Reaction of a copper-dioxygen complex with nitrogen monoxide (?NO) leads to a copper(II)-peroxynitrite species

Article abstract of DOI:10.1021/ja801540e

A discrete peroxynitrite-copper(II) complex, [(TMG₃tren)Cu^II(^-OON=O)]⁺(3), has been generated in solution (ESI-MS, m/z = 565.15; tetragonal EPR) by reacting ·NO(_g) with superoxo complex [(TMG₃tren)Cu^II(O₂·^-)]⁺ (2). Complex 3 undergoes a thermal transformation to give Cu^II-nitrite complex [(TMG₃tren)Cu^II(-ONO)]⁺ (4) (X-ray) along with ca. 0.5 molar equiv dioxygen. A DFT calculation derived structure with cyclic bidentate k²-O,O′-OONO bound peroxynitrite moiety and d_x2-y2 ground state is proposed. Experiments using ¹⁸O₂ suggest that the adjacent peroxo oxygen atoms in 3 are derived from molecular oxygen. Further, ¹⁸O₂ containing 3 undergoes O-O bond cleavage to form singly 18-O-labeled 4. The results suggest the viability of biological Cu^I/O₂/(·NO) peroxynitrite formation and chemistry, that is, not coming from free superoxide plus ·NO reaction. Copyright

Full text of DOI:10.1021/ja801540e

Published on Web 05/06/2008
Reaction of a Copper-Dioxygen Complex with Nitrogen Monoxide (•NO)
Leads to a Copper(II)-Peroxynitrite Species
Debabrata Maiti,† Dong-Heon Lee,†,| Amy A. Narducci Sarjeant,† Monita Y. M. Pau,§
Edward I. Solomon,§ Katya Gaoutchenova,‡ Jörg Sundermeyer,‡ and Kenneth D. Karlin*,†
Departments of Chemistry, The Johns Hopkins UniVersity, Baltimore, Maryland 21218, Chonbuk National
UniVersity, Jeonju, Korea 561-756, and Stanford UniVersity, Stanford, California 94305, and Fachbereich Chemie,
Philipps-UniVersität Marburg, Hans-Meerwein-Strasse, 35032 Marburg, Germany
Received February 29, 2008; E-mail: karlin@jhu.edu
Peroxynitrite (oxoperoxonitrate (1-), -OONdO) is a reactive agent
Scheme 1
generated by the near diffusion controlled combination of •NO (often
called nitric oxide) and the superoxide anion (O2•-) and is considered
as a likely mediator of nitric oxide biochemistry and oxidative/nitrative
stress injury.1,2 Metal ions in biological systems may be important in
-OONdO generation, stabilization, thermal transformation reactions
(e.g., isomerization to nitrate (NO3-) or production of nitrite (+1/
2O2)), or activation toward substrate oxidation/nitration.2–4 Heme
proteins have been recently well-studied with respect to their mediation
of peroxynitrite formation and subsequent transformation to nitrate;1a,2,5
NO dioxygenases convert NO to nitrate using O2, putatively via
peroxynitrite intermediates.6 Metal complexes with Fe, heme, Mn, and
Cu act as peroxynitrite decomposition (i.e., to nitrate) catalysts and
may possess therapeutic applications.1,7 Discrete metal-peroxynitrite
complexes are rare2 but are suggested to form as transients from
metal-NO + O2(g) or metal-O2 + •NO(g) reactions.3,8
Following our interest in Cu oxidative chemistries, we note that
the literature solution chemistry of copper ion with peroxynitrite is
limited;4,9 no discrete copper-peroxynitrite species have been de-
scribed. Here, we report the reaction of •NO(g) with a CuI/O2
adduct, [(TMG3tren)CuII(O2•-)]+ (2), with end-on bound
superoxo ligand, Cu-O-O ) 123.5°, O-O ) 1.280 Å.10 The
product is a discrete peroxynitrite-CuII complex, formulated as
[(TMG3tren)CuII(-OONdO)]+ (3) (Scheme 1). This under-
goes a thermal transformation to give a nitrite complex, [(TMG3tren)-
CuII(-ONO)]+ (4), plus dioxygen. The results suggest the viability of
biological CuI/O2/(•NO) peroxynitrite formation, that is, not coming
from free superoxide plus •NO reaction (vide supra) and as perhaps
already observed for CuZn superoxide dismutase (SOD)11 and
cytochrome c oxidase.12 Peroxynitrite has been discussed with respect
to CuZn-SOD, a vector for disease states; might mutant SODs not
abrogate -OONO toxicity (i.e., downstream oxidative or nitrative
stress) or even produce peroxynitrite?11,13
that the peroxynitrite-CuII peak shifted (by 4 mass units) to m/z 569.34
[Figure 1b; 65% incorporation (also with appropriate 63,65Cu isotope
pattern)], indicating that [(TMG3tren)CuII(-18O18ONdO)]+ has
formed;15 the adjacent peroxo oxygen atoms are derived from O2
(Scheme 1).16
As mentioned, X-ray structures are not known for peroxynitrite-
metal species.2 For the one known isolated complex from Koppenol
and co-workers, a k1-O-OONO binding in [(NC)5Co(-OONO)]3- is
expected.2,17 O- and N-bound -OONO ligation in various geometries
has been considered, especially for iron porphyrinate adducts.5b,18 DFT
calculations, using B3LYP and a mixed triple-ꢀ basis set, suggest two
possible structures for [(TMG3tren)CuII(-OONdO)]+ (3), a lower
energy (by 9.3 kcal/mol in THF) form with monodentate k1-O-OONO
2
ligation in an overall trigonal bipyramidal (TBP) coordination (dz
2
2
ground state), and a more square pyramidal (SP) form (dx -y ground
Bubbling O2(g) through a colorless solution of [(TMG3tren)-
CuI]B(C6F5)4 (1) in 2-methyltetrahydrofuran (MeTHF) at -80 °C leads
to
the
EPR
silent
light
green
colored
complex
[(TMG3tren)CuII(O2•-)]B(C6F5)4 (2) [λmax ) 447, 680, 780 nm (Figure
S1)].14,15 With excess O2 removed by vacuum/purging(Ar), bubbling
2 with •NO(g) (-80 °C; subsequent excess NO(g) removed) gives a
yellowish green complex, formulated as the peroxynitrite species
[(TMG3tren)CuII(-OONdO)]B(C6F5)4 (3) (Figure S1, λmax ) 314 nm,
ε ) 6900 M-1 cm-1).15 Direct evidence for the formation of 3 comes
from electrospray ionization mass spectrometry (ESI-MS).15 Injection
of -80 °C MeTHF solutions of 3 gives rise to a parent peak cluster
with m/z
)
565.15 and expected 63,65Cu pattern for the
[(TMG3tren)CuII(-OONdO)]+ cation (Figure 1a).15 When 18O2(g) is
used for the generation of 2, subsequent addition of •NO(g) reveals
† The Johns Hopkins University.
| Chonbuk National University.
‡ Philipps-Universita¨t Marburg.
§ Stanford University.
Figure 1. ESI-MS spectra: (a) [CuII(TMG3tren)(-OONdO)]+ (3) at m/z
) 565.15; (b) [CuII(TMG3tren)(-18O18ONO)]+ (3), m/z ) 569.34.
9
6700 J. AM. CHEM. SOC. 2008, 130, 6700–6701
10.1021/ja801540e CCC: $40.75
2008 American Chemical Society

C O M M U N I C A T I O N S
Acknowledgment. This work was supported by a grant from the
NIH (K.D.K., GM28962; E.I.S., DK31450).
Supporting Information Available: Details of synthesis; reactivity,
product analyses, ESI-MS findings, DFT calculations, and CIF files. This
material is available free of charge via the Internet at http://pubs.acs.org.
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state) possessing a cyclic bidentate k2-O,O′-OONO peroxynitrite
moiety, with one short equatorial and one long axial Cu-O distance
(1.95 and 2.58 Å, respectively).15 One (TMG3tren) guanidine arm
functionality in the SP form is dangling, that is, not ligated, and this
arm is replaced by the long Cu-O in the axial position. See Supporting
Information for structural diagrams.15 The EPR spectrum of 3 is
2
2
distinctly tetragonal with a dx -y ground state (Figure 2a), thus
consistent with the latter (SP) and not the former (TBP) structure. In
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literature observations: (i) displacement of one arm of the tris(2-
aminoethyl)amine (tren) derivative five-coordinate Cu(II) complexes
in solution is well-established;19 (ii) the solid-state structure of
[(TMG3tren)-Mo(CO)3] reveals one ligand arm to be uncoordinated;20
and (iii) SP geometries for many pentacoordinate Cu(II) with tridentate
analogues of tren (i.e., [(N3)CuIIX2]n+) and bidentate analogues of
TMG3tren are documented via X-ray crystallography.21
The thermal transformation properties of [(TMG3tren)CuII-
(-OONdO)]+ (3) support its formulation and provide insights into
the observed peroxynitrite chemistry. Prolonged storage of -80 °C
solutions of 3, or warming to room temperature leads to >90% yields
-
of the green CuII-nitrite (NO2
)
complex [(TMG3tren)-
CuII(-ONO)]B(C6F5)4 (4) [λmax ) 350 (sh) (3200), 610 (700) nm,
Figure S1], accompanied by the evolution of dioxygen (30-35% yield,
50% theoretical), as determined by trapping with a known Cu-based
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(15) See Supporting Information.
2
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The identification of nitrite complex 4 and O2, along with their yields
(vide supra), further confirms the Scheme 1 stoichiometry and
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For 4, m/z ) 549.45,15 but when the reaction sequence (Scheme 1)
18
is carried out with
O
2(g)
, this shifts to m/z ) 551.12 (78%
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(
-18ONO)]+ (4) has formed. Clearly, an O-O cleavage reaction has
occurred. An extensive literature1a,24,25 known for HOONO conversion
to nitrite and O2 may apply; further studies are needed. In fact, related
copper(aq) chemistry has been described.4,9c
(23) We separately synthesized the nitrato-CuII complex [(TMG3tren)CuII-
(-ONO2)]B(C6F5)4 and determined its X-ray structure, UV-vis, EPR, and ESI-
MS properties.15
In summary, we have described here the formation, spectroscopic
features, and thermal transformation chemistry of the first discrete
Cu(II)-peroxynitrite complex. Further studies will focus on the
reactivity of this peroxynitrite complex, likely involving peroxynitrite
O-O cleavage chemistry. The work described here suggests that
copper ion in biological media may facilitate Cu/O2/•NO and thus
peroxynitrite chemistry, that is, oxidation and/or nitration.
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