A trans-Hyponitrite Intermediate in the Reductive Coupling and Deoxygenation of Nitric Oxide by a Tricopper-Lewis Acid Complex

Article abstract of DOI:10.1021/jacs.6b01083

The reduction of nitric oxide (NO) to nitrous oxide (N₂O) is a process relevant to biological chemistry as well as to the abatement of certain environmental pollutants. One of the proposed key intermediates in NO reduction is hyponitrite (N

Full text of DOI:10.1021/jacs.6b01083

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Communication
A Trans-Hyponitrite Intermediate in the Reductive Coupling and
Deoxygenation of Nitric Oxide by a Tricopper-Lewis Acid Complex
Davide Lionetti, Graham de Ruiter, and Theodor Agapie
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.6b01083 • Publication Date (Web): 30 Mar 2016
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A Trans-Hyponitrite Intermediate in the Reductive Coupling
and Deoxygenation of Nitric Oxide by a Tricopper-Lewis Acid
Complex
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Davide Lionetti, Graham de Ruiter, and Theodor Agapie*
Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Boulevard,
MC 127-72, Pasadena, California 91125, United States
Supporting Information Placeholder
involved in biological NO reduction (Fe, Cu).1c,1e,8 Complexes
ABSTRACT: The reduction of nitric oxide (NO) to nitrous
of other transition metals have also been reported to display
NO reduction activity.1c,1d,9 Despite these many investiga-
tions, only a handful of metal complexes that contain the
hyponitrite motif have been reported, in which hyponitrite
ligands adopt a variety of binding modes to metal centers
(Figure 1). Formation of hyponitrite from NO has been re-
ported for Pt, Co, Ru, Ni, and Y compounds.9-14 In some cas-
es, treatment of hyponitrite complexes with H+ sources re-
sults in the formation of N2O.1d,9c-f,10,14 A single hyponitrite
complex featuring biologically relevant metals (based on the
precedent of CcO and NOR) has been reported in which a
trans-hyponitrite ligand bridges two Fe-porphyrin units.6h,15
This complex also generates N2O upon reaction with HCl.
However, the hyponitrite ligand is obtained from hyponi-
trous acid rather than from reduction of NO.
oxide (N2O) is a process relevant to biological chemistry as
well as to the abatement of certain environmental pollutants.
One of the proposed key intermediates in NO reduction is
hyponitrite (N2O22–), the product of reductive coupling of
two NO molecules. We report the reductive coupling of NO
by an yttrium-tricopper complex generating
a trans-
hyponitrite moiety supported by two μ-O-bimetallic (Y,Cu)
cores, a previously unreported coordination mode. Reaction
of the hyponitrite species with Brønsted acids leads to the
generation of N2O, demonstrating the viability of the hyponi-
trite complex as an intermediate in NO reduction to N2O.
The additional reducing equivalents stored in each tricopper
unit are employed in a subsequent step for N2O reduction to
N2, for an overall (partial) conversion of NO to N2. The com-
bination of Lewis acid and multiple redox active metals facili-
tates this four electron conversion via an isolable hyponitrite
intermediate.
Nitric oxide (NO) has attracted much attention due to its
relevance to biochemistry as well as environmental science.1
Coupling of NO to form a N–N bond and generate N2O and
H2O is a pivotal step in the anaerobic respiration cycle.1b,2
Reduction of NO is also of interest for its potential to con-
tribute to the abatement of NOx pollutants.3 In nature, one of
the systems responsible for the reduction of NO to N2O is
the bacterial nitric oxide reductase (NOR) enzymes, which
contain a heme/non-heme diiron active site.1b,4 Evolutionari-
ly related cytochrome c oxidases (CcOs) display a similar
active site architecture (with Cu in place of the non-heme
Figure 1. Binding modes of literature hyponitrite ligands.
We previously reported a series of [MCu3] complexes sup-
ported by a tripodal multinucleating ligand framework as
models of the multicopper oxidases (Scheme 1).16 [CuI3] com-
plex 1 displays intramolecular metal cooperativity in reduc-
tion of O2 at low temperature to a [CuIIICuII (3-O)2]3+ inter-
2
mediate. The pre-assembly of the three Cu centers in 1 was
found to be essential to this reactivity, as related mononucle-
ar or [YCu] complexes failed to generate the same intermedi-
ate. Herein, we describe the reactivity of 1 with NO to form a
trans-hyponitrite complex, with subsequent reduction to
N2O and N2.
Fe), and can also catalyze the reduction of NO, albeit at low-
1b,1e,5
er efficiencies than O2.
A key step in the mechanism of
NO reduction by these enzymes is the formation of a hyponi-
trite motif ([N2O2]2-).1e,6 Studies of NO reduction by hetero-
geneous catalysts have indicated that hyponitrite species are
also relevant to their activity.7
The mechanism of the reduction of NO to N2O has been
probed in synthetic model systems based on both the metals
1
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Figure 2. (a) Solid-state structure of the cationic portion of 2. Hydrogen atoms and outer-sphere anions and solvent molecules
omitted for clarity. Thermal ellipsoids shown at the 50% probability level. (b) Cropped representation highlighting the hyponi-
trite motif in 2. Relevant bond distances (in Å) are included.
resulting from reductive coupling of two NO molecules (2).
At each [YCu3] unit, the oxygen atom from the N2O2 ligand
Scheme 1
6+
2–
N
N
N
N
N
N
O
N
O
(O(13) and O(13’)) bridges between a Cu center and the Y
center bound to the heptadentate site of the ligand frame-
work (Figure 2), which represents a new binding mode for
hyponitrite species. A second bridge between Cu and Y is
provided by a phenoxide oxygen from the multinucleating
ligand (O(1) and O(1’)). The hyponitrite-bound Cu center is
five-coordinate and displays a square pyramidal geometry,
and was therefore assigned as CuII. The other two Cu centers
remained essentially unchanged in their distorted tetrahedral
geometries from the structure of the starting material 1,16 and
were assigned as CuI.
N
N
Cu
O
Y
N
O
N
Cu
Cu
O
N
N
N
N
O
N
Y
Cu
N
O
N
O
N
N
N
N
•6OTf
•4CH3CN
2
Cu
N
N
N
1.2 equiv. NO
-78 °C to rt
EtCN
H
N
The overall reaction between 1 and NO corresponds to a 2-
e– reduction of two NO molecules by two CuI centers to give
N2O22– and two CuII. The Lewis acidic Y3+ center is key to this
transformation as it provides an additional coordination site
for stabilization of the hyponitrite ligand. Coordination of
hyponitrite to Y3+ can be regarded as a Lewis acid/base ana-
log to the Brønsted acid/base reaction with H+ to ultimately
generate N2O in the natural system. While effects of Lewis
acids on reduction of O2 have previously been reported,17 this
is a rare demonstration of the effect of a Lewis acid on activa-
tion of NO. Notably, formation of 2 was the result of inter-
molecular activation of NO by two Cu and two Y centers, in
contrast to the activation of O2, which occurred intramolecu-
larly.16 Although the multinucleating ligand framework was
shown to hold the three Cu centers in close proximity, there-
by engendering cooperative O2 activation, it is sufficiently
flexible to allow coordination of an eighth ligand to Y3+, im-
portant for the stabilization of the hyponitrite in 2. Interest-
ingly, the reduction of NO has been reported in a MOF dis-
playing Fe and Lewis acid Zn2+ in close proximity, although a
multinuclear reaction mechanism was not invoked.18 Com-
plex 2 is the first hyponitrite complex of a metal relevant to
OTf
(6 equiv.)
N
N
N
N
3+
N
Cu
N
Cu
Cu
N
N
N
N2O + N2
O
O
O
Y
N
N
N
N
N
N
N
N
N
1
2
xs NO
-78 °C to rt
EtCN
4+
O
N
TfO
N
N
N
O
Cu
Cu
N
N
O
N
N
O
N
O
N
N
N
O
N
O
O
Y
N
Cu
O
N
N
N
N
N
O
Cu
N
Y
•4OTf
O
O
O
N
N
N
N
Cu
N
N
O
N
O
N
O
O
N
N
N
N
Cu
OTf
O
5
2–
biological NO reduction (Cu as in CcO) in which the N2O2
ligand is derived from nitric oxide.1d
To test for multimetallic reactivity with NO a degassed
propionitrile (EtCN) solution of 1 was exposed to gaseous NO
(1.2 equiv.) at -78 °C (Scheme 1). The solution was stirred for
6 hours at -78 °C, after which it was allowed to warm to room
temperature. Analysis by proton nuclear magnetic resonance
(1H NMR) of the yellow-green product revealed the disap-
pearance of the sharp signals for 1 and the appearance of
broad features, indicating formation of a paramagnetic spe-
cies. Single crystal X-ray diffraction (XRD) analysis reveals a
dimer of [YCu3] cores bridged by a trans-hyponitrite moiety
The structural parameters for complex 2 were found to be
very similar to those of literature trans-hyponitrite species.
Both N–N and N–O bond distances in 2, 1.254(8) and 1.376(4)
Å, respectively, are within the ranges of values reported in
the literature, consistent with an N–N double bond and N–O
single bonds. Hyponitrite complexes have been reported to
display characteristic bands in their infrared (IR) spectra
corresponding to N–N and N–O stretching vibrations.1c
However, due to the symmetric nature of 2 (an inversion
2
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center is present in the middle of the N(17)–N(17’) bond), the
N2O). IR analysis of the product in a gas IR cell revealed for-
N–N (1400-1500 cm-1) and symmetric N–O (900-1000 cm-1)
stretching vibrations are not expected to be IR active, akin to
what was observed for an analogously symmetric porphyrin-
supported Fe complex.15 The IR-active asymmetric N–O
stretch was observed at 980 cm-1 in the ATR-IR spectrum of 2
((15NO) = 970 cm-1), similar to previously reported trans-
hyponitrite complexes (Figure S4).
mation of N2O by comparison to an authentic sample (Figure
S5) confirming the viability of 2 as an intermediate in the
reduction of NO by 1.
1
2
3
4
5
6
7
8
Given the presence of four CuI centers in 2, potential for
further in situ reduction of N2O (to N2) produced upon
treatment with H+ was hypothesized. Notably, N2O reduc-
tion to N2 is performed in nature by nitrous oxide reductase
at a tetracopper active site, although the exact mechanism
for this transformation is under debate.19 Consistent with this
hypothesis, complex 1 was found to react with N2O to give
Scheme 2.
9
(OTf)
NO2
OMe
(OTf)
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N
OMe
(albeit more slowly) the same [CuIIICuII (3-O)2]3+ intermedi-
Cu
2
N
Cu
xs NO
N
N
ate obtained via reaction with O2 (UV-Vis, Figure S10). To
explore the possibility of N2 release from 2, via N2O, the reac-
tion of 15N-labeled 2 with pyridinium triflate under an Ar
atmosphere was monitored by sampling the headspace and
analyzing by gas chromatography mass-spectrometry (GC-
MS). After 24 hours, a peak at m/z=46 for 15N2O was ob-
served, consistent with the IR results. Beginning at 48 hours,
however, a peak at m/z=30 appeared that was absent in blank
experiments as well as at earlier reaction timepoints, con-
sistent with the formation of 15N2. These results suggest that
N2O generated in situ can be further reduced by the remain-
ing CuI centers. Complex 1 can therefore engage in nitric
oxide reductase as well as nitrous oxide reductase activity,
performing the overall four-electron reduction of two NO
molecules to N2. Although reduction of mononuclear FeII
nitrosyl complexes by sulfite and bisulfite to generate N2O
and N2 has been reported,20 and heterogeneous catalysts for
reduction of NO (including to N2) have also been extensively
studied,3b to our knowledge the present study is the first ex-
ample of the two-step reduction of NO to N2 by a discrete
multimetallic complex without the need for an external re-
ductant.
N
N
4
EtCN
-78 °C to rt
tBu
tBu
3
To gain insight into the role of the multimetallic nature of
the precursor on the formation of 2, the reactivity of mono-
copper complex 3 with NO was explored (Scheme 2). Treat-
ment of 3 with NO (1 equiv.) under analogous conditions to
those used for 1 resulted in a change in color from yellow to
dark green. Analysis by 1H NMR revealed only partial conver-
sion to a species with broad features. Complete conversion of
-
3 to a CuII nitrite (NO2 ) complex, 4, (Figure 3, XRD) occurs
only upon addition of excess NO (5 equiv). Observation of a
nitrite complex and of a different stoichiometry suggests that
treatment of 3 with NO results in reductive disproportiona-
-
tion to NO2 supporting the notion that the presence of the
Y3+ center in 1 is essential to stabilization of the bound hypo-
nitrite moiety.
In summary, the reactivity of an yttrium-tricoppper com-
plex with NO reveals coupling and deoxygenation chemistry.
Reductive coupling of two NO molecules by two distinct
[YCu3] units results in formation of a trans-hyponitrite com-
2–
plex, 2, in which each oxygen of the N2O2 ligand bridged
between Y and a Cu center on different [YCu3] cores. Binding
of Lewis acidic Y3+ is proposed to stabilize the hyponitrite
intermediate. Reaction of 2 with H+ leads to the generation
of N2O. These results provide direct structural evidence for
the intermediacy of hyponitrite species in the Cu-mediated
reductive coupling of NO to N2O relevant to biological sys-
tems. Additionally, reduction of N2O generated in situ to N2
was also observed, highlighting the ability of tricopper com-
plex 1 to perform both nitric oxide reductase and nitrous
oxide reductase activities. More broadly, the combination of
Lewis acid and multiple redox active metals was demonstrat-
ed to facilitate four electron chemistry, involving coupling
and deoxygenation of NO via a detectible hyponitrite inter-
mediate.
Figure 3. Solid-state structure of complex 4. Hydrogen atoms
and an outer-sphere triflate anion omitted for clarity. Ther-
mal ellipsoids shown at the 50% probability level.
The reactivity of 1 with excess NO was investigated for
comparison to 3 and a similar outcome was observed
(Scheme 1). One of the products of this reaction was charac-
terized by XRD and, although the obtained dataset was not
of high enough quality for comparison of structural parame-
ters, atom connectivity could be determined. The solid state
structure of complex 5 displays three NO2- ligands per [YCu3]
core (Figure S9), consistent with NO disproportionation re-
activity of 1 in the presence of excess NO.
To determine whether hyponitrite complex 2 was a feasi-
ble intermediate in the reduction of NO to N2O by 1, its reac-
tivity with Brønsted acids was explored. Complex 2 was
ASSOCIATED CONTENT
Supporting Information
1
found to react with pyridinium triflate as observed by H
Experimental procedures and characterization data. This
material is available free of charge via the Internet at
http://pubs.acs.org.
NMR. Addition of excess acid (up to ~5 equiv.) led to com-
plete consumption of starting material. To study the gaseous
products of this reaction, after 3 hours, N2 was removed by
freeze-pump-thaw cycles at -196 °C, and the remaining vola-
tiles were vacuum-transferred to vessels cooled to -78 °C (to
trap solvent CH3CN) and -196 °C (to condense any produced
AUTHOR INFORMATION
Corresponding Author
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Am. Chem. Soc. 2013, 135, 4902; (n) Speelman, A. L.; Lehnert, N.
*agapie@caltech.edu
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Ruiter, G.; Thompson, N. B.; Lionetti, D.; Agapie, T. J. Am. Chem.
Soc. 2015, 137, 14094.
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Notes
The authors declare no competing financial interests.
ACKNOWLEDGMENT
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This work was supported by Caltech and the PRF (T.A.). T.A.
is grateful for Sloan, Dreyfus, and Cottrell fellowships. We
thank Dr. Michael K. Takase and Lawrence M. Henling for
assistance with X-ray crystallography. We thank Professor
Jonas C. Peters for use of two infrared spectrometers. D.L.
gratefully acknowledges a graduate fellowship from the Res-
nick Sustainability Institute at Caltech. The Bruker KAPPA
APEXII X-ray diffractometer was purchased via an NSF
Chemistry Research Instrumentation award to Caltech (CHE-
0639094).
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