Copper(I)/NO(g) Reductive Coupling Producing a trans-Hyponitrite Bridged Dicopper(II) Complex: Redox Reversal Giving Copper(I)/NO(g) Disproportionation

Article abstract of DOI:10.1021/jacs.7b07808

A copper complex, [Cu^I(tmpa)(MeCN)]⁺, effectively reductively couples NO_(g) at RT in methanol (MeOH), giving a structurally characterized hyponitrito-dicopper(II) adduct. Hydrogen-bonding from MeOH is critical for the hyponitrite complex formation and stabilization. This complex exhibits the reverse redox process in aprotic solvents, giving Cu^I + NO_(g), leading to Cu^I-mediated NO_(g)-disproportionation. The relationship of this chemistry to biological iron and/or copper mediated NO_(g) reductive coupling to give N₂O_(g) is discussed.

Full text of DOI:10.1021/jacs.7b07808

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Communication
(g)
Copper(I) / NO Reductive Coupling Producing a trans-
Hyponitrite Bridged Dicopper(II) Complex – Redox
(g)
Reversal Giving Copper(I) / NO Disproportionation
Gayan B. Wijeratne, Shabnam Hematian, Maxime A. Siegler, and Kenneth D. Karlin
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.7b07808 • Publication Date (Web): 18 Aug 2017
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Copper(I) / NO(g) Reductive Coupling Producing a trans-
Hyponitrite Bridged Dicopper(II) Complex – Redox Reversal
Giving Copper(I) / NO(g) Disproportionation
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Gayan B. Wijeratne,§ Shabnam Hematian,§ Maxime A. Siegler, and Kenneth D. Karlin*
Department of Chemistry, Johns Hopkins University, Baltimore, Maryland 21218, United States.
Supporting Information Placeholder
ABSTRACT: A copper complex, [CuI(tmpa)(MeCN)]+, ef-
fectively reductively couples NO(g) at RT in methanol,
giving a structurally characterized hyponitrito-dicopper(II)
adduct. Hydrogen-bonding from MeOH is critical for the
hyponitrite complex formation and stabilization. This
complex exhibits the reverse redox process in aprotic sol-
vents, giving CuI + NO(g), leading to CuI-mediated NO(g) dis-
proportionation. The relationship of this chemistry to bio-
logical iron and/or copper mediated NO(g) reductive cou-
pling to give N2O(g) is discussed.
gram above). Evolutionarily related heme-Cu oxidases
(HCO’s) effect this reaction, albeit with lower efficien-
cy.6
Our own interests encompass hemes and/or Cu,2a,7
and in this report we focus on the latter. In addition to
HCO NO(g) reductive coupling, copper nitrite reductases
may also couple excess NO(g) present to give N2O(g).1a
Further, in the presence of O2(g), Cu–NO reactivity can
lead to peroxynitrite (O=NOO–).2b,8 Also, copper com-
plexes are efficient at NO-disproportionation, 3NO(g)
+
–
CuI ➔N2O(g) + CuII(NO2 ), possibly also involving hyponi-
trite-type intermediates.1b,9 As well, copper ion loaded
zeolites are effective catalysts to decompose NOx to N2
and O2; automobile catalytic converters may utilize Cu
as a catalyst for NO(g) reduction to N2O(g).10
The interactions and reactivity of redox active metal
ions with nitrogen oxides has widespread implica-
tions/importance in environmental, practical and bio-
logical chemistries. Iron and copper provide for facile
redox shuttling and one and/or the other in the pres-
ence of proton sources chemically or enzymatically facil-
With this background, we highlight the need to eluci-
date fundamental aspects of NO(g) reductive coupling,
details/requirements for (i) N–N bond formation and (ii)
N–O bond cleavage for hyponitrite formation and N2O
elimination, respectively. Even though hyponitrite in-
termediates have been proposed/observed within en-
zymatic systems, details pertaining to their binding
mode within the binuclear active site, protonation
state(s), and the metal oxidation states, all remain elu-
sive.11 In this report, employing the copper(I) complex
[CuI(tmpa)(MeCN)](B(C6F5)4) (TMPA = tris-(2-pyridyl-
methyl)amine), we describe (i) the first example of a
copper(I) complex whose NO(g) reactivity leads to effi-
cient reductive coupling to give the hyponitrite complex
[{CuII(tmpa)}2(µ-N2O22–)]2+, (ii) the first structurally char-
acterized Cu-only hyponitrite complex, and (iii) the ef-
fective reversal of NO reductive coupling occurring for
the hyponitrite complex in tetrahydrofuran (THF), i.e.,
formation of a putative {[CuI(tmpa)]+ + NO(g)} solution
mixture, followed by NO-disproportionation (Figure 1).
–
itates reactions such as reduction of nitrite (NO2 ) to
nitrogen monoxide (NO(g); nitric oxide), reductive cou-
pling of NO(g) to nitrous oxide (N2O(g)) and reduction of
1
N2O(g) to N2(g)
.
–
–
cis-Hyponitrite
O
O
O
2 e–
N N
or
2 H+
2 NO
N2O
H2O
+
–
N–N bond
formation
N–O bond
cleavage
N N
O
– trans-Hyponitrite
Biological roles of NO include it as a signaling agent,
yet it can be toxic under oxidative conditions; NO is uti-
lized in the human immune response, produced in ele-
vated levels to effect invading pathogen biomolecule
destruction (e.g., by oxidation or nitration).2 Fighting
back, bacteria/pathogens can upregulate NO-reductase
(NOR) activity to eliminate toxic NO by its reductive
coupling to give benign N2O.3 Bacterial NOR’s1d,4 pos-
sess heme/non-heme diiron active sites, effecting the
coupling through a putative hyponitrito (N2O22–) inter-
mediate;5 the metal ion centers provide electrons (dia-
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[CuI(tmpa)]+ + xs. NO(g) ➔{[ Cu(tmpa)(NO)]n}
➔[{CuII(tmpa)}2(-N2O22–)]2+
MeOH
THF
+
N
1
2
3
4
5
6
7
8
N
+
N
2+
CuI
N
(Eq. 1)
2
N
NO
N
N
CuI
N
N
N
2/3
NCMe
N
CuII
O
N
[CuI(tmpa)(MeCN)]+
With the intention of further supporting our complex
formulation, we probed the CuI/NO(g) stoichiometry;
[CuI (tmpa)(MeCN)]+ was titrated with varying amounts
of NO(g) from a NO(g)-saturated MeOH solution {[NO(g)] =
14.5 mM at RT}.12 The data clearly indicates that the
CuI/NO(g) stoichiometry, as measured in this manner,
lies between 1 and 1.5, very close to the expected 1:1
stoichiometry.12-13 It is presumed that NO(g) reaction
with [CuI(tmpa)(MeCN)]+ gives a CuI-NO adduct, per-
haps like that previously reported on (but in EtCN),14
prior to NO(g)-coupling to give the hyponitrito-
dicopper(II) complex (Eq. 1).5
N
N
1/3 N2O
O
CuII
N
+
N
N
N
N
N
Ag2N2O2
+
N
CuII
N
2
N
1/3
N
CuII
N
OH
N
[{CuII(tmpa)}2(µ-N2O22–)]2+
[CuII(tmpa)(OH)]+
NO2
Figure 1. Divergent synthetic routes to [{CuII(tmpa)}2(-
N2O22–)]2+ in MeOH, and its unique redox behavior in THF,
effecting CuI-mediated NO-disproportionation.
When excess NO(g) is bubbled through a RT MeOH so-
lution of [CuI(tmpa)(MeCN)]+, the initial pale yellow so-
lution immediately transforms to forest green giving
electronic absorption features: λmax = 310 (ε = 3800 M-1
cm-1), 675 (ε = 180 M-1 cm-1), and 870 (ε = 240 M-1 cm-1))
(Figure 2). An EPR spectrum of the green solution re-
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[{CuII(tmpa)}2(µ-N2O22–)]2+ can also be generated by a
metathesis reaction involving the CuII-OH complex,
[CuII(tmpa)(OH)]+, generated and isolated by reaction of
veals a classic reverse axial pattern (g > g||) indicating a

tetrabutylammonium
hydroxide
with
dz2 ground state, with a single type of mononuclear
copper(II) environment occurring in a trigonal bipyrami-
dal (TBP) geometry; this also indicates that the cop-
per(II) ions are electronically site-isolated, i.e., no mag-
netic/electronic interaction between the two copper(II)
ions occurs. Upon solvent removal, this new complex
was obtained in near stoichiometric yields (> 97%) and
[CuII(tmpa)(MeCN)]-(ClO4)2 in MeCN at RT ((O–H) =
3533 cm-1).12 Freshly generated CuII(tmpa)(OH)]+ mixing
with ½ equiv Ag2N2O2 in MeOH, with sonication, gave a
color change from light green to forest green. The UV-
vis changes correspond with those seen for the hyponi-
trito-dicopper(II) complex obtained via the {[CuI + NO(g)}
reaction.12 Isolation of the solid product and redissolu-
tion into a MeOH/EtOH = 1:1 solution also gives the
same EPR spectrum (20 K).12
it is the hyponitrito complex [{CuII(tmpa)}2(-N2O2
2–
)](B(C6F5)4)2•2H2O•2CH3OH, (Eq. 1).12
X-ray quality crystals of [{CuII(tmpa)}2(µ-N2O2
2–
)](ClO4)2 could be obtained from MeOH at –35 °C, and
the structure of the dicationic portion is shown in Figure
3. The complex possesses a dicopper-bridged η1-O-
trans-hyponitrite species with a Cu…Cu distance of
5.5647(5) Å; the dication possesses a centrosymmetric
structure. Each copper(II) ion is pentacoordinate, with
the four N-atoms from the TMPA chelate plus the anion-
ic hyponitrito O-atoms (O1 or O1’; Figure 3). However,
there also exists a clear interaction of Cu ions with the
distal N-atom of the N2O22– moiety, (Cu–N = 2.851(2) Å),
i.e., Cu1 interacts with N5’, with Cu1’ interacting with
N5 (Figure 3, shown in broken lines). See the SI (page
S10) for information and arguments in support of this
point. We hypothesize that this weak interaction trans-
forms into
a
“true” metal-ligand bond when
[{CuII(tmpa)}2(µ-N2O22–)]2+ is put into aprotic solvents
(vide infra; Scheme 1).
Figure 2. Top: Electronic absorption spectrum resulting
from the NO(g) reactivity with 1 mM [CuI(tmpa)(MeCN)]+ in
MeOH at RT. Bottom: EPR spectra (experimental (green)
and simulated (red)) of [{CuII(tmpa)}2(µ-N2O22–)]2+ (2 mM in
MeOH/EtOH = 1:1 glass) at 20 K (g = 2.18, g|| = 1.99; A =
82 G, A|| = 90 G).
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cal to that (5.566 Å) of the Agapie’s19 copper-yttrium
1
2
3
4
5
6
7
8
N2
complex with bridged copper-bound hyponitrite adduct.
(d) A number of differing structures have been pro-
posed based on computational analyses for HCO, NOR
or other protein hyponitrite species (see diagram be-
low; M = Fe or Cu).4e,6d,20
N4
N3
Cu1
N1
2.851 Å
O1
N5'
N5
2.851 Å
O1'
N1'
9
Cu1'
N2'
N3'
N4'
10
11
12
13
When solid samples of [{CuII(tmpa)}2(µ-N2O22–)]2+ (as
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Figure 3. X-ray diffraction ORTEP diagram (50% probability
thermal ellipsoids) of [{CuII(tmpa)}2(µ-N2O22–)]2+ along with
the atom numbering scheme. Hydrogen atoms and nonco-
ordinating perchlorate counteranions are omitted for clari-
ty.12
–
–
(B(C6F5)4 or ClO4 salts) are dissolved in THF, or excess
THF is added to the complex already dissolved in MeOH,
a reaction takes place, and a mixture of products are
formed (Figure 1), which we hypothesize to arise from a
2–
rearrangement of the N2O2 ligand,21 followed by
Thus, the copper(II) ions in this structure are distorted
octahedrally ligated (six-coordinate), which contrasts
greatly with other many well characterized
[CuII(tmpa)(X)]n+ species such as those with X = Cl– (n =
transformations leading to the products seen from reac-
tion of CuI(tmpa)]+ + NO(g) in non-alchoholic solvents,
namely NO(g)-disproportionation, 3NO(g) + CuI ➔N2O(g) +
–
CuII–NO2 . We speculate that either THF effects a “re-
–
1),15 X = nitrito (NO2 , O-bound; n = 1)16 and X = NCCH3
verse” reaction to give a {[CuI(tmpa)]+ + NO} solutions,
or [{CuII(tmpa)}2(µ-N2O22–)]2+ reacts to give N2O(g) and
the CuII-nitrito complex by an as yet undetermined
mechanism. However, since there is only one equiv. of
NO(g) per Cu(I) ion present, excess {[CuI(tmpa)]+ is left
over, giving the mixture of products described by
Scheme 1.
(n = 2).17
Recall that methanolic solutions of
[{CuII(tmpa)}2(µ-N2O22–)]2+ possess a well-defined TBP
coordination geometry, as distinctly and unambiguously
observed from frozen solution EPR spectra (vide supra).
In fact, this hyponitrito-dicopper(II) complex
[{CuII(tmpa)}2(µ-N2O22–)]2+ is only stable in alcoholic
solvents; we thus conclude that the latter observation
2–
Scheme 1. Proposed decay of [{CuII(tmpa)}2(µ-N2O22–)]2+
placed in THF, giving a final product mixture consisting of
[CuI(tmpa)]+, [CuII(tmpa)(NO2)]+, and N2O(g).
indicates that MeOH hydrogen-bonds to the N2O2 lig-
and of the complex, probably with the lone pairs on the
central N-atoms. Such an interaction has recently been
suggested by Liaw and coworkers18 although in that case
H-bonding to the CoII-NO O-atom is proposed, which
aids the formation of a hyponitrite meta-stable species.
Such H-bonding in solution would ‘relieve’ the structur-
ally observed weak interaction between N5 or N5’ with
copper(II) ion, leaving only the O1-to-Cu1 (and O1’-to-
Cu1’) bond interaction in addition to N4 ligation from
TMPA, allowing for strict TBP coordination (as expected
from EPR spectra).
Further aspects of the solid-state structure of
[{CuII(tmpa)}2(µ-N2O22–)]2+ are as follows: (a) The N−N
and N−O distances of the trans-hyponitrite moiety are
1.257(3) Å and 1.361(2) Å respectively, which compare
well with the N=N double bond (1.256(2) Å) and N−O
single bond (1.3622(11) Å) distances of trans-sodium
hyponitrite.5b (b) The Cu…Cu distance of 5.565(7) Å is
much shorter compared with the Fe–Fe distance (6.7 Å)
in [(OEP)FeIII-ONNO-FeIII(OEP)] (OEP = octaethylporphy-
rinate), with extended hyponitrito; O,O’ bonding to
iron(III) occurs, but there are no Fe…N(hyponitrite) interac-
tions.20c (c) The Cu…Cu distance here is virtually identi-
2+
2+
N
N
N
N
CuII
CuII
N
N
N
N
N
–
O
O
N
N
O
N
–
O
N
CuII
N
N
CuII
N
N
N
N
N
+
+
N
N
N
N
CuI
1/3 N2O
CuII
N
2/3
N
1/3
N
N
NO2
Experiments carried out on the final product solution
confirm the identity, yields and relative-yields of the
transformation of [{CuII(tmpa)}2(µ-N2O22–)]2+ originally
formed by the {CuI + NO(g)} reaction (vide supra) (with
stoichiometry of Scheme 1). (a) Cooling the decay prod-
o
uct mixture in THF to –80 C and bubbling with O2(g) led
to the formation of the well-known trans-peroxo-
dicopper(II) complex, [{CuII(tmpa)}2(µ-O22–)]2+;22 with
known molar absorptivities, one could related back to
the finding of a 96% yield of [CuI(tmpa)]+.12,22 (b) Previ-
ously published methodologies16 were followed to de-
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termine and quantify the nitrite content in the final de-
1
2
3
4
5
6
7
8
cay mixture, giving >85 % yields,12 and (c) the head-
space of the decay product mixture was sampled by gas
chromatographic analysis for the identification and
quantitation of product N2O(g); yields of ~85 % were
obtained.12 The decay of [{CuII(tmpa)}2(µ-N2O22–)]2+ orig-
inally formed by the {CuII-OH + Ag2N2O2} method (vide
supra), gave 96 % [CuI(tmpa)]+, > 85 % yield of nitrite
and 98 % yield N2O(g),12 again all based on the Scheme 1
reaction stoichiometry.
AUTHOR INFORMATION
Corresponding Author
*karlin@jhu.edu
Author Contributions
§These authors contributed equally.
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Funding Sources
Finally, to further verify the solvent effect for the
{[CuI(tmpa)]+ + NO(g)} reaction, we carried out separate
experiments. When [Cu(tmpa)(MeCN)]+ is subjected to
excess NO(g) in THF solution at RT, the pale yellow solu-
tion immediately turns to an olive green color exhibiting
the UV-vis features corresponding to the nitrito com-
plex [CuII(tmpa)(NO2)]+ (96 % yield) λmax = 303 (ε = 3360
M-1 cm-1), 420 (ε = 1340 M-1 cm-1) nm. N2O(g) is also
produced, so we can conclude that NO-
disproportionation occurs.1b As described in detail
above, in MeOH as solvent, the hyponitrito dicopper(II)
complex forms. It is remarkable how the reactivity be-
tween [CuI(tmpa)]+ and NO(g) modify to such great ex-
tent merely by altering the solvent properties.
No competing financial interests have been declared.
ACKNOWLEDGMENT
The research support of the National Institutes of Health
(GM 060353) is gratefully acknowledged.
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In summary, herein we report the first Cu-only system
that mediates the reductive coupling of NO(g), stoichio-
metrically yielding the corresponding hyponitrito-
dicopper(II) complex in MeOH at RT. We suggest that H–
2–
bonding to the N2O2 ligand is key to its stabilization
and this course of reaction. Unlike other synthetic bio-
inspired examples,5a,7b,19,23 this reaction does not re-
quire any low-temperature conditions, and is independ-
ent of the equiv of added NO(g). The new hyponitrito
complex possesses versatile synthetic pathways, and is
characterized by X-ray crystallography. Dissolution in
aprotic solvents triggers its decay with essentially the
reversal of NO(g) coupling, leading to products of CuI-
mediated NO-disproportionation. We should also note
that addition of HCl to [{CuII(tmpa)}2(µ-N2O22–)]2+ in
MeOH gives rise to the release of N2O(g).12 Such unique
redox behavior involving copper and NO(g) is unprece-
dented, and may have implications in metalloenzyme
related NO(g)/nitrogen-oxide biochemistry. A deeper
understanding is needed as pertains to the NO-coupling
mechanism (N–N bond formation), the oxidation and/or
protonation state of the N2O2-type intermediate
formed6a,9,11,24 and the mechanism of (N–O bond cleav-
age) N2O(g) formation.
ASSOCIATED CONTENT
Synthetic and analytical details (methodologies and UV-
Vis, EPR, NMR and FT-IR spectra; gas chromatograms); X-
ray diffraction data collection details and CIF file. This ma-
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(10) (a) Kwak, J. H.; Tran, D.; Szanyi, J.; Peden, C. H. F.; Lee, J.
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Granger, P.; Parvulescu, V. I. Chem. Rev. 2011, 111, 3155. (d)
Mohiuddin, A. K. M. Adv. Mater. Res. 2015, 1115, 462.
(11) (a) Yi, J.; Morrow, B. H.; Campbell, A. L. O. C.; Shen, J. K.;
Richter-Addo, G. B. Chem. Comm. 2012, 48, 9041. (b) Daskalakis,
V.; Ohta, T.; Kitagawa, T.; Varotsis, C. Biochim. Biophys. Acta
2015, 1847, 1240.
(20) (a) Blomberg, M. R. A.; Siegbahn, P. E. M. J. Comput.
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possible, although the calculations of Richter-Addo and Lehnert
suggest it to be higher energy then that for O-coordination. (b)
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Richter-Addo, G. B.; Lehnert, N. Inorg. Chem. 2014, 53, 6398.
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15660.
(12) See Supporting Information.
9
(13) NO(g)-saturated solutions used likely lose some NO(g) into
the headspace of the Ar-filled cuvette containing
[CuI(tmpa)(MeCN)]+ during each experiments, while NO(g)
equilibrates between the liquid-gas interface. Thus, the actual
CuI:NO(g) stoichiometry could be slightly smaller than the
experimentally observed ratio.
(14) Paul, P. P.; Karlin, K. D. J. Am. Chem. Soc. 1991, 113, 6331.
(15) Karlin, K. D.; Hayes, J. C.; Shi, J.; Hutchinson, J. P.; Zubieta,
J. Inorg. Chem. 1982, 21, 4106.
(16) Hematian, S.; Siegler, M. A.; Karlin, K. D. J. Am. Chem. Soc.
2012, 134, 18912.
(17) Fox, S.; Nanthakumar, A.; Wikström, M.; Karlin, K. D.;
Blackburn, N. J. J. Am. Chem. Soc. 1996, 118, 24.
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(24) (a) Even the N2O21– radical form of the intermediate in NO
reductive coupling has been observed spectroscopically24b or
proposed.6.9 (b) Brozek, C. K.; Miller, J. T.; Stoian, S. A.; Dincă, M.
J. Am. Chem. Soc. 2015, 137, 7495.
TOC Graphic
THF
NO
MeOH
NO
2+
Disproportionation
N
Reductive Coupling
N
+
+
CuII
O
N
N
N
+
N
N
N
2/3
N CuIN
CuI
2
N
N
N
N
O
CuII
N
NCMe
+
N2O
1/3
N
N
N
N
N
1/3
N CuII
N
NO
[{CuII(tmpa)}2(µ-N2O22–)]2+
NO2
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