A Structurally Characterized Nonheme Cobalt-Hydroperoxo Complex Derived from Its Superoxo Intermediate via Hydrogen Atom Abstraction

Article abstract of DOI:10.1021/jacs.6b08642

Bubbling O₂ into a THF solution of Co^II(BDPP) (1) at -90 °C generates an O₂ adduct, Co(BDPP)(O₂) (3). The resonance Raman and EPR investigations reveal that 3 contains a low spin cobalt(III) ion bound to a superoxo ligand. Significantly, at -90 °C, 3 can react with 2,2,6,6-tetramethyl-1-hydroxypiperidine (TEMPOH) to form a structurally characterized cobalt(III)-hydroperoxo complex, Co^III(BDPP)(OOH) (4) and TEMPO^?. Our findings show that cobalt(III)-superoxo species are capable of performing hydrogen atom abstraction processes. Such a stepwise O₂-activating process helps to rationalize cobalt-catalyzed aerobic oxidations and sheds light on the possible mechanism of action for Co-bleomycin.

Full text of DOI:10.1021/jacs.6b08642

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Communication
A Structurally Characterized Nonheme Cobalt-Hydroperoxo Complex
Derived from its Superoxo Intermediate via Hydrogen Atom Abstraction
Chun-Chieh Wang, Hao-Ching Chang, Yei-Chen Lai, Huayi Fang, Chieh-Chin
Li, Hung-Kai Hsu, Zong-Yan Li, Tien-Sung Lin, Ting-Shen Kuo, Frank Neese,
Shengfa Ye, Yun-Wei Chiang, Ming-Li Tsai, Wen-Feng Liaw, and Way-Zen Lee
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.6b08642 • Publication Date (Web): 11 Oct 2016
Downloaded from http://pubs.acs.org on October 11, 2016
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A Structurally Characterized Nonheme Cobalt-Hydroperoxo
Complex Derived from its Superoxo Intermediate via Hydro-
gen Atom Abstraction
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Chun-Chieh Wang,†‡ Hao-Ching Chang,† Yei-Chen Lai,‡ Huayi Fang,§ Chieh-Chin Li,‡ Hung-Kai
⊥
Hsu,† Zong-Yan Li,† Tien-Sung Lin, Ting-Shen Kuo,† Frank Neese,§ Shengfa Ye,*,§ Yun-Wei
Chiang,*,‡ Ming-Li Tsai,*,# Wen-Feng Liaw,*,‡ and Way-Zen Lee*,†
†Department of Chemistry and Instrumentation Center, National Taiwan Normal University, Taipei 11677, Taiwan
‡Department of Chemistry, National Tsing Hua University, Hsinchu 30013, Taiwan
§Max-Planck Institut fꢀr Chemische Energiekonversion, Mꢀlheim an der Ruhr D-45470, Germany
⊥
Department of Chemistry, Washington University, St. Louis, Missouri 63130, United States
#Department of Chemistry, National Sun Yat-sen University, Kaohsiung 80424, Taiwan
Supporting Information Placeholder
ABSTRACT: Bubbling O2 into a THF solution of CoII(BDPP)
the corresponding hydroperoxo complex, akin to the iron
congeners. Note that Fe-/Co-OOH species, presumably gen-
erated by O2 activation via the superoxo intermediate, have
long been believed to be responsible for DNA cleavage in the
mechanism of cancer treatment by bleomycin, a broad-
spectrum antitumor agent.8-10 Based on our previous investi-
gation of a nonheme iron-superoxo complex produced from
its iron(II) precursor, Fe(BDPP)11 (H2BDPP = 2,6-bis((2-(S)-
diphenylhydroxylmethyl-1-pyrrolidinyl)methyl)pyridine), we
herein present a structurally characterized nonheme co-
balt(III) hydroperoxo complex derived from its superoxo
intermediate via HAA (Scheme 1, 3→4).
(1) at −90 °C generates an O2 adduct, Co(BDPP)(O2) (3). The
resonance Raman and EPR investigations reveal that 3 con-
tains a low spin cobalt(III) ion bound to a superoxo ligand.
Significantly, at −90 °C, 3 can react with 2,2,6,6-tetramethyl-
1-hydroxypiperidine (TEMPOH) to form a structurally char-
acterized cobalt(III)-hydroperoxo complex, Co(BDPP)(OOH)
(4) and TEMPO•. Our findings show that cobalt(III)-
superoxo species are capable of performing hydrogen atom
abstraction processes. Such a stepwise O2-activating process
helps to rationalize cobalt-catalyzed aerobic oxidations and
sheds light on the possible mechanism of action for Co-
bleomycin.
Scheme 1
Transformation of superoxo to peroxo is a critical step in the
catalytic cycles of a range of O2-activating iron enzymes. For
instance, the iron-superoxo intermediates of isopenicillin-N-
synthase (IPNS)1 and myo-inositol oxygenase (MIOX)2 un-
dertake hydrogen atom abstraction (HAA), leading to for-
mation of hydroperoxo species. In the case of homoproto-
catechuate 2,3-dioxygenase (Fe-HPCD), the superoxo species
is shown to attack an electron-deficient carbon to yield an
alkylperoxo intermediate.3 Unexpectedly, parallel investiga-
tions on the Co-reconstituted HPCD (Co-HPCD) demon-
strated that its reactivity is even superior to that of Fe-HPCD
under O2-saturating conditions,4 implying that cobalt, a
nonphysiological metal cofactor, may play a similar role as
iron in O2 reduction. Although a series of heme and non-
heme cobalt-superoxo complexes have been synthesized and
spectroscopically and structurally characterized since
1970s,5,6 their reactivity towards organic substrates is barely
discussed. Recently, aerobic oxidation of p-hydroquinone
catalyzed by a salophen-based cobalt complex was reported,7
for which the DFT calculations suggested that the cobalt-
superoxo species can exhibit HAA reactivity and convert to
A purple cobalt(II) complex, Co(BDPP) (1), was synthe-
sized from the reaction of CoCl2 with the deprotonated
BDPP2− ligand in THF-CH3CN mixed solvent and structurally
characterized by X-ray crystallography (Figure 1A). Similar to
Fe(BDPP), 1 features a distorted square pyramidal geometry
(τ5 = 0.58, cf. τ5 = 0.48 for Fe(BDPP)) in an N3O2 coordination
environment, providing a substrate binding site on the metal
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center. The selected bond lengths of 1 are listed in Table 1. In
the stabilizing enthalpy ΔH contribution; thus, the O2 coor-
1
2
3
4
5
6
7
8
contrast to highly air-sensitive Fe(BDPP), 1 is quite stable
under air. Cyclic voltammetry of 1 in CH2Cl2 shows one re-
versible redox wave at −476 mV (E1/2 vs Fc+/Fc); chemical
oxidation of 1 by FcBF4 in acetone affords a six-coordinate
cobalt(III) complex, [Co(BDPP)(H2O)](BF4) (2, Figure 1B),
with a shrunk first coordination sphere (Table 1). The fitting
of SQUID data (Figures S10, S11) show that 1 contains a high-
spin CoII center (S = 3/2) with a giso ~ 2.48 and a large axial
zero-field splitting (ZFS) parameter (|D| = 15.4 cm−1). The
EPR spectrum of a frozen CH2Cl2 solution of 1 exhibits a
dination is thermodynamically unfavorable. In comparison
with 1, the O2 binding to Fe(BDPP) is reversible at −80 °C.10
Different O2 affinity at ambient temperature is also observed
for Co- and Fe-HPCD.4
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pseudo-axial pattern with effective g values at 4.287 (geff,⊥
and 1.994 (geff,∥, A = 310 MHz, Figure 2A). The simulation
gives the intrinsic g at 2.253 and g at 1.991 with D = −13 ± 3
)
∥
⊥
∥
cm−1 and the rhombicity parameter |E/D| = 0.04 ± 0.005
(Figure 2A), consistent with the SQUID measurements. Con-
sidering the large D value, the transitions between the two
Kramers’ doublets (ms = ±3/2, ±1/2) are impossible with the
X-band frequency. The g values observed arise from the ms =
±1/2 transition and shifted by large g anisotropy. The analo-
gous spin Hamiltonian parameters were found for the recent-
ly characterized cobalt(II) complexes as well.6,7,12,13
Figure 2. X-band EPR spectra (red) of (A) 1 at 4 K and (B) 3
at 77 K in CH2Cl2. Simulations (gray) were performed by
EasySpin.
The resonance Raman (rRaman) and EPR measurements
evidence that 3 is a cobalt(III)-superoxo complex. The
rRaman spectra of 3 (λex at 457 nm, Figure S15) show an O–O
stretching vibration at 1135 cm−1, which shifts to 1070 cm−1 (∆
= −65 cm-1) upon 18O substitution. Both values fall within the
typical range of O–O stretching frequencies found for mono-
nuclear end-on superoxo complexes (Table 2). The EPR spec-
trum of 3 generated in CH2Cl2 at −90 °C (Figure 2B) exhibits a
rhombic signal with g values at 2.098, 2.011, and 1.980, sug-
gesting an S = 1/2 ground state for 3. An octet arising from
the Co superhyperfine interaction is clearly resolved in the
first g component; for the other two, such superhyperfine
interactions cannot be readily identified. The computer sim-
ulation gives A = 54, 35, 30 MHz for the three principal axis of
the g tensor. Compared to 1, the significantly attenuated A
value implies that the unpaired electron mainly localizes in
the O2•− ligand instead of the Co center, demonstrating that 3
consists of a low spin cobalt(III) ion. In fact, analogous EPR
spectra with a similar magnitude of Co superhyperfine inter-
actions have been observed for porphyrin cobalt(III)-
superoxo complexes,5a,14 the Co-reconstituted oxyhemoglo-
bin,5b and CoHPCD,4 all featuring the same electronic struc-
tures as 3. The electron spin echo envelope modulation
(ESEEM) measurements at 30 K (Figure S12) detect another
weak hyperfine interaction, originating from the nitrogen
atoms of the BDPP2− ligand. The nuclear quadrupole interac-
tion (NQI) parameters, Aiso, Aaniso, e2qQ/h, η are determined
to be 1.9, 0.13, 2.55 and 0.3 MHz, respectively, indicating
Figure 1. ORTEP of (A) 1 and (B) 2 with ellipsoids set at 50%
probability. Anion and hydrogen atoms except water mole-
cule are omitted for clarity.
Table 1. Selected Bond Lengths of 1, 2 and 4
1
2
4
Co–N1 (Å )
Co–N2 (Å )
Co–N3 (Å )
Co–O1 (Å )
Co–O2 (Å )
Co–O3 (Å )
O3–O4 (Å )
2.229(3)
2.052(5)
2.229(3)
1.913(3)
1.913(3)
1.991(4)
1.837(4)
1.990(3)
1.881(3)
1.862(3)
1.966(4)
2.000(2)
1.875(2)
1.999(2)
1.8819(19)
1.9203(19)
1.9005(19)
1.497(3)
Monitored by UV-Vis spectroscopy, no reaction of 1 with
O2 in THF is detected at room temperature (Figure S7). On
the other hand, an O2 adduct, Co(BDPP)(O2) (3), forms be-
low −70 °C as indicated by the color of the reaction solution
varying from pale purple to marigold with the new absorp-
tion bands at 485 and 580 nm (Figure S3). Furthermore, at an
even lower temperature, −90 °C, vigorously bubbling N2
through the marigold solution does not cause discernible
changes in the electronic absorption spectrum. The UV–Vis
absorption, however, converts back to that of 1 upon rapidly
raising the temperature of the solution. As elaborated by an
earlier systematic study on a series of cobalt complexes, the
O2 addition is an equilibrium with ΔS around −50 ± 10
cal/mol·K and ΔH about −11 ± 4 kcal/mol.5a Therefore, at am-
bient temperature the –TΔS factor substantially outweighs
Figure 3. UV–vis spectra derived from conversion of 3 (blue)
to 4 (red). Complex 4 was prepared from the reaction of 3
with TEMPOH (2 equiv) added in situ at −90 °C.
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an electron-nucleus interspin distance of 3.5 Å with Euler
angles (0o, 17o, 0o) between the NQI and g tensors.
1
2
3
Treatment of with 2,2,6,6-tetramethyl-1-
3
hydroxypiperidine (TEMPOH, BDEO–H = 69.7 kcal/mol)15 at
−90 °C yields a navy blue product, Co(BDPP)(OOH) (4), as
demonstrated by the growth of the three new UV–vis absorp-
tion bands at 375, 585 and 660 nm (Figure 3). Complex 4 is
stable at −80 °C for weeks and even at 10 °C for twelve hours,
making successful crystallization of 4 possible. The crystal
structure of 4 reveals that the cobalt center is coordinated by
an OOH group in addition to the BDPP2- ligand in a pseudo-
octahedral coordination environment (Figure 4). All the
bond lengths in the first coordination sphere of 4 are similar
to those of 2, and the determined O–O bond distance of the
OOH ligand is typical for a metal-bound hydroperoxide re-
ported in literature (Table S4),16 indicating that 4 is a co-
balt(III)-hydroperoxo complex (Table 1). The Co–OOH moie-
ty exhibits a significantly bent Co–O–O angle of 113.93(14)°.
Notably, the Co–O2 bond is elongated by ~0.038 Å , as com-
pared to Co–O1 bond, which can be traced back to the pres-
ence of an intramolecular hydrogen bond between the hy-
droperoxo proton and O2. In comparison with the O
4
5
6
7
8
9
Figure 4. X-ray structure of Co(BDPP)(OOH) (4). ORTEP
drawing of 4 is at 50% probability and hydrogen atoms ex-
cept hydroperoxo hydrogen are omitted for clarity.
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can be prepared by the reaction of 2 with excess H2O2 and
NEt3 (Scheme 1, 2→4, Figure S8), similar to previous re-
ports.18
Density functional theory (DFT) calculations were con-
ducted to compute the geometry and electronic structures of
1, 3, and 4. The calculations at the BP86/TZVP level predict
the O-O stretching frequencies at 1141 cm-1 for 3 and 820 cm-1
for 4; both values are in a good agreement with those deter-
mined by rRaman spectroscopy. As shown in Figure 5, the
cobalt(III) ion of 3 resides at the center of the distorted octa-
hedral coordination environment similar to that observed in
the crystal structure of 4. In addition, the computed average
distance (~3.2 Å ) between the center of the superoxo ligand
and the coordinated pyrrolidyl nitrogens in 3 (Figure 5)
matches that estimated from ESEEM (~3.5 Å ). The optimized
structure of 4 reproduces the intramolecular hydrogen bond
observed in the X-ray structure, and the hypothetical com-
plex without this interaction (4’, Figure S18) is destabilized
by ~6 kcal/mol relative to 4.
O
−
stretching frequency of 3, that of 4 shifts to 795 cm−1 (λex at
457 nm, ∆ = −47 cm-1 with 18O2, Table 2, Figures S16, S17).
The EPR spectra of the reaction solution only show an iso-
tropic feature with the g value at 2.006, which is attributed to
TEMPO•, thereby suggesting a low spin ground state for 4 as
1
expected for a six-coordinate cobalt(III) complexes. The H
NMR spectra of 4 revealed the chemical shift of the hydrop-
eroxo proton at 9.88 ppm, and the signal diminished when
D2O was added (Figure S1). All these observations further
confirm the above electronic-structure description for 4.
More importantly, the conversion from 3 to 4 is nearly quan-
titative in a yield of 90% quantified by the double integration
of the radical EPR signal. The yield of TEMPO• decreases as
the reaction temperature increases, consistent with the tem-
perature-dependent O2-binding behavior (vide supra). Taken
together, we have presented compelling experimental evi-
dences for stepwise formation of a cobalt(III)-hydroperoxo
complex from free O2 through the superoxo intermediate.
The similar HAA reactivity has been found for
Fe(BDPP)(O2)11 and Cr(14-TMC)(O2).17 Furthermore, 4 also
Table 2. Raman Data for Superoxo and Hydroperoxo
Species
complexa
ν(16O–16O), cm−1 ν(18O–18O), cm−1 reference
3
1135
1125
1260
1168b
1150
1144
795
1070
1062
1183
1090
1090
1082
748
this work
•
Fe(BDPP)(O2 )
[Fe(TAML)(η2-O2 )]2−
Fe(TpMe2)(LPh)(O2 )
Co(TpMe2)(LPh)(O2 )
11
•
19
•
6
•
6
Figure 5. The represented d-manifold splitting patterns and
O2•−/HOO− π* orbitals of DFT-optimized 1, 3, and 4 where
the orbital energies are obtained from their corresponding -
spin orbitals, respectively. The notions i and o of O2•−/HOO−
π* orbitals are referred to “in-plane” and “out-of-plane”, re-
spectively. The planes for the notations are defined as Co-O-
O for 3 and O-O-H for 4.
•
Co(salen)(py)(O2 )
20
4
this work
[Fe(14-TMC)(OOH)]2+
Fe(TpMe2)(LPh)(OOH)a
Co(bleomycin)(OOH)
868
820
21
6
778
738
828
784
8a
aLPh = bis(2-N-methylimizadolyl)methylphenylborate; salen =
N,N′-ethylenebis(salicylideneiminato). bCenter of Fermi dou-
blet.
Regarding the d-manifold splitting patterns and the bond
formation between Co(BDPP) and O2•−/OOH−, the corre-
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sponding orbital energies of 1, 3, and 4 are depicted in Figure
Gastel for fruitful discussions, and to Marion Stapper and
Dennis Skerra for rRaman measurements.
1
2
3
5. Complex 1 possesses a high-spin quartet ground state (S =
3/2) with an electron configuration of {dxz2, dxy2, dyz1, dz21, dx2-
1}. Upon O2 coordination to 1, the O2-π*i orbital overlaps
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Co-O-O for 3) forms. This bonding interaction dramatically
increases the energy gap among the frontier orbitals and
facilitates one-electron transfer from CoII to O2, yielding a
•−
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•−
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balt(III)-superoxo species is capable of performing a HAA
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•
detailed reactivity study of 3 and Fe(BDPP)(O2 ) towards a
series of substrate with differential C-H bond strengths, aim-
ing to pinpoint pivotal features that govern the HAA effi-
ciency of metal-superoxo species, is in process.
ASSOCIATED CONTENT
Supporting Information
Experimental procedures, UV–vis, EPR, rRaman spectra and
computational results. Crystallographic data of 1, 2, 4 in CIF
format. These materials are available free of charge via the
Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*wzlee@ntnu.edu.tw
*wfliaw@mx.nthu.edu.tw
*mltsai@mail.nsysu.edu.tw
*ywchiang@mx.nthu.edu.tw
*shengfa.ye@cec.mpg.de
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ACKNOWLEDGMENT
This work is supported by the Ministry of Science and Tech-
nology of Taiwan (MOST 102-2113-M-003-007-MY3 to W.-Z.L.;
MOST 103-2113-M-007-002-MY3 to W.-F.L.; MOST 104-2113-
M-110-013-MY2 to M.-L.T.). We also thank National Center
for High-performance Computing (NCHC, Taiwan) for com-
puter time and facilities. H.F., F.N. and S.Y. gratefully
acknowledge the financial support from the Max-Planck So-
ciety. We are indebted to Drs. Eckhard Bill and Maurice van
(21) Cho, J.; Jeon, S.; Wilson, S. A.; Liu, L. V.; Kang, E. A.; Braymer, J.
J.; Lim, M. H.; Hedman, B.; Hodgson, K. O.; Valentine, J. S.; Solomon,
E. I.; Nam, W. Nature 2011, 478, 502.
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