Macromolecular salen catalyst with largely enhanced catalytic activity

Article abstract of DOI:10.1021/ol702672k

(Chemical Equation Presented) A dinuclear copper(II) Schiff-base complex was immobilized in a poly(acrylate) matrix by emulsion polymerization. The spheric microbeads were used for aerobic catalytic oxidation of 3,5-di-tert-butylcatechol into 3,5-di-tert-

Full text of DOI:10.1021/ol702672k

ORGANIC
LETTERS
2
008
Vol. 10, No. 2
41-244
Macromolecular Salen Catalyst with
Largely Enhanced Catalytic Activity
2
Susanne Striegler,*,†,‡ Moses G. Gichinga, and Michael Dittel‡
†
Department of Chemistry and Biochemistry, Auburn UniVersity, 179 Chemistry
Building, Auburn, Alabama 36849, and DiVision of Inorganic Chemistry II,
UniVersity of Ulm, Albert-Einstein-Allee 11, 89069 Ulm, Germany
susanne.striegler@auburn.edu
Received November 3, 2007
ABSTRACT
A dinuclear copper(II) Schiff-base complex was immobilized in a poly(acrylate) matrix by emulsion polymerization. The spheric microbeads
were used for aerobic catalytic oxidation of 3,5-di-tert-butylcatechol into 3,5-di-tert-butylquinone in methanol at ambient temperature to study
the contribution of the macromolecular matrix to the overall rate acceleration of the reaction. The polymeric catalyst catalyzes the oxidation
about 1 order of magnitude faster (kcat/knon
) 470 000) than its low molecular weight analogue (kcat/knon ) 60 000).
Enzymes are macromolecules, while many enzyme mimics
are not.1 The macromolecular structure of an enzyme,
however, contributes to the overall catalytic activity. En-
hanced catalytic turnover was achieved in a predominantly
linear macromolecular enzyme mimic compared to a small
addition to the coordinative bonds at a metal complex-
containing active site. The immobilization of a well-explored
catalyst in a polymeric environment lends itself as a
promising strategy toward this goal.
In view of the great importance of oxidation reactions for
industrial and synthetic processes and the ongoing search
2
2
molecular weight entity. Along these lines, we and others
3
hypothesize that a reagent immobilized in a polymer matrix
will support selective interactions between a catalytic site
and a substrate due to the rigidity imposed by the polymer
backbone. This might be achieved by appropriate building
blocks of the macromolecular matrix that enable hydrophobic
interactions, π-π stacking, and/or hydrogen bonding in
for new and efficient oxidation catalysts, we chose the
catalytic oxidation of catechol as a model reaction to test
our hypothesis. Quite a number of mono- and dinuclear
copper coordination compounds have been investigated as
(3) (a) Schultz, M. J.; Hamilton, S. S.; Jensen, D. R.; Sigman, M. S. J.
Org. Chem. 2005, 70, 3343. (b) Mirica, L. M.; Ottenwaelder, X.; Stack, T.
D. P. Chem. ReV. 2004, 104, 1013. (c) Stahl, S. S. Angew. Chem., Int. Ed.
2004, 43, 3400. (d) Marko, I. E.; Gautier, A.; Dumeunier, R.; Doda, K.;
Philippart, F.; Brown, S. M.; Urch, C. J. Angew. Chem., Int. Ed. 2004, 43,
1588. (e) Zhang, C. X.; Liang, H.-C.; Humphreys, K. J.; Karlin, K. D. In
Catalysis by Metal Complexes; ACS Symp. Ser. 26; American Chemical
Society: Washington, DC, 2003; p 79. (f) Sheldon, R. A.; Arends, I. W.
C. E.; ten Brink, G.-J.; Dijksman, A. Acc. Chem. Res. 2002, 35, 774.
†
Auburn University.
University of Ulm.
‡
(
1) Liu, L.; Zhou, W. J.; Chruma, J.; Breslow, R. J. Am. Chem. Soc.
004, 126, 8136.
2) Klotz, I. M.; Suh, J. In Artificial Enzymes; Breslow, R., Ed.; Wiley-
VCH: Weinheim, Germany, 2005.
2
(
1
0.1021/ol702672k CCC: $40.75
© 2008 American Chemical Society
Published on Web 12/15/2007

4
biomimetic catalysts toward this end. While no clear relation
anthracene-9-carboxylate, terephthalate, formate, or malate,
have failed so far. Similar observations were reported for
the preparation of the nonpolymerizable dinuclear copper-
(II) complex {N,N′-1,3-bis[(2-hydroxy)benzylideneamino]-
between the catalytic activity and the redox potential of the
copper species has emerged, dinuclear copper complexes
are generally found to be more reactive than mononuclear
5
4
compounds.
propan-2-ol}ato (µ-acetato) dicopper(II) diperchlorate [4,
8
Keeping all these factors in mind, we herein report the
synthesis of a polymerizable dinuclear copper(II) complex,
its composition in methanolic solution, and its catalytic
activity in comparison to a nonpolymerizable analogue and
a macromolecular catalyst.
Cu
2
(bsdpo)(Ac)], derived from N,N′-1,3-bis[(2-hydroxy)-
9
benzylideneamino]propan-2-ol (5, bsdpo) (Figure 1).
For preparation of the complex, commercially available
4
-hydroxysalicylaldehyde was reacted with p-vinylbenzyl
chloride in a Williamson ether synthesis yielding 2-hydroxy-
-[(4-vinylbenzyl)oxy]benzaldehyde 1 in high purity and
4
more than 70% yield after modification of a reported
6
procedure. Consecutive condensation of 1 with 1,3-diami-
nopropanol at ambient temperature afforded polymerizable
N,N′-1,3-bis[(2-hydroxy-4-vinylbenzyloxy)benzylideneami-
no]propan-2-ol (2, bssdpo) in good yields and high purity
after recrystallization from ethyl acetate. Ligand 2 was
reacted with copper(II) acetate or copper(II) benzoate to
obtain the new {N,N′-1,3-bis[(2-hydroxy-4-vinylbenzyloxy)
benzylideneamino]propan-2-ol}ato (µ-acetato) (or µ-ben-
Figure 1. Structures of nonpolymerizable backbone ligand 5 and
the dinuclear copper(II) complex 4 derived thereof.
2
zoato) dicopper complexes 3a [Cu (bssdpo)(Ac)] and 3b
[
(bssdpo)(benzoato)] (Scheme 1).7
Cu
2
The composition of complexes 3a and 3b in the solid state
is confirmed by elemental analysis and mass spectrometry.
Coordination of 2 to copper(II) acetate resulting in complex
3
a is indicated by IR spectroscopy. The asymmetric (and
Scheme 1. Synthesis of Polymerizable Ligand 2 and Related
Dinuclear Copper(II) Complexes 3a and 3b
symmetric) C-H valence bond vibrational bands are shifted
from 1446 cm (1420 cm ) in copper acetate to 1424 cm
-1
-1
-1
-1
(1397 cm ) in 3a. The C-O valence bond vibrational band
-
1
of the aliphatic hydroxyl group at 1116 cm in 2 is located
-
1
at 1123 cm in 3a. Similar alterations are observed upon
coordination of copper(II) benzoate to ligand 2 resulting in
complex 3b (see the Supporting Information).
A single-crystal X-ray structure analysis of complex 3a
reveals a nearly planar N O coordination environment for
1 3
each of the metal centers in 3a and 3b. The interatomic
Cu‚‚‚Cu distance in 3a of 3.51(5) Å and in 3b of 3.50(1) Å
is comparable to that of nonpolymerizable analogue 4
1
0
(
3.49(5) Å). The X-ray structure analyses of various
dinuclear copper(II) salen complexes will be discussed in
1
1
detail elsewhere.
We then explored the composition of 3a in solution to
determine whether or not the bridging acetate anion is
abstracted in methanol by using the spectrophotometric
1
2
titration method developed by Zuberb u¨ hler. The non-
polymerizable backbone ligand 5 was used instead of polym-
(
6) Fujii, Y.; Matsutani, K.; Kikuchi, K. J. Chem. Soc., Chem. Commun.
1
985, 415.
(
(
7) Michael Dittel, Ph.D. Thesis, Ulm University, 2003.
8) Mazurek, W.; Kennedy, B. J.; Murray, K. S.; O’Connor, M. J.;
Attempts to prepare dinuclear copper(II) complexes con-
taining other bridging anions, including gluconate, gallate,
Rodgers, J. R.; Snow, M. R.; Wedd, A. G.; Zwack, P. R. Inorg. Chem.
1
985, 24, 3258.
9) (a) Ku, S.-M.; Wu, C.-Y.; Lai, C. K. J. Chem. Soc., Dalton Trans.
000, 3491. (b) Mendelson, W. L.; Holmes, M.; Dougherty, J. Synth.
(
2
(
4) Ackermann, J.; Meyer, F.; Kaifer, E.; Pritzkow, H. Chem. Eur. J.
002, 8, 247 and refs 8-13 cited therein.
5) (a) Torelli, S.; Belle, C.; Gautier-Luneau, I.; Pierre, J. L.; Saint-Aman,
E.; Latour, J. M.; Le Pape, L.; Luneau, D. Inorg. Chem. 2000, 39, 3526.
b) Malachowski, M. R.; Huynh, H. B.; Tomlinson, L. J.; Kelly, R. S.;
Furbee, J. W., Jr. J. Chem. Soc., Dalton Trans. 1995, 31.
Commun. 1996, 26, 593.
2
(10) (a) Kruger, P. E.; Moubaraki, B.; Fallon, G. D.; Murray, K. S. J.
Chem. Soc., Dalton Trans. 2000, 713. (b) Mazurek, W.; Berry, K. J.; Murray,
K. S.; O’Connor, M. J.; Snow, M. R.; Wedd, A. G. Inorg. Chem. 1982, 21,
3071.
(
(
(11) Gichinga, M. G.; Striegler, S.; Bray, T. Manuscript in preparation.
242
Org. Lett., Vol. 10, No. 2, 2008

Figure 2. UV/vis spectra and corresponding distribution of species obtained during titration of 2 mM L (L ) bsdpo; 5) with (A) copper(II)
acetate monohydrate, (B) copper(II) perchlorate hexahydrate, and (C) sodium acetate in the presence of excess copper(II) perchlorate
hexahydrate in methanol, 25 °C.
erizable 2 for these titrations assuming that the polymeriz-
able substituent in 4 has no pronounced electronic effect on
the metal core. First, titrating 5 with copper(II) acetate in
di-tert-butylcatechol (3,5-DTBC, 6) to 3,5-di-tert-butylquino-
ne (7, 3,5-DTBQ) (Scheme 2). Various groups have used
1
3
methanol reveals formation of a dinuclear copper(II) com-
plex with UV/vis absorption spectra identical to 4 (λmax
)
Scheme 2. Model Reaction
640 nm, Figure 2A). Second, titrating 5 with copper(II)
perchlorate results in formation of a complex with signifi-
cantly different UV/vis absorption spectra compared to 4
(Figure 2B). Third, titration of 5 with sodium acetate in the
presence of 2 equiv of copper(II) chloride results in the
same UV/vis absorption spectra as are observed for 4 (Figure
2
C), when equimolar amounts of sodium acetate and 5 are
present.
If the acetate anion were abstracted from the complex and
this procedure to establish catechol oxidase-like activity for
structurally related dinuclear copper(II) complexes.14
The reaction proceedings were followed by UV/vis
spectroscopy at 420 nm. The reaction rates at constant
substrate concentration increase in a linear fashion with
increasing catalyst concentration, and the kinetic data of the
oxidation can be analyzed using the Michaelis-Menten
exchanged by coordinating solvent molecules upon solvation
of 4, the titration of 5 with copper(II) perchlorate should
show an UV/vis spectrum identical with that of dissolved 4.
As this is clearly not observed (Figure 2B), the bridging
acetate anion is crucial for the formation of the dinuclear
copper(II) complex 4 and remains coordinated to the metal
core, even in methanol. The complex composition is therefore
identical in solid state and solution.
model. The initial rates of product formation revealed a rate
-1
m
constant kcat of 0.04 min and a Michaelis constant K of
4
0 mM in the presence of 200 µM dinuclear copper(II)
complex 4 at 30 °C.
By analogy, we assume the same coordination behavior
of the counteranion for the dinuclear copper(II) complexes
The rate constant of the spontaneous reaction knon is 7 ×
7 -1
10- min at 30 °C and corresponds to the self-oxidation
of the substrate under aerobic conditions without catalyst.15
The rate acceleration of the oxidation by catalyst 4 is
calculated from these values as 60 000 (kcat/knon).
3a and 3b. A coordinated counteranion, however, does not
prevent bidentate substrate coordination to the dinuclear
metal core in a catalytic transformation due to the overall
planar complex structure.
Performing the oxidation in the presence of 200 µM
-
1
polymerizable complex 3a yields a kcat of 0.04 min and a
The synthesized dinuclear copper(II) complexes 3a and 4
were initially employed as catalysts for the oxidation of 3,5-
K
m
of 37 mM at 30 °C. Derivatization of the ligand backbone
(
14) Selected reviews for dinuclear metal complexes with catechol
(
12) Binstead, R. A.; Jung, B.; Zuberb u¨ hler, A. D. SPECFIT/32 Global
Analysis System, 3.0 ed.; Spectrum Software Associates: Marlborough, MA,
000.
13) Typical procedure for spectrophotometric titrations: All experiments
oxidase-like activity may be found in: (a) Belle, C.; Selmeczi, K.; Torelli,
S.; Pierre, J.-L. C. R. Chim. 2007, 10, 271. (b) Koval, I. A.; Gamez, P.;
Belle, C.; Selmeczi, K.; Reedijk, J. Chem. Soc. ReV. 2006, 35, 814. (c)
Chaudhuri, P.; Wieghardt, K.; Weyhermueller, T.; Paine, T. K.; Mukherjee,
S.; Mukherjee, C. Biol. Chem. 2005, 386, 1023. (d) Selmeczi, K.; Reglier,
M.; Giorgi, M.; Speier, G. Coord. Chem. ReV. 2003, 245, 191. (e) Kaim,
W. Dalton Trans. 2003, 761.
(15) Control reactions were performed (a) without oxygen and (b) without
copper(II) complex. While the oxidation was completely inhibited in a sealed
cuvette containing degassed, nitrogen-purged methanol, slow spontaneous
oxidation of 3,5-DTBC to 3,5-DTBQ was observed in the presence of
oxygen. The rate constant was determined from spectral data collected over
a 1 h period.
2
(
were performed in methanol at 25.0 ( 0.1 °C. The pH value was measured
with a Beckman Φ 250 pH meter equipped with a refillable long
combination Futura pH electrode of 0.7 mm thickness. Typically, 2 mL of
stirred ligand solutions (2 mM) was titrated with methanol solutions of
copper acetate monohydrate, copper perchlorate hexahydrate, or sodium
acetate (c ) 10 mM) by addition of 25 µL portions. The UV/vis spectra
were recorded independent of the pH value measured in the reaction vessel
after equilibration in a range of 200-900 nm. The spectral data were
computed by the fitting procedures provided by the program Specfit.12
Org. Lett., Vol. 10, No. 2, 2008
243

(acrylate). TEM imaging revealed formation of spherical
particles with 50 nm diameter on average. Isothermal titration
calorimetry disclosed accessibility of the copper(II) ions to
the ligand core and quantitative complex formation with
immoblized 2 in a 2:1 molar ratio (see the Supporting
Information). The addition of appropriate amounts of copper-
(II) acetate solution activated the dormant catalyst pol3a that
was then used for transformation of the model substrate 6
into 7 under the described conditions (see Scheme 2).
The initial rates of product formation promoted by pol3a
were analyzed using the Michaelis-Menten model (Figure
3
). The reaction proceeds in the presence of 1.5 µM pol3a
Figure 3. The oxidation of 3,5-DTBC by pol3a follows Michae-
lis-Menten kinetics and is more than 470 000-fold accelerated over
-1
with a rate constant kcat of 3.3 min and a Michaelis-
of 200 µM.17 The acceleration of the
Menten constant K
-
1
m
background; kcat ) 3.3 min , K ) 200 µM.
M
reaction by pol3a over background is deduced from these
values as 470 000, which is almost 10-fold faster than for
the low molecular weight salen analogues 3a or 4. The
macromolecular structure of pol3a does therefore signifi-
cantly contribute to its overall catalytic activity. A thorough
investigation of this effect to the catalytic oxidation and a
detailed physical characterization of the polymeric catalyst
will be reported in due course.
with a p-vinylbenzyloxy group consequently does not alter
the catalytic activity. The rate constant kcat for the catalytic
oxidation of DTBC by other dinuclear copper(II) complexes
with similar Cu(II)‚‚‚Cu(II) distances of 3.50 Å is reported
-
1 14
to be in the same order of magnitude (kcat ) 0.04 min ).
Subsequently, complex 3a was immobilized in a poly-
1
6
(
acrylate) matrix by microemulsion polymerization. As
Acknowledgment. Partial support of this project by an
award to S.S. in the Competitive Research Grant Program
at Auburn University is gratefully acknowledged.
radical polymerizations are inhibited in the presence of
paramagentic metal ion radicals, such as Cu(II) ions, we
copolymerized the ligand 2 into a poly(acrylate) matrix, and
activated the catalyst by addition of metal ions afterward.
Elemental analysis of the dried beads confirmed quantitative
incorporation of the polymerizable ligand 2 into the poly-
Supporting Information Available: Representative ex-
perimental procedures and full characterization of all new
compounds and a table with selected bond lengths and angles
of complexes 3a and 3b. This material is available free of
charge via the Internet at http://pubs.acs.org.
(16) Typical procedure for emulsion polymerization: Poly(acrylate) beads
were prepared by mixing of 3 g of butyl acrylate and 3 g of styrene in 500
mg of decane with 48 mL of water containing 144 mg of sodium dodecyl
sulfate (SDS). Ligand 2 (144 mg, 0.26 mmol) dissolved in 1 g of DMSO
was then added and the resulting mixture was stirred vigourously for 1 h
followed by sonication for 2 min. The polymerization was initiated by
addition of aqueous potassium peroxysulfate at 72 °C and allowed to proceed
for 3 h. The polymer particles obtained were purified by ultracentrifugation
using micropore filters with a 10 000 MW cutoff. A sample aliquot of the
aqueous polymer solution was dried for elemental analysis.
OL702672K
(17) The kinetic experiments were conducted after addition of appropriate
amounts of aqueous copper(II) acetate solution to prepare a 0.09 mM
aqueous catalyst stock solution that was subsequently diluted into methanol
to yield a final 1.5 µM concentration of catalyst pol3a.
244
Org. Lett., Vol. 10, No. 2, 2008