Enantioselective induction of helical chirality in cyclooctapyrroles by metal-complex formation

Article abstract of DOI:10.1002/anie.200803538

(Chemical Equation Presented) Fixed chirality: The treatment of cyclooctapyrroles (see picture) with a metal source with optically active carboxylate or amine ligands leads to enantioselective metalation to give stereochemically stable helical mononuclear

Full text of DOI:10.1002/anie.200803538

Angewandte
Chemie
DOI: 10.1002/anie.200803538
Helical Porphyrinoids
Enantioselective Induction of Helical Chirality in Cyclooctapyrroles by
Metal-Complex Formation**
Jun-ichiro Setsune,* Aki Tsukajima, Naho Okazaki, Juha M. Lintuluoto, and Masami Lintuluoto
Linear oligopyrroles generate helical structural motifs that
are of great interest in supramolecular chemistry.[1] Not only
are helicates formed by the tetradentate coordination of
bisdipyrrin ligands to a single metal, but two bisdipyrrin units
assemble into dinuclear metal complexes of double helicates,
such as 1 (Scheme 1).[2] Homohelicity induction in these
helicates has been the focus of a number of studies in view of
their application to chirality sensing and asymmetric catalysis.
Helical chirality is usually controlled by introducing a chiral
auxiliary to cause the generation of a particular helical form
in diastereomeric excess. For example, the axial coordination
of chiral amines to bilinone–zinc complexes and the addition
of a homochiral binol linker or homochiral amide substituents
to a bisdipyrrin skeleton led to the successful induction of
homohelicity.[3,4] However, at present it is difficult to generate
stereochemically stable double-helicate metal complexes.
Furthermore, the enantioselective induction of helicate for-
mation with a chiral promoter molecule in the absence of
chiral auxiliaries has not been reported. This point is
important, because the binding of a chiral guest to a host in
a mixture of diastereomers would be too much complicated.
Stereochemically stable helicate metal complexes closely
related to 1 can be prepared by using cyclooctapyrroles, such
as 2, in which p-conjugated bisdipyrrin units are linked by sp3-
Scheme 1. Helical structures of bisdipyrrin dinuclear complexes.
hybridized carbon atoms (Scheme 1).[5] The figure-eight loop
of cyclooctapyrroles is preorganized with metal-binding sites
formed from four pyrrole nitrogen atoms. Mononuclear and
dinuclear metal complexes of these macrocycles have been
reported.[6] However, studies on the helical chirality of
cyclooctapyrroles are limited.[7] Vogel et al. investigated the
optical resolution of [36]octaphyrin(2.1.0.1.2.1.0.1) (3)[8] and
its dinuclear palladium(II) complex 3Pd2 by HPLC on a
chiral phase, and the helicity of each enantiomer of 3Pd2 was
determined unambiguously by X-ray crystallography.[7a] How-
ever, the circular dichroism (CD) spectra of 3Pd2 have not
been reported, and there is some complexity derived from
rotation about the bond between the pyrrole a carbon atom
and the ethylene carbon atom in the ethylene-bridged
bipyrrole moiety at the crossing point upon the conversion
of 3 into 3Pd2. A conformational change due to rotation
about this bond might be the reason why the order of HPLC
elution of the two enantiomers was reversed after metal
incorporation.
[*] Prof. Dr. J. Setsune, A. Tsukajima, N. Okazaki
Department of Chemistry, Graduate School of Science
Kobe University, Kobe 657-8501 (Japan)
Fax: (+81)78-803-5770
E-mail: setsunej@kobe-u.ac.jp
Dr. J. M. Lintuluoto
Department of Synthetic Chemistry and Biological Chemistry
Graduate School of Engineering
Kyoto University, Kyoto 615-8510 (Japan)
Since the CD Cotton effect is very important in a
discussion on chirality, it seemed necessary to confirm the
relationship between the helical handedness of cyclooctapyr-
roles and their CD Cotton effect. The macrocycle 3 contains a
helicene-like bisdipyrrin p system surrounding each metal site
and an ethylene-bridged bisdipyrrin p system connecting the
two metal sites. Thus, the application of the exciton chirality
method to predict the helical handedness of 3 on the basis of
the CD Cotton effect is not straightforward.[9] The framework
of 2, in which a pair of electronically isolated bisdipyrrin
chromophores cross over, may be better suited for the exciton
Prof. Dr. M. Lintuluoto
Division of Applied Life Science
Graduate School of Life and Environmental Science
Kyoto Prefectural University, Kyoto 606-8522 (Japan)
[**] This research was supported by a Grant-in-Aid for Scientific
Research (No. 18550058) from the Ministry of Education, Culture,
Sports, Science, and Technology (Japan). We are also grateful to the
CREST program (Japan Science and Technology Agency) and the
VBL project (Kobe University).
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.200803538.
Angew. Chem. Int. Ed. 2009, 48, 771 –775
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
771

Communications
chirality method. We describe herein the synthesis, optical
resolution, and chiroptical properties of the stereochemically
stable cyclooctapyrrole metal complexes 2M2. The helical
chirality of 2M2 was determined unambiguously on the basis
of the theoretical simulation of the CD spectra by using the X-
ray crystallographic data. Furthermore, we have found that
metal sources with optically active carboxylate and amine
ligands cause the enantioselective metalation of 2 to give
helically asymmetric metal complexes with no chiral auxiliary.
Inversion of the figure-eight loop of the cyclooctapyrrole-
free base 2 occurs through unwinding of the molecular twist
and then rewinding in the opposite direction. This molecular
1
motion was detected in variable-temperature H NMR spec-
troscopic experiments in [D10]o-xylene (see the Supporting
Information). Two signals due to the diastereotopic methyl-
ene hydrogen atoms of the isobutyl groups, at d = 3.0 and
1.9 ppm at 608C, coalesced at temperatures over 1208C. The
inversion barrier was estimated to be at least 77 kJmolꢀ1 on
the basis of the frequency difference (Dn = 435 Hz) and the
coalescence temperature (Tc > 393 K). As interconversion
between the enantiomeric forms is prohibited in their metal
complexes, optical resolution of the complexes is possible.
The treatment of the free base 2 with one molar equivalent of
Cu(OAc)2·H2O in CH2Cl2–MeOH at room temperature for
1 h afforded a mononuclear copper(II) complex, 2Cu, in 43%
yield, whereas the treatment of 2 with 10 molar equivalents of
Cu(OAc)2·H2O in the presence of triethylamine at room
temperature for 5 h gave a dinuclear copper(II) complex,
2Cu2, in 50% yield. The absorption band in the visible region
of the UV/Vis spectrum shifted from 541 to 570 and then
584 nm upon consecutive metalation of 2 with Cu (Figure 1a).
The mononuclear cobalt(II) complex 2Co was also obtained
in 85% yield by the treatment of 2 with excess Co-
(OAc)2·4H2O at room temperature for 2 h. The treatment
of 2Co with excess Cu(OAc)2·H2O at room temperature
afforded a heterodinuclear complex, 2CoCu, in 78% yield.
The absorption band in the visible region of the UV/Vis
spectrum shifted from 541 to 569 and then 591 nm upon
consecutive metalation of 2 with Co and Cu (Figure 1b).
X-ray crystallographic analysis of 2Cu, 2Cu2, 2Co, and
2CoCu indicated that 2,2’-bipyrrole units in the s-trans
conformation are located at the crossing point of the figure-
eight loop, and that the metal atom is disordered between two
sites in the complexes 2Cu, 2Co, and 2CoCu (Figure 2). The
side view of these complexes shows the rhombic cavity
enclosed by four panels of the planar dipyrrin unit connected
Figure 1. a) UV/Vis spectra of 2, 2Cu, and 2Cu2 in CH2Cl2; b) UV/Vis
spectra of 2, 2Co, and 2CoCu in CH2Cl2; c) CD spectra of optically
resolved 2Cu2 (first (1st) and second (2nd) HPLC eluate) in CH2Cl2;
d) CD spectra of optically resolved 2CoCu (first and second HPLC
eluate) in CH2Cl2.
ꢀ
with two hinges in the form of bipyrrole C2 C2’ bonds and
two gem-dimethyl-substituted bridging carbon atoms.
The dinuclear complexes 2Cu2 and 2CoCu were resolved
by HPLC with a chiral column (Daicel chiralpak IB) by
eluting with n-hexane/CH2Cl2 (40:1). The first fraction of
2Cu2 showed positive CD signals at 697 and 496 nm and a
negative CD signal at 583 nm (Figure 1c). Similarly, the first
fraction of 2CoCu showed positive CD signals at 711 and
492 nm and a negative CD signal at 590 nm (Figure 1d).
Theoretical UV/Vis and CD spectra (Figure 3a,b) were
calculated on the basis of the atom coordinates obtained
from the X-ray crystallographic structure of 2Cu2 in the M,M
helical form; all peripheral substituents were omitted (see the
Figure 2. ORTEP drawings of 2Cu2 at the 50% level with atom
numbering; left: top view, right: side view. Four phenyl substituents
are omitted at C5, C14, C24, and C33, and eight alkyl substituents are
omitted at the bipyrrole b positions.
Supporting Information). The calculated spectra are in good
agreement with the observed spectra for the enantiomer of
2Cu2 eluted second in terms of band position and intensity.
Furthermore, calculations based on time-dependent density
772
www.angewandte.org
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2009, 48, 771 –775

Angewandte
Chemie
and a positive CD signal at 564 nm. These wavelengths are
only slightly blue-shifted (12–28 nm) relative to those of
2Cu2, which suggests that the monocopper complex also has
M,M helicity. This monocopper complex was converted into
the dicopper complex by using excess Cu(OAc)2·H2O in the
presence of triethylamine at room temperature. CD analysis
of the product verified the ee value of 12%. Thus, the ee value
was not affected by the second metalation process to give
2Cu2. The reaction of 2 with the copper(II) carboxylate
derived from (R)-(ꢀ)-mandelic acid led to 2Cu2 with 13% ee
and with a positive first Cotton effect at 697 nm.
Optically active amines were used under homogeneous
reaction conditions for the asymmetric synthesis of 2Cu and
2Cu2 in a much shorter reaction time than the 24 h required
for the complete conversion of 2 under the heterogeneous
reaction conditions with mandelic acid. When 2 was added to
a solution of (R)-(+)-1-(1-phenyl)ethylamine (10 equiv) and
CuCl2·2H2O (5 equiv) in CH2Cl2, 2 reacted completely to give
2Cu in 2 h. However, the ee value for helical chirality was
very small (Table 1, entry 1). An increase in the concentration
of (R)-(+)-1-(1-phenyl)ethylamine (80 equiv) retarded the
Figure 3. a) Theoretical and experimental UV/Vis spectra; b) theoret-
ical and experimental CD spectra; c) coupling electronic transitions
that give rise to the absorption band 18 and the sign of the
corresponding Cotton effect in the left-handed cyclooctapyrrole
M,M enantiomer. The theoretical spectra were calculated for the
macrocyclic core of (M,M)-2Cu2, and the experimental spectra were
recorded for the enantiomer of 2Cu2 that was eluted second by HPLC.
The bars indicate the positions and oscillator strength (f) or rotary
strength (Rr) of the transitions (18, 21, 22) calculated by TDDFT.
Table 1: Asymmetric synthesis of 2Cu in the presence of (R)-(+)-1-
(1-phenyl)ethylamine.[a]
functional theory (TDDFT) revealed that the electronic
transitions along the long axes of the p-conjugated bisdipyrrin
chromophores connecting the two copper sites are respon-
sible for the absorption band 18 in the theoretical UV/Vis
spectra. Since this absorption band correlates with a negative
sign in the theoretical CD spectrum, the absolute configu-
ration of 2Cu2 determined by calculation is in agreement with
that determined on the basis of the CD exciton chirality
method. In the figure-eight screw shown in Figure 3c, the
transition in the front bisdipyrrin chromophore couples with
the transition in the back bisdipyrrin chromophore. When the
coupling dipole direction is counterclockwise, as for the
M,M enantiomer, a negative Cotton effect can be predicted
according to the CD exciton chirality method.[9] Thus, M,M
helicity was assigned to the enantiomer of 2Cu2 eluted second
from the HPLC column.
Entry
Molar ratio
t [h]
T [8C]
CD sign
(669 nm)
ee [%][b]
(2Cu)
(amine/Cu/2)
1
2
3
4
10:5:1
80:5:1
800:400:1
800:400:1
2
5
0.25
1.5
RT
RT
RT
0
+
+
+
+
2
13
11
19
[a] A solution of 2 (0.07–0.28 mm) in CH2Cl2 was treated with CuCl2·2H2O
and the amine. [b] The ee value was determined by using jDe583ꢀDe496
j
as an index after conversion into 2Cu2 with Cu(OAc)2·H2O.
metalation reaction, but the ee value of 2Cu was improved to
13% (Table 1, entry 2). The use of a large excess of a mixture
of (R)-(+)-1-(1-phenyl)ethylamine and CuCl2·2H2O in a 2:1
ratio at low temperature further improved the ee value of 2Cu
(Table 1, entry 4).
We reported previously that porphyrinoids can be induced
to adopt a particular unidirectional helical conformation
preferentially by protonation with optically active carboxylic
acids.[7b,10] In fact, the addition of 200 equivalents of (S)-(+)-
mandelic acid to a solution of 2 in CH2Cl2 caused the
appearance of a CD spectrum that is quite similar to that of
(M,M)-2Cu2 (see the Supporting Information). This result led
us to investigate the enantioselective formation of stable
cyclooctapyrrole metal complexes. The copper(II) salt pre-
pared by the addition of (S)-(+)-mandelic acid sodium salt
(4 equiv) in MeOH to CuCl2·2H2O in water was used as the
metal source. The treatment of copper(II) (S)-(+)-mandelate
(30–40 equiv) with 2 in CH2Cl2 for 24 h resulted in the
formation of a mixture of 2Cu and 2Cu2. The CD spectrum of
the product 2Cu2 showed a negative first Cotton effect at
697 nm. The ee value of 2Cu2 based on the CD intensity
(12% ee) was in good agreement with that determined by
HPLC analysis (14% ee). Complex 2Cu formed in this
experiment showed negative CD signals at 669 and 484 nm
As noted above, the rates for the first metal-insertion
process to give (M,M)-2Cu and (P,P)-2Cu (k1M and k1P,
respectively) are dependent on the temperature and the
amount of the optically active amine used (Table 1 and
Scheme 2). To gain insight into the effect of the optically
active amine on the second metalation step, a racemic mixture
of 2Cu was treated with (R)-(+)-1-(1-phenyl)ethylamine
(10 equiv) and CuCl2·2H2O (5 equiv) in CH2Cl2. Although
these reaction conditions do not lead to a remarkable
difference between k1M and k1P (Table 1, entry 1), an ee value
of 33% was observed for the P,P helical form of 2Cu2 in the
initial stages of the second metalation step (Table 2, entry 1).
Thus, the rate (k2P) for the metal insertion into (P,P)-2Cu is
twice as high as the rate (k2M) for the metal insertion into
(M,M)-2Cu. As the metalation proceeds, (P,P)-2Cu is con-
sumed faster, which is consistent with the development of an
excess of the M,M helical form of 2Cu. Thus, 72% ee was
observed for the M,M helical form of 2Cu in the final stage of
the metalation (Table 2, entry 5). These results show that
Angew. Chem. Int. Ed. 2009, 48, 771 –775
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
773

Communications
Experimental Section
2Cu2 (50% yield): UV/Vis (lmax (loge), CH2Cl2): 384 (4.63), 584
(4.92), 660 (shoulder, 4.61), 711 nm (shoulder, 4.38); ESIMS: m/z
calcd for C86H88N8Cu2: 1360.58; found: 1360.30; magnetic moment
(Evans method, CDCl3): 3.14; elemental analysis: calcd (%) for
C86H88N8Cu·C6H14·H2O: C 75.43, H 7.16, N 7.65; found: C 75.51, H
6.94, N 7.65. Recrystallization from CH2Cl2/hexane gave crystals for
X-ray crystallographic analysis. Crystal data: C92H102N8Cu2·2C6H14,
Mr = 1533.07, triclinic, space group Pca21, a = 22.2077(16), b =
16.1092(12), c = 22.2493(16) ꢀ, a = 90, b = 90, g = 908, V=
7959.7(10) ꢀ3, Z = 4, 1calcd = 1.279 Mgmꢀ3 m(MoKa) = 0.589 mmꢀ1
, ,
T= 296(2) K, crystal size: 0.50 ꢁ 0.40 ꢁ 0.10 mm. A total of 15899
unique reflections were collected (3.62 < 2q < 54.728) by using graph-
ite-monochromated MoKa radiation. The structure was solved by the
direct method by using the SHELX97 package. The positions of all
non-hydrogen atoms were refined anisotropically (930 parameters).
All hydrogen atoms were placed at ideal positions and included in the
refinement. R1 = 0.0427, wR2 = 0.1051 for 13648 reflections with I >
2.00s(I); R1 = 0.0546, wR2 = 0.1156 for all data; GOF (on F2) = 1.041.
CCDC 698457 contains 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.
Scheme 2. Metalation of 2 and 2Cu with an optically active metal
source. L*=(R)-(+)-1-(1-phenyl)ethylamine.
Received: July 21, 2008
Revised: October 2, 2008
Published online: December 18, 2008
Table 2: Conversion of racemic 2Cu into 2Cu2 with CuCl2·2H2O in the
presence of (R)-(+)-1-(1-phenyl)ethylamine at room temperature.[a]
Entry t [h]
2Cu
CD sign
(669 nm)
2Cu2
Molar ratio
Keywords: helical structures · helicity · macrocycles ·
porphyrinoids · transition metals
ee [%][b] CD sign
ee [%][b] 2Cu/2Cu2
.
(697 nm)
1
2
3
4
5
3
9
12
16
24
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
3
15
25
36
72
+
+
+
+
+
33
29
25
19
6
9:1
6:4
5:5
3:7
1:9
[1] a) S. E. Boiadjiev, D. A. Lightner, Tetrahedron: Asymmetry
1999, 10, 607 – 655; b) A. Thompson, D. Dolphin, J. Org.
Chem. 2000, 65, 7870 – 7877; c) Y. Zhang, Z. Wang, C. Yan, G.
Li, J. Ma, Tetrahedron Lett. 2000, 41, 7717 – 7721; d) G. D. Panto,
M. S. Rodrꢂguez-Morgade, T. Torres, V. M. Lynch, J. L. Sessler,
Chem. Commun. 2006, 2132 – 2134; e) T. E. Wood, A. Thomp-
son, Chem. Rev. 2007, 107, 1831 – 1861.
[2] a) G. Wagniere, G. Blauer, J. Am. Chem. Soc. 1976, 98, 7806 –
7810; b) S. E. Boiadjiev, D. A. Lightner, Tetrahedron: Asymme-
try 1999, 10, 2535 – 2550; c) M. Brꢃring, C. D. Brandt, J. Lex, H.-
U. Humpf, J. Bley-Escrich, J.-P. Gisselbrecht, Eur. J. Inorg.
Chem. 2001, 2549 – 2556; d) M. Brꢃring, S. Link, C. D. Brandt,
E. C. Tejero, Eur. J. Inorg. Chem. 2007, 1661 – 1670.
[3] a) T. Mizutani, S. Yagi, A. Honmaru, S. Murakami, M. Furusyo,
T. Takagishi, H. Ogoshi, J. Org. Chem. 1998, 63, 8769 – 8784;
b) T. Mizutani, S. Yagi, T. Morinaga, T. Nomura, T. Takagishi, S.
Kitagawa, H. Ogoshi, J. Am. Chem. Soc. 1999, 121, 754 – 759.
[4] a) T. E. Wood, N. D. Dalgleish, E. D. Power, A. Thompson, X.
Chen, Y. Okamoto, J. Am. Chem. Soc. 2005, 127, 5740 – 5741;
b) A. Al-Sheikh Ali, R. E. Benson, S. Blumentritt, T. S.
Cameron, A. Linden, D. Wolstenholme, A. Thompson, J. Org.
Chem. 2007, 72, 4947 – 4952.
[a] A solution of 2Cu (0.36 mm) in CH2Cl2 was treated with the amine and
CuCl2·2H2O in an amine/CuCl2·2H2O/2 molar ratio of 10:5:1. [b] The
ee value was determined by using jDe583ꢀDe496 j as an index after
conversion into 2Cu2 with Cu(OAc)2·H2O if necessary.
kinetic resolution may be a potential approach to the
preparation of metal porphyrinoids with high optical purity.
The unique figure-eight loop structure of cyclooctapyr-
roles has potential application to the synthesis of chiral
functional materials. For this purpose, an understanding of the
chiroptical properties of cyclooctapyrroles on the basis of
their structure is of great importance. Mononuclear cobalt(II)
and copper(II) complexes and homo and heterodinuclear
complexes of a cyclooctapyrrole with two gem-dimethyl-
substituted bridging carbon atoms were prepared in this study.
The crossing of discrete bisdipyrrin chromophores in the
figure-eight loop is an advantageous structural feature for the
determination of the absolute configuration on the basis of
the exciton chirality method. The absolute configuration was
confirmed by the theoretical CD spectrum calculated for
(M,M)-2Cu2 on the basis of X-ray crystallographic data. The
induction of excess unidirectional helicity in the metalation
processes not only gives insight into the mechanism of
chirality transfer but also provides a convenient method for
the preparation of optically active metal cyclooctapyrroles for
further applications.
[5] J. Setsune, A. Tsukajima, J. Watanabe, Tetrahedron Lett. 2006,
47, 1817 – 1820.
[6] a) E. Vogel, M. Michels, L. Zander, J. Lex, N. S. Tuzun, K. N.
Houk, Angew. Chem. 2003, 115, 2964 – 2969; Angew. Chem. Int.
Ed. 2003, 42, 2857 – 2862; b) Y. Tanaka, W. Hoshino, S. Shimizu,
K. Youfu, N. Aratani, N. Maruyama, S. Fujita, A. Osuka, J. Am.
Chem. Soc. 2004, 126, 3046 – 3047; c) S. Shimizu, Y. Tanaka, K.
Youfu, A. Osuka, Angew. Chem. 2005, 117, 3792 – 3795; Angew.
Chem. Int. Ed. 2005, 44, 3726 – 3729; d) Y. Tanaka, S. Saito, S.
Mori, N. Aratani, H. Shinokubo, N. Shibata, Y. Higuchi, Z. S.
Yoon, K. S. Kim, S. B. Noh, J. K. Park, D. Kim, A. Osuka,
Angew. Chem. 2008, 120, 693 – 696; Angew. Chem. Int. Ed. 2008,
774
www.angewandte.org
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2009, 48, 771 –775

Angewandte
Chemie
47, 681 – 684; e) J. Setsune, M. Mori, T. Okawa, S. Maeda, J. M.
Lintuluoto, J. Organomet. Chem. 2007, 692, 166 – 174; f) M.
Mori, J. Setsune, Chem. Lett. 2007, 36, 244 – 245.
Houk, Angew. Chem. 1995, 107, 2705 – 2709; Angew. Chem. Int.
Ed. Engl. 1995, 34, 2511 – 2514.
[9] M. Hatano, Induced Circular Dichroism in Biopolymer-Dye
Systems, Springer, Berlin, 1986; N. Harada, K. Nakanishi,
Circular Dichroic Spectroscopy, University Science Books,
New York, 1983.
[10] J. Setsune, A. Tsukajima, J. Watanabe, Tetrahedron Lett. 2007,
48, 1531 – 1535.
[7] a) A. Werner, M. Michels, L. Zander, J. Lex, E. Vogel, Angew.
Chem. 1999, 111, 3866 – 3870; Angew. Chem. Int. Ed. 1999, 38,
3650 – 3653; b) J. M. Lintuluoto, K. Nakayama, J. Setsune, Chem.
Commun. 2006, 3492 – 3494.
[8] E. Vogel, M. Brꢃring, J. Fink, D. Rosen, H. Schmickler, J. Lex,
K. W. K. Chan, Y. D. Wu, D. A. Plattner, M. Nendel, K. N.
Angew. Chem. Int. Ed. 2009, 48, 771 –775
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
775