Biomimetic Hydroxylation Catalysis Through Self-Assembly of a Bis(pyrazolyl)methane Copper-Peroxo Complex

Article abstract of DOI:10.1002/ejic.201402957

We synthesised and characterised four copper complexes (with copper in the oxidation states I and II) with the bis(pyrazolyl) methane ligands HC(3-tBuPz)₂(Py) and HC(3-tBuPz)₂-(Qu). With the quinolinyl ligand (2-quinolinyl)bis(3-tert

Full text of DOI:10.1002/ejic.201402957

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DOI:10.1002/ejic.201402957
Biomimetic Hydroxylation Catalysis Through Self-
Assembly of a Bis(pyrazolyl)methane Copper–Peroxo
Complex
Claudia Wilfer,[a] Patricia Liebhäuser,[a] Hannes Erdmann,[a]
Alexander Hoffmann,[a] and Sonja Herres-Pawlis*[a]
Keywords: Bioinorganic chemistry / Oxygen activation / Self-assembly / Copper / N ligands
We synthesised and characterised four copper complexes
(with copper in the oxidation states I and II) with the bis(pyr-
azolyl)methane ligands HC(3-tBuPz)2(Py) and HC(3-tBuPz)2-
(Qu). With the quinolinyl ligand (2-quinolinyl)bis(3-tert-but-
ylpyrazolyl)methane [HC(3-tBuPz)2(Qu)] we obtained the
tetrahedral monofacial complex [CuCl{HC(3-tBuPz)2(Qu)}]
(C1) and with the pyridinyl ligand (2-pyridinyl)bis(3-tert-but-
ylpyrazolyl)methane [HC(3-tBuPz)2(Py)] we obtained the
lecular structures were analysed and compared with density
functional theory calculations, which included natural bond
orbital (NBO) analysis. C1 can, when generated in situ, serve
as part of a precursor, used for the activation of oxygen as
tyrosinase model. We observe the self-assembly of a peroxo–
dicopper complex
P with the HC(3-tBuPz)2(Qu) ligand,
which is able to perform catalytic hydroxylation catalysis
with phenols. DFT calculations were also carried out to
understand the electronic transitions responsible for the UV/
Vis bands in the corresponding spectra of the peroxo species.
three
complexes
[CuCl{HC(3-tBuPz)2(Py)}]
(C2),
[CuBr2{HC(3-tBuPz)2(Py)}] (C3) and [CuCl2{HC(3-tBuPz)2-
(Py)}] (C4), which are also monofacially coordinated. The mo-
acterised well by using UV/Vis spectroscopy owing to their
significant UV/Vis bands and their characteristic intensity
ratio.[10,11] Experimental evidence for the unique O2 binding
mode in the structurally related oxy-hemocyanin was pre-
viously obtained from the structural characterisation of a
Cu/O2 model species by Kitajima et al. in 1989.[12–14]
Finally, in 2006, Matoba et al. were able to present the first
crystal structure of tyrosinase, which also proved that
histidine residues surround the copper atoms in the active
site.[8] Tyrosinase catalyses the reaction of melanin from
tyrosine. Melanin itself is a brown pigment that is wide-
spread in mammals, birds and plants.[15–18]
A multitude of ligand families such as tris(pyrazolyl)-
borates,[12] tris(pyrazolyl)methanes,[19] alkylamines,[20] pyr-
idines,[21] ketiminates[22] and guanidines[23,24] have been in-
vestigated as building blocks of hemocyanine and tyr-
osinase models in recent years. When treating CuI species
with O2, there are two major products that can be gener-
ated: the (μ-η2:η2)-peroxide core (SP core) and the bis(μ-
oxo)dicopper(III) core (O core), which are nearly isoenerg-
etic and exist in equilibrium at low temperatures.[11,25,26]
However it was discovered that whether the SP or the O
core is preferably generated depends on the steric properties
and mostly on the basicity of the ligands used. A hybrid
permethylated amine–guanidine ligand, for example, only
forms the O core, which suggests that bidentate sterically
nondemanding strong σ donors shift the equilibrium to-
ward the CuIII O complex.[11,27,28] After reaction with the
O and P complex, sometimes bis(μ-hydroxo)dicopper(II)
Introduction
Bis(pyrazolyl)methane ligands represent a group of ver-
satile heteroscorpionate ligands[1] that play an increasingly
important and promising role in the investigation of tyrosi-
nase models.[2,3] Several changes throughout the years con-
cerning substituents and steric properties of the substituents
led to the so-called second generation of bis(pyrazolyl)-
methane ligands, which refers to the fact that these ligands
carry substituents (e.g., alkyl groups) at their pyrazolyl
moieties and therefore enforce a monofacial coordination
mode.[4] The most common donors, besides the two pyraz-
olyl substituents, are pyridinyl, imidazolyl and quinolinyl as
they represent aromatic nitrogen donors that in part re-
semble the biological surrounding of metal atoms in the
active centre of enzymes (e.g., histidine).[5]
Tyrosinase is a widespread type III copper enzyme that
catalyses the ortho-hydroxylation of monophenols and the
subsequent oxidation of the resulting catechols to o-quin-
ones.[5–8] Tyrosinase therefore has monophenolase and di-
phenolase activity.[5,9] The first step in the reaction cycle is
the activation of dioxygen, which results in a (μ-η2:η2)-
dicopper(II) peroxide core.[5,6,10] These species can be char-
[a] Department of Chemistry, Ludwig-Maximilians-Universität
München,
Butenandtstraße 5–13, 81377 München, Germany
E-mail: sonja.herres-pawlis@cup.uni-muenchen.de
http://www.cup.lmu.de/ac/herres-pawlis/
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejic.201402957.
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complexes can be isolated as products of hydrolysis.[29] In
the Cu2O2 model chemistry a large variety of further Cu2O2
species have been observed, but for tyrosinase activity, O
and P cores are mainly discussed.[5,7]
Results and Discussion
The reaction of the ligands HC(3-tBuPz)2(Qu) and
HC(3-tBuPz)2(Py) with various copper salts led to the
formation of four complexes (C1–C4; Scheme 1). Single
crystals for X-ray crystallography were obtained by cooling
the reaction solutions to 5 °C for a couple of days or by
simply storing the solution in a vibration-free environment
at room temperature (see the Experimental Section for de-
tails). With the ligand HC(3-tBuPz)2(Qu) we isolated
[CuCl{HC(3-tBuPz)2(Qu)}] (C1); with the ligand HC(3-
tBuPz)2(Py) we isolated [CuCl{HC(3-tBuPz)2(Py)}] (C2),
[CuBr2{HC(3-tBuPz)2(Py)}](C3)and[CuCl2{HC(3-tBuPz)2-
(Py)}] (C4). All four complexes are coordinated by only one
heteroscorpionate ligand owing to steric shielding of alkyl
groups in the 3-position of the pyrazolyl units (Fig-
ure 1).[1,4] Selected bond lengths and bond angles are shown
in Table 1, which also includes the τ value, which provides
an easy determination of the coordination mode around the
metal centre.[38,39] All relevant crystallographic data are
collected in Table 4. Complex C2 appears in the solid state
in two slightly differing conformers, dubbed C2a and C2b,
whereas in C3 both molecules of the asymmetric unit
exhibit the same conformer (see Table S1 in the Supporting
Information).
When investigating enzyme models, it is clear that an ex-
tremely important part of the work, in addition to the imi-
tation of the active site, lies in the testing of the catalytic
abilities of the model. With regard to the reaction mecha-
nism of tyrosinase, in 2009 Casella et al. proved that during
substrate transformation of Streptomyces antibioticus
tyrosinase, the (μ-η2:η2)-peroxide core remained the only
enzyme species present.[30] Until now only three systems
achieved significant catalytic phenol hydroxylation using di-
oxygen. The first one was discovered by Réglier et al.,[31]
the second one by Tuczek et al.[32] and the third one by
Herres-Pawlis et al.[2] Tuczek et al. recently published an-
other related catalytic system that uses ligands that consist
of imine and benzimidazole and imine and pyrazole
moieties, respectively.[33,34] Very recently, Lumb et al. made
use of catalytic copper–dioxygen chemistry to generate
valuable organic products out of simple substituted phen-
ols.[35,36] This indicates the general importance of bioinor-
ganic copper chemistry as a synthetic tool. It has to be
noted that the peroxide species is constructed by means of
self-assembly, which means that when all components are
mixed, the ordered peroxide builds itself without influence
from the outside. However, different possibilities of “self-
assembly” exist. For instance, Stack et al. showed that the
peroxide core is formed by mixing imidazole ligands, copper
salts and dioxygen, but the phenolate had to be added after-
wards for hydroxylation reactivity.[10] Tuczek et al. observed
the self-assembly with catalytic activity for tyrosinase
models with pyridine–imine ligands by mixing copper
phenolates, ligands and dioxygen.[32] The role of the stabilis-
ing ligands is crucial for the formation and reactivity of the
species. We recently explored how different donor proper-
ties influence the coordination chemistry and complex
structure of different transition-metal bis(pyrazolyl)meth-
ane complexes.[37]
Here we report four new bis(pyrazolyl)methane–copper
complexes with the HC(3-tBuPz)2(Py) and HC(3-tBuPz)2-
(Qu) ligands. We have investigated the structure of these
complexes and analysed their donor situation by means of
density functional theory calculations. We studied the
donor rivalry between pyridinyl/quinolinyl and pyrazolyl
nitrogen atoms by comparing their charge-transfer energies.
Moreover, the formation of the peroxo species
[Cu2O2{HC(3-tBuPz)2(Qu)}2][SbF6]2 was monitored by
means of UV/Vis spectroscopy. By using the self-assembly
Scheme 1. Synthesis of C1–C4.
In C1 and C2 the metal ion is four-coordinate. The nitro-
approach, we observed catalytic activity in the ortho- gen donors of the bis(pyrazolyl)methane ligand occupy
hydroxylation of the substrate para-methoxyphenol and three coordination sites; the remaining one is occupied by
subsequent oxidation to quinones when using the new one halogenido ligand, thereby resulting in an overall dis-
[Cu2O2{HC(3-tBuPz)2(Qu)}2][SbF6]2 system. Finally, natu- torted-tetrahedral geometry (Figure 1) with nearly identical
ral bond orbital (NBO) and natural transition orbital τ4 values.
(NTO) calculations were carried out for the peroxo complex
Bond angles deviate more from the ideal tetrahedral
to understand the bonding situation in this species, and angle for C1. In both complexes C1 and C2b Cu–NPz bond
furthermore to gain insight into the electron transitions that lengths are shorter than the corresponding Cu–NPy or Cu–
generate the UV/Vis bands.
NQu bond lengths, which is in contrast to C2a, C3 and C4.
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Figure 1. Molecular structures of C1–C4.
Table 1. Selected bond lengths [Å] and angles [°] of C1–C4.
C1[a]
C2a[a]
C2b[a]
C3[b]
C4[a]
Cu–NPz
2.124(2)
2.106(2)
2.183(2)
2.120(2)
2.199(1)
2.082(2)
2.120(2)
2.132(2)
2.187(1)
2.117(6)
2.421(6)
2.051(6)
2.388(1)
2.409(1)
1.441(9)
1.458(9)
1.503(10)
115.2(2)
151.7(2)
93.5(2)
95.2(2)
92.2(2)
176.6(2)
92.1(2)
83.2(2)
2.233(3)
Cu–NPy/Cu–NQu
Cu–X
*
2.149(2)*
2.215(1)
2.058(4)
2.225(2)
2.267(1)
1.448(3)
Capical–NPz
1.456(2)
1.449(3)
1.449(3)
1.519(4)
130.0(1)
127.2(1)
–
1.450(3)
1.460(3)
1.507(3)
130.9(1)
129.3(1)
–
Capical–CPy/Capical–CQu
NPz–Cu–X(1)
*
1.511(4)*
124.2(1)
124.2(1)
–
1.515(6)
133.6(1)
133.6(1)
93.5(2)
93.5(1)
93.3(1)
175.9(1)
92.2(2)
83.8(1)
93.8(1)
90.8(1)
0.71*
NPz–Cu–X(2)
N
Py–Cu–X(1)/NQu–Cu–X(1)*
129.2(1)*
–
89.1(1)
89.1(1)*
89.1(1)*
–
121.5(1)
–
90.5(1)
88.5(1)
86.0(1)
–
118.1(1)
–
86.6(1)
90.8(1)
88.7(1)
–
NPy–Cu–X(2)/NQu–Cu–X(2)*
NPz–Cu–NPz
NPz–Cu–NPy/NPz–Cu–NQu
*
83.7(2)
90.6(1)
0.42*
X(1)–Cu–X(2)
τ4[c], τ5*[d]
0.76
0.73
0.71
360° – (α + β)
(β – α)
[a] X = Cl. [b] X = Br. [c] τ4 =
. [d] τ5 =
.
141
60
In general, bis(pyrazolyl)methane complexes show a donor Cl(2) reside at the axial positions, whereas the two pyrazolyl
competition between their N donors, which appears here
again.[37,40] This effect is discussed in more detail in the next
paragraph.
N donors and Cl(1) form the equatorial positions.
Capical–NPz bond lengths are the same for C3 and C4.
We performed density functional theory calculations to
In C3 and C4 the metal ion is five-coordinate. The nitro- analyse the coordination of all four complexes. The TPSSh
gen donors of the bis(pyrazolyl)methane ligand occupy functional in combination with the double-ζ basis set 6-
three coordination sites; the other two are occupied by 31G(d) was used, since this combination yielded good re-
halogenido ligands, thereby resulting in an overall distorted sults in the benchmarking of Cu2O2 complexes.[3] Key geo-
square-pyramidal geometry for C3 and a distorted trigonal- metric parameters of the theoretical calculations of C1–C4
bipyramidal one for C4 (Figure 1). In both C3 and C4, Cu– are listed in Table 2. These data show that another con-
NPy bond lengths are shorter than the corresponding Cu– former was found for C2, which is reflected by the signifi-
NPz ones. It is difficult to determine which nitrogen is the cantly smaller NQu–Cu–Cl angle, so that these data are not
stronger donor, as basicity and nucleophilicity have to be discussed in this section. All attempts to find the other con-
taken into account. Normally the donor competition is won former failed. However, the experimental structure of C1 is
by pyrazolyl (see C1 and C2b with distorted-tetrahedral in good agreement with the theoretical values for bond
environments),[37] but in C3 and C4 with fivefold coordina- lengths and angles. Only the predicted Cu–NQu bond length
tion it is the other way round. The sterically demanding is a bit too short. The NPz–Cu–NPz and NQu–Cu–NPz
tert-butyl groups might hinder the pyrazolyl unit from com- angles are predicted to be about 4° too large. Moreover the
ing closer to the metal ion. The Cu–Cl bond length in C4
NQu–Cu–Cl(1) bond angle is predicted to be too small, but
is naturally shorter than the Cu–Br bond length in C3, the NPz–Cu–Cl(1) angle is in good agreement with the ex-
which is in agreement with common Cu–X bond lengths. perimental data.
The NPz–Cu–Cl(1)/NPz–Cu–Br(1) and NPz–Cu–Cl(2)/NPz–
For the five-coordinate complexes C3 and C4 it can be
Cu–Br(2) bond angles reflect (as already suggested by the τ seen that the theoretical data are in accord with the experi-
values) that C3 is distorted and cannot really be assigned mental data as well. In complex C3 all relevant bond
to a specific geometry and that C4 is of distorted trigonal- lengths are predicted well. The mirror plane in C4 is also
bipyramidal geometry. For C4 the pyridinyl N donor and found for the ground-state calculation. In C4, with the ex-
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Table 2. Key bond lengths [Å] and angles [°] of C1–C4 [Gaussian ral, the larger the charge-transfer energy is, the shorter is
09, TPSSh/6-31G(d)].[41]
the respective M–N bond. Both four-coordinate complexes
C1[a]
C2[a]
C3[b]
C4[a]
C1 and C2 show similar charge-transfer energy values. Ad-
ditionally, in C1 the bond lengths for the Cu–NPz and Cu–
NQu bonds are similar, which is also reflected in the similar
values for the charge-transfer energies. Different charge-
transfer energies for the NPz–M bond are represented by
different NPz–M bond lengths. In C2a the charge-transfer
energy of pyridinyl to copper is smaller than the respective
energy for pyrazolyl. This does not correlate with the me-
dium-long Cu–NPy bond. A better correlation is found in
C3 and C4. Charge-transfer energies for NPz–Cu are dif-
ferent in C3, which is in accord with different Cu–NPz bond
lengths. The donor ability is predicted to be slightly higher
for pyridinyl, therefore the Cu–NPy bond length should be
shorter than the Cu–NPz bond length, as found experimen-
tally. In C4 the charge-transfer energies are exactly the same
for both pyrazolyl–M interactions. Theoretical calculations
showed equal Cu–NPz bond lengths owing to the mirror
plane in C4, so the values for the charge-transfer energy
tie in with that. Moreover the charge-transfer energy for
pyridinyl is slightly larger than that for the pyrazolyl, which
again is reflected in the shorter Cu–NPy bond length. To
summarise, our NBO analysis shows that for the five-
coordinate complexes the pyridinyl units donate slightly
more than the pyrazolyl units. The opposite applies to C2a.
Here the donor rivalry between pyrazolyl and pyridinyl/
quinolinyl that has been observed before can be seen
clearly.[37]
In addition to structural determinations, the bis(pyr-
azolyl)methane complex C1 was used as a precursor in the
activation of oxygen. As described in the introduction, bis-
(pyrazolyl)methane ligands can be used as promising build-
ing blocks for tyrosinase models for the activation of oxy-
gen. However, owing to its insolubility, C1 could not be
used directly but had to be generated in situ from the start-
ing compounds following the synthetic route described by
Herres-Pawlis et al.[2] The resulting species was hence
treated with AgSbF6 immediately and the precursor
[Cu{HC(3-tBuPz)2(Qu)}][SbF6] could be obtained. This
precursor was then injected into an O2-saturated CH2Cl2
solution at 195 K (see Scheme 2). The formation of the re-
sulting peroxo complex [Cu2O2{HC(3-tBuPz)2(Qu)}2]-
[SbF6]2 (P[SbF6]2) was monitored by means of UV/Vis
spectroscopy (Figure 2). The spectrum shows a band at
345 nm and an almost unidentifiable one at 550 nm. These
two bands stem from ligand-to-metal charge-transfer
(LMCT) transitions. They are in good analogy with the
UV/Vis bands found for oxy-tyrosinase and oxy-hemo-
cyanin.[45] Additional bands in the area of 305–320 nm
originate from intraligand transitions. It could be noticed
that the reaction is very slow, so that the peroxo species
was only formed in 80% yield after 8 h (Figure 2). Longer
reaction times led to the decay of P[SbF6]2. This excluded
Raman or X-ray absorption spectroscopy (XAS) studies.
This is in contrast to the parent P species [Cu2O2{HC(3-
Cu–NPz
2.011 1.982
2.071
2.397
2.056
2.342
2.352
1.459
1.449
1.521
121.6
138.9
87.4
90.7
163.2
95.8
98.6
77.7
2.161
Cu–NPy/Cu–NQu
Cu–X
*
1.975 2.009
2.262 2.243
2.060
2.274
2.264
1.453
Capical–NPz
1.458 1.460
Capical–CPy/Capical–CQu
Pz–Cu–X(1)
*
1.522 1.524
122.7 130.0
1.520
130.2
N
NPz–Cu–X(2)
–
–
90.4
NPy–Cu–X(1)/NQu–Cu–X(1)* 122.4 106.3
NPy–Cu–X(2)/NQu–Cu–X(2)*
NPz–Cu–NPz
168.6
93.0
98.2
82.1
–
93.7
93.8
–
94.1
92.2
NPz–Cu–NPy/NPz–Cu–NQu
*
84.0
98.6
0.41*
X(1)–Cu–X(2)
–
0.81
–
0.88
98.4
0.64*
τ4,[39] τ5*[38]
360° – (α + β)
(β – α)
[a] X = Cl. [b] X = Br. [c] τ4 =
. [d] τ5 =
.
141
60
ception of the Cu–NPz bond length, which is predicted to
be too short, all other bond lengths conform to the experi-
mental data. Looking at the bond angles in complexes C3
and C4, it its noteworthy that the NPz–Cu–Cl(1) and NPz–
Cu–Cl(2) angles in C4 are predicted quite well, whereas the
corresponding angles in C3 are predicted to be either too
large or too small. With the exception of the NPy–Cu–Cl(2)
angle, which is predicted to be too small, the remaining
bond angles are predicted to be 3–8° too large with the one
other exception of the NPz–Cu–NPy angle in C3. As for τ
values, the predicted and experimental ones coincide well.
For C3 the experimental and calculated τ values match al-
most exactly. For C2 a comparison would not make sense,
as different conformers were found. The geometry of C1 is
predicted to be a bit more distorted tetrahedral than
observed experimentally. For C4 the calculated τ5 value
identifies a slightly less distorted trigonal-bipyramidal
geometry than the experimental data suggests.
In addition to DFT calculations, NBO analyses were
performed of the optimised structures of C1–C4
(Table 3).[42–44] The second-order perturbation theory yields
the charge-transfer energies for the donation from the pyr-
azolyl or pyridinyl units to copper.
Table 3. Charge-transfer energies [kcalmol–1] for C1–C4 and P
[Gaussian 09, TPSSh/6-31G(d) and NBO 6.0].
C1
C2a[a]
C3
C4
P
CT energies
N
N
Pz ǞM
Pz ǞM
32.4
32.4
32.5*
29.7
27.0
24.2
17.9
8.5
18.4
14.4
14.4
17.4
39.2
32.2
17.2*
NPy/NQu*ǞM
[a] Data obtained directly from crystal structure (not optimised).
At a glance it can be seen that the charge-transfer ener- tBuPz)2(Py)}2][SbF6]2, which is formed within seconds and
gies mostly correlate with the M–N bond lengths. In gene- stable for days at –78 °C.[2] Further analyses involved the
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determination of the kinetics for the formation of the per- pyrazolyl units donate more strongly to copper than the
oxo compound. It could be shown that for the first 250 min quinolinyl units (Table 3), which underlines the complicated
the reaction follows pseudo-first-order kinetics with a reac- donor situation at CuII in comparison to C3 and C4 once
tion rate of k = 5.4ϫ10–3 s–1 (see Figure S1 in the Support- more.
ing Information). After formation, the P core decays at
–78 °C with t1/2 of 1.46 min at 0 °C (Figure S2).
Scheme 2. Formation of [Cu2O2{HC(3-tBuPz)2(Qu)}2][SbF6]2
Figure 3. NTO analysis of [Cu2O2{HC(3-tBuPz)2(Qu)}2]2+ (P).
(P[SbF6]2).
Despite the low stability of the P species, we observed an
astonishing hydroxylation reactivity of this species when all
components were combined in a self-assembly reaction [i.e.,
copper(I) precursor, 4-methoxyphenol (25 equiv.) and tri-
ethylamine (50 equiv.) and subsequent addition of oxygen
following the protocol of Tuczek et al.].[32] The hydroxyl-
ation and subsequent oxidation yielded the biomimetic
quinone product, which can be observed by UV/Vis spec-
troscopy owing to its intense absorption at 418 nm (see Fig-
ure 2). Hereby, a turnover number of 10 in 1 h could be
monitored. This shows that the P species formed as a reac-
tive intermediate during oxygenation. The direct capture of
the P species at room temperature was not possible. How-
ever, the formation of P[SbF6]2 and phenol hydroxylation
is fast enough to compete with the decay and we assume
the same mechanism here as for the parent P species
[Cu2O2{HC(3-tBuPz)2(Py)}2][SbF6]2. The NBO donor
study on P and the related complexes indicates that the in-
Figure 2. UV/Vis spectrum of [Cu2O2{HC(3-tBuPz)2(Qu)}2]-
terplay between pyridinyl and pyrazolyl units explains the
[SbF6]2 (P[SbF6]2) (experimental in red and theoretical in black)
hydroxylation chemistry; the pyrazolyl appears to donate
and the final UV/Vis spectrum of the formation of the quinone in
more strongly (Table 3) but the smaller steric requirements
of the pyridinyl allows the approach of substrates. This re-
sult shows that bis(pyrazolyl)pyridinylmethane copper com-
plexes possess a large potential for further catalytic
hydroxylation applications in synthetic organic chemistry.
the self-assembly mode (green).
NTO analysis[46] of the UV/Vis transitions (Figure 3) ob-
tained by time-dependent DFT [TPSSh/6-31G(d)] reveals
that the visible transition at 550 nm is the classical out-of-
plane πv*Ǟdxy LMCT. The accepting orbital is called the
lowest unoccupied NTO (LUNTO). With regard to sym-
metry and composition it is in accord with the classical
Cu2O2 theory.[6] The broad shoulder stems from a transition
from pyrazolyl π- and quinolinyl σ-donating orbitals into
Conclusion
Herein we have presented four bis(pyrazolyl)pyridinyl-
the same LUNTO. This is in accord with the NTO analysis methane copper complexes (with copper in the oxidation
performed for the original pyridinyl peroxo system.[2] The states I and II) with the bis(pyrazolyl)methane ligands
UV transitions all have mixed character; they are transi- HC(3-tBuPz)2(Py) and HC(3-tBuPz)2(Qu). With the
tions between the in-plane πσ* orbital and the ligands into quinolinyl ligand HC(3-tBuPz)2(Qu) we obtained the tetra-
the dxy copper orbital. It is highly remarkable that in P, the hedral monofacial complex [CuCl{HC(3-tBuPz)2(Qu)}]
Eur. J. Inorg. Chem. 0000, 0–0
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FULL PAPER
CCDC-1025415 (for C1), CCDC-1025416 (for C2), CCDC-
1025417 (for C3) and CCDC-1025418 for (for C4) contain the
supplementary crystallographic data for this paper. These data can
be obtained free of charge from The Cambridge Crystallographic
Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
(C1) and with the pyridinyl ligand HC(3-tBuPz)2(Py) we
obtained the tetrahedral complex [CuCl{HC(3-tBuPz)2-
(Py)}] (C2), the distorted square-pyramidal complex
[CuBr2{HC(3-tBuPz)2(Py)}] (C3) and the distorted trigo-
nal-bipyramidal complex [CuCl2{HC(3-tBuPz)2(Py)}] (C4).
The donor situation was studied by NBO analysis but a
mixed picture was found. Depending on the coordinative
situation both pyrazolyl and pyridinyl units can win the
competition. C1 can – when generated in situ – serve as
part of a precursor that can be used for the activation of
oxygen as tyrosinase models. We observed the self-assembly
of a peroxo–dicopper complex with the HC(3-tBuPz)2(Qu)
ligand, which is able to perform catalytic hydroxylation
catalysis with phenols. The observed coordinative flexibility
of the bis(pyrazolyl)pyridinylmethane ligands might be im-
portant for the functionality of the generated P species.
Computational Details: DFT calculations were performed with the
Gaussian 09 program suite.[41] The geometries of C1 to C4 and the
geometry of the peroxo species were optimised (Table 2) using the
nonlocal hybrid meta GGA TPSSh functional[56] and the double-ζ
basis set 6-31G(d) as implemented in Gaussian on all atoms. The
starting geometries for complexes C1 to C4 were generated from
the molecular structures. Frequency calculations did not show
imaginary values. NBO calculations for the complexes were ac-
complished by using the NBO 6.0 program suite.[42–44] Continuous
spectra were plotted with the AOMix program.[57,58]
(2-Quinolinyl)bis(3-tert-butylpyrazolyl)methanecopper(I) Chloride
[CuCl{HC(3-tBuPz)2(Qu)}] (C1): A yellow solution of HC(3-
tBuPz)2(Qu) (0.39 g, 1.00 mmol) dissolved in acetone (5 mL) was
added dropwise to
a colourless solution of CuCl (0.10 g,
1.00 mmol) dissolved in acetonitrile (20 mL). The solution turned
orange and after 18 h a red solid precipitated. After removing the
solid matter by filtration, red crystals were obtained from the fil-
trate at 278 K after several days (0.32 g, 66%). The crystals were
Experimental Section
General: All experiments that involved moisture- and air-sensitive
compounds were carried out by using standard Schlenk techniques.
All chemicals were purchased from Fluka or ABCR and were used
as received without further purification. The solvents used were
dried by standard literature procedures.[47] The ligands HC(3-
tBuPz)2(Py) and HC(3-tBuPz)2(Qu) were synthesised according to
the literature, as was CuCl.[48,49]
characterised by means of X-ray crystallography. IR (ATR): ν =
˜
3106 [vw (ν, CHarom)], 2960 (w), 2904 (vw), 2862 (vw), 1619 (vw),
1596 (w), 1572 (vw), 1556 (vw), 1518 (m), 1480 (w), 1456 (w), 1439
(w), 1420 (w), 1392 (vw), 1378 (w), 1363 (w), 1352 (w), 1335 (w),
1307 (vw), 1236 (m), 1186 (vw), 1157 (w), 1124 (vw), 1057 (m), 977
(w), 930 (w), 873 (vw), 842 (w), 827 (w), 806 (m), 790 (m), 775 (vs),
746 (w), 727 (w), 687 (vw), 668 (w), 653 (vw) cm–1. MS (FAB+):
m/z (%) = 487.1 (2) [Cu37Cl{HC(3-tBuPz)2(Qu)}]+, 485.1 (2)
[Cu35Cl{HC(3-tBuPz)2(Qu)}]+, 450.4 (26) [Cu{HC(3-tBuPz)2-
(Qu)}]+, 388.5 (9) [{HC(3-tBuPz)2(Qu)} + H]+, 275.1 (7) [{HC(Pz)2-
(Qu)}]+. C24H29ClCuN5 (486.52): calcd. C 59.3, H 6.0, N 14.4;
found C 59.2, H 6.0, N 14.3.
Physical Methods: Fast-atom bombardment (FAB) mass spectra
were obtained with a Thermo Finnigan MAT 95 mass spectrometer
for C1–C3, whereas mass spectra for C4 were recorded with a
Thermoquest Finnigan spectrometer in the ESI-MS mode (70 eV).
Infrared spectra were recorded with a Jasco FTIR 460 spectro-
photometer in the range of 650–3500 cm–1. UV/Vis spectra were
recorded with a Varian Cary 60 spectrophotometer. Elemental
analyses were performed with a Vario EL or Vario MICRO CHNS
Analyser.
(2-Pyridinyl)bis(3-tert-butylpyrazolyl)methanecopper(I)
Chloride
[CuCl{HC(3-tBuPz)2(Py)}](C2):AyellowsolutionofHC(3-tBuPz)2-
(Py) (0.34 g, 1.00 mmol) dissolved in acetone (5 mL) was added
dropwise to a colourless solution of CuCl (0.10 g, 1.00 mmol) dis-
solved in acetonitrile (20 mL). The solution turned yellow and was
stored at 278 K overnight, during which time the solution turned
light green. Concentration of the solvent until a solid precipitated
and storage of the filtrate at 278 K resulted in yellow crystals
(0.11 g, 25%). The crystals were characterised by means of X-ray
X-ray Analyses: The crystal data for C1–C4 are presented in
Table 4. The data for C1 was collected with a KappaCCD (Bruker
AXS BV), for C2 with a D8 Quest and for C3 with a Bruker D8
Quest diffractometer with graphite-monochromated Mo-Kα radia-
tion (λ = 0.71073 Å). Data reduction and absorption correction
was performed with HKL Denzo and Scalepack (C1)[50] or with
SAINT and SADABS (C2 and C3).[51] The structure was solved by
direct and conventional Fourier methods and all non-hydrogen
atoms were refined anisotropically with full-matrix least-squares
cycles based on F2 (XPREP,[52] SHELXS[53] and ShelXle[54]).
Hydrogen atoms were derived from difference Fourier maps and
placed at idealised positions, riding on their parent C atoms, with
crystallography. IR (ATR): ν = 3107 [vw (ν, CHarom)], 2957 (w),
˜
2904 (w), 2862 (w), 1597 (w), 1574 (vw), 1519 (m), 1478 (w), 1443
(w), 1415 (w), 1392 (vw), 1362 (w), 1348 (w), 1335 (w), 1271 (w),
1236 (m), 1158 (w), 1053 (m), 1013 (w), 1004 (w), 879 (w), 869 (w),
843 (m), 823 (w), 776 (s), 757 (vs), 737 (m), 728 (m), 675 (m), 656
(w) cm–1. MS (FAB+): m/z (%) = 437.1 (30) [Cu37Cl{HC(3-
tBuPz)2(Py)}]+, 435.1 (40) [Cu35Cl{HC(3-tBuPz)2(Py)}]+, 400.4
(100) [Cu{HC(3-tBuPz)2(Py)}]+. C20H27ClCuN5 (436.46): calcd. C
55.0, H 6.2, N 16.1; found C 54.9, H 6.3, N 16.1.
isotropic displacement parameters Uiso(H)
= 1.2Ueq(C) and
1.5Ueq(C methyl). All methyl groups were allowed to rotate but not
to tip. Data for C4 was collected with a XcaliburS diffractometer
from Oxford Diffraction by using the programs CRYSALIS (Ox-
ford, UK, 2008) and CRYSALIS RED (Oxford, UK, 2008) and
with graphite-monochromated Mo-Kα radiation (λ = 0.71073 Å).
The structure was solved by direct methods using SHELXS97[53]
and successive difference Fourier syntheses. For refinement full-
matrix least-squares methods were applied (SHELXL97).[55] The
hydrogen atoms were placed in geometrically calculated positions
using a riding model with Uiso constrained by 1.2 times Ueq for the
carrier atom.
(2-Pyridinyl)bis(3-tert-butylpyrazolyl)methanecopper(II)
Bromide
[CuBr2{HC(3-tBuPz)2(py)}] (C3): A yellow solution of HC(3-
tBuPz)2(Py) (0.34 g, 1.00 mmol) dissolved in methanol (5 mL) was
added dropwise to a suspension of CuBr2 (0.22 g, 1.00 mmol) in
methanol (7 mL). The mixture was stirred for 20 h. During this
time the solution turned dark green and a violet solid precipitated
(0.11 g, 19%). Dark red crystals could be obtained by filtration and
storage of the filtrate at 278 K for several days. The crystals were
characterised by means of X-ray crystallography. IR (ATR): ν =
˜
Eur. J. Inorg. Chem. 0000, 0–0
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Table 4. Crystallographic data and parameters of C1–C4.
C1
C2
C3
C4
Empirical formula
Formula mass [gmol–1]
Crystal size [mm]
T [K]
Crystal system
Space group
a [Å]
b [Å]
c [Å]
α [°]
C24H29ClCuN5
486.51
0.16ϫ0.13ϫ0.10
200
orthorhombic
Pnma
15.017(3)
15.970(3)
10.398(2)
90
C20H27ClCuN5
436.46
0.18ϫ0.17ϫ0.11
200
monoclinic
P21/c
15.9899(4)
16.4751(4)
16.5686(5)
90
C20H27Br2CuN5
560.83
0.17ϫ0.11ϫ0.09
173
monoclinic
P21/c
8.0820(6)
17.3088(14)
32.561(2)
90
C20H27Cl2CuN5
471.91
0.18ϫ0.14ϫ0.02
173
orthorhombic
Pnma
15.9418(18)
17.563(4)
8.0627(14)
90
β [°]
90
90
2493.7(8)
4
1.296
94.82(2)
90
4349.3(2)
8
1.333
1.141
91.68(2)
90
4553.0(6)
8
1.636
4.485
90
90
2257.4(7)
4
1.389
γ [°]
V [Å3]
Z
ρcalcd. [gcm–3]
μ [mm–1]
1.003
1.219
λ [Å]
F(000)
0.71073
1016
0.71073
1824
0.71073
2248
0.71073
980
hkl range
Ϯ18, Ϯ19, –11/12
15160
2403
Ϯ19, Ϯ19, –19/20
38340
8081
Ϯ10, Ϯ21, –36/40
50615
9286
Ϯ19, Ϯ21, Ϯ9
164968
2175
Reflections collected
Independent reflections
Rint.
0.0412
0.0400
0.0327
0.1243
Reflections observed
Number of parameters
R1 [IՆ2σ(I)]
wR2 (all data)
Goodness-of-fit
Largest diff. peak, hole [eÅ–3]
2403
163
0.0318
0.0851
1.083
–0.302, 0.269
8081
499
0.0358
0.0916
1.080
–0.443, 0.479
9286
517
0.0776
0.1794
1.262
–0.851, 2.053
2175
142
0.0353
0.0514
0.649
–0.255, 0.380
3106 [w (ν, CHarom)], 3068 [vw (ν, CHarom)], 2958 (w), 2920 (w), 0.17 mmol) in dry CH2Cl2 (2.5 mL) was added in one portion to
2868 (vw), 1604 (w), 1522 (m), 1475 (w), 1468 (w), 1447 (m), 1435 CuCl (0.017 g; 0.18 mmol). After stirring the mixture for 1 h, a
(w), 1417 (w), 1393 (vw), 1362 (w), 1343 (w), 1302 (w), 1267 (m), solution of AgSbF6 (0.062 g, 0.17 mmol) in dry THF (0.25 mL)
1236 (s), 1207 (m), 1163 (m), 1111 (w), 1065 (m), 1022 (m), 1000 was added dropwise to the vigorously stirred solution. The re-
(w), 928 (vw), 880 (m), 838 (m), 819 (m), 770 (vs), 739 (m), 727
sulting slurry, which contained AgCl, was filtered through Celite,
(m), 677 (m), 643 (m), 608 (m) cm–1. MS (FAB+): m/z (%) = 481.4 thereby resulting in a red-orange solution.
(53) [Cu81Br{HC(3-tBuPz)2(Py)}]+, 479.4 (47) [Cu79Br{HC(3-
Preparation of [Cu2O2{HC(3-tBuPz)2(Qu)}2][SbF6]2 (P[SbF6]2): Oxy-
tBuPz)2(Py)}]+, 400.5 (100) [Cu{HC(3-tBuPz)2(Py)}]+, 338.5 (61)
[HC(3-tBuPz)2(Py)]+, 214.4 (98) [HC(3-tBuPz)(Py)]. C20H27Br2-
CuN5 (560.82): calcd. C 42.8, H 4.9, N 12.5; found C 42.5, H 4.9,
N 12.4.
genation of CuI complexes was performed by rapid injection of the
60 mm solution of [Cu{HC(3-tBuPz)2(Qu)}]SbF6 (500 μL) into a
solution of oxygen in CH2Cl2 (9.5 mL) at 195 K.[2] The dichloro-
methane has been saturated with dioxygen at 195 K for a higher
O2 concentration. In the following, the colour of the solution
changed from red-orange to light purple. The formation of
P[SbF6]2 was followed by UV/Vis spectroscopy. The pseudo-first-
order kinetics (Figure S1) was determined at 195 K and for these
measurements we used the same conditions as for the preparation
of [Cu{HC(3-tBuPz)2(Qu)}]SbF6.
(2-Pyridinyl)bis(3-tert-butylpyrazolyl)methanecopper(II) Chloride
[CuCl2{HC(3-tBuPz)2(Py)}] (C4):
A solution of CuCl2·2H2O
(0.17 g, 1.00 mmol) dissolved in methanol (10 mL) was added drop-
wise to a light yellow solution of HC(3-tBuPz)2(Py) (0.34 g,
1.00 mmol) dissolved in methanol (6 mL). After several days the
formation of green crystals was visible (0.40 g, 85%) IR (KBr): ν
˜
= 3153 [vw (ν, CHarom)], 3116 [m (ν, CHarom)], 3098 [w (ν,
CHarom)], 3068 [w (ν, CHarom)], 3028 [vw (ν, CHarom)], 2962 (m),
2907 (w), 2867 (w), 1605 (m), 1576 (vw), 1559 (vw), 1522 (m), 1477
(w), 1450 (m), 1438 (m), 1419 (w), 1391 (vw), 1361 (m), 1351 (m),
1333 (w), 1303 (vw), 1268 (m), 1238 (vs), 1207 (m), 1163 (m), 1110
(vw), 1064 (m), 1022 (m), 1004 (m), 881 (m), 838 (m), 820 (w), 776
(vs), 739 (m), 727 (m), 677 (w), 645 (w), 609 (w), 588 (vw), 520
(vw), 425 (vw) cm–1. MS (ESI+, CH3OH): m/z (%) = 437.1 (4)
[Cu37Cl{HC(3-tBuPz)2(Py)} +], 435.1 (8) [Cu35Cl{HC(3-tBuPz)2-
(Py)} +], 402.2 (10), 401.3 (8), 400.2 (20) [Cu{HC(3-tBuPz)2(Py)}+],
215.2 (20), 214.2 (100) [{HC(3-tBuPz)(Py)}+]. C20H27N5Cl2Cu
(471.91) calcd. C: 50.9, H: 5.8, N: 14.8; found C 50.6, H: 5.8, N:
14.6.
Oxidation of Catalytic Amounts of Exogenous Substrate: This
method is analogous to that reported by Tuczek et al.[32] A solution
of 4-methoxyphenol (25 equiv.) and triethylamine (50 equiv.) in
dichloromethane (200 μL) was added to the solution of [Cu{HC(3-
tBuPz)2(Qu)}]SbF6 in CH2Cl2 at 195 K and with a fine needle O2
was bubbled through this solution. The reaction was monitored by
means of UV/Vis spectroscopy. Upon bubbling through O2, an in-
tense 418 nm feature developed owing to the formation of the 4-
methoxy-1,2-benzoquinone.[59] The quantity of the quinone formed
was determined from the extinction coefficient of the quinone
minus the residual extinction coefficient of thermally decayed
P[SbF6]2, thus yielding ten turnovers per dinuclear copper peroxide
species after 1 h.
Preparation of [Cu{HC(3-tBuPz)2(Qu)}]SbF6: This complex is the
CuI precursor for optical and reactivity studies of the copper di-
Supporting Information (see footnote on the first page of this arti-
oxygen species.
A
solution of HC(3-tBuPz)2(Qu) (0.064 g,
cle): Selected bond lengths [Å] and angles [°] for both molecules in
Eur. J. Inorg. Chem. 0000, 0–0
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FULL PAPER
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Financial support by the Deutsche Forschungsgemeinschaft
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FULL PAPER
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Received: October 7, 2014
Published Online: ᭿
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Date: 20-12-14 13:17:32
Pages: 10
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FULL PAPER
Bioinorganic Chemistry
C. Wilfer, P. Liebhäuser, H. Erdmann,
A. Hoffmann, S. Herres-Pawlis* ..... 1–10
Herein, we present four new bis(pyrazolyl)-
methane–copper complexes. Furthermore,
we studied the self-assembly of a peroxo–
dicopper species with catalytic hydroxyl-
ation activity of phenols by UV/Vis spec-
troscopy. The donor competition between
pyrazolyl and pyridinyl units as well as the
UV transitions of the tyrosinase model
have been investigated by density func-
tional theory.
Biomimetic
Hydroxylation
Catalysis
Through Self-Assembly of a Bis(pyrazolyl)-
methane Copper–Peroxo Complex
Keywords: Bioinorganic chemistry / Oxygen
activation / Self-assembly / Copper / N
ligands
Eur. J. Inorg. Chem. 0000, 0–0
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© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim