aromatic ring system with delocalized π bonds. For
semiquinone species more pronounced differences in C–C bond
lengths would be expected.25 The semiquinone radical species
are essential for a reaction with dioxygen.
Owing to the limiting bite of the ligands the cis angles (N(2)–
Fe(1)–N(1)/N(3)/N(4)) are small. This is a typical structural
feature in complexes of tripodal tetradentate ligands.
In compounds 2 and 3 the counter ions are stabilized by
hydrogen bonds from the NH function of the benzimidazole
group and of the OH group of one ethanol solvate molecule,
respectively.
All four complexes described above differ mainly in the aro-
matic donor set of one ligand arm. The influence of this ligand
arm can be described by the angle O(2)–Fe(1)–N(4) as depicted
in Fig. 8 and Table 2. This angle correlates with an increasing
steric demand of the ligand residue. Accordingly, the largest
value was determined for complex 4 with the ligand me1tpa,
caused by one methyl substituent.
observed due to coordination of the ligands to the iron() ion.
Bands at high wavenumbers are found due to incorporation of
solvent into the crystal.
The cyclic voltammograms of complexes 1–4 are rather com-
plicated. Both the iron center and the catecholate ligand are
redox active. The redox chemistry at the iron center is affected
by the instability of the electrochemically produced iron()
semiquinone species.6,9 Such species disintegrate yielding
iron() complexes and quinone when working with Lewis acidic
iron cores, resulting in irreversible and ill defined redox
features.6,9 On the basis of these cyclic voltammograms a com-
plete assignment of redox processes was not possible. There-
fore, in situ prepared iron chloro complexes and the catechols
were examined separately electrochemically.
In order to determine the spin-state properties of the metal
ions we performed temperature-dependent magnetic suscepti-
bility measurements on powdered samples of 1–4. All four
complexes show the expected paramagnetic behavior of mono-
nuclear high-spin iron(). They follow the Curie–Weiss law
(χm = C/(T Ϫ θ)) in the temperature range 40–300 K. The mag-
netic moments for 1, 3 and 4 were measured to be 5.7, 6.0 and
6.0µB indicative for high-spin iron() ions with S = 5/2
(expected spin only moment µeff = 5.9µB).26 Usually values in the
range of 5.7–6.2µB are found.26 For 2 a very low moment
of 4.8µB was measured. This value is obviously not indicative
of a high-spin S = 5/2 center but is also really too high to be
considered as a pure S = 3/2 intermediate spin or S = 1/2
low-spin system. So far there are no hints of a quantum
mechanical mixing of two states that can occur to create a new,
discrete spin-admixed ground state that has elements of two
spin states.26,27 The system is under further spectroscopic
investigation.
Spectroscopic characterization of complexes 1–4
The different Lewis acidities of the iron() center, influenced
by the tripodal ligands, are reflected in the position of the two
tetrachlorocatecholate to iron() charge transfer bands
(located in the visible region of the spectra at around 500–1000
nm; Table 2).6,9 With increasing Lewis acidic character the
higher energy absorption bands are shifted to lower energies
(i.e. higher wavelengths) in the order 1 < 2 < 4. For complex 3
there was found to be only one broad CT absorption band at
590 nm. The reason for this, i.e. veiling of one band by other
more intense bands, merging of the two bands, or a different
binding mode of tcc in solution, remains unclear. Therefore, the
iron core in 4 shows the highest electron accepting character.
More strongly electron donating catechols (e.g. in [Fe(tpa)-
(dbc)]BPh4 or [Fe(N4Me2)(cat)]ClO4) yield complexes with
UV/Vis bands at higher wavelengths (Table 2).
Investigation of the in situ prepared iron complexes
The iron() complexes with general formula [Fe(L)]3ϩ (L =
tripodal ligand) were prepared from iron() perchlorate and
studied in solution using UV/Vis spectroscopy. Ligand metal-
lation (bpia; Fig. 9) is accompanied by distinct spectral changes
Typical bands of the ligands are found in the vibrational
spectra of the complexes. A characteristic shift of CN bands is
J. Chem. Soc., Dalton Trans., 2001, 828–837
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Table 3 Redox potentials of the catechols (Fig. 3) and the UV/Vis spectroscopic and kinetic data of the [Fe(bpba)(catecholate)]ϩ complexes for the
reaction with air (T = 298 K)
E1/2/mV
(H2cat–Q)
EC/mV
Catechol
(Hϩcat–¹H2)
λ/nm (ε/MϪ1 cmϪ1
)
k/MϪ1 sϪ1
¯
²
H2dbc
H2moc
H2bc
H2mc
H2cat
H2tcc
Ϫ222
Ϫ885
Ϫ973
Ϫ912
Ϫ927
Ϫ922
Ϫ855
569 (1443), 877 (2095)
656, sh (1471), 827 (1653)
525 (1345), 824 (1836)
520 (1283), 835 (1862)
503 (1201), 785 (1665)
532 (1817), 678 (2041)
2.9
2.4
Ϫ152
Ϫ142
Ϫ123
Ϫ46
0.76
0.91
0.031
ϩ312
<10Ϫ5
Abbreviations: H2bc = 4-tert-butylcatechol; H2mc = 4-methylcatechol; H2moc = 3-methoxycatechol.
the in situ prepared complexes are identical. It can therefore be
excluded that simple iron() catecholate complexes are formed
upon demetallation of the tripodal ligand.
Unambiguous assignment of redox features was not possible
in the cyclic voltammograms of the crystallized iron()–tcc
complexes 1–4. Thus, the electrochemical features of the in situ
formed iron() chloro complexes of type [Fe(L)Cl2]ϩ using
iron() chloride were investigated with cyclic voltammetry. All
of the complexes exhibit at positive potentials a coupled pair
of redox waves that are assigned to the iron()–iron() couple
(Table 2). The cyclic voltammograms of structurally character-
ized iron() chloro complexes show similar features.13,14,16
The order of the complex series [Fe(bpia)]3ϩ < [Fe(bpba)]3ϩ
< [Fe(me1tpa)]3ϩ < [Fe(bpqa)]3ϩ indicates increasing Fe3ϩ–Fe2ϩ
redox potential of the complexes caused by the electron accept-
ing character of the tripodal ligand. The high redox potentials
of the me1tpa and bpqa complexes are the result of the
extended aromatic systems of one donor moiety. For com-
parison purposes we also investigated the electrochemical prop-
erties of the catechol derivatives. The cyclic voltammograms of
the six catechols exhibit one reduction peak between Ϫ850
and Ϫ980 mV with no observable anodic peak coupled to it
(Table 3). This feature can be associated with the reduction of
catechol protons.28 At higher voltages (Ϫ370 to 350 mV) all
catechols show an additional cathodic as well as an anodic wave
(Table 3). These peaks correspond to a two-electron process of
the couple H2cat–Q (Q = quinone).28,29 In the series H2dbc,
H2moc, H2bc, H2mc, H2cat, and H2tcc the redox potentials
increase due to the decreasing electron donating potential of
the catechol substituents and the resulting decrease in Lewis
basicity of the catechols. The redox potentials of the various
substrates are listed in Table 3.
Fig. 9 Titration of bpia (c = 0.1 mmol LϪ1) with 0.2 equivalent
portions of Fe(ClO4)3ؒ9H2O solution in methanol at 295 K followed by
UV/Vis spectroscopy. Inset: plot of absorbance vs. c(FeIII)/c(bpia) at 261
nm.
Fig. 10 Titration of [Fe(bpia)]3ϩ (c = 0.25 mmol LϪ1) and piperidine
(c = 0.5 mmol LϪ1
)
with 0.2 equivalent portions of tetrachloro-
Catechol cleavage of iron(III) complexes
catecholate monohydrate solution in methanol at 295 K followed
by UV/Vis spectroscopy. Inset: plot of absorbance vs. c(tcc)/c(FeIII) at
734 nm.
After the characterization of the in situ prepared complexes
their catechol 1,2-dioxygenase activity was examined. This
reactivity and the positions of the two ligand-to-metal charge
transfer bands which are formed upon addition of catechol to a
solution of [Fe(L)]3ϩ strongly depend on the amount of base
added for deprotonation of the catechol. The fastest reactions
take place when approximately 2.0 to 2.5 equivalents of base
(piperidine) are added and the UV/Vis bands are shifted to a
minimum of energy. At higher concentrations of base the reac-
tion rates decrease and a shift to lower wavelengths is observed
due to competitive coordination of base to the iron center. Our
experiments were carried out for each complex at the highest
possible reaction rate (details are given in the Experimental
section; Table 7). For comparable kinetic results the exact
amount of base was determined before each reaction.
of the ligand bands with an isosbestic point at 274 nm in the
ratio range of 0 : 1 to 1 : 1. The isosbestic point disappears at
higher amounts of iron(). This implies that the tripodal
ligands exclusively coordinate a single iron() ion. In a similar
manner, the [Fe(L)]3ϩ complexes (L = tripodal ligand) were
titrated with catecholate (tcc). The original spectrum of the
[Fe(bpia)]3ϩ complex (Fig. 10) changes dramatically upon
addition of tcc due to the formation of two ligand to metal
charge transfer bands in the visible region. The intensities of
the charge transfer bands increase with increasing catecholate
to complex ratio. These spectral changes were observed until
the ratio of concentration of the ligand and Fe3ϩ was 1 : 1
(inset Fig. 10). At higher catechol concentrations the spectra
remained essentially unchanged. These experiments underscore
the assumption that the in situ complex syntheses exclusively
yield mononuclear catecholate species with general formula
[Fe(L)(cat)]ϩ (L = tripodal ligand; cat = catecholate). The
UV/Vis spectra of the structurally characterized complexes and
As an example, the progress of the reaction of the bpba
complex with dbc and dioxygen is shown in Fig. 11. The inset
displays the logarithm of the absorbance versus time. Upon
addition of catechol the reaction solution changes from red
to dark purple as a result of catechol binding (the resulting
bands in the spectrum can be assigned to moderately intense
832
J. Chem. Soc., Dalton Trans., 2001, 828–837

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Table 4 UV/Vis spectroscopic and kinetic data of [Fe(L)]3ϩ complexes
for the reaction with the substrate H2moc in the presence of air
(T = 298 K)
k/MϪ1 sϪ1
(∆max=15%)
Complex
λ/nm (ε/MϪ1 cmϪ1
)
[Fe(bpia)(moc)]ϩ
[Fe(bpba)(moc)]ϩ
[Fe(bipa)(moc)]ϩ
[Fe(me1tpa)(moc)]ϩ
[Fe(bpqa)(moc)]ϩ
644, sh (1490), 818 (1745)
656, sh (1471), 827 (1653)
627, sh (1792), 797 (2113)
681, sh (1571), 866 (1686)
688, sh (1902), 869 (2052)
5.3
2.4
0.47
0.093
0.017
Fig. 12 Top: correlation of LMCT energies and redox potential of
the catechol. Bottom: relation between the reaction rate constant (k)
and the redox potential of the catechol. Both series were recorded for
complexes of general formula [Fe(bpba)(catecholate)]ϩ.
On the other hand, the variation of the tripodal ligand in the
[Fe(L)]3ϩ complexes during the dioxygenation reaction shows a
more complicated behavior. The spectroscopic investigation of
the complexes suggests an order of reactivity according to the
Lewis acidity of the iron center (Table 2). Instead, the complex
reactivity decreases in the series bpia > bpba > bipa > me1tpa
> bpqa. Small reaction rate constants are observed for iron
complexes with a high redox potential and with CT bands at
low energies. The rate constant of the iron complexes
[Fe(L)]3ϩ for the reaction with one chosen substrate (H2moc;
Table 4) drops by two orders of magnitude from 5.3 (bpia) to
0.017 (bpqa). This is a result of the different steric requirements
of the ligand moieties. A very reactive complex always contains
a sterically low demanding ligand. Under such conditions the
iron ion is easily accessible to both the catechol and oxygen.
The values of the O(2)–Fe(1)–N(4) angles determined by
structure analyses explain this finding. The complex with the
relatively small ligand bpia has a smaller angle and, accord-
ingly, the highest reactivity. On the other hand, larger substitu-
ents attached to the tertiary amine (e.g. in me1tpa or bpqa) yield
slowly reacting complexes due to the interference of the ligand
substituents with the substrate and oxidant (large O(2)–Fe(1)–
N(4) angle). Nevertheless, the Lewis acidity of the iron center in
the me1tpa complex is high; bipa is the smallest ligand but the
Lewis acidity of the iron() core is comparably low due to the
ligand’s two imidazole residues.
These results support the mechanism of Que and co-workers
proposing a substrate activation.1,3,4,6–9 With a lower electron
accepting character (lower redox potential) of the complex and
a lower electron donating character (higher redox potential) of
the substrate, respectively, the semiquinone character of the
catechol is decreased. Under these circumstances the attack of
dioxygen is disfavored. On the other hand, an electron rich
catechol with a low redox potential leads to more contribution
of the FeII–semiquinone species and, thus, to faster reaction
rates. A highly reactive catechol 1,2-dioxygenase modeling sys-
tem always consists of an electron accepting iron() complex
and of an electron donating catechol.
Fig. 11 Progress of the reaction of [Fe(bpba)(dbc)]ϩ with air (meas-
urement interval: 30 s). Inset: plot of ln(abs) vs. time for the [Fe(bpba)-
(dbc)]ϩ reaction at 298 K.
catecholate-to-iron() LMCT transitions in the visible region).
The disintegration of the complex is indicated by the dis-
appearance of the purple color. Finally, the color of the
catecholate free iron complex is observed at the end of each
experiment.
The reactions of all [Fe(L)]3ϩ complexes with any catechol
(1 : 1 ratio for Fe : catechol) and O2 show pseudo-first-order
kinetics due to the excess of dioxygen.6,10,13,14,19 The pseudo-
first-order constants were determined by linear fitting of
the logarithmic plot (inset in Fig. 11). The second-order con-
stants were calculated with [O2] = 2.12 × 10Ϫ3 M at 298 K in
methanol.13,14,30 Representative results of the UV/Vis spectro-
scopic and kinetic analyses for the reactions in the presence of
air are given in Tables 3 and 4. Under our conditions, no
catechol cleavage activity was found for iron() ions alone.
The reaction rates observed by varying the catechol while
maintaining one iron complex show a direct dependence on the
redox potential of the catechol derivative. The energies of
the CT bands in the UV/Vis spectra show inverse correlations.
Fig. 12 demonstrates this relation in wavenumber/redox poten-
tial and reaction rate constant/redox potential diagrams for one
representative iron complex. By far the most unreactive
catechol is H2tcc as a result of its relatively high redox potential.
Accordingly, the LMCT bands of the tcc containing complex
occur at the lowest wavelengths observed within this series. Iron
tcc complexes are so stable that they can be handled in an oxy-
gen atmosphere. In contrast, H2dbc and H2moc are the most
reactive catechols as a result of their electron donating groups.
The LMCT bands of their complexes are found at high wave-
lengths. The dbc complexes with the ligands me1tpa and bpqa
have iron cores with the highest Lewis acidities (Table 2) and
the catechol with the highest Lewis basicity (Table 3). Con-
sequently, the LMCT bands are observed at low energies. This
is consistent with the UV/Vis spectroscopic features of the
structurally characterized complexes (Table 2) with the weakly
electron donating catecholate tcc. A similar relationship for
phenolate bearing tripodal ligand systems is reported by
Viswanathan et al.16 The catecholate-to-iron() LMCT bands
are found at higher energies (lower wavelengths). This is due
to the higher electron donor character of the phenolate
moieties.
All systems investigated are highly reactive towards dioxygen
yielding the desired product of intradiol cleavage. In the
stoichiometric reactions neither the products of the extradiol
cleavage nor the products of the simple oxidation reaction,
quinones (VII in Fig. 13), could be isolated as by-products. In
previous studies on reactions with other iron() dbc complexes
I was identified as the main oxidation product.9,17,18 Mialane
etal. observedasthemajorproduct3,5-di-tert-butyl-5-(carboxy-
methyl)-2-furanone (IV with R1 = R2 = tert-butyl) which was
due to longer reaction times.12 We found that the product
formation depends on the catechol used. With H2dbc and
H2moc, the catechols with the lowest redox potentials and,
therefore, the highest reactivities, stable 3,5-di-tert-butyl-
muconic acid anhydride (I) and 2-methoxymuconic acid
J. Chem. Soc., Dalton Trans., 2001, 828–837
833

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Fig. 13 Products of catechol cleavage mediated by iron() complexes with 3,5-di-tert-butylcatechol, 3-methoxycatechol, 4-tert-butylcatechol,
4-methylcatechol and pyrocatechol as substrates.
Table 5 Yields (%) of the catalytically cleaved highly reactive catechols
H2dbc and H2moc (∆max=11%)
10 equivalents
H2dbc
100 equivalents
H2dbc
10 equivalents
H2moc
Complex
[Fe(bpia)]3ϩ
[Fe(bpba)]3ϩ
[Fe(bipa)]3ϩ
84
69
68
68
65
30
74
74
46
the result of the formation of an antiferromagnetically coupled
dinuclear complex.10,13,19,31 The best performance was observed
for the complex [Fe(bpia)]3ϩ with a turnover number of 68 for
the reaction with 100 equivalents of H2dbc. 1% of the catalyst
converts H2dbc into the oxygenated product over 0.5 (bpia) to
3 days (bipa) (Table 5). According to their reactivity the
catalytic activities of the complexes decrease in the series
[Fe(bpia)]3ϩ > [Fe(bpba)]3ϩ > [Fe(bipa)]3ϩ. This result is also
consistent with the different Lewis acidities of the iron cores
and the different steric demands of the ligands revealed in the
crystal structures. Therefore, small aromatic nitrogen-donor
moieties with electron accepting character improve the catalytic
activity (higher yield and a faster reaction) of iron() com-
plexes with tripodal ligands in contrast to the behavior of
phenolate bearing tripodal ligands.16 All product yields of the
oxidative cleavage of H2dbc and H2moc are listed in Table 5.
Fig. 14 Progress of the catalytic reaction of [Fe(bpba)]3ϩ with 10
equivalent H2dbc and air in the presence of 2 equivalents of piperidine
at 295 K followed by 1H NMR spectroscopy.
monomethyl ester (II, III), respectively, are formed. The
catechols with lower reactivities (H2bc, H2mc, and H2cat) yield
furanones (IV, V, VI) as oxygenated products. These furanones
are formed upon methanolysis of the unstable muconic acid
anhydride as the Markovnikov product of γ-lactonization.
Owing to its extremely low reactivity no products could be
isolated using H2tcc as a substrate.
These systems model the functional and structural behavior
of catechol 1,2-dioxygenases. The complexes with the highest
reactivities show catalytic cleavage of the substrates H2dbc and
H2moc. In the presence of 0.1 equivalent catalyst H2dbc and
H2moc are converted rapidly (over 40–160 min) and effi-
ciently into the dioxygenated products. The undesired products
of the simple oxidation (VII in Fig. 13) were formed only in
very small yields (<6%). The reactions (with 0.1 and 0.01
Conclusion
The synthesized mononuclear iron() complexes with tripodal
N4-donor ligands and catecholate are structural and functional
model compounds for catechol 1,2-dioxygenase enzyme–
substrate adducts. The ligand groups imidazole, pyridine, and
quinoline have different steric demands clearly influencing the
shielding of the iron() center.
With the tripodal tetradentate ligands only mononuclear
complexes with one bound substrate molecule are formed in
solution. All in situ prepared complexes are highly reactive with
respect to aerial oxidation of various catechols to their corre-
sponding cleavage products. A clear relationship between the
1
equivalent of complex) were followed using H NMR spectro-
scopy and the yields could be determined by integration of the
product signals in the range between δ 6 and 7 with CH3NO2 as
internal standard. As an example, the trace of the reaction of
[Fe(bpba)]3ϩ with H2dbc is shown in Fig. 14. In the beginning
of the reaction broad signals of the substrate are observed due
to the paramagnetic behavior of the mononuclear catalyst.
Upon dioxygenation the peaks of 3,5-di-tert-butylmuconic acid
anhydride appear and the width of the signals decreases. This is
834
J. Chem. Soc., Dalton Trans., 2001, 828–837

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electrochemical properties of the catechols, the UV/Vis absorp-
tion features and the reaction rate constant is observed. Accord-
ingly, a catechol with a high redox potential (H2tcc) results in
low reaction rate constants and LMCT transitions at low wave-
lengths. Also a correlation between the steric demand of the
ligands and the reactivity of the complexes is found. A large
angle O(2)–Fe(1)–N(4) causes low reaction rate constants.
Therefore, a highly reactive complex requires a ligand that
induces a high Lewis acidity at the iron() center and that
consists of small coordinating groups. An electron transfer
mediated substrate activation mechanism as proposed by Que
and co-workers can be supported.1,3,4,6–9
in water (200 mL) and the pH value adjusted to 8–9 with
aqueous NH3. Impurities were removed by extraction of the
mixture with CH2Cl2 (2 × 50 mL). The product precipitated as
colorless needles from the aqueous layer upon cooling to 4 ЊC.
After drying with CaCl2 in vacuo, it can be stored under Ar at
room temperature. Yield: 22.6 g (0.154 mol, 35%). mp 44 ЊC.
δH (300 MHz; D2O; standard H2O) 3.78 (s, 2H, CH2), 7.14–7.17
(m, 2H, CHBim) and 7.41–7.44 (m, 2H, CHBim).
[(Benzimidazol-2-yl)methyl]bis[(2-pyridyl)methyl]amine
(bpba). 2-(Chloromethyl)pyridine hydrochloride (3.9 g, 0.024
mol) was suspended in 40 mL of CH2Cl2 and cooled to 0 ЊC.
[(Benzimidazol-2-yl)methyl]amine (1.04 g, 0.007 mol) sus-
pended in 10 mL of CH2Cl2 was added, followed by dropwise
addition of a solution of 5.6 g (0.055 mol) triethylamine in 20
mL of CH2Cl2. After stirring for 72 h at ambient temperature
the organic mixture was extracted with water (50 ml) and dried
with magnesium sulfate. The solvent was removed in vacuo. The
resulting brown oil was extracted with hot CCl4 and the product
precipitated as colorless needles upon standing at Ϫ20 ЊC; bpba
can be stored under argon under these conditions. Yield: 1.9 g
(0.006 mol, 83%). mp 58 ЊC. δH (300 MHz; CDCl3; standard
SiMe4) 3.93 (s, 4H, CH2Py), 4.12 (s, 2H, CH2Bim), 7.15–7.23 (m,
4H, CHBim), 7.31 (m, 2H, CHPy), 7.57–7.64 (m, 4H, CHPy) and
8.62 (m, 2H, CHPy). δC (75 MHz; CDCl3; standard SiMe4) 45.9
(CH2Bim), 59.9 (CH2Py), 121.9 (Car), 122.5 (Car), 123.7 (Car),
136.8 (Car), 149.1 (Car), 153.4 (Car) and 158.5 (Car). MS (70 eV,
165 ЊC) m/z 329 (Mϩ, 5), 237 (M Ϫ C6H6N, 44), 198 (59),
The complexes with the highest reactivities show catalytic
behavior with respect to the oxidative cleavage of H2dbc and
1
H2moc. In H NMR experiments product yields up to 84%
could be obtained depending on the catechol and on the
catalyst, respectively. The catalytic activities strongly depend on
(a) the reactivity of the complex and (b) the reactivity of the
substrate. Both are influenced by the steric demands and the
Lewis acidities of the iron complex and the Lewis basicities of
the substrate, respectively. Small ligand moieties cause high
reactivities. Under these conditions the iron complex is more
open to approach of both the catechol as well as oxygen.
Additionally, the small imidazole moiety supports a rapid
replacement of the oxygenated product.
Experimental
Physical measurements
132 (26), 131 (C8H7N2ϩ, 41), 119 (11), 107 (C6H7N2ϩ, 49), 93
ϩ
,
(C6H7Nϩ, 100), 92 (C6H6Nϩ, 36), 78 (C5H4Nϩ, 11), 65 (C5H6
27), 51 (C4H3ϩ, 8), 39 (C3H3ϩ, 13) and 28 (C2H4ϩ, 18%).
1H and 13C NMR spectra were recorded on a Bruker WH 300
instrument. The experiments on the catalytic cleavage of
catechols were performed at 303 K on a Bruker AM 360-FT-
NMR spectrometer (360 MHz). Elemental analyses were
recorded on a Heraeus CHN-O-RAPID analyzer. Electronic
spectra were recorded on a Hewlett Packard diode array spec-
trometer using quartz cuvettes (d = 1 cm; T = 298 K). Cyclic
voltammetric experiments were performed on a BAS CV-50W
instrument in acetonitrile (for complexes 1–4; c = 5 × 10Ϫ4 mol
CAUTION: in general, perchlorate salts of metal complexes
with organic ligands are potentially explosive. The shock
sensitivities of the present perchlorate complexes are not
proven, yet. Nevertheless, care is recommended while handling.
[Fe(bpia)(tcc)]ClO4 1. Fe(ClO4)3ؒ9H2O (52 mg, 0.1 mmol),
tetrachlorocatechol monohydrate (26 mg, 0.1 mmol), and bpia
(29 mg, 0.1 mmol) were each dissolved in 2 mL of methanol–
acetone (3 : 2) in separate vessels. The hot solutions were mixed
and after addition of piperidine (20 µL) the reaction mixture
was refluxed for a few seconds. Dark purple needles of complex
1 formed within a few days upon slow cooling and standing.
Yield: 20 mg (0.029 mmol, 29%). mp decomp. >200 ЊC (Found:
C, 39.6; H, 2.7; N, 9.8%. C23H19Cl5FeN5O6 requires: C, 39.8; H,
2.8; N, 10.1%). λmax/nm (ε/MϪ1 cmϪ1) (methanol) 529 (2080) and
729 (3100).
L
Ϫ1) or in methanol (for the in situ synthesized [Fe(L)Cl2]ϩ
complexes and for the catechols; for both c = 5 × 10Ϫ4 mol LϪ1
)
with tetrabutylammonium perchlorate as supporting electrolyte
(c = 0.1 mol LϪ1). A three-electrode system with a glassy carbon
working electrode, an Ag–AgCl–3 mol LϪ1 NaCl reference
electrode, and a platinum wire as the auxiliary electrode was
used. Under these conditions ferrocene has a potential of
370 mV. Mass spectra were measured on a Varian MAT 212
instrument, IR (in KBr) on a Bruker IF 113v spectrometer.
The starting materials were purchased from commercial
sources (Fluka, Aldrich) and used as received unless otherwise
noted.
[Fe(bpba)(tcc)]ClO4ؒ(CH3)2CO 2. Fe(ClO4)3ؒ9H2O (52 mg,
0.1 mmol) was dissolved in acetone (2 mL). With stirring, solu-
tions of the ligand bpba (33 mg, 0.1 mmol) and tetrachloro-
catechol monohydrate (26 mg, 0.1 mmol), both in 2 mL
acetone, were added. After addition of 27.5 µL NEt3 the reac-
tion mixture was refluxed for a few seconds and complex 2
precipitated as dark purple needles upon cooling and standing
for several days. Yield: 32 mg (0.04 mmol, 39%). mp 278 ЊC
(Found: C, 44.7; H, 3.4; N, 9.3%. C29H25Cl5FeN5O7 requires: C,
44.2; H, 3.2; N, 8.9%). λmax/nm (ε/MϪ1 cmϪ1) (methanol) 532
(1817) and 678 (2041).
Syntheses
[(1-Methylimidazol-2-yl)methyl]bis[(2-pyridyl)methyl]amine
(bpia), [(6-methyl-2-pyridyl)methyl]bis[(2-pyridyl)methyl]amine
(me1tpa),
bis[(2-pyridyl)methyl][(2-quinolyl)methyl]amine
(bpqa), and bis[(1-methylimidazol-2-yl)methyl][(2-pyridyl)-
methyl]amine (bipa). The precursor compounds bis[(2-
pyridyl)methyl]amine,
2-chloromethyl-1-methylimidazole
hydrochloride, and 2-(bromomethyl)quinoline for the ligand
syntheses were prepared as described elsewhere.13,32 The ligands
bpia, me1tpa, bpqa, and bipa were synthesized according to
literature procedures.13,22–24
[Fe(bpqa)(tcc)]ClO4ؒCH3CH2OH 3. Solutions of Fe(ClO4)3ؒ
9H2O (52 mg, 0.1 mmol), tetrachlorocatechol monohydrate (26
mg, 0.1 mmol), and bpqa (32 mg, 0.1 mmol) were each dis-
solved in 2 mL ethanol and combined. After addition of NEt3
(27.5 µL) the reaction mixture was refluxed for a few seconds.
Dark purple crystals precipitated upon slow cooling to
ambient temperature and standing for several days. Yield: 55
mg (0.07 mmol, 65%). mp 242 ЊC (Found: C, 45.3; H, 3.3;
N, 7.0%. C30H26Cl5FeN4O7 requires: C, 45.7; H, 3.3; N, 7.1%).
λmax/nm (ε/MϪ1 cmϪ1) (methanol) 590 (1989).
[(Benzimidazol-2-yl)methyl]amine. Similar to previously
reported methods, glycine (33 g, 0.44 mol) and ortho-
phenylenediamine (47.5 g, 0.44 mol) were dissolved in hydro-
chloric acid (200 mL, 7 M)33 and refluxed with stirring for 72
hours. The product precipitated as its hydrochloride upon cool-
ing to ambient temperature. The primary product was dissolved
J. Chem. Soc., Dalton Trans., 2001, 828–837
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Table 6 Crystallographic data and experimental details
1
2
3
4
Formula
C23H19Cl5FeN5O6
694.53
C29H25Cl5FeN5O7
788.64
C30H26Cl5FeN4O7
787.65
C25H20Cl4FeN5O5
668.11
M/g molϪ1
Crystal system
Space group
a/Å
b/Å
c/Å
α/Њ
β/Њ
Monoclinic
P21/c (no. 14)
9.120(2)
35.402(7)
8.666(2)
Triclinic
P1 (no. 2)
8.512(2)
9.754(2)
19.977(4)
88.17(3)
82.94(3)
88.38(3)
1644.7(6)
2
Monoclinic
P21/n (no. 14)
9.553(2)
17.660(4)
20.095(4)
Triclinic
P1 (no. 2)
8.366(2)
9.211(2)
17.890(4)
83.04(3)
82.43(3)
89.25(3)
1356.5(5)
2
92.93(3)
102.13(3)
γ/Њ
V/Å3
2794.3(10)
4
1.066
3314.5(12)
4
0.911
Z
µ/mmϪ1
0.919
0.997
T/K
213
18772
5445
4025
362
150
7647
7152
5633
173
12000
5824
3801
426
213
8599
4442
2319
Measured reflections
Unique reflections
Observed reflections [I > 2σ(I)]
Parameters
426
362
R1, wR2 [I > 2σ(I)]
0.0592, 0.1312
0.0416, 0.1173
0.0850, 0.2119
0.0756, 0.1576
Table 7 The equivalents of base needed for the dioxygenation
reactions of the catechols mediated by the [Fe(L)]3ϩ complexes
[Fe(me1tpa)(tcc)]NO3 4. Tetrachlorocatechol monohydrate
(26 mg, 0.1 mmol) and me1tpa (31 mg, 0.1 mmol), each
dissolved in 2 mL ethanol, were added with stirring to a
solution of Fe(NO3)3ؒ9H2O (41 mg, 0.1 mmol) in 2 mL ethanol.
The resulting dark purple solution was treated with 27.5 µL of
NEt3 and refluxed for several seconds. Upon cooling and stand-
ing for a few days at ambient temperature dark purple needles
were obtained. Yield: 27 mg (0.04 mmol, 44%). mp 233 ЊC
(Found: C, 44.8; H, 3.1; N, 10.3%. C25H20Cl4FeN5O5 requires:
C, 44.9; H, 3.0; N, 10.5%). λmax/nm (ε/MϪ1 cmϪ1) (methanol)
577 (2746) and 743 (3199).
Complex
H2dbc
H2moc
H2bc
H2mc
H2cat
[Fe(bpia)]3ϩ
[Fe(bpba)]3ϩ
[Fe(bipa)]3ϩ
[Fe(me1tpa)]3ϩ
[Fe(bpqa)]3ϩ
2.0
2.0
2.5
2.4
2.3
2.0
2.1
2.5
2.0
2.0
2.5
2.3
2.3
2.3
2.0
2.1
2.0
2.0
2.5
2.0
2.0
2.1
a
a
a
—
—
—
a No experiments were carried out for these systems due to very small
reaction rates.
Single crystal X-ray diffraction
bpia as well as two equivalents of piperidine) was titrated with
a solution of tetrachlorocatechol monohydrate (in steps of 0.2
equivalent). After each addition the thermodynamic equi-
librium was reached instantly. 2 mL of a complex solution (0.5
mmol LϪ1 for Fe(ClO4)3ؒ9H2O and the ligand bpia in methanol)
were treated with one equivalent of the catechol. This solution
was titrated with piperidine (0.02 mol LϪ1; up to 4 equivalents of
base) and the decomposition of the catecholate monitored by
UV/Vis spectroscopy.
Intensity data of complexes 1 and 4 were collected on a STOE
IPDS diffractometer (Mo-Kα, λ = 0.71073 Å, graphite mono-
chromator), those for 2 and 3 on a Syntex P21 and a Siemens P3
four-cycle diffractometer, respectively (Mo-Kα, λ = 0.71073 Å,
graphite monochromator), by using the ω-scan technique. The
intensities of two reflections were monitored and no significant
crystal deterioration was observed. Further data collection
parameters are summarized in Table 6. The structure of 1 was
solved by direct methods and those of 2–4 by Patterson
syntheses (program SHELXS 97).34 A series of full-matrix
least-squares refinement cycles on F 2 (program SHELXL 97)
followed by Fourier syntheses gave all remaining atoms.35 The
positions of the NH proton in 2 and the hydroxo proton of the
ethanol solvate molecule in 3 were taken from the Fourier
difference maps and refined with 1.5 times the Ueq value of
the corresponding atom. All other hydrogen atoms were placed
on calculated positions and constrained to ride on the atom to
which they are attached. The isotropic thermal parameters for
the methyl protons were refined with 1.5 times the Ueq value of
the corresponding atom and for all other hydrogen atoms with
1.2 times Ueq. The non-hydrogen atoms were refined with
anisotropic thermal parameters.
Determination of the catechol 1,2-dioxygenase activity
The catechol cleaving activities of the in situ prepared com-
plexes were tested according to a procedure described else-
where.12 To 2 mL of a 5 × 10Ϫ4 mol LϪ1 solution consisting
of Fe(ClO4)ؒ9H2O and the ligand were added 0.02 mL of a
5 × 10Ϫ2 mol LϪ1 (1 equivalent) solution of catechol. For each
complex the amount of base yielding the highest reaction rate
possible was determined according to the spectrophotometric
titration described above (individually for each catecholate
complex using piperidine as base). The equivalents of base
needed for each reaction are listed in Table 7. Then the dis-
integration of the complexes was followed at least three times
by UV/Vis spectroscopy.
CCDC reference numbers 139042–139045.
See http://www.rsc.org/suppdata/dt/b0/b008511l/ for crystal-
lographic data in CIF or other electronic format.
Catalytic cleavage of catechols
An excess of the catechol (0.2 mmol or 2 mmol) was added to a
solution consisting of equimolar amounts of the ligand and
Fe(ClO4)3ؒ9H2O (0.02 mmol in ca. 1 ml solvent). Immediately
after this addition two equivalents of piperidine (0.04 mmol
with respect to Fe) were added and the reaction mixture was
stirred vigorously. Only the cleavage of the rapidly reacting
catechols 3,5-di-tert-butylcatechol (using CD3CN as solvent)
and 3-methoxycatechol (using CD3OD as solvent) was deter-
mined. The reactions with a tenfold excess of catechol were
Spectrophotometric titrations
A solution containing the ligand bpia (0.1 mmol LϪ1) in
methanol (2 mL) was titrated in portions of 0.2 equivalent with
a solution of Fe(ClO4)3ؒ9H2O in methanol. The same amount
of iron solution was added to the solvent containing reference
cuvette. After addition of the metal solution thermodynamic
equilibrium was reached instantly. A complex solution (2 mL)
in methanol (0.25 mmol LϪ1 for Fe(ClO4)3ؒ9H2O and the ligand
836
J. Chem. Soc., Dalton Trans., 2001, 828–837

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monitored by 1H NMR spectroscopy. Yields of the cleavage (10
and 1% catalyst) of at least three independent experiments were
determined by H NMR spectroscopy using nitromethane as
10 W. O. Koch and H.-J. Krüger, Angew. Chem., 1995, 107, 2929;
W. O. Koch and H.-J. Krüger, Angew. Chem., Int. Ed. Engl., 1995,
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1
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935.
standard (singlet at δ 4.3; 0.2 mmol).
Identification of the dioxygenated products
2 equivalents piperidine were added with stirring to a reaction
mixture (10 mL methanol) consisting of Fe(ClO4)3ؒ9H2O, the
tripodal ligand, and catechol (0.2 mmol). After all catechol
had reacted (monitored by TLC) the solvent was evaporated
under reduced pressure at ambient temperature. The cleav-
age products were separated from this residue by column
chromatography (SiO2; H2dbc, CH2Cl2–CHCl3 1 : 2; all other
substrates, methanol). After evaporation of the solvent the
products were dried in vacuo and identified by 1H NMR or mass
spectrometry. 3,5-Di-tert-butyl-1-oxacyclohepta-3,5-diene-2,7-
dione I: 1H NMR (300 MHz, CDCl3) δ 1.15 (s, 9 H, C(CH3)3),
1.27 (s, 9 H, C(CH3)3), 6.12 (m, 1 H, CH) and 6.42 (m, 1 H,
CH). 2-Methoxyhexa-2,4-dienedioic acid monomethyl ester II,
1
III: H NMR (300 MHz, DMSO-d6) δ 3.68 (s, 3H, CO2CH3),
3.81 (s, 3H, OCH3), 5.74 (d, 1H, CH), 7.10 (t, 1H, CH) and 7.74
(d, 1H, CH). (2-tert-Butyl-5-oxo-2,5-dihydrofuran-2-yl)acetic
acid methyl ester IV (R2 = tert-butyl): 1H NMR (300 MHz,
CDCl3) δ 1.01 (s, 9 H, C(CH3)3), 2.95 (m, 2 H, CH2CO2), 3.64
(s, 3 H, OCH3), 6.09 (d, 1 H, CH) and 7.51 (d, 1 H, CH).
(2-Methyl-5-oxo-2,5-dihydrofuran-2-yl)acetic acid methyl ester
1
IV (R2 = methyl): H NMR (300 MHz, CDCl3) δ 2.01 (s, 3 H,
CH3), 2.91 (m, 2 H, CH2CO2), 3.66 (s, 3 H, OCH3), 6.03 (d, 1 H,
CH) and 7.65 (d, 1 H, CH). (3-tert-Butyl-5-oxo-2,5-dihydro-
furan-2-yl)acetic acid methyl ester V (R2 = tert-butyl) 1H NMR
(300 MHz, CDCl3) δ 1.26 (s, 9 H, C(CH3)3), 2.55 (dd, 1 H, CH2),
3.05 (dd, 1 H, CH2), 3.71 (s, 3 H, OCH3), 5.40 (m, 1 H, OCH)
and 5.85 (d, 1 H, CH). (3-Methyl-5-oxo-2,5-dihydrofuran-2-
yl)acetic acid methyl ester V (R2 = methyl): 1H NMR (300 MHz,
CDCl3) δ 2.26 (s, 3 H, CH3), 2.61 (dd, 1 H, CH2), 2.85 (dd, 1 H,
CH2), 3.71 (s, 3 H, OCH3), 5.22 (m, 1 H, OCH) and 5.84 (m,
1 H, CH). (5-Oxo-2,5-dihydrofuran-2-yl)acetic acid methyl
ester VI: MS m/z, 157 [MH]ϩ.
20 F. Schweppe, H. Sirges, M. Pascaly, M. Duda, Ç. Nazikkol,
W. Steinforth and B. Krebs, Peroxide Chemistry. Mechanistic and
Preparative Aspects of Oxygen Transfer, ed. W. Adam, Wiley-VCH,
Weinheim, 2000, p. 232.
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Inorg. Chem., 1996, 35, 6909.
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1994, 33, 1177.
25 W. O. Koch, V. Schünemann, M. Gerdan, A. X. Trautwein and
H.-J. Krüger, Chem. Eur. J., 1998, 4, 1255.
Acknowledgements
26 R. L. Carlin, Magnetochemistry, Springer Verlag, Berlin,
Heidelberg, New York, Tokyo, 1986; O. Kahn, Molecular
Magnetism, VCH Verlag, Weinheim, New York, Cambridge, 1993.
27 M. M. Maltempo, J. Chem. Phys., 1974, 61, 2540; E. L. Bominaar
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Financial support from the Henkel KGaA, Degussa-Hüls AG,
the Deutsche Forschungsgemeinschaft, the Katalyseverbund
NRW, and the Fonds der Chemischen Industrie is gratefully
acknowledged. M. P. thanks the Ministerium für Schule und
Weiterbildung, Wissenschaft und Forschung des Landes
Nordrhein-Westfalen for a Graduiertenstipendium.
29 M. E. Nabi, M. A. Islam and A. H. Khan, J. Bangl. Acad. Sci., 1998,
22, 285; M. Born, P.-A. Carrupt, R. Zinn, F. Brée, J.-P. Tillement,
K. Hostettmann and B. Testa, Helv. Chim. Acta, 1996, 79, 1147;
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30 Gmelins Handbuch der Anorganischen Chemie, Sauerstoff, 8. Auflage,
Verlag Chemie, Weinheim, 1958.
31 We were able to obtain single crystals of a dinuclear iron()
complex from one solution utilized in the NMR dioxygenation
experiments. The structural features of the complex [Fe2(µ-O)-
(bpba)2Cl2][ClO4]2 are very similar to those of [Fe2(µ-O)(bpia)2-
Cl2]Cl2ؒ4MeOH with antiferromagnetically coupled iron() centers
described in ref. 13. The complete details of this compound are
under current investigation.
32 B. Rieger, A. S. Abu-Surrah, R. Fawzi and M. Steiman,
J. Organomet. Chem., 1995, 497, 73.
33 M. A. Phillips, J. Chem. Soc., 1929, 172, 2393; E. S. Lane, J. Chem.
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34 G. M. Sheldrick, SHELXS 97, Program for Crystal Structure
Determination, University of Göttingen, 1997.
35 G. M. Sheldrick, SHELXL 97, Program for Crystal Structure
Refinement, University of Göttingen, 1997.
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