A three-coordinate copper(II) amide from reductive cleavage of a nitrosamine

Article abstract of DOI:10.1002/anie.200905171

A NO-velty: A copper(1) β-diketiminate activates the nitrosamine Ph₂NNO to give a rare, three-coordinate copper(II) amide, [(Me ₂NN)Cu-NPh₂]. Reaction of this amide with NO_gas returns Ph₂NNO as well as a mixed-valence species with NOfunctionalized β-diketiminate ligands (see scheme; Cu light blue, N dark blue, O red). Thus, both the cleavage and formation of R₂N-NO bonds may take place at a common copper center. (Figure Presented)

Full text of DOI:10.1002/anie.200905171

Communications
DOI: 10.1002/anie.200905171
Nitric Oxide
A Three-Coordinate Copper(II) Amide from Reductive Cleavage of a
Nitrosamine**
Marie M. Melzer, Susanne Mossin, Xuliang Dai, Ashley M. Bartell, Pooja Kapoor,
Karsten Meyer, and Timothy H. Warren*
ꢀ
Nitrosamines R2N NO are endogenous species present at
submicromolar concentrations in mammalian plasma[1,2] and
tissues.[2] They are similar in physiological abundance and
perhaps function as well[2] to S-nitrosothiols RS NO, which
ꢀ
have received a great deal of attention in signaling path-
ways.[3] For instance, each elicits responses such as vaso-
relaxation.[4] Nitrosamines may serve as sources of NO+ as in
Scheme 1. Equilibrium of reductive nitrosylation (metal reduced) and
ꢀ
reversible transnitrosation reactions with thiols to give S-
reductive cleavage (R2N NO bond reduced).
nitrosothiols.[5] In addition, they may serve as donors of the
free radical NO,[6] but possess markedly higher R2N NO
ꢀ
ꢀ
ꢀ
homolytic dissociation energies (e.g. Ph2N NO 87.7 kcal
sylation to generate O NO bonds also occurs at copper
molꢀ1)[7] than RSNO compounds (RS NO 20–32 kcal
centers in the enzymes cytochrome c oxidase and laccase.[14]
ꢀ
molꢀ1).[8] Despite their natural occurrence, nitrosamines
Depending on the nature of the metal center, the reverse
ꢀ
may be carcinogenic, especially N-alkyl derivatives with a-
process, R2N NO reductive cleavage, may be favored (Sche-
me 1b). We recently reported that an electron-rich nickel(I)
[9]
ꢀ
C H atoms. Nitrosamines are found in common pollutants
such as tobacco smoke, motivating approaches for their
passivation which involve the use of Cu-exchanged zeolites to
trap and decompose nitrosamines to NOx.[10]
b-diketiminate
(Me3NN = 2,4-bis(2,4,6-trimethylphenylimido)pentyl)
cleaves the E NO bond of O-, S-, and N-organonitroso
species to give the nickel nitrosyl [(Me3NN)Ni NO] along
with dimeric nickel(II) alkoxide or thiolate complexes
[{(Me3NN)Ni}2(m-E)2] or the mononuclear nickel(II) amide
complex
[(Me3NN)Ni(2,4-lutidine)]
ꢀ
ꢀ
Nitrosamine formation can take place within a metalꢀs
coordination sphere through reductive nitrosylation:[11]
reduction of an oxidizing metal center by NO with concom-
itant nitrosylation of an amine or anionic amide equivalent by
NO+ (Scheme 1a).[12] For instance, a small-molecule NO
sensor developed by Ford et al. based on a [CuII(dac)]
macrocycle (dac = 1,8-bis(9-anthracylmethyl)cyclam) reacts
[15]
ꢀ
[(Me3NN)Ni NPh2].
Herein we report the reactivity of
diphenylnitrosamine (Ph2NNO) with the related copper(I) b-
diketiminate [{(Me2NN)Cu}2] (Me2NN = 2,4-bis(2,6-dime-
thylphenylimido)pentyl).[16]
ꢀ
with NO to form a new N NO bond with concomitant
Addition of 2.0 equivalents Ph2NNO[15,17] to 1.3 equiva-
lents [{(Me2NN)Cu}2] at ꢀ358C in diethyl ether results in a
color change from light yellow to dark brown (Scheme 2).
reduction to CuI which removes fluorescence quenching
present in the CuII-coordinated cyclam.[13] Reductive nitro-
[*] Dr. M. M. Melzer, Dr. X. Dai, A. M. Bartell, P. Kapoor,
Prof. T. H. Warren
Department of Chemistry, Georgetown University
Box 571227, Washington, DC 20057-1227 (USA)
Fax: (+1)202-687-6209
Scheme 2. Reaction of [{(Me2NN)Cu}2] with Ph2NNO.
E-mail: thw@georgetown.edu
Dr. S. Mossin,[+] Prof. Dr. K. Meyer
Department of Chemistry and Pharmacy
Friedrich-Alexander-University Erlangen-Nꢀrnberg
Egerlandstrasse 1, 91058 Erlangen (Germany)
Formation of a copper mirror indicates that this reaction
follows a complex course; crystallization attempts from
diethyl ether reveal both dark brown and green crystals.
X-ray characterization of the brown crystals revealed the
[+] Current address: Centre for Catalysis and Sustainable Chemistry,
II
I
ꢀ
dinuclear [(Me2NN)Cu (ON Me2NN)2Cu ] (1; Figure 1) iso-
lated in 16% yield based on total moles of Cu. This species
has two copper ions in vastly different coordination environ-
ments. Cu1 is linear (N1-Cu1-N3 176.6(2)8), a geometry
observed in copper coordination complexes in the + 1
oxidation state (d10). The coordination environment of Cu2
is square planar completed by two O donors resulting from
Department of Chemistry, Technical University of Denmark
[**] The authors acknowledge funding from the National Science
Foundation (CHE-0135057 and CHE-0716304 to T.H.W.), the
Deutsche Forschungsgemeinschaft (SFB 583), and the Alexander
von Humboldt Foundation (re-invitation award to T.H.W.). M.M.M.
thanks the Luce Foundation for a pre-doctoral fellowship. We are
grateful to Prof. Tom Cundari of the University of North Texas for
helpful suggestions.
ꢀ
the nitrosation of the former b-diketiminato backbone C H
groups in the two modified b-diketiminate ligands coordi-
nated to the linear Cu1 center in 1. Both the square planar
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.200905171.
904
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Chemie
ꢀ
Figure 2. X-ray structure of [(Me2NN)Cu NPh2] (2).
II
I
ꢀ
Figure 1. X-ray structure of [(Me2NN)Cu (ON Me2NN)2Cu ] (1).
ꢀ
[(Me2NN)Cu NPh2] (2) represents a rare example of a
crystallographically characterized three-coordinate cop-
per(II) amide. Peters et al. have recently reported the
configuration at Cu2 as well as the axial EPR spectrum of 1 in
frozen toluene glass (gk = 2.20(1), g? = 2.05(1) with Ak(Cu) =
563(10), A?(Cu) = 70(10) MHz) are consistent with assign-
ment of a CuII center in 1 (see the Supporting Information,
Figures S12 and S13).
structure
of
the
diphosphinoborate
[k2-{Ph2B-
ꢀ
ꢀ
(CH2PtBu2)}Cu N(p-tolyl)2] which exhibits a Cu N bond
distance of 1.906(2) ꢁ.[18] Based on several spectroscopic
measurements, this species was best described as a CuI-
coordinated aminyl radical.[19] Employing chelating ligands,
X-ray structures of two square planar copper(II) amides with
electron-deficient sulfonyl amido substituents[20] as well as
distorted tetrahedral phosphine amide species[21] have been
reported. In copper(I) chemistry, Gunnoe et al. described the
Pentane recrystallization of the green product isolated
from the reaction of Ph2NNO with [{(Me2NN)Cu}2] uncov-
ꢀ
ered the three-coordinate copper(II) amide [(Me2NN)Cu
NPh2] (2) in 31% yield. Identified by a preliminary single-
crystal X-ray diffraction study, a higher-quality X-ray struc-
ture of 2 was obtained through its independent synthesis.
Reaction of [{(Me2NN)Cu}2] with 1 equivalent I2 in diethyl
ether gives [(Me2NN)CuI] (3) in 37% yield. Curiously, this
iodo complex crystallizes as dinuclear [{(Me2NN)Cu}2(m-I)2]
structures of three- and two-coordinate amides such as
[(tBu2PCH2CH2PtBu2)Cu NHPh] and the N-heterocyclic
[22]
ꢀ
ꢀ
carbene based [(IPr)Cu NHPh] (IPr= 1,3-bis(2,6-diisopro-
from
pentane
and
mononuclear,
three-coordinate
pylphenyl)imidazol-2-ylidene).[23]
[(Me2NN)CuI] from diethyl ether as demonstrated by X-ray
structures (Figures S7 and S8). Reaction of 3 with LiNPh2 in
THF delivers copper amide 2 as green crystals in 81% yield
from pentane (Scheme 3).
The electronic spectrum of 2 in diethyl ether exhibits four
bands in the visible to near IR at 426 nm (530mꢀ1 cmꢀ1),
532 nm (280mꢀ1 cmꢀ1), 774 nm (1200 mꢀ1 cmꢀ1), and 908 nm
(1200 mꢀ1 cmꢀ1). TD-DFT analysis suggests that the two
ꢀ
lowest-energy bands at 774 and 908 nm correspond to Cu
N
amide s–p* and p–p* transitions, respectively (Figure S10 and
Table S1). As monitored by UV/Vis spectroscopy, toluene
solutions of 2 (1.2 mm) have a half-life of approximately 7 h at
room temperature, turning colorless after a day. GC/MS
studies reveal that Ph2NH is the primary organic product of
decomposition.
ꢀ
Scheme 3. Independent synthesis of [(Me2NN)Cu NPh2] (2).
Simulation of the X-band EPR spectrum of 2 in frozen
toluene glass (Figure 3) indicates a rhombic signal (g1 =
2.146(3), g2 = 2.043(5), g3 = 2.018(5)) with A1(Cu) =
298(5) MHz. The hyperfine coupling to Cu is modest relative
to that found in other three-coordinate b-diketiminato
copper(II) halide species such as [(Me2NN)CuI] (3) and
[LCuCl][24] (A1(Cu) = 410(5) and 400 MHz, respectively; L =
related b-diketiminate ligand with 2,6-iPr2C6H3 N-aryl
groups). Instead, the A1(Cu) observed in 2 is more similar
to that in Tolmanꢀs three-coordinate CuII phenoxide
[LCuOAr] (Ar= p-MeOC6H4; g1 = 2.22, g2 = 2.07, g3 = 2.02,
A1(Cu) = 280 MHz) in which delocalization of the unpaired
The X-ray crystal structure of 2 (Figure 2) shows a short
ꢀ
ꢀ
Cu Namide distance of 1.841(6) ꢁ with Cu Nb-dik distances of
1.914(6) and 1.885(6) ꢁ. Both the Cu atom and Namido atoms
are planar (sum of angles 359.7(3) and 357.2(5)8, respec-
tively). One of the two N-aryl rings is coplanar with the N
center, while the other is twisted out of the Cu-N-C plane by
ca. 658. The metal–nitrogen distances in 2 are longer than in
ꢀ
the related b-diketiminato nickel(II) amide [(Me3NN)Ni
NPh2][15] (Ni Namide = 1.823(1); Ni Nb-dik = 1.826(1) and
ꢀ
ꢀ
1.833(3) ꢁ).
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905

Communications
(A(N) = 22(7) MHz), DFT suggests a highly anisotropic
interaction with the amido N atom (A2(N) = 37, A1,3(N) =
4(1) MHz) leading to a low predicted value of Aiso(N) =
15 MHz. Complete simulation of the experimental spectrum
of 2 at room temperature (Figure 3) with giso = 2.071(3) and
Aiso(Cu) = 103(3) MHz is best achieved with two different sets
of Aiso(N) values of 27(2) MHz (two N atoms) and 14 MHz
(one N atom). Confirming that Aiso(N) for the amido N atom
is smaller than that of the b-diketiminate
N donors,
[(Me2NN)Cu 15NPh2] leads to very similar EPR spectra
with Aiso(15N) simulated as 18(10) MHz (Figures S14 and
S15).
ꢀ
ꢀ
Figure 3. EPR spectra of [(Me2NN)Cu NPh2] (2) at room temperature
(left) and 30 K (right) in toluene (liquid solution or frozen glass).
The presence of unpaired electron density at the amido N
atom in 2 identifies it as a site of potential reactivity with
other radical species such as NO. We observe the immediate
formation of Ph2NNO when 1 equivalent NOgas is added to
electron onto the phenoxide ring is possible.[25] The EPR
spectrum of 2 is distinct from Petersꢀ CuI aminyl complex [k2-
isolated [(Me2NN)Cu NPh2] (Scheme 4), though at this stage
ꢀ
ꢀ
{Ph2B(CH2PtBu2)}Cu N(p-tolyl)2] which exhibits g values
(2.030, 2.008, 2.008) close to that of the free electron with a
significantly depressed A1(Cu) of 170 MHz.[18]
Nonetheless, DFT analysis of 2 points to appreciable
radical character on the amido N atom as a result of the three-
electron/two-center p interaction between the Cu d orbital
most destabilized by s interactions with the b-diketiminate
ligand (dyz) and the filled lone pair of an sp2 hybridized amido
N atom (py; Figure 4). The d9 CuII center of the b-diketiminato
Scheme 4. Reaction of NOgas (1 equiv) with [(Me2NN)Cu-NPh2] (2).
we cannot discriminate between the location of initial attack
by NO (at Cu or N) in this low-coordinate species. We were
unable to quantify the Ph2NNO initially formed since it can be
consumed by any {(Me2NN)CuI} species formed in solution to
II
I
ꢀ
give [(Me2NN)Cu (ON Me2NN)2Cu ] (1).
This model system allows for the observation of both the
ꢀ
cleavage and formation of the Ph2N NO bond at a common
copper center. While the b-diketiminate ligand is not an
innocent spectator, it provides a framework to allow for the
isolation of the novel three-coordinate copper(II) amide
ꢀ
[(Me2NN)Cu NPh2]. Additionally, the electron-rich b-dike-
timinato coordination environment enables the reductive
ꢀ
cleavage of a nitrosamine N NO bond whereas the reverse
process has been observed in other copper systems. This may
be of particular relevance in the biologically important
generation of NO at copper sites[27] from S-nitrosothiols
RSNO such as S-nitrosoglutathione which serve as circulating
reservoirs of NO in blood plasma.[3,28]
Figure 4. Copper amido two-center/three-electron p-orbital interactions
(left) and net spin density plot for 2 (right; isospin value 0.001).
fragment possesses one electron in this dyz orbital, which
interacts with the lone pair of the sp2 hybridized amido N
Received: September 15, 2009
Revised: October 31, 2009
Published online: December 18, 2009
ꢀ
donor to singly populate the Cu N p* orbital, representing
the SOMO of 2. The DFT spin densities at Cu and N are 0.30
and 0.27eꢀ, respectively, with significant delocalization of
unpaired electron density over the two aryl rings (Figure 4).
These values track opposite to those calculated for Petersꢀ
conceptually related CuI aminyl radical complex (Cu and N
spin densities 0.13 and 0.49eꢀ, respectively).[18] Spectroscopic
and theoretical analysis indicates that the Cu amido p inter-
action in 2 is rather covalent consistent with the modest value
of A1(Cu) observed in the EPR spectrum of 2. This bonding
description for 2 is qualitatively similar to that for related
Keywords: amide ligands · copper · nitric oxide · nitrosylation
.
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