Catalytic conversion of monophenols to ortho-quinones in a tyrosinase-like fashion: Towards more biomimetic and more efficient model systems

Article abstract of DOI:10.1002/zaac.201300065

A new tyrosinase model based on the mononuclear copper(I) complex CuL _bzm1 is synthesized and characterized. The ligand L_bzm1 of this system contains a combination of an imine and a benzimidazole function which renders the system more biomimetic in comparison to the recently published L_py1 model of tyrosinase (M. Rolff, J. Schottenheim, G. Peters, F. Tuczek, Angew. Chem. Int. Ed. 2010, 122, 6583). As shown by UV/Vis and NMR spectroscopy, the CuL_bzm1 complex catalytically mediates the conversion of the monophenol DTBP-H to the o-quinone DTBQ with a TON of 31. This reaction was also conducted in a stoichiometric fashion to get information about the involved intermediates and identify possible reasons for the observed increase in catalytic performance with respect to the L_py1 system. DFT calculations were performed for the μ-catecholato dicopper intermediate, compound 4^bzm. These calculations indicate a mixed valent Cu ^I-semiquinone-Cu^II structure, indicating that one-electron transfer from the monohydroxylated substrate to the copper centers has already occurred at this stage. Copyright

Full text of DOI:10.1002/zaac.201300065

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ARTICLE
DOI: 10.1002/zaac.201300065
Catalytic Conversion of Monophenols to Ortho-Quinones in a Tyrosinase-
Like Fashion: Towards More Biomimetic and More Efficient Model Systems
Julia Schottenheim,[a] Natalie Fateeva,[a] Wulf Thimm,[a] Jan Krahmer,[a] and
Felix Tuczek*[a]
Keywords: Type 3 copper proteins; Tyrosinase; Enzyme models; Catalysis; Bioinorganic chemistry
Abstract. A new tyrosinase model based on the mononuclear copper(I) tion was also conducted in a stoichiometric fashion to get information
complex CuLbzm1 is synthesized and characterized. The ligand Lbzm
1
about the involved intermediates and identify possible reasons for the
of this system contains a combination of an imine and a benzimidazole observed increase in catalytic performance with respect to the Lpy
1
function which renders the system more biomimetic in comparison
system. DFT calculations were performed for the μ-catecholato di-
to the recently published Lpy1 model of tyrosinase (M. Rolff, copper intermediate, compound 4bzm. These calculations indicate a
J. Schottenheim, G. Peters, F. Tuczek, Angew. Chem. Int. Ed. 2010, mixed valent CuI-semiquinone-CuII structure, indicating that one-
122, 6583). As shown by UV/Vis and NMR spectroscopy, the electron transfer from the monohydroxylated substrate to the copper
CuLbzm1 complex catalytically mediates the conversion of the mono-
phenol DTBP-H to the o-quinone DTBQ with a TON of 31. This reac-
centers has already occurred at this stage.
The function of tyrosinase comprises two processes: the
monophenolase activity involves the o-hydroxylation and sub-
sequent two-electron oxidation of monophenols to o-quinones,
and the diphenolase activity refers to the two-electron
oxidation of catechols to o-quinones (Scheme 2).[7]
Introduction
The type 3 copper enzyme tyrosinase mediates the o-hy-
droxylation of monophenols to catechols and the subsequent
two-electron oxidation to o-quinones.[1] Melanine synthesis
starts with these two steps catalyzed by tyrosinase; i.e., the
conversion of tyrosine to dopaquinone.[2,3] The active site of
Streptomyces castaneoglobisporus tyrosinase has recently been
characterized by X-ray crystallography.[4] It contains a
binuclear copper center whereupon each copper is coordinated
by three histidines. In the meantime more tyrosinases have
been structurally characterized.[5] In analogy to the other two
important type 3 copper proteins hemocyanin and catechol
oxidase, tyrosinase binds dioxygen in the characteristic side on
geometry (μ-η2:η2),[6] changing the CuI atoms in the deoxy
state to CuII atoms in the oxy state (Scheme 1).
Scheme 2. Monophenolase activity (top) and diphenolase activity (bot-
tom) of tyrosinase.
Numerous examples of small-molecule model systems re-
producing the mono- and diphenolase activities of type 3
copper proteins have been published.[8–10] However, the number
of tyrosinase models exhibiting monophenolase activity in a
catalytic fashion is still small.[1] The first success in this field
was achieved by the research group of Bulkowski employing
dicopper systems supported by macrocyclic ligands.[11] In
1990, Réglier et al. published the ligand bis-2,2Ј-[2-(pyrid-2-
yl)ethyl]-iminobiphenyl (BiPh-(impy)2) which contains two
pyridylethylimine sidearms bridged by a biphenyl spacer. The
corresponding binuclear copper(I) complex is able to generate
3,5-di-tert-butyl-o-quinone (DTBQ) with a turnover number
(TON) of 16 upon addition of 100 equiv. 2,4-di-tert-butyl-
phenol (DTBP-H) and 200 equiv. triethylamine (NEt3) within
one hour.[12,13] At about the same time another catalytic model
system of tyrosinase was published by Casella and co-workers,
Scheme 1. Deoxy and oxy state of the active site in Streptomyces cas-
taneoglobisporus tyrosinase.
* Prof. Dr. F. Tuczek
Fax: +49-431-880-1520
E-Mail: ftuczek@ac.uni-kiel.de
[a] Institut für Anorganische Chemie
Christian-Albrechts-Universität zu Kiel
Max-Eyth-Straße 2
D-24118 Kiel, Germany
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/zaac.201300065 or from the au-
thor.
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J. Schottenheim, N. Fateeva, W. Thimm, J. Krahmer, F. Tuczek
ARTICLE
which is based on the ligand α,αЈ-bis{bis[2-(1-methyl-
benzimidazol-2-yl)ethyl]-amino}-m-xylene (L66).[14]
We recently presented the first tyrosinase model system
based on a mononuclear copper(I) complex exhibiting catalytic
monophenolase activity, [CuILpy1(CH3CN)2]PF6.[15,16] It was
shown to generate DTBQ upon addition of 50 equiv. DTBP-
H, 100 equiv. NEt3 and molecular oxygen with a turnover
number (TON) of 18 after 8 hours. The reaction course was
monitored via the UV/Vis absorption of DTBQ at 407 nm (ε =
1830 m–1·cm–1)[17] and by NMR spectroscopy.[15] Moreover,
we were able to characterize relevant intermediates of the cata-
lytic cycle (except the side on peroxo complex) by performing
the reaction in a stoichiometric mode[18] and draw some con-
clusions with respect to the reactivity of tyrosinase. Neverthe-
less, there are still open questions concerning the exact mecha-
nism in this model system and the factors limiting its catalytic
performance.
Like the parent BiPh-(impy)2 system, our Lpy1 tyrosinase
model contained a mixed pyridine-imine ligand, which we
showed to be essential for the catalytic conversion of DTBP-
H to DTBQ. Specifically, modifications of the ligand design
to two pyridine or two imine functions (ligands L2 and L3,
respectively) were found to delete the catalytic activity.[15,19]
An interesting question is now how smaller changes in the
ligand design affect the catalytic DTBQ formation. To this end
we decided to keep the imine function and replace the pyridine
by a benzimidazole group, which renders the system more bio-
mimetic. Furthermore, we wanted to know how this change
affects the reaction rate and the yield of DTBQ. Herein, we
present the ligand Lbzm1 which contains a combination of
an imine and a benzimidazole function (Figure 1) and its
copper(I) complex, CuLbzm1.
Scheme 3. Synthesis of ligand Lbzm1 and the corresponding copper(I)
complex CuLbzm1.
solution of CuLbzm1 in dichloromethane were given 50 equiv.
DTBP-H and 100 equiv. NEt3. The system generates catalyti-
cally DTBQ with molecular oxygen, which was detected by
the evolution of the 407 nm absorption band (Figure 2). Based
on an ε-value of 1830 m–1· cm–1 the Lbzm1 system produces
28 TON per dicopper unit during the first 3.5 hours. The rate
of DTBQ formation decreases with time, and after 6.5 hours
the yield reaches a maximum value of 31 turnovers (Figure 3,
top). During the first 10 minutes of oxygenation the turnover
frequency (TOF) is about 1 TON per minute and is halved
after 30 min. The reaction rate decreases continuously until it
is almost zero after 8 hours (Figure 3, bottom). The CuLbzm1
system thus is able to catalytically mediate the conversion of
DTBP-H to DTBQ, in analogy to the Lpy1 system investigated
before.[21]
Figure 1. Ligands Lpy1 (left) and Lbzm1 (right) of this study.
The synthesis (Scheme 3) starts with a cyclization of N-
methyl-o-diaminoethylene and β-alanine in hydrochloric acid
to give 1-methyl-2-(2-aminoethyl)-benzimidazole dihydro-
chloride,[14] which was neutralized by addition of methanolic
sodium hydroxide solution.[20] Imine condensation of 1-
methyl-2-(2-aminoethyl)-benzimidazole
and
trimethyl-
acetaldehyde provided Lbzm1, which was converted into the
corresponding copper(I) complex CuLbzm1 by addition of
tetrakis(acetonitrile)copper(I) hexafluoro-phosphate under
anaerobic conditions. All the compounds were obtained in
satisfactory yields and purity (experimental section).
Figure 2. Oxygenation of a 500 μmolar solution of CuLbzm1 in
dichloromethane in the presence of 50 equiv. DTBP-H and 100 equiv.
NEt3 during the first 3.5 hours at room temperature; l = 1 mm.
Results and Discussion
The catalytic activity of CuLbzm1 was monitored by in situ
Compared with the catalytic oxygenation mediated by the
UV/Vis spectroscopy at room temperature. To a 500 μmolar CuLpy1 complex both the rate and the yield of the DTBQ
2
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Catalytic Conversion of Monophenols to Ortho-Quinones in a Tyrosinase-Like Fashion
Figure 4. 1H-NMR spectrum of the organic phase after HCl quench
(1 h oxygenation) with detected compounds (grey: DTBP-H, black full
line: DTBQ; black dotted line: C–C coupling product).
the Lpy1 system produces 19 TON per dicopper unit during
the first 3.5 hours and reaches a maximum of 22 turnovers
after 5.5 hours (Figure 3, top). The turnover frequency (TOF)
is about 0.5 TON per minute during the first 5 min of oxygena-
tion, is halved after 35 min and further decreases continuously
until it is almost zero after 8 hours (Figure 3, bottom). In com-
parison with the Lpy1 complex the Lbzm1 system thus achieves
an increase in the TON for the catalytic formation of DTBQ
by 10 and an increase in TOF during the first hour by a factor
of 2.
Upon oxygenation of DTBP-H mediated by the CuLbzm1
complex, the color of reaction mixture changes from light
yellow to orange-brown and afterwards to dark green. After
15 hours the color of the solution is blue and the final UV/Vis
Figure 3. Turnover number per dicopper unit (top) and turnover fre-
quency per minute (bottom) as a function of time over 8 hours of
oxygenation at room temperature.
formation thus are increased for the CuLbzm1 system. How- spectrum shows substantial changes in comparison to that
ever, the concentration of the former complex was lower in the shown in Figure 2; i.e., next to the characteristic band at
2010 publication (20 μmolar, see below).[15]
407 nm, two new absorption maxima at 381 nm and 588 nm
In order to monitor the reaction course a small amount of appear (see Figure S2 for further information). At this point of
the reaction mixture was taken after about 1 h of oxygenation the catalytic reaction we repeated the HCl quench and with
1
and diluted to a concentration of 25 μmolar CuLbzm1 in help of H-NMR spectroscopy again determined the composi-
dichloromethane. This solution was treated with 6 m hydro- tion of the organic phase. Now only 18% of the starting
chloric acid and extracted with dichloromethane to eliminate amount of DTBP-H are still existing, 7% are present as DTBQ
the existing copper species (see Figure S1 for further infor- and 75% are converted into the C–C-coupling product
mation). The solvent was removed and the resulting residue 3,3Ј,5,5Ј-tetra-tert-butyl-2,2Ј-biphenol (see Figure S3 for
1
investigated by H-NMR spectroscopy (Figure 4).
further information). Via atomic absorption spectroscopy
This way it was found that after 1 h of oxygenation 63% (AAS) 10% of the reaction mixture in the blue fraction could
of the starting amount of DTBP-H are unchanged, 22% are be associated with a copper complex. The intense blue color
converted into the C–C-coupling product 3,3Ј,5,5Ј-tetra-tert- might indicate the formation of a copper(I) semiquinone com-
butyl-2,2Ј-biphenol,[22,23] and in accordance with the TON of plex.
15 determined spectrophotometrically, 15% of the product
DTBQ are generated.
To check if the mechanism of the catalysis is the same as
for the Lpy1 system, the catalytic reaction was also performed
in a stoichiometric fashion. To this end, we synthesized the
For a direct comparison between the CuLpy1 and CuLbzm
1
model systems we also performed the oxygenation of 50 equiv. complex [CuILbzm1(DTBP)(NEt3)] (2bzm) by the reaction of
DTBP-H in the presence of 100 equiv. NEt3 for a 500 μmolar CuLbzm1 with 1 equiv. of K-DTBP (Potassium-2,4-di-tert-
solution of CuLpy1 in dichloromethane. This gave almost iden- butylphenolate) and 1 equiv. NEt3 in dry dichloromethane
tical results to the 20 μmolar solution investigated before; i.e., under Schlenk conditions (Scheme 4).
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J. Schottenheim, N. Fateeva, W. Thimm, J. Krahmer, F. Tuczek
ARTICLE
Figure 5. Stoichiometric oxygenation of a 500 μmolar solution of
compound 2bzm in dichloromethane; l = 10 mm.
Scheme 4. Proposed mechanistic cycle of the CuLbzm1 system.
The UV/Vis spectrum of a 500 μmolar solution of com-
pound 2bzm in dry CD2Cl2 is shown in Figure 5 (black line).
The spectrum exhibits a phenolate Ǟ Cu transition at about
350 nm, which decreases while molecular oxygen is bubbled
through the solution over 30 min. In case of the CuLpy1 sys-
tem formation of a μ-catecholato complex (“compound 4")
could be evidenced at this stage of the reactive cycle.[15] We
assume that an analogous intermediate, 4bzm, is formed in case
of the CuLbzm1 system (Scheme 4). However, the change in
the absorption spectrum at about 350 nm is rather insignificant
(Figure 5; dark grey line). Moreover, we were unable to isolate
compound 4bzm as a well-defined complex. Further infor-
mation on this putative intermediate was therefore obtained by
DFT (see below). Nevertheless, we were able to show that
4bzm is also catalytically competent. To this end the solution
was rinsed with argon, 50 equiv. DTBP-H and 100 equiv. NEt3
Figure 6. DFT optimized structure of compound 4bzm; inset: reduced
presentation of 4bzm
.
I
were added and oxygen was passed through the solution for show that compound 4bzm exhibits a mixed valent CuA -semi-
II
30 min. The resulting spectrum again exhibited the absorption quinone-CuB structure (Figure 6).
at 407 nm, which is caused by DTBQ (Figure 5; dashed line).
In particular, the geometry of the ligands around CuA indi-
This observation is fully analogous to that obtained with the cates a tetrahedral coordination, corresponding to copper(I),
Lpy1 system; it thus appears that the catalytic mechanism in while the coordination sphere around CuB is distorted square
the Lbzm1 system is very similar. However, the reaction rate is pyramidal, which is typical for copper(II) centers. Thus
much faster and the intermediates are less stable. In particular, oxidation of the catechol to semiquinone has already taken
we were unable to detect the peroxo complex 3bzm via in situ place at this stage, and one electron has been transferred to
low-temperature UV/Vis spectroscopy. The proposed mechan- one copper center (CuA), forming CuI.
istic cycle of the CuLbzm1 system is shown in Scheme 4.
Figure 7 shows the HOMO and the LUMO of the 4bzm inter-
To obtain further insight into the reactivity of the new mediate obtained by DFT. Importantly, the HOMO exhibits a
system DFT calculations were performed for compound 4bzm bonding interaction between the catecholato (= cat2–) homo
(for details see Exp. Sect.). Importantly, these calculations and CuB while the LUMO of 4bzm exhibits an antibonding
4
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Catalytic Conversion of Monophenols to Ortho-Quinones in a Tyrosinase-Like Fashion
interaction between the cat2– homo and CuB. For CuA the catalytically mediates the conversion of DTBP-H to DTBQ
corresponding copper-cat2– interactions are antibonding both with a TON of 31 which is 72% higher than that of CuLpy1
in the HOMO and in the LUMO of 4bzm. These findings are and a TOF which is about twice as large as that of the latter
compatible with a bonding-antibonding interaction of a complex. Apart from the well-documented capability of
catecholato ligand having a singly occupied homo (i.e., a semi- copper-benzimidazole complexes to mediate the ortho-
quinone = sq·– somo) with one d9 CuII atom (CuB) and a σ- hydroxylation of phenolic substrates,[18,24] a possible reason
nonbonding interaction of this species with a second, closed- for the observed increase in catalytic performance is a lowered
shell d10CuI atom, CuA.
barrier for the two-electron oxidation of the bound catechol,
leading to the quinone product. This would account for the
increased lability of the catecholato adduct of CuLbzm1 (4bzm
)
in comparison to the CuLpy1 system. In agreement with this
hypothesis, DFT treatment of this intermediate shows a mixed
valent CuI-semiquinone-CuII structure, indicating that one-
electron oxidation of the catecholate ligand by one copper cen-
ter has already taken place at this stage. Further one-electron
oxidation (probably induced by protonation of the bridging
hydroxo group)[1,15] would then lead to the CuI-CuI species
and quinone, closing the catalytic cycle.
Experimental Section
Materials and Techniques
Figure 7. DFT calculated molecular orbitals of the bonding HOMO
sq·–-CuB (left) and the antibonding LUMO sq·–-CuB (right) for com-
All reagents were used as received from Sigma-Aldrich Co. and abcr
GmbH & Co. KG. Solvents were all reagent grades. Dichloromethane
and acetonitrile have been further purified by refluxing over calcium
hydride and distilled under nitrogen atmosphere. Elemental analyses
were performed using a Euro Vector CHNS-O-element analyzer (Euro
EA 3000) and the samples were burned in sealed tin containers in an
oxygen stream. The content of chloride was determined according to
Schöniger[25] with a potentiograph E536 from Metrohm, Herisau,
using ion selective electrodes. The NMR spectra were recorded at
300 K on a Bruker Avance 400 Pulse Fourier Transform spectrometer
operating at a 1H frequency of 400.13 MHz and a 13C frequency of
100.62 MHz and were referenced on residual protons of the solvent.
Optical absorption spectra were recorded in solution on an Agilent
pound 4bzm
.
II
The conventional CuAII-cat2–-CuB and the unusual
I
II
CuA -sq·–-CuB structures are compared in Scheme 5. In the
former case the cat2– homo is below the singly occupied
copper orbitals which undergo a bonding-antibonding interac-
tion via the bridging ligand(s), leading to antiferromagnetic
coupling. In the latter case the cat2– homo is at about the same
energy as the singly occupied copper orbitals such that one-
electron transfer to one copper center can occur, leading to
a coordinated semiquinone ligand. This description obviously
applies to the intermediate 4bzm
.
Technologies 8453 UV/Vis Spectrophotometer (l
l = 10 mm).
= 1 mm and
DFT Calculations
For the optimization and the calculation of molecular orbitals the struc-
ture of Compound 4bzm was simplified by replacement of the tert-
butyl groups by methyl functions. The DFT calculations were per-
formed with Gaussian09[26] using the UB3LYP functional. The
Def2-TZVPP basis set was used for copper and the Def2-SVP basis
set for all other atoms.
II
Scheme 5. Simplified MO schemes for the CuAII-cat2–-CuB structure
of intermediate 4bzm (left) and CuAI-sq·–-CuB structure evidenced by
II
Synthesis of 1-Methyl-2-(2-aminoethyl)-benzimidazole
DFT calculations (right).
This compound was obtained as dihydrochloride by stirring a solution
of N-methyl-o-phenylenediamine (3.12 g, 25.6 mmol) and β-alanine
(3.42 g, 38.4 mmol) in 6 m hydrochloric acid (30 mL) under reflux for
4 d. After cooling to room temperature the solvent was evaporated.
The residue was diluted in a minimum amount of water and ethanol
(200 mL) was added. After 1 d at 8 °C the precipitate was collected
by filtration and washed with ethanol to yield 6.12 g (97%) of a light
blue solid.
Conclusions
A modified small-molecule model system of tyrosinase,
CuLbzm1, has been synthesized and characterized with respect
to the conversion of DTBP-H to DTBQ. The new system is
similar to the CuLpy1 complex presented earlier,[15] but
instead of the pyridine group of the latter system contains a
C10H15Cl2N3 (M = 248.15 g·mol–1); C 48.39 (calcd. 48.40); H 6.52
benzimidazole moiety. Importantly, the CuLbzm1 complex (6.09); N 16.83 (16.93); Cl 27.86 (28.57)%.
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J. Schottenheim, N. Fateeva, W. Thimm, J. Krahmer, F. Tuczek
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Synthesis of [CuILbzm1(DTBP)(NEt3)] (2bzm
)
In order to remove HCl, 1-methyl-2-(2-aminoethyl)-benzimidazole
dihydrochloride (1.00 g, 4.03 mmol) was diluted in a methanol-chloro-
form mixture (250 mL, 4:1) and a 1 m methanol sodium hydroxide
solution (12.5 mL) was added. The solution was stirred at room tem-
perature for 4 h and the solvent was removed under reduced pressure.
The residue was diluted in a minimum amount of water and toluene
(100 mL) was added. The aqueous phase was extracted three times
with toluene (25 mL) and the combined organic phases were evapo-
rated to give 430 mg (61%) of 1-methyl-2-(2-aminoethyl)-benzimid-
azole as a pink solid.
A solution of NEt3 (19.0 mg, 187 μmol) and K-DTBP (Potassium-2,4-
di-tert-butyl-phenol) (45.6 mg, 187 μmol) in dichloromethane (5 mL)
was added under Schlenk conditions to a solution of CuLbzm
(100 mg, 187 μmol) in dichloromethane (5 mL) and stirred under nitro-
gen for 15 min at room temperature. The reaction mixture was filtered
through a frit and the solution was evaporated to obtain 60 mg (40%)
of a brown powder.
1
1H NMR (400 MHz, CD2Cl2, 300 K): δ = 7.27 (d, 1 H, DTBP H-3),
7.76 (s, 1 H, imine H), 7.26–7.14 (m, 4 H, bzm H-4, H-5, H-6, H-7),
7.05 (dd, 2 H, DTBP H-5, H-6), 4.14 (s, 2 H, CH2-imine), 3.62 (s,
3 H, CH3-N), 3.28 (s, 2 H, CH2-bzm), 1.39 (s, 9 H, (-CH3)3)-DTBP),
1.28 (s, 9 H, (-CH3)3)-DTBP), 1.26 (s, 2 H, CH2-triethylamine),
1.24 (s, 2 H, CH2-triethylamine), 1.16 (s, 18 H, (-CH3)3)-Lbzm1,
CH3-triethylamine), 1.03 (s, 2 H, CH2-triethylamine).
C10H13N3 (M = 175.23 g·mol–1); C 68.62 (calcd. 68.54); H 8.92 (8.48);
N 23.98 (22.94); Cl 0.00 (0.00)%. 1H NMR (400 MHz, MeOD,
300 K): δ = 7.50–7.32 (m, 2 H, bzm H-4, bzm H-7), 7.13 (m, 2 H, bzm
H-5, bzm H-6), 3.69 (s, 3 H, CH3-N), 3.73 (s, 3 H, CH3-N), 3.01 (m,
4 H, CH2-bzm, CH2-amine). 13C NMR (100 MHz, MeOD, 300 K): δ
= 154.98 (Cq, bzm C-2), 142.95 (Cq, bzm C-3a), 136.92 (Cq, bzm
C-7a), 123.56 (CH, bzm C-6), 123.21 (CH, bzm C-5), 119.02 (CH, bzm
C-4), 110.73 (CH, bzm C-7), 40.40 (CH2, CH2-imine), 31.02 (CH2,
CH2-bzm), 30.10 (CH3, CH3-N).
Supporting Information (see footnote on the first page of this article)
Acknowledgments
The authors thank Deutsche Forschungsgemeinschaft (DFG) and CAU
Kiel for support of this research.
Synthesis of Lbzm
1
For the preparation of Lbzm1 a mixture of 1-methyl-2-(2-aminoethyl)-
benzimidazole (240 mg, 1.37 mmol), trimethylacetaldehyde (120 mg,
1.39 mmol) and a catalytic amount of p-toluenesulfonic acid mono-
hydrate in toluene (20 mL) was stirred under reflux and removal of
water using a Dean–Stark trap for 5 d. After cooling to room tempera-
ture the solution was decanted from the catalyst. The solution was
evaporated and there 309 mg (93%) of yellow-brown oil were
obtained. The ligand was used without further purification for the syn-
thesis of the CuLbzm1 complex (see below).
References
[1] M. Rolff, J. Schottenheim, H. Decker, F. Tuczek, Chem. Soc. Rev.
2011, 40, 4077.
[2] A. Sanchez-Ferrer, J. N. Rodrι´guez-López, F. Garcι´a-Cánovas, F.
Garcι´a-Carmona, Biochim. Biophys. Acta Prot. Struct. Mol. En-
zym. 1995, 1247, 1.
[3] K. E. van Holde, K. I. Miller, H. Decker, J. Biol. Chem. 2001,
276, 15563.
[4] Y. Matoba, T. Kumagai, A. Yamamoto, H. Yoshitsu, M. Sugi-
yama, J. Biol. Chem. 2006, 281, 8981.
1H NMR (400 MHz, CDCl3, 300 K): δ = 7.44 (s, 1 H, imine H), 7.28–
7.12 (m, 4 H, bzm H), 3.86 (t, 2 H, CH2-imine), 3.73 (s, 3 H, CH3-N),
3.17 (t, 2 H, CH2-bzm), 0.91 (s, 9 H, CH3). 13C NMR (100 MHz,
CDCl3, 300 K): δ = 173.80 (CH, imine C), 153.62 (Cq, bzm C-2),
142.54 (Cq, bzm C-3a), 135.52 (Cq, bzm C 7a), 121.98 (CH, bzm C-
6), 121.78 (CH, bzm C-5), 119.02 (CH, bzm C-4), 108.92 (CH, bzm
C-7), 59.71 (CH2, CH2-imine), 35.93 (Cq, C-(CH3)3), 29.95 (CH3,
CH3-N), 28.81 (CH2, CH2-bzm), 26.62 (CH3, (-CH3)3).
[5] a) M. Sendovski, M. Kanteev, V. S. Ben-Yosef, N. Adir, A. Fish-
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[7] C. Eicken, C. Gerdemann, B. Krebs in Handbook of Metallo-
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104, 1013.
Synthesis of [CuILbzm1(CH3CN)2] PF6 (CuLbzm1)
A
solution of tetrakis(acetonitrile)copper(I) hexafluorophosphate
[10] I. A. Koval, P. Gamez, C. Belle, K. Selmeczi, J. Reedijk, Chem.
Soc. Rev. 2006, 35, 814.
[11] J. E. Bulkowski, US patent 4545937, 1984.
[12] M. Réglier, C. Jorand, B. Waegell, J. Chem. Soc., Chem. Com-
mun. 1990, 1752.
(152 mg, 409 μmol) in acetonitrile (10 mL) was added dropwise under
Schlenk conditions to a solution of Lbzm1 (100 mg, 411 μmol) in ace-
tonitrile (10 mL) and stirred for 30 min at room temperature. The solu-
tion was evaporated to yield 154 mg (70%) of a light brown oil.
[13] M. Réglier, E. Amadéi, E. H. Alilou, F. Eydoux, M. Pierrot, B.
Waegell in Bioinorganic Chemistry of Copper (Eds.: K. D.Karlin,
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Int. Ed. 2010, 49, 6483.
[16] For a clear distinction of the different ligands, the ligand L1 [15]
was renamed Lpy1.
[17] M. Réglier, C. Jorand, B. Waegell, J. Chem. Soc., Chem. Com-
mun. 1990, 1752.
C19H27CuF6N5P (M = 533.96 g·mol–1); C 42.24 (calcd. 42.74); H 4.52
(5.10); N 13.76 (13.12)%. H NMR (400 MHz, [D6]acetone, 300 K):
1
δ = 8.07 (s, 1 H, imine H), 7.96 (dd, 2 H, bzm H-6, H-5), 7.37 (m, 2
H, bzm H-4, H-7), 4.26 (t, 2 H, CH2-imine), 3.93 (s, 3 H, CH3-N),
3.62 (t, 2 H, CH2-bzm), 2.29 (s, 6 H, CH3-CN), 1.27 (s, 9 H, CH3).
13C NMR (100 MHz, [D6]acetone, 300 K): δ = 183.25 (CH, imine C),
156.91 (Cq, bzm C-2), 141.83 (Cq, bzm C-3a), 136.46 (Cq, bzm
C-7a),125.73 (Cq, CN), 125.42 (CH, bzm C-6), 125.09 (CH,
bzm C-5), 119.27 (CH, bzm C-4), 112.43 (CH, bzm C-7), 60.92 (CH2,
CH2-imine), 37.84 (Cq, C-(CH3)3), 28.30 (CH3, CH3-N), 27.10 (CH2,
CH2-bzm), 24.53 (CH3, (-CH3)3), 2.68 (CH3-CN).
[18] L. Casella, E. Monzani, M. Gullotti, D. Cavagnino, G. Cerina, L.
Santagostini, R. Ugo, Inorg. Chem. 1996, 35, 7516.
6
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Catalytic Conversion of Monophenols to Ortho-Quinones in a Tyrosinase-Like Fashion
[19] A. J. Canty, N. J. Minchin, Aust. J. Chem. 1986, 39, 1063.
[20] The synthesis was slightly altered [18], see experimental section.
Cardellach, I. Gamba, M. Güell, L. Casella, L. Que Jr., X. Ribas,
J. M. Luis, M. Costas, Angew. Chem. Int. Ed. 2010, 49, 2406.
[25] W. Schöniger, Microchim. Acta 1955, 123.
[21] In
a
control experiment,
a
500 μmolar solution of
[CuI(CH3CN)4]PF6 in dichloromethane was reacted with
50 equiv. DTBP-H, 100 equiv. NEt3 and molecular oxygen. In this
system a weakly catalytic generation of DTBQ (5.5 TON) was
observed. Moreover, the reaction was finished after 1 hour, in
contrast to the CuLbzm1 system where buildup of 31 TON of
quinone was observed over 8 hours.
[26] M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A.
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Cross, V. Bakken, C. Adamo, J. Jaramillo, R. Gomperts, R. E.
Stratmann, O. Yazyev, A. J. Austin, R. Cammi, C. Pomelli, J. W.
Ochterski, R. L. Martin, K. Morokuma, V. G. Zakrzewski, G. A.
Voth, P. Salvador, J. J. Dannenberg, S. Dapprich, A. D. Daniels,
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[22] G. J. H. Buisman, P. C. J. Kamer, P. W. N. M. van Leeuwen, Tet-
rahedron: Asymmetry 1993, 4, 1625.
[23] The coupling product is known to be formed by reaction of DTBP
in the presence of CuCl2 and amine [22].
[24] a) E. Monzani, L. Quinti, A. Perotti, L. Casella, M. Gullotti, L.
Randaccio, S. Geremia, G. Nardin, P. Faleschini, G. Tabbì, Inorg.
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Chem. Commun. 2003, 726; d) S. Palavicini, A. Granata, E. Mon-
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cia-Bosch, A. Company, J. R. Frisch, M. Torrent-Sucarrat, M.
Received: February 1, 2013
Published Online: ᭿
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© 0000 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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Job/Unit: Z13065
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Date: 26-04-13 16:27:20
Pages: 8
J. Schottenheim, N. Fateeva, W. Thimm, J. Krahmer, F. Tuczek
ARTICLE
J. Schottenheim, N. Fateeva, W. Thimm, J. Krahmer,
F. Tuczek* .......................................................................... 1–8
Catalytic Conversion of Monophenols to Ortho-Quinones in a
Tyrosinase-Like Fashion: Towards More Biomimetic and More
Efficient Model Systems
8
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