Catalytic and regiospecific extradiol cleavage of catechol by a biomimetic iron complex

Article abstract of DOI:10.1039/c3cc44124e

An iron(iii)-catecholate complex of a facial tridentate ligand reacts with dioxygen in the presence of ammonium acetate-acetic acid buffer to cleave the aromatic C-C bond of 3,5-di-tert-butylcatechol regiospecifically resulting in the formation of an extradiol product with multiple turnovers.

Full text of DOI:10.1039/c3cc44124e

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Catalytic and regiospecific extradiol cleavage of
catechol by a biomimetic iron complex†
Cite this: Chem. Commun., 2013,
4
9, 10251
Sayanti Chatterjee, Debobrata Sheet and Tapan Kanti Paine*
Received 1st June 2013,
Accepted 10th September 2013
DOI: 10.1039/c3cc44124e
www.rsc.org/chemcomm
An iron(III)–catecholate complex of a facial tridentate ligand reacts
with dioxygen in the presence of ammonium acetate–acetic acid
buffer to cleave the aromatic C–C bond of 3,5-di-tert-butylcatechol
regiospecifically resulting in the formation of an extradiol product
with multiple turnovers.
Extradiol catechol dioxygenases oxidatively cleave the C1–C6 bond
of catecholate in the biodegradation of aromatic molecules to
aliphatic products with incorporation of both atoms of dioxygen
Fig. 1 Ligand and substrate.
1
into cleavage products. Substrate-bound crystal structures of
2
,3-dihydroxybiphenyl 1,2-dioxygenase (BphC), protocatechuate catalytic and specific extradiol cleavage reactivity in the presence of
4
,5-dioxygenase (LigAB), and 3,4-dihydroxyphenylacetate 2,3-dioxy- dioxygen.
2
genase (2,3-HPCD) have revealed a ‘2-His-1-carboxylate facial triad
motif’ at the active site. The mechanism of the extradiol functional models of nonheme iron oxygenases, we have designed
cleavage reaction of catechol has been substantiated by enzymatic, a new urea-based facial tridentate ligand. In this communication, we
biomimetic and theoretical studies. The oxidative C–C bond report the synthesis and characterization of an iron(II)–chloro
2
cleavage takes place via Criegee rearrangement of an iron–peroxo complex, [(tBu-L )Fe (Cl) (MeOH)] (1), and of an iron(III)–catecholate
As a part of our ongoing research on the development of
3
9
4
Me
II
1b
Me
III
4
intermediate. The catalytic activity and selectivity of the enzymatic complex, [(tBu-L )Fe (DBC)](ClO ) (2), where DBC = dianionic
reaction is controlled not only by the active site but also by the 3,5-di-tert-butylcatecholate, supported by the facial tridentate
Me
secondary structure of the proteins. Structural and biochemical ligand, tBu-L (Fig. 1). The oxidative C–C bond cleavage of DBC
studies on enzymes revealed a distinct role of the second- on the iron complexes and their efficiencies as catalytic functional
sphere residues in the catalytic activities of regiospecific clea- models are discussed. The effect of acid/base on the catalytic and
1
a,5
vage of catechol.
Escherichia coli, 2,3-dihydroxyphenylpropionate 1,2-dioxygenase
MhpB) obtained by replacing either His-115 or His-179, lacks reaction of bis(6-methylpyridin-2-yl)methanamine with tert-butyl
extradiol activity, indicating that each of these conserved histidine isocyanate in dry tetrahydrofuran (Scheme S1, ESI†). The iron(II)–
The mutant of catechol dioxygenase from regiospecific extradiol cleavage of catechol is highlighted.
Me
The ligand tBu-L was synthesized in good yield from the
(
5a,b,6
residues is essential for acid–base catalysis.
Therefore, control chloro complex (1) was prepared by mixing the ligand with FeCl in
2
of both first- and second-sphere interactions is necessary to achieve methanol. Complex 2 was isolated from the reaction of ligand,
7
functional models that are expected to display enzyme-like activity.
iron(III) perchlorate and 3,5-di-tert-butylcatechol (H DBC) in the
2
Despite the existence of a large number of iron–catecholate com- presence of two equivalents of triethylamine in methanol under an
8
plexes as functional models of extradiol catechol dioxygenases,
inert atmosphere (see experimental, ESI†). The blue solution of
there is no example of a biomimetic iron complex that exhibits complex 2 in acetonitrile displays an intense and broad absorption
band at around 600 nm typical of catecholate-to-iron(III) charge-
transfer (CT) transition (Fig. S1, ESI†). A similar optical spectrum is
Department of Inorganic Chemistry, Indian Association for the Cultivation of
obtained when complex 1 is treated with a basic solution of H DBC
in acetonitrile. The H NMR spectrum of 1 shows paramagnetically
shifted resonances of the protons (Fig. S2, ESI†). The room
2
Science, 2A&2B Raja S. C. Mullick Road, Jadavpur, Kolkata-700032, India.
1
E-mail: ictkp@iacs.res.in; Fax: +91-33-2473-2805; Tel: +91-33-2473-4971
†
Electronic supplementary information (ESI) available: Detailed experimental
B B
temperature magnetic moments of 4.86 m for 1 and 5.98 m for
2 are in excellent agreement with the spin-only values for high-spin
procedure, crystal data and figures. CCDC 915749. For ESI and crystallographic
data in CIF or other electronic format see DOI: 10.1039/c3cc44124e
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presence of one equivalent of pyridinium perchlorate. Acid plays a
crucial role in controlling the regiospecific C–C bond cleavage of
H DBC, and an optimum pK value brings out the best yield of the
2
a
extradiol cleavage product.
Interestingly, complex 2 reacts with oxygen at room temperature
in a mixture of MeCN and NH OAc–AcOH buffer (4 : 1) during
which the catecholate-to-Fe(III) CT band decays much faster (kobs
4
=
ꢁ3
ꢁ1
3.86 ꢀ 10
s
) compared to normal decay or decay in the presence
of protic acid only. A ten-fold increase in the reaction rate is
observed (Fig. S9, ESI†). Analyses of the organic product after the
reaction clearly suggest the formation of 94–95% extradiol cleavage
product within 40 min. The final solution of 2 reacts further with
excess H DBC at pH = 5.5 to regenerate the characteristic CT band.
2
Fig. 2 ORTEP plot of complex 1 with 40% thermal elliposid parameters. All
Moreover, complex 2 was found to be stable in the presence of 100
hydrogen atoms except those on C7, N3 and N4 have been omitted for clarity. Selected
bond lengths [Å] and angles [1] for 1: Fe(1)–N(1) 2.237(2), Fe(1)–N(2) 2.336(2), Fe(1)– fold excess of H
DBC at pH = 5.5. These intriguing results prompted
us to study the catalytic activity of 2 in MeCN–NH OAc–AcOH
buffer. With increasing amounts of catechol the turnover number
TON) is increased giving rise to 4,6-di-tert-butyl-2-pyrone as the only
2
N(3) 2.345(3), Fe(1)–O(2) 2.1410(19), Fe(1)–Cl(1) 2.5063(7), Fe(1)–Cl(2) 2.3640(7),
N(1)–Fe(1)–N(3) 74.50(8), N(1)–Fe(1)–N(2) 84.12(8), N(1)–Fe(1)–O(2) 158.56(9), N(2)–
Fe(1)–O(2) 83.62(7), N(3)–Fe(1)–O(2) 84.75(8), Cl(1)–Fe(1)–Cl(2) 93.09(3), Cl(1)–Fe(1)–
N(1) 92.00(6), Cl(1)–Fe(1)–N(2) 162.51(6), Cl(2)–Fe(1)–N(3) 173.35(6).
4
(
product (Scheme 1 and Fig. S10, ESI†). A maximum TON of 34 at
pH = 5.5 after 8 h is observed with 100 equiv. of H DBC (Fig. S11,
2
iron(II) and iron(III) complexes, respectively. The X-band EPR ESI†). When complex 1 is used as a catalyst under the same
spectrum of 2 at 77 K exhibits a rhombic signal at g = 4.2 typical experimental conditions, a maximum TON of 33 is observed. The
of high-spin iron(III) complexes (Fig. S3, ESI†).
catalytic results obtained with complex 1 support the in situ
The X-ray crystal structure of the neutral complex (1) reveals a formation of 2 during the reaction. The catalytic activities of iron
six-coordinate distorted octahedral coordination geometry at the complexes not only depend on the concentration of the substrate,
iron center (Fig. 2). The tridentate ligand occupies one face of but are also affected by the pH of the reaction medium. The use of
the octahedron through two pyridine nitrogens (N1 and N2) and buffer with higher or lower pH exhibits a lower catalytic TON
the nitrogen atom N3 of the urea moiety. The other face is occupied (Fig. 3). After 8 h, the pH of the reaction solution increases above
by two chloride ions and a solvent methanol molecule. Two 6 possibly due to hydrolysis of the urea ligand and as a result no
pyridine nitrogens (N1 and N2), one chloride atom (Cl1) and the change in TON is observed (Fig. S12, ESI†). Of note, the native
ꢁ
1
oxygen atom (O2) of a methanol molecule occupy the equatorial enzyme MhpB exhibits a kcat value of 29 s on the basis of the
5b
plane. The urea nitrogen (N3) and the other chloride donor (Cl2) catalytic ability per 80 kDa subunit.
occupy the axial positions with the Cl2–Fe1–N3 angle of 173.35(6)1. In biomimetic chemistry, only a few model complexes are
The metal–ligand bond distances are typical of a high-spin iron(II) known which catalytically oxidize H
complex (Table S1, ESI†). The average iron–nitrogen distance These model complexes however exhibit low selectivity towards
2.30 Å) is found to be unusually longer. Such a long iron–nitrogen extradiol cleavage. An efficient and catalytically active functional
11
2
DBC with molecular oxygen.
(
tBu
+
0
bond has been observed in the ( PNP)FeCl complex of a PNP- model, [(L-N Me )Fe(dbc)] (L-N Me = N,N -dimethyl-2,11-diaza-
pincer ligand ( PNP = 2,6-bis(di-tert-butylphosphinomethyl)- [3.3](2,6)pyridinophane), of intradiol cleaving dioxygenases has
pyridine). All attempts to isolate the single crystal of the
iron(III)–catecholate complex (2) were unsuccessful.
2
4 2 4 2
tBu
1
0
The iron(III)–catecholate complex 2 reacts with dioxygen in
acetonitrile during which the CT band at around 600 nm slowly
decays and the blue solution turns light green over a period of
1
5
h (Fig. S4, ESI†). The H NMR spectrum of the organic product
reveals only 25% conversion of catechol to an extradiol cleavage
product, 4,6-di-tert-butyl-2-pyrone (Fig. S5, ESI†). Labelling
1
8
experiment with
atom from dioxygen into the cleavage product (Fig. S6, ESI†).
Complex 1, otherwise unreactive towards O , reacts with H DBC
2
O supports the incorporation of one oxygen
2
2
in the presence of dioxygen to afford almost the same amount
of the extradiol product. The analysis of the catechol-cleavage
product in the presence of different protic acids like acetic acid
(
pK
a
a
= 4.74), pyridinium perchlorate (pK = 5.25) and piperidinium
perchlorate (pK
a
= 11.29) indicates that pyridinium perchlorate is
the best acid (Fig. S7, ESI†). The amount of pyridinium perchlorate
also has an effect on the yield of the catechol cleavage product
Scheme 1 Proposed catalytic pathway for regiospecific C–C bond cleavage of
(
Fig. S8, ESI†). Complex 2 affords 95% extradiol product in the catechol in the presence of molecular dioxygen.
1
0252 Chem. Commun., 2013, 49, 10251--10253
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theoretical studies to get insight into the role of the urea moiety
in the regiospecific catechol cleavage pathway are in progress.
TKP acknowledges the Indian National Science Academy
(Project for INSA Young Scientist Awardee) for financial sup-
port. SC and DS thank CSIR, India, for fellowships. Single
Crystal X-ray diffraction data were collected at the Department
of Inorganic Chemistry, IACS.
Notes and references
1
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Fig. 3 Dependence of pH on the catalytic TON of extradiol products with 1 and 2.
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2
2
1
2
been reported. The catalytic and regiospecific extradiol product
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examples of catalytically active functional models of extradiol-
cleaving catechol dioxygenases.
Studies with enzymes and models have established that
both iron(II) and iron(III) can catalyze the extradiol cleavage of
3
4
1
b,5a,8c
catechol.
iron(III)–catecholate (2) and also by the iron(II)–chloro complex
1) supports that the catalytic cycle proceeds through an iron(III)
The catalytic extradiol reactivity shown by the
(
complex. The catalytic mechanism shown in Scheme 1, there-
fore, is not valid for the catalytic cycle of the enzyme. The
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2
5
(Scheme 1). The facial coordination of the supporting ligand
1
2
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6
7
1
b,4e
the extradiol cleavage product.
It is important to mention
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III
8d
[(TACN)Fe (DBC)(Cl)] (3) (TACN=1,4,7-triazacyclononane),
which exhibits regioselective (98%) extradiol products, does
not exhibit catalytic extradiol cleavage under our experimental
conditions (Fig. S13 and S14, ESI†). In the reaction, quinone
is formed catalytically with negligible formation of extradiol
products (Table S2, ESI†). Therefore, the presence of urea ligand
and use of a buffer play crucial roles in directing the regio-
specific extradiol cleavage reaction of 1 and 2. The urea group of
the supporting ligand is expected to interact with the iron–
peroxo species thereby facilitating the heterolytic O–O bond
9
(a) T. K. Paine, S. Paria and L. Que, Jr., Chem. Commun., 2010,
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(
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4
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AcOH buffer with a pH of 5.5 provides protons required for C–C
bond cleavage of catechol and also deprotonates the excess catechol
to coordinate to the metal center making the system catalytic.
In conclusion we have prepared and characterized two iron
complexes supported by a urea-derived facial tridentate ligand.
The iron–catecholate complex is reactive towards dioxygen and
specifically cleaves the C–C bond adjacent to the phenolic OH
group of 3,5-di-tert-butylcatechol mimicking the function of
extradiol-cleaving catechol dioxygenases. Proton has a dramatic
effect in controlling the regiospecific C–C bond cleavage of
catechol on the model complex. The C–C bond cleavage reac-
tion rate increases many fold in the presence of a buffer and the
1
1
(
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This journal is c The Royal Society of Chemistry 2013
Chem. Commun., 2013, 49, 10251--10253 10253