Catalytic O2activation with synthetic models of α-ketoglutarate dependent oxygenases

Article abstract of DOI:10.1039/d0cc05942k

An iron complex bearing the facially capping tridentate 1,4,7-triazacyclononane ligand mimics structural and functional features of alpha-ketoglutarate (α-KG) dependent enzymes, and engages in enzyme-like catalytic O2 activation coupled to α-ketoacid decarboxylation, oxygenating sulfides. This system constitutes a rare case of non-enzymatic catalytic O2 activation, cycling between FeII and FeIV(O).

Full text of DOI:10.1039/d0cc05942k

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Catalytic O2 activation with synthetic models of -ketoglutarate
dependent oxygenases
Brenda N. Sánchez-Eguía,a Joan Serrano-Plana,a Anna Company,*,a Miquel Costas*a
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
An iron complex bearing the facially capping tridentate 1,4,7- center (Figure 1, B and C) is coupled to decarboxylation of the
triazacyclononane ligand mimics structural and functional features ketoglutarate bound ligand, and results in the formation of a
of alpha-ketoglutarate (-KG) dependent enzymes, and engages in FeIV-oxo species (Figure 1, D) which has been spectroscopically
enzyme-like catalytic O2 activation coupled to -cetoacid characterized in several members of this family,7, 13 and it is the
decarboxylation, oxygenating sulfides. This system constitutes a substrate oxidizing species.
rare case of non-enzymatic catalytic O2 activation, cycling between
FeII and FeIV(O).
Small molecule iron coordination complexes have contributed
to the understanding of the chemistry displayed by these
O2 activation is a long standing problem in bioinorganic enzymes.14 Functional models include iron complexes bearing a
chemistry and in catalysis.1-6 O2 is often incorporated into tri- or tetradentate N-based ligand together with an -KG
autooxidation, free-radical chains, but its use to generate surrogate such as benzoyl formate (BF) or pyruvate (PV).14
metal-based oxygen atom transfer agents susceptible to engage Reaction of these model complexes with O2 produces oxidants
in selective transformations in a catalytic manner is rare.
that can undergo intramolecular oxidation of the ligand, or can
be intercepted by an external substrate. A major standing goal
has been the implementation of these O2 activation reactions in
catalytic processes but still successful examples remain very
rare.15-17 Presumably, this reflects the difficulty in finding iron
catalysts that activate O2 and engage in a FeII-FeIV cycle, without
decaying into the inactive ferric forms. In this work we describe
a synthetic model of -KG iron enzymes that overcomes this
challenge and shows catalytic O2 activation activity.
O-
O-
O
O-
O
O-
O
O
O
O
O
N
O2
N
N
N
O
O
O
O
N
N
O
N
N
N
N
N
N
O
O
O
O
O
O
FeIII
FeIV
FeII
FeIV
O
O
H2
O
H2
O
O
CO2
O
O
O
N
N
N
N
O
O
O
O
B
(
)
A
D
)
(
)
C
(
(
)
Figure 1. O2 activation mechanism of -KG dependent
oxygenases.7
Reaction of iPr3tacn18 (Figure 2) with equimolar amounts of
[Fe(CF3SO3)2(CH3CN)2] and sodium benzoylformate (NaBF) in
acetonitrile under an inert atmosphere led to the formation of
Several iron dependent metalloproteins catalyze O2 activation
reactions.8 An important class are -ketoglutarate (-KG)
dependent enzymes, which contain a non-heme center that
carries out substrate oxidation concomitantly with the oxidative
decarboxylation of an -keto carboxylate using O2 as the
oxidant.9-11 X-ray diffraction (XRD) analyses of several members
of this family reveal that in the active site the iron center is
coordinated to the 2-histidine-1-carboxylate facial triad12
occupying one face of the metal coordination octahedron
(Figure 1, A), leaving the three extra coordination sites available
for co-substrate (ketoacid) and O2 binding. O2 activation at this
the
corresponding
iron-benzoylformate
complex
[Fe(BF)(CF3SO3)(iPr3tacn)] (1BF), which was isolated as purple
crystals in 76% yield after slow diffusion of ether to an
acetonitrile solution of the complex (Figure 2). Analogously, but
replacing NaBF by sodium benzoate (NaBz), the carboxylate
complex [Fe(Bz)(iPr3tacn)(CH3CN)](CF3SO3) (1Bz) was prepared
and isolated as pale yellow crystals in 92% yield. The solid state
molecular structures of 1BF and 1Bz (Figure 2) can be
established by X-ray diffraction analysis. Most notable, the
iPr3tacn ligand affords mononuclear architectures (1BF and 1Bz)
featuring rare cases of non-bridging ketocarboxylate and
carboxylate moieties (Figure 2). The structure of 1BF is also
interesting because the BF ligand adopts the k2-chelating mode
observed in several α-KG-dependent iron(II) enzymes.10, 19 The
a. Institut de Química Computacional I Catalysis (IQCC). Universitat de Girona.
Facultat de Ciències, Campus de Montilivi, 17003, Girona, Spain.
† Footnotes relating to the title and/or authors should appear here.
Electronic Supplementary Information (ESI) available: [details of any supplementary
information available should be included here]. See DOI: 10.1039/x0xx00000x
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ketocarboxylate is nearly coplanar, and chelates the iron center the chelated ketocarboxylate ligand.22 As eVxipewecArtteicdle,Onlninoe
DOI: 10.1039/D0CC05942K
via a carboxylate and a carbonyl O atoms (Fe-O distances of absorption in this low energy region was detected for 1Bz. In
2.039 Å and 2.215 Å, respectively).
the case of 2BF-ClO4 (dimeric species) the observed bridging
In order to explore the impact of the steric bulk of the tacn coordination of the BF unit is expected to afford no absorption
ligand, we synthesized the less sterically encumbered iBu3tacn in 500 – 600 nm region. Nevertheless, weak bands are observed
ligand. Several attempts to prepare iron complexes from the in acetonitrile in this region, suggesting that the dimeric
triflate salt proved unsuccessful. Alternatively, we assembled structure may be partially broken in solution (to yield a minor
the [Fe(iBu3tacn)]2+ complex in situ by reacting the ligand with amount of the k2-chelated iron complex), or alternatively, rapid
equimolar amounts of anhydrous FeCl2 in acetonitrile, followed oxidation to form a oxo-bridged diferric complex, which also
by addition of 2 equiv AgClO4. The subsequent addition of 1 display characteristic weak bands in this region.18e,23
equiv NaBF gives rise to a deep brown solution. Filtration to
remove the AgCl precipitate and slow diethyl ether diffusion
over the resulting solution unexpectedly led to the formation of
[Fe2(BF)2(-Cl)(iBu3tacn)2](ClO4) (2BF-ClO4) as orange crystals
suitable for X-ray diffraction in 74%. The peculiarity of this
complex compared to 1BF and 1Bz is that the benyozlformate is
not bound in a chelate fashion and instead a carboxylate
bridged (Fe-O distances are undistinguishable, ~ 2.1 Å) diiron
compound is formed. Presumably, the ligand iPr3tacn, featuring
tertiary alkyl sites  to the N atoms, exerts a steric protection
that disfavors carboxylate bridged species. The introduction of
a methylenic unit  to the N in each of the substituents of the
triazacyclononane ring in iBu3tacn alleviates the steric
hindrance and enables the formation of dimeric compounds.
Figure 3. a) UV-vis monitoring of the reaction of 1BF with O2 in the
presence of 100 equiv p-methyl tolyl sulfide in acetone at room
temperature [1BF]0 = 1.3 mM. b) Time trace of the decay of the band
at 570 nm together with the quantification over time of the
production of HBz and p-methyl tolyl sulfide.
Reaction of 1BF with O2 at room temperature was followed by
means of UV-vis spectroscopy by monitoring the decay of its
characteristic MLCT band at 570 nm in different solvents. The
rate of decay of this band upon reaction with O2 could be fitted
to a single exponential function and it was dependent on the
Figure 2. Chemical structure of iPr3tacn and iBu3tacn, along with
X-ray structures of 1BF, 1Bz and 2BF-ClO4 (CCDC 2026906-
2026908). Hydrogen atoms and noncoordinating anions have
been omitted for clarity.
solvent used. While the decay was complete in about 1 h in
acetone (kobs = (1.15 ± 0.07) x 10-3 s-1, t1/2 = 10 min), the reaction
was ~5 times slower in acetonitrile (kobs = (2.62 ± 0.02) x 10-4 s-
1, t1/2 = 44 min). 1H-NMR analysis reveals that 0.85 and 0.8 equiv.
of benzoic acid (HBz) per iron center are formed in acetone and
acetonitrile, respectively. This strongly suggests that O2
activation is coupled to -KG decarboxylation (Figure 1). The
nearly equivalent formation of benzoic acid per iron center
observed upon reaction of 1BF with O2 in acetone and
acetonitrile points towards a reaction mechanism where the
The absorption spectra of the complexes are informative of the
coordination mode of the BF ligand. The UV-Vis spectrum of 1BF
in acetonitrile exhibits broad absorption bands at 520 nm (300
M-1cm-1) and 570 nm (300 M-1cm-1), which gives 1BF its
characteristic purple color of iron(II)-bidentate α-keto acid
units.20, 21 The origin of these absorption bands is attributed to
MLCT transitions from the iron(II) center to the π* orbitals of
2 | J. Name., 2012, 00, 1-3
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ferrous center is two-electron oxidized, analogous to the The electronic nature of the reaction between VtiehweArpticuletaOtnilvinee
enzymatic cycle (Figure 1).
iron(IV)-oxo intermediate and the sulfideDsOuIb: 1s0t.r1a0t3e9/wDa0CsCst0u5d94ie2dK
Irrespective of the solvent, attempts to trap reaction by performing competitive oxidation experiments using pairs of
intermediates from O2 binding were unsuccessful. However, p-X-substituted methyl phenyl sulfides, (X = OCH3, CH3, Cl, CN,
evidence for the formation of an intermediate capable of NO2). A Hammett analysis revealed a linear correlation with a 
engaging in two-electron oxygen atom transfer was gained by value of -1.1 (Figure S29). This is indicative of the electrophilic
interception with an external substrate. Thus, 1BF oxygenation nature of the oxidant. Similar values between -0.9 and -1.5 have
was performed in the presence of 100 equiv methyl p-tolyl been reported for the oxidation of sulfides by spectroscopically
sulfide. GC-FID analysis after the reaction performed in acetone trapped iron(IV)-oxo.25-27
revealed that 0.99 equiv. methyl p-tolyl sulfoxide with respect We obtained more indirect evidence for the formation of an
to iron were formed. When the reaction was performed in iron(IV)-oxo compound by performing experiments with H218O.
acetonitrile,
Experiments using 1Bz or [Fe(CF3SO3)2(CH3CN)2] instead of 1BF of 100 equiv of methyl p-tolyl sulfide and increasing amounts of
did not afford any oxidized product.
H218O (10 to 80 equiv, Figure S30) was carried out. GC-MS
The oxygenation of 2BF-ClO4 was also studied. Reaction of the product analysis revealed
linear increment of 18O-
a similar result was obtained (0.8 equiv.). In order to do so, oxygenation of 1BF in acetone in the presence
a
complex dissolved in acetone proceeds fast (< 10 min). 1H- NMR incorporation into the sulfoxide product from 3% to 11%. The
analysis after reaction also revealed the formation of benzoic same trend was observed when the p-chlorophenyl derivative
acid (60% yield) but in this case, benzoic acid formation was not was used as substrate (increment of 18O incorporation from 5%
coupled to sulfoxide production which was obtained in only 18% to 15%). Control experiments indicated that sulfoxides do not
yield. Overall, these observations suggest that the presence of exchange their oxygen atoms with water under the reaction
a mononuclear iron center coordinating the BF moiety in a conditions studied. It is known that iron(IV)-oxo species can
bidentate fashion as observed in 1BF is necessary to achieve O2 exchange their oxo ligand with water,28, 29 which reinforces the
activation reactions where a two-electron oxidant is formed.
idea of the formation of such compounds upon reaction of 1BF
The mechanistic model considered for the reaction of 1BF with and O2.
O2 is based in the mechanism proposed for -KG dependent The sum of the experimental evidence indicates that O2
enzymes (Figure 1); O2 binding and activation at the iron center activation at 1BF proceeds via a mechanism resembling -KG-
is coupled to decarboxylation, generating a high valent iron(IV)- dependent oxygenases, and cycles between FeII and FeIV
oxo species that is then responsible for substrate oxidation. In species. The consequence of this conclusion is that sulfide
order to validate this hypothesis, we monitored simultaneously oxidation could be rendered catalytic, provided the reactions
the reaction of 1BF with O2 (UV-Vis), the production of HBz (1H- would be performed in the presence of an excess of BF. To test
NMR) and the formation of sulfoxide (GC). Interestingly, this hypothesis, 1BF was reacted with O2 in the presence of a
analysis of the HBz and sulfoxide produced over time in acetone large excess of methyl p-tolyl sulfide and excess of
and acetonitrile confirmed that the decarboxylation and benzoylformic acid (HBF). In all cases, the equivalents of HBF
sulfoxidation reactions occur concomitantly with the dictate the maximum turnover number (TN) that can be
consumption of 1BF (Figure 3 and S26). Thus, the time trace for achieved. Initially 10 equiv HBF were used in combination with
the decomposition of 1BF upon reaction with O2 in the presence 100 equiv sulfide (Table 1, entry 1) which resulted in 8 TN of the
of
a sulfide inversely correlates with the time trace corresponding sulfoxide. Decreasing the amount of HBF to 3
corresponding to the amount of HBz and sulfoxide produced in equiv afforded the maximum expected TN of 3, while the use of
both acetone and acetonitrile solvents, indicating that these 5 equiv HBF resulted in 4 TN of sulfoxide product (Table 1, entry
three events are coupled. This result substantiates the 2 and 3). Further increase in the amount of HBF did not afford
hypothesis that benzoylformate oxidative decarboxylation higher turnover numbers (6 TN when 50 equiv HBF were used
occurs with the concomitant formation of the ferryl species, or only 2.5 TN in the presence of 100 equiv HBF, Table 1 entries
that oxidizes the sulfide, following a set of events similar to 5 and 6). The highest substrate conversion was achieved when
those taking place in -KG dependent oxygenases (Figure 1). 10 equiv HBF were combined with 20 equiv p-methyl phenyl
However, oxidation by a peroxide intermediate (intermediate c sulfide in the presence of 10 equiv HBF, affording 6 TN of
in Figure 1) should be also considered.24
sulfoxide product that represent a notable 30% conversion of
Isotope labeling experiments were used to get further insight the substrate into the sulfoxide. Delivery of HBF by syringe
into the reaction mechanism. Following the same procedure as pump did not improve product yields (see Table S3).
above, 1BF was reacted with 18O2 in acetone in the presence of Although these results may be seen as modest from a synthetic
100 equiv methyl p-tolyl sulfide. GC-MS analysis of the reaction perspective, they represent a very rare example of a biomimetic
products revealed 90% incorporation of 18O in the methyl p-tolyl iron catalyzed O2-activation reactions.30-32 Insight into the
sulfoxide product (Figure S32). Likewise, 90% 18O incorporation catalyst deactivation mechanism was gained by performing an
was found in HBz (ESI-MS, negative mode, Figure S34). The fact ESI-MS analysis of the reaction mixture after a catalytic
that both products incorporate one 18-oxygen atom aligns with reaction. The spectrum was dominated by a prominent peak at
the mechanism that operates in -KG dependent oxygenases m/z = 256.2 corresponding to the protonated iPr3tacn ligand,
(Figure 1), where the oxygen atoms incorporated into the suggesting
that
catalyst
deactivation
occurs
via
products originate from molecular oxygen.
protodemetallation (Figure S36). In addition, product inhibition
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J. Name., 2013, 00, 1-3 | 3
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10. M. A. McDonough, C. Loenarz, R. Chowdhury, I.VJie.wCAlirftticolenOanlninde
C. J. Schofield, Curr. Opin. StrucDt.OBI:i1o0l..1,02309/1D00,C2C00,5694529K-
672.
11. S.-S. Gao, N. Naowarojna, R. Cheng, X. Liu and P. Liu, Nat.
Prod. Rep., 2018, 35, 792-837.
12. E. L. Hegg and L. Que, Jr. Eur. J. Biochem., 1997, 250, 625-629.
13. J. M. Bollinger, Jr., W. C. Chang, M. L. Matthews, R. J. Martinie,
A. K. Boal and C. Krebs, In RSC Metallobiology, 2015,
January, 95-122.
was discarded because the reaction is not affected by the initial
presence of a sulfoxide. Attempts to recover the catalyst after
2h of reaction by addition of reducing agents or FeOTf2 proved
unsuccessful (see Table S3 for details).
Table 1. Catalytic activation of O2 with 1BF
O
1BF
(1 equiv)
S
S
HBF (3 - 100 equiv)
acetone, O2, 4 h, r.t.
14. T. K. Paine and L. Que, Jr. in Molecular Design in Inorganic
Biochemistry, ed. D. Rabinovich, Springer Berlin
Heidelberg, Berlin, Heidelberg, 2014, pp. 39-56.
15. D. Sheet and T. K. Paine, Chem. Sci., 2016, 7, 5322-5331.
16. D. Sheet, A. Bera, Y. Fu, A. Desmecht, O. Riant and S. Hermans,
Chem. Eur. J., 2019, 25, 9191-9196.
(20 - 100 equiv)
HBF (equiv.)a
Substrate (equiv.)a
Entry
TN
8
1
2
3
4
5
6
7
10
3
100
100
100
50
3
5
4
10
50
100
10
4
17. D. Sheet, P. Halder and T. K. Paine, Angew. Chem. Int. Ed.,
2013, 52, 13314-13318.
100
100
20
6
2.5
6
18. For previous use of tacn ligands in modelling O2-activating
mononuclear iron enzymes see; a) J. B. Gordon, A. C.
Vilbert, I. M. DiMucci, S. N. MacMillan, K. M. Lancaster,
P. Moënne-Loccoz and D. P. Goldberg, J. Am. Chem. Soc.,
2019, 141, 17533-17547. b) A. Diebold; A. Elbouadili,; K.
S. Hagen, Inorg. Chem. 2000, 39, 3915. c) D.-H. Jo; L.
Que, Jr., Angew. Chem. Int. Ed. 2000, 39, 4284. d) G. Lin,
; G. Reid, T. D. H. Bugg, J. Am. Chem. Soc. 2001, 123,
5030. e) J. R. Hartman, R. L. Rardin, P. Chaudhuri, K. Pohl,
K. Wieghardt, B. Nuber, J. Weiss, G. C. Papaefthymiou,
R. B. Frankel and S. J. Lippard, J. Am. Chem. Soc., 1987,
109, 7387-7396.
aWith respect to 1BF
In conclusion, the current work describes the preparation of
small molecule models of the active site of -KG-dependent
enzymes and exhibit catalytic O2 activation. Mechanistic studies
suggest that the reaction of 1BF with O2 proceeds via a
biomimetic FeII/FeIV cycle and formation of ferric species is
prevented. The work also demonstrates the viability of this
biologically inspired approach to activate O2 with small
molecule coordination compounds, operating via a mechanism 19. Z. Zhang, J. Ren, D. K. Stammers, J. E. Baldwin, K. Harlos and
C. J. Schofield, Nat. Struct. Biol., 2000, 7, 127-133.
20. R. Y. N. Ho, M. P. Mehn, E. L. Hegg, A. Liu, M. J. Ryle, R. P.
Hausinger and L. Que, Jr., J. Am. Chem. Soc., 2001, 123,
5022-5029.
fundamentally distinct from a free radical autooxidation
process.
21. M. P. Mehn, K. Fujisawa, E. L. Hegg and L. Que, Jr., J. Am.
Chem. Soc., 2003, 125, 7828-7842.
22. E. G. Pavel, J. Zhou, R. W. Busby, M. Gunsior, C. A. Townsend
and E. I. Solomon, J. Am. Chem. Soc., 1998, 120, 743-
753.
Conflicts of interest
“There are no conflicts to declare”.
23. R. E. Norman, R. Holz, S. Ménage, C. J. O'Connor and J. Q.
Zhang, Jr. , L., Inorg. Chem., 1990, 29, 4629-4637.
24. Y. M. Kim, K.-B. Cho, J. Cho, B. Wang, C. Li, S. Shaik and W.
Nam, J. Am. Chem. Soc., 2013, 135, 8838-8841.
25. A. Company, I. Prat, J. R. Frisch, D. R. Mas-Ballesté, M. Güell,
G. Juhász, X. Ribas, D. E. Münck, J. M. Luis, L. Que Jr. and
M. Costas, Chem. Eur. J., 2011, 17, 1622-1634.
26. O. Planas, M. Clemancey, J.-M. Latour, A. Company and M.
Costas, Chem. Commun., 2014, 50, 10887-10890.
27. C. V. Sastri, M. S. Seo, M. J. Park, K. M. Kim and W. Nam, Chem.
Commun., 2005, 11, 1405-1407.
28. M. S. Seo, J.-H. In, S. O. Kim, N. Y. Oh, J. Hong, J. Kim, L. Que
Jr. and W. Nam, Angew. Chem. Int. Ed., 2004, 43, 2417-
2420.
29. M. Puri, A. Company, G. Sabenya, M. Costas and L. Que, Jr.
Inorg. Chem., 2016, 55, 5818-5827.
30. I. Siewert and C. Limberg, Angew. Chem. Int. Ed., 2008, 47,
7953-7956.
31. K. Schröder, B. Join, A. J. Amali, K. Junge, X. Ribas, M. Costas
and M. Beller, Angew Chem. Int. Ed., 2011, 50, 1425-
1429.
32. A. Gonzalez-de-Castro and J. Xiao, J. Am. Chem. Soc., 2015,
137, 8206-8218.
Notes and references
‡ Footnotes relating to the main text should appear here. These
might include comments relevant to but not central to the matter
under discussion, limited experimental and spectral data, and
crystallographic data.
1. T. Punniyamurthy, S. Velusamy and J. Iqbal, Chem. Rev., 2005,
105, 2329-2364.
2. D. Wang, A. B. Weinstein, P. B. White and S. S. Stahl, Chem.
Rev., 2018, 118, 2636-2679.
3. Z. Z. Shi, C. Zhang, C. H. Tang and N. Jiao, Chem. Soc. Rev.,
2012, 41, 3381-3430.
4. H. Sterckx, B. Morel and B. U. W. Maes, Angew. Chem. Int. Ed.,
2019, 58, 7946-7970.
5. K. P. Bryliakov, Chem. Rev., 2017, 117, 11406-11459.
6. S. Sahu and D. P. Goldberg, J. Am. Chem. Soc., 2016, 138,
11410-11428.
7. J. C. Price, E. W. Barr, B. Tirupati, J. M. Bollinger, Jr. and C.
Krebs, Biochemistry, 2003, 42, 7497-7508.
8. E. G. Kovaleva and J. D. Lipscomb, Nat. Chem. Biol., 2008, 4,
186-193.
9. M. S. Islam, T. M. Leissing, R. Chowdhury, R. J. Hopkinson and
C. J. Schofield, Annual Rev. Biochem., 2018, 87, 585-620.
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