Synthesis and characterization of a series of (diphenyldipyrazolylmethane) copper complexes as possible precursors to type I blue copper protein active site models

Article abstract of DOI:10.1002/ejic.200300547

A series of copper complexes employing the neutral, bidentate, pyrazole-based ligand diphenyldipyrazolylmethane was synthesized and fully characterized by various techniques, including elemental analysis, EPR, and structure elucidation by single-crystal X-ray diffraction. The structures of compounds 3-8 reveal variable coordination environments at the copper center, ranging from square pyramidal to tetrahedral, depending on the steric bulk at the pyrazole periphery and on the identity of the counterion. Cyclic voltammetry data on these compounds show a positively shifted reduction potential as compared to those observed employing the negatively charged pyrazolylborates or β-diketiminates. These results indicate that these compounds may lead to (thiol)copper complexes that more accurately reproduce the reduction potentials observed during electron-transfer processes in blue copper proteins. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.

Full text of DOI:10.1002/ejic.200300547

FULL PAPER
Synthesis and Characterization of a Series of
(Diphenyldipyrazolylmethane)copper Complexes as Possible Precursors to
Type I Blue Copper Protein Active Site Models
Janet L. Shaw,[a] Thomas B. Cardon,[b] Gary A. Lorigan,[b] and Christopher J. Ziegler*[a]
Keywords: Copper / N ligands / Pyrazolylmethanes / Scorpionates
A series of copper complexes employing the neutral, bident-
these compounds show a positively shifted reduction poten-
ate, pyrazole-based ligand diphenyldipyrazolylmethane was tial as compared to those observed employing the negatively
synthesized and fully characterized by various techniques,
including elemental analysis, EPR, and structure elucidation
charged pyrazolylborates or β-diketiminates. These results
indicate that these compounds may lead to (thiol)copper
by single-crystal X-ray diffraction. The structures of com- complexes that more accurately reproduce the reduction po-
pounds 3−8 reveal variable coordination environments at the
copper center, ranging from square pyramidal to tetrahedral,
depending on the steric bulk at the pyrazole periphery and
on the identity of the counterion. Cyclic voltammetry data on
tentials observed during electron-transfer processes in blue
copper proteins.
( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2004)
model complexes that can more accurately model the ge-
ometry and electronic structure of metal ions in proteins.
Introduction
Small models of the active sites of metalloenzymes re-
main important for understanding the structureϪfunction
relationships that exist between immediate metal-ion coor-
dination environments and activities such as electron trans-
port or dioxygen activation. Scorpionate ligands, such as
the sterically hindered pyrazolylborates (see Figure 1), have
been successful in mimicking many of the coordination geo-
metries observed in the active sites of metalloproteins.[1Ϫ3]
In addition to numerous zinc complexes,[4Ϫ6] pyrazolylbo-
rates have been employed for generating models of both
type I blue copper proteins[7Ϫ10] and type III dicopper pro-
teins,[11] such as plastocyanin and hemocyanin,
respectively.[12Ϫ13] The ease of synthesis, the ability to add
additional bulk to the pyrazole moieties, and the favorable
multidentate binding mode are all responsible for the con-
tinued interest in pyrazolylborates as ligands for small
model complexes. However, pyrazolyborates are negatively
charged and can lead to complexes with higher oxidation
states than those of the metal sites in native proteins.[14]
Therefore, work continues toward the development of
Figure 1. Schematic drawings of the ligands tris(pyrazolyl)borate
(left) and diphenyldipyrazolylmethane (right) where R ϭ RЈ ϭ H
(1), R ϭ RЈ ϭ CH3 (2) and R ϭ CH3, RЈ ϭ H (3)
We have begun to explore the synthesis of active site
models for copper proteins using the ligand diphenyldipyraz-
olylmethane, shown in Figure 1. Synthesized previously for
use in polymerization catalysis,[15Ϫ16] this ligand is neutral
and contains two pyrazole moieties available for bidentate
metal-ion coordination. Like the pyrazolylborates, the pyra-
zole rings may be functionalized to incorporate more steric
bulk around the copper center. This can be exploited to
enforce desired geometries, inhibit the formation of bridg-
ing species, or promote low-coordination-number end prod-
ucts. Once synthesized, these compounds may be useful as
starting materials in reactions with thiol or carboxylate-
containing ligands to produce small model complexes of
copper-enzyme active sites. Since these models incorporate
a neutral ligand, we believe that they will exhibit redox po-
tentials that more closely resemble those observed in nature
[a]
University of Akron, Department of Chemistry,
Akron, OH 44325, U.S.A.
Fax: (internat.) ϩ1-330-972-7370
E-mail: ziegler@uakron.edu
[b]
Miami University, Department of Chemistry,
Oxford, OH 45056, U.S.A.
Supporting information for this article is available on the
WWW under http://www.eurjic.org or from the author.
Eur. J. Inorg. Chem. 2004, 1073Ϫ1080
DOI: 10.1002/ejic.200300547
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J. L. Shaw, T. B. Cardon, G. A. Lorigan, C. J. Ziegler
FULL PAPER
for type I blue copper proteins. Here we report our results propriate ligand in a number of organic solvents. In most
on the synthesis and characterization of some (diphenyldi- cases the final product remained soluble throughout the re-
pyrazolylmethane)copper complexes including crystal struc- action and was isolated by recrystallization from the appro-
tures, cyclic voltammetry, and electron paramagnetic reson- priate solvent. All reactions produce X-ray quality crystals
ance spectra. We observe high potentials for the CuII/CuI with little purification required.
redox couple, and increased steric bulk at the periphery of
the pyrazole ring enforces lower coordination numbers.
A survey of the literature uncovers few examples of 1:1
complexes forming between dipyrazolyalkanes and either
copper() or copper(),[18Ϫ21] with the preference instead
being 2:1 ligand-to-metal complexation.[22Ϫ23] Of these, less
crystallographic information is available and the com-
pounds have instead been characterized by other techniques
such as IR spectroscopy, magnetic susceptibility, EPR, and
1H NMR spectroscopy. The stoichiometry of the observed
final products in the literature appears to depend on the
starting copper salt (chloride salt vs. nitrate salt) and the
degree of steric hindrance at the pyrazole periphery.
Results and Discussion
The diphenyldipyrazolylmethanes (Figure 1, right) were
synthesized using a modified procedure reported by Trofi-
menko that involves the generation of a pyrazolide ion and
subsequent reaction with a dihalomethane.[17] These ligands
have previously been employed in molybdenum[15] and pal-
Unlike in the dipyrazolylalkane complexes, the majority
ladium[16] complexes for use as catalysts. Figure 2 shows the of the compounds reported here form 1:1 complexes. The
crystal structures elucidated for ligands 1 and 2. The geometries of compounds 4Ϫ8 range from square pyrami-
˚
C(1)ϪN(1,3) bond lengths in 1 are 1.490(4) A and 1.484(4) dal to tetrahedral, depending on the steric bulk at the pyra-
˚
˚
A, respectively, while in 2 they are 1.4753(17) A and zole periphery and the counterion identity. Table 2 and
˚
1.4754(16) A. The angle formed by N3ϪC1ϪN1 in 1 is Table 3 present relevant bond lengths and angles and the
108.0(2)°, while in 2 it is 104.85(10)°. Based on their struc- crystallographic data for compounds 4Ϫ8, respectively.
tural characteristics, these ligands should act as bidentate Compound 4 (see Figure 3) is best described as having a
chelators. A comparison of the bond angles and lengths for distorted square-pyramidal geometry. The copper() center
these two ligands can be found in Table 1.
is ligated by one bidentate 1 ligand, two nitrates and one
The copper complexes were synthesized by a reaction of water molecule in the axial position. The methanol em-
either copper() nitrate or copper() chloride with the ap- ployed in this reaction was not dried prior to use, and the
Figure 2. Structures of compounds 1 and 2 with thermal ellipsoids drawn at 50 % probability
˚
Table 1. Comparison of bond lengths (A) and angles (°) in 1 and 2
1
2
CϪN
CϪC
C1ϪN1 1.490(4)
C1ϪC2 1.535(4)
C1ϪN3 1.484(4)
C1ϪC8 1.521(4)
C1ϪN1 1.4753(17)
C1ϪC12 1.5459(18)
C1ϪN3 1.4754(16)
C1ϪC18 1.5455(18)
NϪCϪN
CϪCϪC
NϪCϪC
N1ϪC1ϪN3 108.0(2)
C2ϪC1ϪC8 113.3(3)
N1ϪC1ϪC2 109.0(2) N3ϪC1ϪC2 108.6(3)
N1ϪC1ϪN3
C12ϪC1ϪC18 107.26(10)
N1ϪC1ϪC12 112.68(10) N3ϪC1ϪC12 109.53(10)
104.85(10)
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Synthesis and Characterization of (Diphenyldipyrazolylmethane)copper Complexes
FULL PAPER
ligated water molecule may have come from residual water fashion. The lack of a coordinating water molecule may be
in the reaction solvent. The nitrates bind in a monodentate due to the increase in steric bulk at the 3 position of the
˚
fashion with CuϪO distances of 1.971(3) A and 1.975(3) pyrazole ring in 5. The coordination sphere of 5 is com-
˚
A. Within the literature, the modes of nitrate bonding can pleted with a bidentate 3 ligand [CuϪN4 1.9344(18) and
vary. For example, in the similar compound CuϪN2 1.9610(18)] and one monodentate nitrate group
˚
Cu(bmpp)(NO3)2 the two nitrates coordinate to the copper [CuϪO1 2.1361(17) A]. Increasing the steric bulk at the
in an unsymmetrical bidentate fashion with CuϪO dis- pyrazole periphery in compound 5 alters the geometry from
tances of 2.026(2) A.[24] The CuϪO distance for the coordi- square pyramidal to pseudotetrahedral. In addition, the co-
˚
˚
nating water molecule is 2.256(4) A and the CuϪN bond ordination geometry at the copper center is affected by the
˚
lengths are both around 1.986(4) A.
binding mode of the nitrate counterion. Whereas in com-
pound 4 both nitrates ligate in a monodentate fashion, in
compound 5 one nitrate is bidentate and the other is mono-
dentate. This variable coordination mode of the nitrate
counterion is not uncommon.
Unlike the CuII compounds, the CuI compound 7, shown
in Figure 5, forms a product with a 2:1 ratio of ligand to
metal ion. The copper ion is in a distorted tetrahedral en-
vironment with two bidentate 1 ligands with CuϪN dis-
˚
˚
tances ranging from 2.007(3) A to 2.045(3) A and with
NϪCuϪN angles ranging from 91.38(10)° to 128.05(10)°.
The intraligand NϪCuϪN angles are closer to 90° while
the interligand NϪCuϪN angles are both near 120°. The
bond lengths compare nicely to those reported for other 2:1
[23]
˚
complexes [Cu(bpp)2](BF4) (about 2.031 A) and [CuL2]-
˚
(ClO4) (about 2.037 A), where L ϭ bis[2,2Ј-bis(2-imidazolyl)-
biphenyl].[25] The bond angles in compound 7 show a slight
compression along the intraligand axes. These bond angles
compare well with those observed in the copper() com-
plexes α- and β-[Cu(bpp)2](BF4)2 (95.23Ϫ127.20° and
91.34Ϫ135.66°, respectively).[23] It is unclear as to why 7
exists as a 2:1 complex, but similar results have been ob-
served in the literature: the ligand-to-metal ratio was found
to depend not only on the steric bulk at the pyrazole per-
iphery but also on the identity of the counterion.[21,26]
Figure 3. Structure of compound 4 with hydrogens omitted for clar-
ity and thermal ellipsoids drawn at 50 % probability
Compound 5 (Figure 4) exhibits a similar geometry to
complex 4, but the water molecule in the coordination
sphere is absent and one of the nitrates binds in a bidentate
˚
fashion with CuϪO distances of 1.9959(16) A and
˚
2.0110(19) A. These distances are somewhat longer than
those seen in 4 for the nitrates bound in a monodentate
˚
Table 2. Comparison of bond lengths (A) and angles (°) in compounds 4Ϫ8
4
5
6
7
8
CuϪN
CuϪX
CuϪN2 1.985(4)
CuϪN4 1.986(4)
CuϪN2 1.9610(18)
CuϪN4 1.9344(18)
CuϪN1 2.008(5)
CuϪN3 1.978(5)
CuϪN5 1.991(5)
CuϪN2 2.032(3)
CuϪN4 2.007(3)
CuϪN5 2.045(3)
CuϪN7 2.007(3)
CuϪN2 1.961(4)
CuϪN4 2.011(4)
CuϪO1 1.975(3)
CuϪO4 1.971(3)
CuϪO7 2.256(4)
CuϪO1 2.1361(17)
CuϪO4 1.9959(16)
CuϪO5 2.0110(19)
CuϪO2 2.310(5)
CuϪO4 2.025(4)
CuϪCl1 2.2071(15)
CuϪCl2 2.2388(16)
NϪCuϪN N2ϪCuϪN4 87.59(15) N2ϪCuϪN4 90.25(8) N1ϪCuϪN3 92.10(2) N2ϪCuϪN4 91.38(10) N2ϪCuϪN4 88.72(16)
N3ϪCuϪN5 89.9(2)
N1ϪCuϪN5 176.1(2)
N5ϪCuϪN7 91.54(10)
N2ϪCuϪN5 105.03(9)
N4ϪCuϪN7 119.18(8)
N2ϪCuϪN7 124.26(10)
N4ϪCuϪN5 128.05(10)
XϪCuϪX O4ϪCuϪO1 93.53(15) O4ϪCuϪO5 64.12(7) O2ϪCuϪO4 84.84(15)
O4ϪCuϪO7 82.03(15) O4ϪCuϪO1 105.44(7)
Cl1ϪCuϪCl2 95.82(6)
O1ϪCuϪO7 81.85(16) O1ϪCuϪO5 105.00(7) O4ϪCuϪN1 85.55(17)
XϪCuϪN O4ϪCuϪN2 176.82(16) O4ϪCuϪN2 101.43(7) O2ϪCuϪN1 88.39(17)
O1ϪCuϪN4 176.71(16) O5ϪCuϪN2 158.02(8) O4ϪCuϪN3 170.72(19)
O1ϪCuϪN2 89.33(15) O1ϪCuϪN2 94.59(7) O4ϪCuϪN5 91.95(18)
O4ϪCuϪN4 89.53(15) O1ϪCuϪN4 96.42(7) O2ϪCuϪN3 104.08(17)
O7ϪCuϪN2 97.00(16) O4ϪCuϪN4 154.12(7) O2ϪCuϪN5 94.33(18)
O7ϪCuϪN4 97.37(16) O5ϪCuϪN4 97.23(7)
Cl1ϪCuϪN2 153.42(13)
Cl1ϪCuϪN4 95.66(12)
Cl2ϪCuϪN2 91.36(12)
Cl2ϪCuϪN4 153.99(12)
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FULL PAPER
Table 3. Crystallographic data for compounds 1؊2 and 4؊8.
1
2
4
5
6
7
8
Molecular formula
Fw
C19H16N4
300.36
Ortho-rhombic
Pna21
C23H24N4
356.46
Monoclinic
P21/n
C19H18CuN6O7 C21H20CuN6O6 C15H24CuN8O6
C38H32N8Cl2Cu2 C19H16Cl2CuN4
505.93
515.97
475.96
798.70
Monoclinic
Cc
434.80
Triclinic
¯
P1
Crystal system
Space group
Cell constants
Monoclinic
P21/n
Orthorhombic Orthorhombic
P212121
Pbca
˚
a (A)
14.857(5)
14.343(5)
7.113(2)
90
90
90
10.5405(11)
10.5904(11)
16.9489(18)
90
93.549(2)
90
10.1001(15)
12.7917(19)
15.494(2)
90
8.7650(8)
9.4840(9)
26.280(2)
90
12.488(3)
11.531(3)
29.564(7)
90
21.0687(15)
11.5004(8)
17.2606(12)
90
115.806(10)
90
7.461(3)
9.126(3)
13.938(5)
81.098(7)
76.729(7)
89.966(7)
2
˚
b (A)
˚
c (A)
α (deg)
β (deg)
γ (deg)
Z
90.176(2)
90
90
90
90
90
4
4
5
4
8
4
3
˚
V (A )
1515.8(9)
0.081
1.316
632
1888.3(3)
0.076
1.254
2001.8(5)
1.437
2.098
2184.6(4)
1.052
1.569
1060
4257.1(17)
1.075
1.485
1976
3765.1(5)
1.310
912.0(6)
1.501
Abs. coeff. µcalc (mmϪ1
δcalc (Mg/m3)
F(000)
)
1.409
1.583
760
1295
1632
442
Cryst. dimens. (mm)
No. of reflcns. collcd.
No. of unique reflcns.
No. of params.
R(F)
0.2 ϫ 0.1 ϫ 0.05 0.3 ϫ 0.2 ϫ 0.05 0.4 ϫ 0.1 ϫ 0.1 0.4 ϫ 0.3 ϫ 0.2 0.1 ϫ 0.03 ϫ 0.03 0.1 ϫ 0.2 ϫ 0.2 0.1 ϫ 0.1 ϫ 0.05
12699
3612
16284
4468
16932
4651
18485
5198
34627
5131
16313
8483
6670
3185
272
340
370
387
289
451
299
0.0702
0.1317
1.035
0.0469
0.1044
1.044
0.0723
0.1321
1.267
0.0325
0.0739
1.074
0.1180
0.1786
1.280
0.0383
0.0919
1.033
0.0576
0.1020
1.037
0.826543
Rw(F2)
GOF
Ratio min/max trans.
0.730155
0.906570
0.632826
0.776535
0.460436
0.892294
Figure 5. Structure of compound 7 with hydrogens omitted for clar-
ity and thermal ellipsoids drawn at 50 % probability
Figure 4. Structure of compound 5 with hydrogens omitted for clar-
ity and thermal ellipsoids drawn at 50 % probability
NϪCuϪN bond angle is 88.72(16)° and the NϪCuϪCl
bond angles range from 91.36(12)Ϫ153.99(12)°, thus exhib-
Exposing an acetonitrile solution of compound 7 to air iting a distorted tetrahedral environment at the copper
causes the clear solution to turn green over a 12 hour per- center.
iod. This color change is due to the oxidation of the d10
Unlike in the synthesis of compounds 4؊8, something
copper() compound (7) to the d9 copper() compound (8). unanticipated occurs upon reacting 2 with copper nitrate:
Crystals of the green solid 8 (see Figure 6) were grown from the ligand decomposes. The product that forms (compound
the air-exposed product by layering a solution of CH2Cl2 6) is a five-coordinate, distorted, square-pyramidal cop-
with hexane at room temperature. The crystal structure was per() complex with three ligating 3,5-dimethylpyrazole
elucidated and was found to contain a CuII ion in a tetra- moieties and two monodentate nitrates (Figure 7). Relevant
hedral-coordination environment with one bidentate 1 li- bond angles and lengths are listed in Table 2. The CuϪN
gand and two ligated chloride ions. The average CuϪN and bond-length values compare nicely to those reported for the
˚
˚
˚
CuϪCl bond lengths are 1.986(4) A and 2.223(16) A, polymeric [Cu(pyrazole)2]x complex [1.992(6)
A
vs.
[27]
˚
respectively. These lengths are in close agreement with those 1.957(2) A].
reported for the tetrahedral complex Cu(bdpp)Cl2, where
Similar examples have been documented in the literature
bdpp is 1,3-bis(3Ј,5Ј-dimethylpyrazol-1Ј-yl)propane.[24] The for the decomposition of pyrazole-based ligands upon reac-
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Synthesis and Characterization of (Diphenyldipyrazolylmethane)copper Complexes
FULL PAPER
ylborates, or carbon, as is the case in this report. We do not
believe that compound 6 is a product of pyrazole impurity
from the previous ligand synthesis because complete
characterization of the PzЈЈ2CPh2 ligand, prior to use in this
metallation reaction, indicates purity. Attempts are cur-
rently under way to synthesize the Cu(PzЈЈ2CPh2) derivative
under anaerobic conditions using dry solvents.
The low-temperature solution state EPR spectra of com-
pounds 4, 5, 6 and 8 are shown in Figure 8. Changes in the
features of such spectra result from the coordinated ligands,
the compound geometry, and the compound charge, in
decreasing order of importance.[30,31] Because the ligands
used here are nearly identical, varying only by one methyl
substituent, and because the coordination geometry of each
complex is similar, as seen in Figures 3 4, 5 and 6, one would
expect little change in the EPR spectrum of each com-
pound, as is seen in Figure 8. Calculated g||, gЌ and A||
values are shown in Table 4 and these values are similar to
those recorded in the literature for compounds with similar
structures.[24,32Ϫ34] The hyperfine splitting pattern for a Cu
3/2 spin is observed but there are no observable superhyper-
fine interactions. Calculated A|| values for 5 reveal a slight
compression in this region of the spectra.
Figure 6. Structure of compound 8 with hydrogens omitted for clar-
ity and thermal ellipsoids drawn at 50 % probability
Table 4. Selected EPR parameters for 4, 5, 6 and 8
g||
gЌ
A||
4
5
6
8
2.492
2.312
2.298
2.287
2.074
2.079
2.063
2.068
160 G
149 G
158 G
164 G
The cyclic voltammogram of 4 is shown in Figure 9. The
quasi-reversible wave at 0.55 V vs. SCE (Epc at 0.48 V, Epa
at 0.62 V, 0.31 V vs. NHE) is attributed to the CuII/CuI
redox couple. A scan rate of 50 mv/s afforded optimal re-
versible behavior. A cyclic voltammogram was also ac-
quired for compound 5 and is shown in Figure 9. The re-
versible wave at 0.63 V vs. SCE (Epc at 0.55 V, and Epa at
Figure 7. Structure of compound 6 with hydrogens omitted for clar-
ity and thermal ellipsoids drawn at 50 % probability
tion with metal salts.[28,29] The proposed mechanism in- 0.71 V, 0.39 V vs. NHE) is also ascribed to the CuII/CuI
volves metal-mediated cleavage of the pyrazole nitrogenϪX redox pair and is shifted by ϩ0.1 V as compared to that
bond, where X may be boron, as is the case with pyrazol- observed for 4. Once again, the best spectra resulted when
Figure 8. EPR spectra of compounds 4 (top, left), 5 (bottom, left), 6 (top, right) and 8 (bottom, right) (9.42 GHz) in MeOH at 120 K
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J. L. Shaw, T. B. Cardon, G. A. Lorigan, C. J. Ziegler
FULL PAPER
a scan rate of 50 mv/s was used. Altering this scan speed steric bulk at the pyrazole periphery from a methyl to a
resulted in a decreased intensity of the voltammogram half- tert-butyl group.
wave features.
Conclusion
Diphenyldipyrazolylmethane reacts with commercially
available copper salts to form low-coordination-number
copper complexes. Reactions with copper() nitrate pro-
duce 1:1 complexes, while the reaction with copper() chlo-
ride yields a 2:1 complex. Similar compounds presented in
the literature, employing dipyrazolylalkanes, produce
mainly 2:1 complexes and it is therefore believed that the
phenyl rings employed here provide additional protection
to the copper ion. Also, the ability of the nitrate counterion
to coordinate in different modes (monodentate or biden-
tate) influences the coordination environment of the copper
ion. Additional counterions may be studied in order to af-
fect changes in the copper ion-coordination environment.
The geometry of these compounds in the solution state can
be further studied by performing conductivity experiments
in alcoholic solutions.
We hope that the diphenyldipyrazolyl ligands will pro-
duce more biologically relevant model complexes than
those that currently exist in the literature because the neu-
trality of our ligand produces copper complexes with more
positive reduction potentials than those observed em-
ploying negatively charged ligands, such as the pyrazolylbo-
rates. We find that increasing the steric bulk on the pyrazole
ring, from compound 4 to compound 5, leads to a slight
preference for copper() rather than copper(), based on the
reduction potentials, because of the nearly tetrahedral ge-
ometry supported by this ligand. A delicate balance be-
tween these two oxidation states is necessary in order to
adequately replicate the redox behavior observed in biology
in type I blue copper proteins.
Figure 9. Cyclic voltammograms of compounds 4 (top) and 5 (bot-
tom) at a scan rate of 50 mV/s in CH3CN with 0.1  [Bu4N]BF4
vs. SCE; y-axis is current measured in uA
These potentials are more positive than those of other
copper-model complexes in the literature. For instance, in
the β-diketiminate copper complex, LCuCl, where L is 2,4-
bis(2,6-diisopropylphenylimido)pentane, a half-potential of
Ϫ0.78 V vs. ferrocene (0.02 V vs. NHE) was reported in
CH2Cl2.[33] This shift to a more negative potential results,
in part, from the negative charge on the diketiminate ligand.
The charge shifts the preference toward a ϩ2 oxidation
state at the copper center, thus resulting in a more negative
potential for the CuII/CuI redox couple. Subsequent thiol
complexes that incorporate either the above mentioned β-
diketiminate or the popular tris(pyrazolyl)borate ligands
also have reduction potentials that are significantly lower
than those observed in copper-active sites in biology.[7,14]
Attempts were made to isolate thiol complexes by re-
acting complexes 3 and 4 with bulky aryl thiols such as
triphenylmethanethiol or bidentate thiols such as 1,2-
benzenedithiol. Each time decomposition occurs forming a
reduced metal compound, indicative of colorless copper(),
and the disulfide. A reaction of compound 5 with 1,2-
benzenedithiol did lead to a stable green complex in DMF,
but crystals were not of X-ray quality. Further work is be-
ing done to determine the identity of this product. In ad-
dition, attempts are currently under way to further protect
Experimental Section
All solvents and starting materials were obtained from commer-
cially available sources and were used without further purification.
Mass spectra were recorded using an ES MS Bruker Esquire-LC
1
ion-trap mass spectrometer. H NMR spectra were measured on a
Gemini 300 MHz spectrometer. The elemental analysis was per-
formed on a CE440 analyzer at the School of Chemical Sciences
Microanalysis Laboratory at the University of Illinois at Urbana-
Champaign. EPR data were collected at the University of Miami
in Ohio. UV/Visible spectra were obtained using a Hitachi U-
3010 instrument.
Synthesis of Diphenyldipyrazolylmethane Pz2CPh2 (1): All three li-
gands were synthesized using a slight modification of the procedure
by Trofimenko.[17] After isolation of the yellow solid, the ligand
was washed with hexanes to yield 1.13 g of white solid (47.7 %
yield). Recrystallization by slow evaporation of a saturated toluene
solution yielded crystals suitable for single-crystal X-ray diffrac-
1
tion. H NMR (300 MHz, CDCl3, 25 °C): δ ϭ 7.65 (d, 2 H, 3-pz),
7.52 (d, 2 H, 5-pz), 7.43Ϫ7.33 (m, 6 H, ph), 7.06Ϫ7.03 (m, 4 H,
the copper ion from reduction chemistry, by increasing the ph), 6.31 (dd, 2 H, 4-pz). ES MS (ϩ ion, MeOH) 323.1 m/z [M ϩ
1078  2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim www.eurjic.org
Eur. J. Inorg. Chem. 2004, 1073Ϫ1080

Synthesis and Characterization of (Diphenyldipyrazolylmethane)copper Complexes
FULL PAPER
Na]. C19H16N4 (300.36): calcd. C 75.97, H 5.38, N 18.64; found C
75.04, H 5.30, N 18.20.
and 1 (0.155 g, 0.52 mmol) were combined in CH3CN (10 mL). The
resultant clear solution was left to stir for 6 hours. Slow evapor-
ation of the reaction solution yielded clear crystals of compound 7
suitable for single-crystal X-ray diffraction (quantitative yield). The
crystal structure was solved in the Cc space group. The literature
reports that this space group can be problematic[35,36] so attempts
were also made to solve the structure using the suggested C2/c
space group, which incorporates a center of symmetry. However,
refinement using C2/c was poor (R1 ca. 20 %) as compared to Cc
(R1 ϭ 3.83 %) and it was determined that the correct space group
for structural elucidation was, in fact, Cc. In addition, the structure
solved using Cc has CϪC phenyl ring bond lengths
Synthesis of Diphenylbis(3,5-dimethylpyrazolyl)methane PzЈЈ2CPh2
(2): Ligand 2 was prepared similarly to ligand 1. After workup,
1.06 g of yellow solid (43.0 % yield) were obtained. Crystals suit-
able for X-ray structural elucidation were grown from a THF/
CH3CN solvent mixture. 1H NMR (300 MHz, CDCl3, 25 °C): δ ϭ
7.30Ϫ7.20 (m, 6 H, ph), 7.05Ϫ6.95 (m, 4 H, ph), 6.01 (s, 2 H, 4-
pz), 2.22 (s, 6 H, 3-methyl), 1.58 (s, 6 H, 5-methyl). ES MS (ϩ ion,
CHCl3/MeOH) 379.2 m/z [M ϩ Na]. C23H24N4 (356.46): calcd. C
77.49, H 6.80, N 15.71; found C 77.04, H 6.75, N 15.45.
Synthesis of Diphenylbis(3-methylpyrazolyl)methane PzЈ2CPh2 (3):
Ligand 3 was prepared similarly to ligands 1 and 2. The resulting
yellow-orange solution was filtered and reduced under vacuum to
afford a yellow oil. Hexanes were added to precipitate out a small
amount of brown solid. A yellow solid resulted upon evaporation
of the hexanes. This was washed with hexanes and deionized water
to yield 1.70 g of a light yellow solid (58.7 %). 1H NMR (300 MHz,
CDCl3, 25 °C): δ ϭ 7.4 (s, 2 H, 5-pz), 7.4Ϫ7.3 (m, 6 H, ph), 7.2Ϫ7.1
(m, 4 H, ph), 6.05 (d, 2 H, 4-pz), 2.3 (s, 6 H, 3-methyl). ES MS (ϩ
ion, CHCl3/MeOH) 351.2 m/z [M ϩ Na]. C21H20N4 (328.41): calcd.
C 76.80, H 6.15, N 17.05; found C 76.79, H 6.17, N 16.43.
˚
˚
[1.373(5)Ϫ1.404(4) A] closer to the literature value of 1.397 A, as
compared to those for the elucidated structure in C2/c
˚
(1.305Ϫ1.434 A). ES MS (ϩ ion, MeOH) 663.3 m/z [M Ϫ CuCl2].
C38H32Cl2Cu2N8 (798.70): calcd. C 57.14, H 4.05, N 14.02; found
C 57.22, H 3.91, N 14.22.
A portion of compound 7 was redissolved in CH3CN and exposed
to air. The white solution of 7 gradually turned green over a 12
hour period. Crystals of the final oxidized green product (8) were
grown by layering CH2Cl2 and hexane at room temperature. Ad-
ditionally, compound 8 was synthesized by the reaction of CuCl2
(0.158 g, 1.1 mmol) in THF (5 mL) with a THF solution of 1
(0.352 g, 1.2 mmol). Upon combining the two solutions a green
precipitate formed immediately. The precipitate was removed via
filtration and washed with additional THF (59.9 % yield). UV/Vis
(CH2Cl2), λ (ε ) ϭ 417.0 nm (644 Ϫ1cmϪ1), 677.0 (86 Ϫ1cmϪ1).
ES MS (ϩ ion, CHCl3) 398.2 m/z [M Ϫ Cl]. C19H16Cl2CuN4
(434.80): calcd. C 52.47, H 3.72, N 12.88; found C 52.10, H 3.72, N
12.37. E1/2 (CH3CN) 0.37 V vs. SCE (Epc at 0.26 V, Epa at 0.47 V).
Synthesis of Cu(Pz2CPh2)(NO3)2 H2O (4): Cu(NO3)2 (0.082 g,
0.44 mmol) in MeOH (10 mL) was combined with a methanol solu-
tion of 1 (0.131 g, 0.44 mmol). The blue copper solution darkened
upon combining the two reagents. The reaction was allowed to stir
for 2 hours at room temperature. This solution was then reduced
under vacuum to yield a blue solid. Recrystallization by layering
of CH2Cl2 and hexane at Ϫ42 °C yielded crystals suitable for sin-
gle-crystal X-ray diffraction (79.1 % yield). UV/Vis (CH2Cl2), λ (ε)
ϭ 716.0 nm (68 Ϫ1cmϪ1). ES MS (ϩ ion, MeOH) 425.0 m/z [M
Ϫ NO3]. C19H16CuN6O6 (505.93): calcd. C 46.77, H 3.31, N 17.22;
found C 46.38, H 3.18, N 16.85. E1/2 (CH3CN) 0.55 V vs. SCE (Epc
at 0.48 V, Epa at 0.62 V).
X-ray crystallography: X-ray intensity data were measured at 100 K
(Bruker KRYO-FLEX) on a Bruker SMART APEX CCD-based
X-ray diffractometer system equipped with a Mo-target X-ray tube
˚
(λ ϭ 0.71073 A) operated at 2000 watts power. Crystals were
mounted on a cryoloop using Paratone N-Exxon oil and placed
under a stream of nitrogen. The detector was placed at a distance
of 5.009 cm from the crystals. Analyses of the data sets showed
negligible decay during data collection. The data were corrected for
absorption with the SADABS program. The structures were refined
using the Bruker SHELXTL Software Package (Version 6.1), and
were solved by direct methods until the final anisotropic full-ma-
trix, least-squares refinement of F2 converged.[37] Experimental de-
tails for all of the structures are provided in Table 3.
Synthesis of Cu(PzЈ2CPh2)(NO3)2 (5): Cu(NO3)2 (0.106 g,
0.56 mmol) dissolved in THF (10 mL) was added to a solution of
3 (0.185 g, 0.56 mmol) in THF (10 mL). The resulting green solu-
tion was stirred for 2 hours at room temperature. This solution was
then reduced under vacuum to yield a green-blue solid. Crystals
were obtained by layering CH2Cl2 with hexane at room tempera-
ture (75.3 % yield). Two crystal morphologies of this compound
formed: blue needles that do not diffract X-rays well, and green
blocks that were suitable for single-crystal X-ray diffraction. UV/
Vis (CH2Cl2), λ (ε ) ϭ 779.0 nm (70 Ϫ1cmϪ1). ES MS (ϩ ion,
THF/MeOH) 453.0 m/z [M Ϫ NO3]. C21H20CuN6O6 (515.97):
calcd. C 48.89, H 3.92, N 16.28; found C 49.61, H 4.11, N 15.94.
E1/2 (CH3CN) 0.63 V vs. SCE (Epc at 0.55 V, and Epa at 0.71 V).
EPR experiments on compounds were carried out using a Bruker
EMX X-band CW-EPR spectrometer consisting of an ER 041XG
microwave bridge and a TE102 cavity coupled with a BVT 3000
nitrogen gas temperature controller (temperature stability of
0.2 K). EPR spectra were acquired by taking a 168 s field-swept
scan with the center field set to 3200 G, a sweep width of 2000 G,
a microwave frequency of 9.42 GHz, the modulation frequency was
set to 100 kHz, and a modulations amplitude of 10.0 G. The spec-
tra were acquired at a temperature of 120 K. The samples were
dissolved in methanol to a final concentration of 1 mg/mL and
transferred to 4 mm 707-SQ-250M fused quartz EPR tubes (Wil-
mad, Buena, NJ).
Synthesis of Cu(PzЈЈ)3(NO3)2 (6): Cu(NO3)2 (0.264 g, 1.4 mmol) in
MeOH (10 mL) was combined with a methanol solution of 2
(0.501 g, 1.4 mmol). The ligand was only partially soluble in meth-
anol. The murky reaction was stirred for 12 hours and then allowed
to evaporate down to afford a bluish-green solid. The solid was
redissolved in CH2Cl2 and filtered to yield two products: a green
solid and a blue solid (63.2 % yield crude product). Crystals of the
blue solid were grown by layering CH2Cl2 and hexane at Ϫ42 °C.
UV/Vis (CH2Cl2), λ (ε ) ϭ 633.0 nm (56 Ϫ1cmϪ1). ES MS (ϩ ion,
THF/MeOH) 317.1 m/z [M Ϫ NO3 Ϫ PzЈЈ]. C15H24CuN8O6
(475.96): calcd. C 37.86, H 5.09, N 23.53; found C 37.99, H 4.95, N
22.59. E1/2 (CH3CN) 0.70 V vs. SCE (Epc at 0.63 V, Epa at 0.77 V).
Cyclic voltammetry measurements were carried out on compounds
4, 5, 6 and 8 using a BAS 100B/W electrochemical workstation
from Bioanalytical Systems, Inc. in West Lafayette, Indiana. HPLC
grade acetonitrile ( Ͻ 0.02 % H2O) was used without further purifi-
Syntheses of [Cu(Pz2CPh2)2]CuCl2 (7) and Cu(Pz2CPh2)Cl2 (8): In cation. A three-electrode setup with a platinum working electrode,
a dry box with a nitrogen atmosphere, CuCl (0.052 g, 0.52 mmol) a platinum wire electrode, and a saturated calomel reference elec-
Eur. J. Inorg. Chem. 2004, 1073Ϫ1080
www.eurjic.org
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1079

J. L. Shaw, T. B. Cardon, G. A. Lorigan, C. J. Ziegler
FULL PAPER
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J. L. S. acknowledges the GAANN fellowship for financial support.
C. J. Z. acknowledges the University of Akron for a faculty re-
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CHE-0116041 for funds used to purchase the Bruker-Nonius dif-
fractometer and the Kresge Foundation and donors to the Kresge
Challenge Program at the University of Akron for funds used to
purchase the NMR instrument used in this work.
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