Synthesis of sterically hindered xanthene-modified iron corroles with catalase-like activity

Article abstract of DOI:10.1039/c3cc40625c

An up to 18-fold increase of the turnover frequency (TOF) in the catalase-like hydrogen peroxide dismutation reaction is observed by incorporation of substituents in the β-position of xanthene-modified iron corroles.

Full text of DOI:10.1039/c3cc40625c

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Synthesis of sterically hindered xanthene-modified
iron corroles with catalase-like activity†
Cite this: Chem. Commun., 2013,
49, 3799
Bjorn Zyska and Matthias Schwalbe*
¨
Received 24th January 2013,
Accepted 15th March 2013
DOI: 10.1039/c3cc40625c
www.rsc.org/chemcomm
Table 1 Catalytic data for H2O2 disproportionation of iron corroles and related
An up to 18-fold increase of the turnover frequency (TOF) in the
catalase-like hydrogen peroxide dismutation reaction is observed
by incorporation of substituents in the b-position of xanthene-
modified iron corroles.
porphyrin analogsa
Compound
TOFb/minÀ1
TONc (time)
7a
7b
558
142
102
27
79
30
365 (5 min)
102 (5 min)
533 (60 min)
147 (60 min)
173 (60 min)
99 (60 min)
75 (2 min)
In the enzyme catalase the reactive center is formed by an iron 1a7
1b7
porphyrin surrounded by a hydrogen bonding network.1,2 The
acid–base functionalities in the second coordination sphere
8
FeCl-cor-(C6F5)3
2a8
promote the very selective and effective disproportionation of 2b9
79
77
2c8
56 (2 min)
hydrogen peroxide to dioxygen and water. A high-valent iron-oxo
2d9
species, compound I (an iron(IV)oxo unit connected to a cationic
a
170
83 (2 min)
In solutions of dichloromethane–methanol (3 : 1), for further details
porphyrin radical), is proposed to play a critical role in the
b
c
see the ESI. TOF recorded over initial 30 s reaction time. Significant
decomposition of corroles after 20 min.
catalytic cycle.3,4
Artificial mimics based on the Hangman architecture were
developed to resemble the hydrogen-bonding network of the
enzymatic reaction center.5 So far, porphyrin,6,7 corrole8,9 and
salen10 based complexes were introduced as active catalysts for
the hydrogen peroxide dismutation reaction.
Hydroxy complexes of iron(III) porphyrins easily form
diiron(III)-m-oxo species,11 which show no catalytic activity in
H2O2-disproportionation.7 The sterically protected mesityl
substituted Hangman porphyrin 1a showed no formation of a
diiron(III)-m-oxo species and, thus, also showed the highest
catalytic activity among Hangman compounds reported so far
(Table 1 and Fig. 1).
Corroles are known to stabilize formally high-valent metal
ions.12 Iron-corroles with catalase-like activity were already
studied in organic solvents8,9 as well as in water.13 In organic
solvents, corroles with the Hangman motif were catalytically
more active than their non-functionalized counterparts and
partly more efficient than their porphyrin analogs.8 In a very
Fig. 1 Hangman porphyrins 1 (ref. 7) and corroles 2 (ref. 8 and 9) investigated in
catalytic disproportionation of hydrogen peroxide.
recent publication Graham et al. introduced Fe(III) corrole core performing slightly better than Fe(IV)Cl compounds (e.g. 2a
compounds 2b and 2d with different apical ligands on the iron and 2c).9 This was ascribed to the avoidance of a highly oxidized
intermediate like [FeV-corrꢀ+] (which is similar to compound I)
during catalysis.8,9 However, Hangman corrole systems still showed
unsatisfactory low overall performance. This was partly due to a
lack of stability – especially against reactive oxygen species. Attack
at the meso-position8 or at the direct pyrrole–pyrrole bond14 causes
the macrocycle to dearomatize and, finally, break apart.
¨
Department of Chemistry, Humboldt-Universitat zu Berlin, Brook-Taylor-Str. 2,
D-12489 Berlin, Germany. E-mail: matthias.schwalbe@hu-berlin.de;
Fax: +49 30 2093 6966; Tel: +49 30 2093 7571
† Electronic supplementary information (ESI) available: Details of the synthesis
and characterization of new compounds as well as catalytic experiments. See DOI:
10.1039/c3cc40625c
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Iron insertion was achieved by refluxing the free base 4 or 5
with an excess of iron trichloride in DMF referring to a
previously reported procedure.8 The m-oxo dimeric species 6
obtained after aerobic work-up was not characterized in detail
but immediately transformed into the mononuclear iron
chloride form. The iron chloride complexes 7a (69%) and 7b
(61%) were isolated in good yields. High-resolution mass
spectrometry confirmed again the formation of the expected
compounds (Fig. S7, ESI†). The presence of the paramagnetic
iron center led to very complex 1H NMR spectra with signals in
the À30 to +50 ppm region (Fig. S4, ESI†).
Compounds 4, 5 and 7 were further characterized by UV-Vis
spectroscopy in dichloromethane (Fig. S10 and Table S3, ESI†).
The spectra of 4a, 4b and 5 are almost identical to each other
with only marginal changes in the absorption maxima and
molar absorptivities. It is also obvious that the bromination in
the b-position only causes minor changes in the absorption
Scheme 1 Synthesis strategy for modified corrole complexes.
Thus, to achieve high catalytic performance the addition of properties compared to the parent non-brominated analogs8
bulky substituents at the b-position of the macrocycle should (Fig. S10, ESI†). For the free-base corroles 4 the Soret-band
protect these sensitive parts of the molecule and increase the shows a more pronounced splitting compared to the parent
longevity during catalytic turnover. We report herein the pre- compounds 3 with absorption maxima at around 417 and
paration of sterically hindered xanthene-modified iron corroles 433 nm. Additionally there is a small change in the Q-band
and show that these species possess a significantly higher region: a red-shift of the absorption maxima as well as an
catalytic activity in the H2O2-dismutation reaction.
alteration of intensity and the position of the maxima. The iron
Free base xanthene-modified corroles and their corre- corrole compounds, however, show almost an identical absorp-
sponding iron complexes were prepared by the synthetic tion behavior when comparing 7 and 2. Only small changes in
strategy outlined in Scheme 1. Compounds 3a and 3b could the Soret-band region around 375 nm are observed.
be obtained in moderate yields of 27% and 32%, respectively,
Because of the very similar analytical data, the structure of
following a reported procedure.15 The subsequent selective the iron corrole complexes 7a and 7b was presumed to be
bromination of the four b-positions close to the pyrrole–pyrrole similar to their non-brominated analogues 2a and 2c although
bond was carried out by an adapted and streamlined literature no single crystals could be obtained, yet, for unambiguous
procedure of Chen et al. (see ESI† and Table S1 for further structural determination.8,15
details).16
Catalytic H2O2 disproportionation was investigated using
Therefore, 3a and 3b were treated in a two-step process with compounds 7a and 7b in a 3 : 1 CH2Cl2 : MeOH solution
N-bromosuccinimide (NBS) to allow for the isolation of 4a exposed at once to an excess of H2O2 (further details can be
(58%) and 4b (59%) in good yields and high purity (see found in ESI†). Table 1 summarizes and compares the catalytic
1H-NMR spectra in Fig. S1 and S2, ESI†). We noticed that the performance of several corrole compounds as well as specific
yield of 4 diminishes when the reaction is executed on a larger examples of Hangman porphyrins. The newly synthesized iron
scale (entries 7–9, Table S1, ESI†) or at longer reaction times for corrole complexes 7a and 7b show higher catalytic activity than
the first step (entries 6 and 7, Table S1, ESI†) as has been found the non-brominated analogs 2. Surprisingly, the Hangman
for other corrole compounds.16
corrole compound 7b is less active and decomposes faster than
1H NMR spectroscopy confirmed the substitution of four 7a. Note that we cannot isolate any m-oxo dimer during or after
b-pyrrolic hydrogen atoms by bromine atoms. Furthermore, the the reaction and fast decomposition was observed. The positive
aromatic signals undergo a shift to a higher field on going from Hangman effect observed earlier9 is, thus, obscured – if not
3 to 4 (Fig. S1 and S2, ESI†). This behavior could be ascribed to non-existing. (Nevertheless, this might actually change on
the electron withdrawing effect of the bromine substituents. going to a [FeIII-corr] precursor form.) It almost seems that
Additional evidence for successful synthesis was provided the Hangman compound stabilizes an energetic intermediate
by high-resolution mass spectrometry whereby the experi- during O–O bond breaking in a way that it also facilitates
mentally determined isotopic patterns fit the calculated ones decomposition pathways. But a final conclusion can only be
(Fig. S5, ESI†).
obtained from further studies.
The deprotection of 4b to form the carboxylic acid 5 was
Comparison of the direct analogs 7a and 2a at the same
accomplished by following a procedure described by Dogutan concentration shows a 4-fold increase of the TON (turnover
et al.15 5 could be obtained under harsh conditions in good number) and a 18-fold increase of the TOF! Complex 7a has a
yields of 65% by treating 4b with 6 N NaOH under microwave TOF of 558 minÀ1 which is the highest value ever obtained with
irradiation. 1H NMR spectroscopy (Fig. S3, ESI†) and high- iron corrole or porphyrin compounds in organic solvents – to
resolution mass spectrometry (Fig. S6, ESI†) confirmed the the best of our knowledge. Hangman complex 7b shows a TON
successful synthesis of 5.
and TOF that is only slightly better (twice as high) than the ones
c
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to the oxidation state of the iron center during catalytic turn-
over (e.g. a compound I species) than the oxidation state of the
pre-catalyst. Further studies on the oxidation state of the iron
center during catalysis and the true mechanism of the reaction
will be done in due course.
We thank Kallol Ray for insightful discussions along with
funding from DFG (SCHW 1454/4-1).
Notes and references
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c
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Chem. Commun., 2013, 49, 3799--3801 3801