Polydopamine - An organocatalyst rather than an innocent polymer

Article abstract of DOI:10.1002/chem.201402532

Polydopamine (PDA) is easily available by oxidation of dopamine and is widely used for persistent coatings of various materials. It is hitherto considered to be inert in many interesting biomedical and other applications. Results presented here, reveal an unexpected behavior of polydopamine as an organocatalyst in direct aldol reactions under mild conditions. Evidence was found for dual catalysis making use of amino and phenolic hydroxy groups found in PDA. Thus scientists must be aware that PDA is not an innocent polymer and can cause unwanted side effects in important applications, such as in biomedicine or as supports in catalysis.

Full text of DOI:10.1002/chem.201402532

DOI: 10.1002/chem.201402532
Full Paper
&
Polymers
Polydopamine—An Organocatalyst Rather than an Innocent
Polymer
Radosław Mrꢀwczynski,[a, b] Alexander Bunge,[b] and Jꢁrgen Liebscher*[a, b]
´
Dedicated to Professor Dr. Johann Mulzer on the occasion of his 70th birthday
Abstract: Polydopamine (PDA) is easily available by oxida-
tion of dopamine and is widely used for persistent coatings
of various materials. It is hitherto considered to be inert in
many interesting biomedical and other applications. Results
presented here, reveal an unexpected behavior of polydop-
amine as an organocatalyst in direct aldol reactions under
mild conditions. Evidence was found for dual catalysis
making use of amino and phenolic hydroxy groups found in
PDA. Thus scientists must be aware that PDA is not an inno-
cent polymer and can cause unwanted side effects in impor-
tant applications, such as in biomedicine or as supports in
catalysis.
Introduction
rence of carbonyl and Michael-acceptor moieties in PDA is ex-
ploited enabling reactions with amines or thiols as nucleo-
philes. Furthermore it is known that PDA can partially be hy-
drolyzed giving rise to the formation of carboxylic acid groups
by opening the catechol ring.[25–26] Reactions of PDA with di-
methyl sulfate or benzoyl chlorides as strong electrophiles
were reported attacking nucleophilic sites such as amino or
phenolic hydroxyl groups.[26] Finally the catechol/o-quinone
moieties found in PDA provide redox properties, which can be
exploited in reduction and deposition of metals, such as Au,
Cu, or Ag.[15,27–29] We disclose here that, surprisingly, PDA and
PDA-coated magnetic nanoparticles exhibit organocatalytic
properties in aldol reactions under mild conditions thus reveal-
ing that PDA is not an innocent polymer as is often assumed.
This observation is of great importance in fields in which PDA
is used as coatings for materials applied in biology, medicine,
and catalysis where it is assumed to be inert.
Phenolic motives in adhesive proteins containing DOPA enable
mussels to fix themselves at almost each surface.[1–2] Chemists
took lessons from this and found out that polydopamine (PDA)
can also form resistant films on a variety of materials, such as
metals, metaloxides, silica, glass, and polymers.[3–7] PDA coat-
ings are considered to be nonpoisonous and biocompatible
and have found various biomedical applications, such as in
drug transport and delivery, as antibacterial coatings,[8–15] in
separation of biological materials or poisonous contami-
nants,[16–17] and as supports for organocatalytic moieties.[18]
PDA is a polymer formed by oxidation of dopamine. Although
its structure is still under discussion, there is a consensus that
it is built up of indole units of different states of hydrogena-
tion, mainly connected by CÀC bonds between the benzene
rings.[19–20] Due to the presence of two oxygen atoms connect-
ed to the benzene ring, tautomerism of quinoid and catechol
units is possible in appropriate substructures. In addition to
indole units, evidence was found that PDA also contains dopa-
mine units in the polymer backbone that are not cyclized, that
is, they contain aminoethyl side chains.[19] So far, PDA is consid-
ered as a robust, relatively inert, and innocent coating material.
On the other hand, PDA coatings also served as a medium for
fixing various biomolecules or enzymes.[5,21–24] Here, the occur-
Results and Discussion
We recently developed PDA-covered magnetite nanoparticles
(MNP) equipped with azido groups that are useful attachment
points for other functions with help of copper-catalyzed azide
alkyne cycloaddition (CuAAC), the most important of the click
reactions, by 1,2,3-triazole formation.[18] In this way it was pos-
sible to link biotin as a biological recognition function, dansyl
as a fluorescence marker, and (S)-proline as an organocatalyst
to PDA-coated MNP. In the further course of our work, we
tested the behavior of these proline-containing nanoparticles
as magnetically supported organocatalysts. The fixation of the
organocatalytic unit to MNP provides easy separation of the
organocatalyst by magnetic decantation and is in the focus of
contemporary research.[30–33] Application of the proline-func-
tionalized MNP as a catalyst in asymmetric direct aldol reac-
tions revealed the formation of the expected aldol product;
´
[a] R. Mrꢀwczynski, J. Liebscher
Department of Chemistry, Humboldt-University Berlin
Brook-Taylor-Str. 2, 12489 Berlin (Germany)
´
[b] R. Mrꢀwczynski, A. Bunge, J. Liebscher
National Institute of Research and Development for Isotopic
and Molecular Technologies (INCDTIM)
Str. Donath 65-103, RO-400293 Cluj-Napoca (Romania)
E-mail: liebscher@chemie.hu-berlin.de
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201402532.
Chem. Eur. J. 2014, 20, 1 – 8
1
ꢂ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
&
&
These are not the final page numbers! ÞÞ

Full Paper
Before applying the PDA-
coated MNP (2, 3, and 4) in cat-
alytic tests they were character-
ized by FTIR spectroscopy (typi-
cal peaks for PDA at 1440–
1620 cmÀ1) (Figures 1 and 2).
TEM investigations showed an
almost spherical shape for MNP
3 and 4 (see the Supporting In-
formation, Figures S1–S3). All
the MNP 2–4 and 10 exhibited
superparamagnetic
behavior
with good saturation magneti-
zation values of 47.7 (2), 32.3
(3), 36.6 (4), and 48.4 emugÀ1
(10), which is important for
their magnetic separation from
reaction mixtures later on (Fig-
ures 3 and 4). In addition, AFM
of PDA 1 is found in the Sup-
porting Information (see the
Supporting Information, Fig-
ure S9) and XPS in refer-
Scheme 1. Synthesis of PDA and PDA-coated MNP.
however, as a racemate. Considering the fact that other
4-hydroxyproline derivatives led to excellent enantioselectivi-
ties,[34] the question appeared as to why our catalyst failed in
this respect. A nonstereoselective background reaction cata-
lyzed by the PDA coating could explain this phenomenon.
To find out if this supposition was justified, we checked PDA
1 and MNP–PDA 2 and 3 in this respect. To exclude eventual
background catalysis by the magnetite support also MNP 10
protected with a silica shell were included as magnetic sup-
ports for PDA leading to MNP 4. The PDA-covered MNP 2, 3,
and 4 were obtained as depicted in Scheme 1 by oxidative
polymerization of dopamine in tris-buffer as the most often
used method[3] in the presence of the respective nanoparticles.
In addition to MNP 2–4 different monomer derivatives 5–9,
which may be important motifs for the catalytic activity of
PDA, were also tested.
Figure 2. FTIR spectra of MNP 4 and silica-coated MNP 10.
Figure 3. Magnetization vs. applied magnetic field dependences at room
&
*
Figure 1. FTIR spectra of MNP 2 and 3.
temperature of MNPs 2 and 3 ( : 2; : 3)
&
&
Chem. Eur. J. 2014, 20, 1 – 8
www.chemeurj.org
2 ꢂ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÝÝ These are not the final page numbers!

Full Paper
magnetic decantation. As in the case of nonsupported PDA
1 (entry 5), the yield of the aldol product dropped after recy-
cling of 2 (entries 12 and 13). To compensate possible loss of
catalytic PDA units from the surface of the nanoparticles in the
case of 2, the Fe3O4@PDA 2 nanoparticles were covered with
a second shell of PDA to give particles 3 (Scheme 1). However,
their application in the aldol reaction showed similar results.
The yield dropped from originally 97 (entry 14) to 70% in the
second run (entry 15). Surprisingly, the reaction resulted in as
little as 13% yield in the third run (entry 16), a phenomenon
which is difficult to understand.
As another interesting issue, the diastereoselectivity of the
aldol model reaction has to be discussed. With dopamine
1 the d.r. was close to 1:1 (Table 1, entries 1–8) while some-
what higher values were observed with the magnetite-sup-
ported PDA NP 2 (entries 11–13). In the case of magnetite NP
3 with a double layer of PDA the situation (entries 14, 15) is
similar to mere PDA 1 but the d.r. increased from 55:45
(entry 14) to 70:30 after two recycling steps (entry 16).
Figure 4. Magnetization vs. applied magnetic field dependences at room
&
*
temperature of MNP 4 ( ) and silica-coated MNP 10 ( ).
ence [19]. PDA-coated magnetite nanoparticles 2 were charac-
terized earlier by XPS. TGA of nanoparticles 2 (see ref [35]), 3
(see the Supporting Information, Figure S7), and 4 (see the
Supporting Information, Figure S8) revealed 19.8, 34, and 19%
organic material, respectively.
Coverage of magnetite NP with silica prior to coating with
PDA (MNP 4) revealed a similar effect in the aldol reaction. A
sharp drop of yield was observed after the first run from 75 to
40% (Table 1, entries 20, 21). To exclude that a shortage of
water for hydrolytic cleavage of intermediates from the catalyt-
ic sites of PDA was responsible for such drops in yield, the
aldol reaction was performed in water. However, the product
was only formed in traces (entry 22) as also observed when 3
was used as the catalyst in water (not shown).
The direct aldol reaction of 4-nitrobenzaldehyde with cyclo-
hexanone served as a test reaction for the presumed catalyst
candidates 1–9 (Scheme 1, Table 1). It was performed at 508C
by using an excess of cyclohexanone as the solvent. Remarka-
bly, the application of mere PDA 1 gave rise to the formation
of the aldol product 12 in 90% yield (Table 1, entry 3). Forma-
tion of the aldol product was only observed if additionally cat-
alytic amounts of water were applied (compare entry 1 with
entries 2–4). To find out if some change of PDA 1 occurred
when it served as a catalyst in the aldol reaction it was separat-
ed from the reaction mixture by centrifugation and reused. In-
terestingly, the yield of aldol product dropped after first recy-
cling (entry 5) but remained more or less constant in the sub-
sequent three runs (entries 6–8). Obviously, some change oc-
curred when PDA (1) was used in the first run resulting in a de-
crease of the catalytic performance. The resulting PDA still
contained catalytic units, which were not affected later on
when the catalyst was used again. To check if possibly
a change in pH caused by PDA were responsible for the cataly-
sis of the aldol reaction, the following experiments were per-
formed: addition of PDA 1 to distilled water caused a change
in the pH from 5.5 to 5.7, which is too small to catalyze the
aldol reaction. On the other hand treatment of cyclohexanone
with 4-nitrobenzaldehyde in water or phosphate buffer gave
rise to the formation of the aldol product 12a in 64 or 90%
yield, respectively (entries 9 and 10). These results demonstrate
that first the aldol reaction is catalyzed by the involvement of
PDA and not by a simple change in pH and second that the
catalytic activity of PDA is likely to occur also under biological
conditions. In further experiments, PDA-coated magnetite
nanoparticles 2 were investigated in direct aldol reactions (en-
tries 11–13). Again, catalytic activity was observed leading to
the aldol product 12 in 86% yield under optimized conditions
(entry 12). The system 2 represents a magnetically supported
organocatalyst and thus can be recovered by straightforward
Magnetite PDA nanoparticles 3 were further tested in reac-
tions with other arylaldehydes (entries 28–30). Whereas 4-bro-
mobenzaldehyde gave a modest 48% yield of the aldol prod-
uct (entry 28), benzaldehyde and anisaldehyde failed (en-
tries 29 and 30). The fact that arylaldehydes lacking electron-
withdrawing groups are less prone to aldol reactions observed
here is a known phenomenon in organocatalyzed aldol reac-
tions.[36]
To get more information on what structural elements in
PDA might be responsible for the altogether unexpected and
hitherto unknown behavior as an organocatalyst, also dopa-
mine 5 and its derivatives 6, 7, and 8 were applied in direct
aldol reactions. Application of dopamine hydrochloride 5 fur-
nished the aldol product 12a in 80% yield (Table 1, entry 23).
If the amino group was blocked by tert-butoxycarbonyl (Boc)
the reaction failed, like in the case of 7 wherein both the
amino group and the hydroxyl groups were protected. On the
other hand, a modest catalytic activity (25% yield) was ob-
served with O,O-dibenzyldopamine (8) in which only the phe-
nolic OH groups of dopamine were blocked. Taking these
facts into consideration it seems that dopamine and probably
also PDA react as dual catalysts wherein the amino group acts
as an imine/enamine-forming organocatalytic unit while the
acidic phenolic hydroxyl groups assist catalysis by H-bonding
with carbonyl O-atoms (Scheme 2). In fact, enhancement of
the catalytic performance of (S)-proline in aldol reactions by
adding catalytic amounts of catechol was observed
before.[37–38] As can be seen by the result obtained with tyro-
sine methyl ester 9 (entry 27) providing the aldol product in
Chem. Eur. J. 2014, 20, 1 – 8
www.chemeurj.org
3
ꢂ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
&
&
These are not the final page numbers! ÞÞ

Full Paper
them by irreversible reactions
with strong electrophiles, such
as by methylation with methyl
iodide (Table 1, entries 17, 18)
or acetylation with acetic anhy-
dride (entry 19) and to check
the products in their catalytic
behavior. Reaction of PDA with
methyl iodide was assumed to
methylate the amino groups to
quaternary ammonium salts
and the hydroxyl groups to
methyl ethers.[26] Acetic anhy-
dride could cause analogous
blocking of these groups by
amide or ester formation, re-
spectively. In our case, the ma-
terials obtained after reaction
with methyl iodide (entries 17,
Table 1. Direct aldol reaction of arylaldehydes 11 with cyclohexanone.
Entry[a]
Product 12
Cat.
Amount [mg]
t [h]
Yield [%]
d.r. syn/anti
1
2
3
4
5
6
7
8
a
a
a
a
a
a
a
a
a
a
a
a
a
a
a
a
a
a
a
a
a
a
a
a
a
a
a
b
c
1[b]
1
100
50
24
8.5
5.5
24
24
24
24
24
36
36
12
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
trace
65
90
93
75
66
70
75
64
90
50
86
70
97
70
13
35
43
37
75
40
traces
80
traces
traces
25%
75
n.d.
56:44
57:43
56:44
48:52
49:51
51:49
53:47
42:58
50:50
65:35
65:35
63:37
55:45
53:47
70:30
57:43
60:40
72:28
55:45
54:46
n.d.
1
100
100
115
125
123
~120
60
60
200
340
1 (1st run)
1 (2nd run)
1 (3rd run)
1 (4th run)
1 (5th run)
9
1[c]
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
1[d]
2
2
18)
or
acetic
anhydride
2 (2nd run)
3 (1st run)
(entry 19) suffered drastic reduc-
tion of the catalytic per-
formance. Thus, strong electro-
philes affect the catalytic sites
in PDA although they do not
completely block the catalytic
activity. This observation may
also be the key for understand-
ing the deactivation of PDA
within the first run of the aldol
reaction. In these reaction mix-
tures are found aldehydes and
ketones as electrophiles capable
of reacting with the amino
groups of the PDA. In fact, the
reaction of PDA amino groups
with the ketone is even neces-
sary to enter the catalytic cycle.
It could be that intermediates
formed in the catalytic cycle
(see Scheme 2) are not cleaved
and thus parts of the catalytic
amino sites remain blocked or
that 4-nitrobenzaldehyde forms
a relatively stable imine with
PDA thus blocking both the cat-
100
3 (2nd run)
3 (3rd run)[e]
3 MeI[f]
85
100
100
100
3 MeI[g]
3 Ac2O[h]
4 (1st run)
4 (2nd run)
4 (3rd run)
5[i]
6[j]
7[j]
8[i]
9[j]
3
in water
10 mol%
10 mol%
10 mol%
10 mol%
10 mol%
100
100
100
100
60:40
n.d.
n.d
49:51
53:47
56:44
n.d.
48
3
3
3[k]
traces
Traces
67
d
a
n.d.
60:40
[a] Reaction conditions: aldehyde (0.25 mmol), cyclohexanone (0.5 mL), H2O (140 mL), 508C. [b] Reaction with-
out addition of water at RT. [c] 11 (0.15 mmol), cyclohexanone (0.3 mL), and water (2 mL) were used instead.
[d] 11 (0.15 mmol), cyclohexanone (0.3 mL), and phosphate buffer (2 mL of 0.18m, pH 7) were used instead.
[e] Catalysts was washed with HCl (5 mL of 1m) for 5 min. [f] MeI in EtOH, RT, was used to methylate nucleo-
philic sites of 3 prior to application. [g] K2CO3 and MeI at 508C were used to methylate nucleophilic sites of 3
prior to application. [h] Acetic anhydride, triethylamine, MeCN, RT, 24 h was applied to acetylate nucleophilic
sites of 3 prior to application. [i] Reactions were performed with 10 mol% of catalyst, aldehyde (1 mm), cyclo-
hexanone (2 mL), H2O (560 mL), 508C and 10 mol% Et3N. [j] Reaction performed with 10 mol% of catalyst, alde-
hyde (1 mm), cyclohexanone (2 mL), H2O (560 mL), 508C. [k] MNPs were reacted with 4-nitrobenzaldehyde for
4 days before reaction.
75% yield, just one phenolic hydroxyl group is sufficient for
an effective dual catalysis as long as an amino group is pres-
ent. Based on these observations, the transition state of the
CÀC bond-forming step of the aldol reaction disclosed in
Scheme 2 seems to be a reasonable rationalization for the cat-
alytic effect of PDA. Taking into consideration our observations
(v.s.), alternative structural proposals for PDA lacking nucleo-
philic aminoalkyl groups are less likely to catalyze the aldol re-
action.[39]
alytic amino groups of PDA and the aldehyde as reactant.
For a better understanding of the deactivation process, cata-
lysts 3 and 4 were investigated by elemental analysis, FTIR,
and XPS after being employed in three cycles of the aldol reac-
tion. Elemental analysis revealed a reduction of the nitrogen
content in 3 from 2.96 to 0.61% and in 4 from 0.83 to 0.42%.
This is an indication that PDA gets lost from the magnetic
nanoparticles. FTIR spectra of used PDA-coated MNPs 3 and 4
showed two new bands (1346 and 1520 cmÀ1; see Figures 5
and 6). They were assigned to the NÀO stretching vibration of
nitro groups. This indicated that uptake of 4-nitrobenzalde-
To obtain more evidence for the involvement of both types
of functional groups of PDA in the catalysis, we tried to block
&
&
Chem. Eur. J. 2014, 20, 1 – 8
www.chemeurj.org
4
ꢂ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÝÝ These are not the final page numbers!

Full Paper
The same appearance of new
bands (1343 and1520 cmÀ1) typ-
ical for nitro groups was ob-
served when PDA-coated NP 3
were treated only with 4-nitro-
benzaldehyde at 508C for four
days (see Figure 7).
In fact, the appearance of
imine and nitro groups was also
evidenced in the high resolu-
tion N 1s XPS-spectrum show-
ing energy values of 398.5 and
404.8 eV,
respectively
(see
Figure 8 and the Supporting In-
formation for further XPS spec-
tra). Catalytic tests performed
with these MNP 3 primarily re-
acted with 4-nitrobenzladehyd-
ed revealing that the yield of
aldol product dropped from 97
(Table 1, entry 14) to 67%
Scheme 2. Rationalization of the mechanistic pathway and the transition state of PDA-catalyzed aldol reactions.
hyde by PDA occurred, presumably by imine formation with
the free amino groups of PDA.
(entry 31), that is, the material still keeps some of its catalytic
properties (compare entry 31 with 14).
Figure 5. FTIR spectra of 3 before and after use in the aldol reaction.
Figure 7. FTIR spectra of 5 before and after reaction with 4-nitrobenzalde-
hyde for 4 days.
Figure 8. High resolution N 1s XPS spectrum of MNP 3 reacted with 4-nitro-
Figure 6. FTIR spectra of 4 before and after use in the aldol reaction.
Chem. Eur. J. 2014, 20, 1 – 8 www.chemeurj.org
benzaldehyde for 4 days.
5
ꢂ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
&
&
These are not the final page numbers! ÞÞ

Full Paper
croscope. FTIR spectra were carried out on a JASCO FTIR 610 spec-
trophotometer. The magnetic measurements were performed at
room temperature using a Vibrating Sample Magnetometer Cryo-
genics.
These results allow the conclusion that two independent
processes are responsible for the deactivation of PDA in aldol
reactions: leaching of PDA and blocking of amino groups of
PDA by arylaldehyde 11. The fact that the catalytic per-
formance dropped remarkably only in the first step and re-
mained more or less constant in subsequent steps can be ex-
plained by the feature that PDA is not a uniform polymer but
contains a mixture of different structures held together not
only by covalent bonds but also by hydrogen bonding, where-
in eventually amino groups are involved.[19,40] These mixtures
can consist of oligomers with relatively many amino groups
(premature, less oxidized, noncyclized dopamine units) and of
others with less amino groups but more indole structures (ma-
tured, more oxidized, cyclized dopamine units, see also
Scheme 1). Obviously, the former will show higher catalytic ac-
tivity than the latter. When the amino groups are involved in
the catalytic cycle of an aldol reaction by forming imines or en-
amines the hydrogen bonding between the subunits of the
PDA is suspended and thus premature oligomers can go into
the solution, that is, get lost from the magnetic support. The
remaining PDA contains less amino groups and is more stable
thus explaining the reduced but persistent catalytic activity in
the subsequent runs of an aldol reaction.
Synthesis of MNP 3, 4, and 5
MNP (1 g) covered with one layer of oleic acid were combined
with EtOH (150 mL) and sonicated. After magnetic separation, this
step was repeated two times. The MNPs were washed with H2O
(50 mL), separated by centrifugation, re-dispersed in tris-buffer
(pH 8.5, 500 mL) and sonicated for 30 min. To this vigorously stirred
suspension dopamine hydrochloride was added (1 g) followed by
stirring at RT in the open air for 24 h. The resulting magnetic nano-
particles 2 were precipitated with EtOH and collected by an exter-
nal magnet. They were washed with H2O and EtOH. This step was
repeated twice. After drying at 508C under vacuum overnight the
MNPs 2 were obtained as a black powder. For the synthesis of
MNPs 3 and 4, the initial washing step with EtOH was omitted.
Silica-coated MNP (1 g) was used for MNP 4 preparation and MNP
2 (1 g) covered with PDA for the preparation of MNP 3.
Catalytic test in the aldol reaction
Arylaldehyde 11 (0.25 mmol) was added to the appropriate
amount of PDA 1 or MNP-supported PDA 2, 3, or 4 (see Table 1).
Cyclohexanone (0.5 mL) and water (140 mL) were added and the
flask was heated to 508C. The mixture was stirred for the required
time (see Table 1). MeOH (10 mL) was added and the MNPs were
collected by an external magnet or in the case of mere PDA by
centrifugation. The washing step was repeated 3 times followed
by washing with Et2O (2ꢃ10 mL). The catalyst was removed by
magnetic separation or centrifugation (in case of PDA) and dried in
the open air before the next run. The separated solutions were
evaporated and the product 12 was purified by column chroma-
tography. The structures of the aldol products 12 were confirmed
by comparison with published NMR spectroscopic data.
Conclusion
PDA, used in many biomedical and separation applications,
turns out not to be an innocent material; rather, it shows an
unexpected and hitherto unknown behavior as an organocata-
lyst in aldol reactions, a transformation also taking place in
biology. Since it is likely that PDA can also catalyze other reac-
tions scientists should be aware that PDA can also exert un-
wanted side effects when it is applied in biological and medici-
nal environment. Our results imply that the PDA acts as a dual
catalyst employing both the amino groups and the phenolic
hydroxyl groups in a combined fashion. PDA was supported
on magnetite nanoparticles rendering them as organocatalysts,
which were easily recycled by magnetic separation. Investiga-
tions using PDA and PDA-coated MNPs as catalysts in other re-
actions are presently underway in our laboratories.
Acknowledgements
This work was supported by the Romanian Ministry of Educa-
tion and Research under the research program POS-CCE-META-
VASINT, project no. 550/2010 and in the project no. PN-II-RU-
TE-2011–3–0130 for young researchers. The authors acknowl-
edge Dr. I. Bratu for FTIR (INCDTIM Cluj-Napoca) measurements
and Dr. L. Magerusan and Dr. C. Leostean (INCDTIM Cluj-
Napoca) for assistance in XPS spectroscopy and magnetic
measurements, and Dr. D. Bogdan and Dr. N. Tosa (INCDTIM
Cluj-Napoca) for performing AFM. We are indebted to Dr. J.
Leistner, Humboldt-University Berlin for TGA analyses.
Experimental Section
General
All reagents were commercially available and used without further
purification, unless otherwise stated. Magnetic nanoparticles cov-
ered with a chemisorbed oleic acid monolayer with an average
size of approximately 7 nm were obtained from the group of Dr.
Ladislau Vekas, Romanian Academy - Timisoara branch. Their prep-
aration was reported elsewhere.[41] Magnetic nanoparticles “MagSil-
ica” 10 covered with silica shell were produced by Evonik. Com-
pounds 9–11 were obtained according to reported protocols.[42] 1H
and 13C NMR were recorded on a 500 MHz Bruker Avance III spec-
trometer; chemical shifts (d) are reported in ppm relative to TMS.
Reactions were monitored by TLC. Flash-chromatography was car-
ried out using Merck silica gel 60. The morphology of functional-
ized MNP was determined by 1010 JEOL transmission electron mi-
Keywords: aldol reaction · coatings · magnetic nanoparticles ·
organocatalysis · polydopamine
[1] J. H. Waite, M. L. Tanzer, Science 1981, 212, 1038–1040.
[2] J. H. Waite, X. X. Qin, Biochemistry 2001, 40, 2887–2893.
[3] H. Lee, S. M. Dellatore, W. M. Miller, P. B. Messersmith, Science 2007, 318,
426–430.
[4] M. E. Lynge, R. van der Westen, A. Postma, B. Stadler, Nanoscale 2011, 3,
4916–4928.
[5] H. Lee, J. Rho, P. B. Messersmith, Adv. Mater. 2009, 21, 431–434.
[6] Q. Ye, F. Zhou, W. M. Liu, Chem. Soc. Rev. 2011, 40, 4244–4258.
&
&
Chem. Eur. J. 2014, 20, 1 – 8
www.chemeurj.org
6
ꢂ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÝÝ These are not the final page numbers!

Full Paper
[7] Y. Liu, K. Ai, L. Lu, Chem. Rev. 2014, 114, 5057–5115.
[8] K. C. L. Black, J. Yi, J. G. Rivera, D. C. Zelasko-Leon, P. B. Messersmith,
Nanomedicine 2013, 8, 17–28.
[9] X. Liu, J. Cao, H. Li, J. Li, Q. Jin, K. Ren, J. Ji, ACS Nano 2013, 7, 9384–
9395.
[10] Y. Wang, S. Wang, H. Niu, Y. Ma, T. Zeng, Y. Cai, Z. Meng, J. Chromatogr.
A 2013, 1283, 20–26.
[11] X. Yu, M. Wei, J. Walsh, RSC Adv. 2014, 3, 7185–7192.
[12] C.-Y. Chien, W.-B. Tsai, ACS Appl. Mater. Interfaces 2013, 5, 6975–6983.
[13] T. Shalev, A. Gopin, M. Bauer, R. W. Stark, S. Rahimipour, J. Mater. Chem.
2012, 22, 2026–2032.
[26] F. Binns, J. A. G. King, S. N. Mishra, A. Percival, N. C. Robson, G. A. Swan,
A. Waggott, J. Chem. Soc. C 1970, 2063–2070.
[27] H. Y. Son, J. H. Ryu, H. Lee, Y. S. Nam, Macromol. Mater. Eng. 2013, 298,
547–554.
[28] T. Zeng, X.-l. Zhang, H.-y. Niu, Y.-r. Ma, W.-h. Li, Y.-q. Cai, Appl. Catal. B
2013, 134–135, 26–33.
[29] H.-W. Hu, J. H. Xin, H. Hu, ChemPlusChem 2013, 78, 1483–1490.
[30] S. Shylesh, V. Schunemann, W. R. Thiel, Angew. Chem. Int. Ed. 2010, 49,
3428–3459.
[31] C. W. Lim, I. S. Lee, Nano Today 2010, 5, 412–434.
[32] Y. H. Zhu, L. P. Stubbs, F. Ho, R. Z. Liu, C. P. Ship, J. A. Maguire, N. S. Hos-
mane, Chemcatchem 2010, 2, 365–374.
[33] K. V. S. Ranganath, F. Glorius, Catal. Sci. Technol. 2011, 1, 13–22.
[34] J. Shah, S. S. Khan, H. Blumenthal, J. Liebscher, Synthesis 2009, 3975–
3982.
[14] J. Cui, Y. Yan, G. K. Such, K. Liang, C. J. Ochs, A. Postma, F. Caruso, Bio-
macromolecules 2012, 13, 2225–2228.
[15] R. Liu, Y. Guo, G. Odusote, F. Qu, R. D. Priestley, ACS Appl. Mater. Interfa-
ces 2013, 5, 9167–9171.
[16] H. Gao, Y. Sun, J. Zhou, R. Xu, H. Duan, ACS Appl. Mater. Interfaces 2013,
4, 425–432.
[35] R. Mrowczynski, R. Turcu, C. Leostean, H. A. Scheidt, J. Liebscher, Mater.
Chem. Phys. 2013, 138, 295–302.
[17] M. Zhang, X. Zhang, X. He, L. Chen, Y. Zhang, Nanoscale 2012, 4, 3141–
3147.
[36] W.-B. Huang, Q.-W. Liu, L.-Y. Zheng, S.-Q. Zhang, Catal. Lett. 2011, 141,
191–197.
´
[18] R. Mrꢀwczynski, R. Turcu, C. Leostean, H. A. Scheidt, J. Liebscher, Mater.
[37] H. G. Luo, R. Tan, Y. Kong, C. Y. Li, D. H. Yin, Chin. J. Catal. 2012, 33,
1133–1138.
Chem. Phys. 2013, 138, 295–302.
[19] J. Liebscher, R. Mrowczynski, H. A. Scheidt, C. Filip, N. D. Harade, R.
Turcu, A. Bende, S. Beck, Langmuir 2013, 29, 10539–10548.
[20] D. R. Dreyer, D. J. Miller, B. D. Freeman, D. R. Paul, C. W. Bielawski, Chem.
Sci. 2013, 4, 3796–3802.
[38] C. Ji, Y. Peng, C. Huang, N. Wang, Z. Luo, Y. Jiang, J. Mol. Catal. A 2006,
246, 136–139.
[39] D. R. Dreyer, D. J. Miller, B. D. Freeman, D. R. Paul, C. W. Bielawski, Lang-
muir 2012, 28, 6428–6435.
[21] Q. Wei, B. Li, N. Yi, B. Su, Z. Yin, F. Zhang, J. Li, C. Zhao, J. Biomed. Mater.
Res. A 2011, 96A, 38–45.
[22] R. Luo, L. Tang, J. Wang, Y. Zhao, Q. Tu, Y. Weng, R. Shen, N. Huang, Col-
loids. Surf., B 2013, 106, 66–73.
[23] M. Sureshkumar, C.-K. Lee, Carbohydr. Polym. 2011, 84, 775–780.
[24] Y. Ren, J. Rivera, L. He, H. Kulkarni, D.-K. Lee, P. Messersmith, BMC Bio-
technol. 2011, 11, 63.
[40] F. Bernsmann, A. Ponche, C. Ringwald, J. Hemmerlꢄ, J. Raya, B. Beching-
er, J.-C. Voegel, P. Schaaf, V. Ball, J. Phys. Chem. C 2009, 113, 8234–8242.
[41] L. Vꢄkꢅs, D. Bica, M. V. Avdeev, China Particuol. 2007, 5, 43–49.
[42] C. Xu, K. Xu, H. Gu, R. Zheng, H. Liu, X. Zhang, Z. Guo, B. Xu, J. Am.
Chem. Soc. 2004, 126, 9938–9939.
Received: March 10, 2014
[25] N. F. Della Vecchia, R. Avolio, M. Alfe, M. E. Errico, A. Napolitano, M.
d’Ischia, Adv. Funct. Mater. 2013, 23, 1331–1340.
Published online on && &&, 0000
Chem. Eur. J. 2014, 20, 1 – 8
www.chemeurj.org
7
ꢂ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
&
&
These are not the final page numbers! ÞÞ

Full Paper
FULL PAPER
&
Polymers
´
R. Mrꢀwczynski, A. Bunge, J. Liebscher*
&& – &&
Re-evaluating PDA: Polydopamine
(PDA) is easily available by oxidation of
dopamine and is widely used for persis-
tent coatings of various materials. It is
hitherto considered to be inert in many
interesting biomedical and other appli-
cations. However, results revealed here
show that PDA is not an innocent poly-
mer and can act as an organocatalyst in
direct aldol reactions under mild condi-
tions (see scheme).
Polydopamine—An Organocatalyst
Rather than an Innocent Polymer
&
&
Chem. Eur. J. 2014, 20, 1 – 8
www.chemeurj.org
8
ꢂ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÝÝ These are not the final page numbers!