Protonation-triggered conversion between single- and triple-stranded helices with a visible fluorescence change

Article abstract of DOI:10.1002/anie.201005613

A flexible viologen carboxylic acid derivative forms single- and triple-stranded helices by hydrogen-bonding interactions, and undergoes pH-triggered helical transformation by a water-mediated solid-state conversion (see picture). This transformation is a

Full text of DOI:10.1002/anie.201005613

DOI: 10.1002/anie.201005613
Helical Transformations
Protonation-Triggered Conversion between Single- and Triple-
Stranded Helices with a Visible Fluorescence Change**
Xu-Hui Jin, Jian Wang, Jian-Ke Sun, Hong-Xing Zhang, and Jie Zhang*
Helical structures are ubiquitous in nature, and are essential
and indispensable for various biological functions. Inspired by
the elaborate functions of biological helices in molecular
recognition, replication, translation, and catalytic activity,
chemists have made great efforts to develop artificial helical
polymers, supramolecules, and oligomers.[1] In particular,
helical systems that can undergo conformational changes
triggered by external stimuli are of significant attraction not
only for gaining deep insight into the biological process, but
also for the development of switchable systems that can be
utilized in the biological and materials sciences.[2] Despite the
great success in obtaining various single-helical architectures,
the molecular designs for multi-stranded helical structures
that consist of more than two strands are limited.[3] Although
some synthetic helices have been shown conformational
changes through the influence of external forces, such as
solvent, pH, and temperature or ion binding,[3,4] the explora-
tion is still in its infancy, and it remains a challenge to control
the unwinding/rewinding or contraction/extension of helices
optimally in water, as occurs in biological systems.[5]
raising the pH.[8] However, the structural transition between
single- and triple-helical conformation by pH manipulation
has been rarely reported. Herein, we report the self-assembly
of the single and triple helices driven by hydrogen-bonding
interactions based on a flexible viologen derivative bearing
two terminal carboxylic groups, and demonstrate how proto-
nation can play a decisive role in the water-mediated helical
transition by manipulating hydrogen bonding modes between
the carboxyl groups. Attractively, this pH-dependent con-
formational conversion was accompanied by a fluorescence
signal change, which can be directly visualized by the naked
eye under a UV lamp at ambient conditions. Therefore the
present system also can be regarded as a proton-triggered
fluorescent switch.
A
flexible viologen derivative, 1,1’-bis(2-carboxybi-
phenyl)-4,4’-bipyridinium dibromide, (H2Bcbpb)Br2, was syn-
thesized by the route shown in Scheme 1. Treatment of the
A change in pH value is a crucial trigger for regulation of
various functions of biosystems, such as biosensors, supra-
molecules, and drugs. The DNA triplex may be a pH-
responsive nanomaterial in which an oligopyrimidine as the
third strand associates with the corresponding DNA duplex
by Hoogsteen hydrogen bonding under acidic conditions but
dissociates to form the original duplex under basic condi-
tions.[6] Although several pH-induced structural conversions
have been reported for artificial helical systems to date, most
of these occur in organic solvents and mainly involve the
folding/unfolding molecular motions of single-stranded heli-
ces.[7] Recently, Yashima and co-workers found that the
double helices of the oligoresorcinols formed in neutral
aqueous solution were dissociated into single strands upon
Scheme 1. Synthesis of the viologen derivative (H2Bcbpb)Br2.
dibromide salt with NaOH solution gave neutral zwitterionic
viologen, which was further treated with aqueous solution of
perchloric acid to afford crystals of H2Bcbpb·2ClO4·H2O (S1)
and HBcbpb·ClO4·3H2O (T2) at various pH values. The two
samples are stable in air and dissolve sparingly in water at
ambient temperature.
[*] X.-H. Jin, J.-K. Sun, Prof. Dr. J. Zhang
State Key Laboratory of Structural Chemistry
Fujian Institute of Research on the Structure of Matter and
Graduate School of the Chinese Academy of Sciences
Fuzhou, Fujian 350002 (P.R. China)
Fax: (+86)591-8371-0051
E-mail: zhangjie@fjirsm.ac.cn
X-ray structure analysis reveals that different kinds of
hydrogen bonds between carboxyl groups can be formed that
link the bipyridinium molecules into single- or triple-stranded
helices through exactly controlling the protonation of two
carboxylate groups with perchloric acid. The bipyridinium
molecules in S1 are completely protonated. There is one
H2Bcbpb2+ dication, two perchlorate anions, and one lattice
water molecule in the asymmetric unit. H2Bcbpb2+ adopts a
trans conformation with respect to the relative orientation of
J. Wang, Prof. Dr. H.-X. Zhang
State Key Laboratory of Theoretical and Computational Chemistry
Institute of Theoretical chemistry, Jilin University
ChangChun (P.R. China)
[**] This work was supported by the NNSF of China (Nos. 20671090/
20973171), the NSF of Fujian Province (No. E0220003), and Key
Project from CAS (KJCX2.YW.H01).
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201005613.
Angew. Chem. Int. Ed. 2011, 50, 1149 –1153
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1149

Communications
the bipyridine group. The dihedral angles between the
adjacent phenyl rings are 55.26 and 47.788, whilst that
between the pyridine rings is 33.908. Interestingly, the
adopts a gauche conformation in which the dihedral angles
between the adjacent phenyl rings are 53.49 and 57.598; the
dihedral angle between the pyridine rings is 46.148. A careful
examination of the structure reveals the formation of strong
COOÀ···HOOC hydrogen bonds between adjacent carboxyl-
ate and carboxylic groups with a O···O distance of 2.507(4) ꢀ.
The HBcbpb+ cations are linked into an infinite strand
extending along the a axis direction through these hydrogen
bonds. The helical pitch, given by the distance between
equivalent atoms generated by one full rotation of the twofold
screw axis, is 41.11 ꢀ. Attractively, the three single-stranded
infinite helices are of the same M handedness and are
intertwined to form a chiral infinite triple-helical structure
(Figure 1d,e). The repeat distance of the braid (13.70 ꢀ) is
one-third of a single helix pitch, which corresponds to the
a axis length. Although some organic triple helices have been
structurally characterized to date,[3a,11] the formation of a
supramolecular triple helix through self-assembly of an
achiral building block based on hydrogen bonding interac-
tions is still rare. It is of interest to note that all of the helices
are of the same chirality and are packed in a parallel manner,
leading to a non-centrosymmetric and chiral supramolecular
framework (Figure 1 f). The hydrogen bonds between the
lattice water molecules and carboxyl oxygen atoms, as well as
À
adjacent carboxylic acid groups form a classic O H···O
hydrogen-bonded dimer with O···O distances of 2.679(8)
and 2.654(8) ꢀ in a R22(8) graph-set motif,[9] linking the
H2Bcbpb2+ cations into a single meso-helical structure which
is characteristic of internal helix reversal (Figure 1a,b).
À
the short C H···O hydrogen-bonding interactions between
perchlorate counterions and the aromatic rings (3.14–3.22 ꢀ)
serve as the driving force for this parallel packing.
Interestingly, different protonated forms of Bcbpb mole-
cule render distinct luminescence characteristics to these two
crystals. T2 does not exhibit a discernable luminescence signal
in solid or solution upon excitation with UV light, whereas
crystals of S1 appear very bright to the eye with a yellow-
green color under a UV lamp at ambient conditions. This
visual observation can be verified by a fluorescence spectros-
copy measurement, which exhibits a broad peak in the range
of 420–750 nm with a maximum at about 522 nm and a small
peak centered at 380 nm upon excitation at 275 nm. Further-
more, S1 also emits detectable fluorescence in diluted
solution. From Figure 2, it can be seen that the photolumi-
nescence spectrum of S1 in CH3CN exhibits a main emission
peak around 551 nm accompanied by a weak emission at
358 nm. The H2Bcbpb2+ cation possesses both carboxybi-
phenyl donor and bipyridinium acceptor units, which are
approximately perpendicular to each other in its crystal
structure. From the fluorescence emission of S1 in different
solvents, the intense low-energy emission band undergoes
obvious red-shift with increasing solvent polarity (more than
100 nm on going from THF to CH3CN). This solvent-
dependent luminescence behavior is similar to the twisted
intramolecular charge-transfer (TICT) emission feature as
observed for some donor–acceptor molecules;[12] therefore,
the TICT-like mechanism is thought to be involved in present
photoluminescence system. For viologen derivatives, contro-
versy exists concerning their fluorescence properties. It has
been often reported that the methyl viologen dication is not
fluorescent in fluid solutions.[13] However, a fluorescence
emission around 350 nm has been repeatedly observed by
several groups for the bipyridinium derivatives in some
solvents, although quantum yields were still low.[13] The short
Figure 1. Structures of S1 (a–c) and T2 (d–f) from single-crystal X-ray
determinations. a) A side view of the single-stranded meso-helix in S1;
b) a top view of the single helix (C gray, Ored, N blue); c) a top view
showing the two neighboring single helices (C blue, H white) in which
perchlorate ions (Cl green, O red) are located. d) A side view of the
triple-stranded helix in T2 (colors indicate strands); e) a top view of
the triple helix; f) a top view showing the arrangement of triple helices
among which perchlorate counterions are located.
Perchlorate anions are wrapped in the helical chain, stabiliz-
ing the helical structure and holding the adjacent helices
together into a three-dimensional supramolecular framework
À
through the C H···O hydrogen bonds (Figure 1c). Meso-
helices are widespread in nature, such as the tendrils of
climbing plants, cycloamylose, and B/Z-DNA structures.
However, in contrast to the well-studied common helices,
meso-helical self-assembling systems still remain less
explored.[10] To date, only a few organic examples of meso-
helical structures have been characterized. Blay et al.
reported the first organic example resulting from the solid-
state aggregation of a dioxamic acid diester derivative,[10c]
whilst Huc and co-workers presented the first example of
rationally designed meso-helices that was obtained by using a
strategy to control the relative orientation of two folded
helical oligomers.[10d]
Compound T2 crystallizes in the chiral space group and
exhibits a triple-stranded helical structure. Its asymmetric unit
is composed of one monoprotonated bipyridinium cation
HBcbpb+, one perchlorate anion, and three lattice water
molecules. In contrast to S1, each HBcbpb+ cation in T2
1150
www.angewandte.org
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2011, 50, 1149 –1153

Figure 2. a) Normalized fluorescence emission spectra of S1 in CH3CN
at 2.5ꢀ10À5 m, THF solutions at 1ꢀ10À5 m (lex =285 nm), and in the
solid state (lex =275 nm). b) The calculated spatial distributions of the
LUMO and the HOMO of S1.
Figure 3. a) Photographs taken under 365 nm UV light illumination at
room temperature to show the stepwise change in fluorescence
emission upon water-mediated solid-state interconversion. b) The
transformation of S1 into T2 in water as observed by powder X-ray
diffraction.
wavelength band observed in our experiments corresponds
well to this emission band.
For a better understanding of the photophysical processes
of S1, molecular orbital calculations were performed using the
Gaussian suite of programs (Gaussian09) and the basis set
TD-TPSSh/6-311G(d). The ground state geometry was
adapted from the X-ray data. The calculation results
showed that S1 exhibited the complete separation of the
HOMO and the LUMO (Figure 2b). The majority of the
electron distribution of the HOMO was located on the 2-
carboxybiphenyl moiety; that of the LUMO was concentrated
on the bipyridinium moiety. The complete localization of
HOMO and LUMO means the HOMO–LUMO transition
becomes a typical photoinduced intramolecular charge trans-
fer transition,[14] which is consistent with our experimental
findings.
Interestingly, the two kinds of crystals exhibit lumines-
cence that variously fade away or grow when they are
immersed in distilled water or perchloric acid solution,
respectively. The photographs given in Figure 3a clearly
manifest the transition between non-emission and emission
for these crystals. Crystals of S1 exhibit brilliant luminescence
under 365 nm UV light at the beginning of the immersion in
water. With increasing immersion time, the luminescence is
found to fade away quickly, and then is barely discernible
after 24 h. In contrast, the non-luminescent triple-helical
compound displays a gradually enhanced fluorescence emis-
sion when it is allowed to stand for as long as 12 h in the
perchloric acid solution with pH 1. These results indicate that
two compounds may undergo a conformational interconver-
sion between one helix to another in response to changes in
pH.
water for one day, several noticeable variations could be
discerned. Some reflections at 2q values of 12.20, 18.06, and
25.628 disappeared; whilst new reflections appeared at 2q
values of 12.86, 17.76, and 18.308, which were in good
agreement with the simulated reflection peaks of T2. Upon
continuing immersion for two additional days, some reflec-
tions underwent small position shifts towards the evolvement
to T2, and the reflections at 2q values of 14.74, 19.02, and
23.928 also disappeared. All of the diffraction peaks of the
sample were found to exhibit good agreement with those of
T2, meaning that the single-helical structure of S1 has been
completely transformed into the triple-helical structure. For
T2, after the original sample was immersed in the perchloric
acid solution for two days, the reflections at the 2q values of
17.24, 18.36, 20.78, and 23.128 disappeared. Additionally,
beside the indicative peaks for S1 occurring at 2q values of
22.06 and 25.588; a new reflection at 2q = 26.308, which
corresponds to none of the simulated peaks of the two
compounds, can also be found. This observation seems to
indicate that an intermediate state was formed during the
transformation from T2 to S1. Upon further treatment with
the perchloric acid solution for 12 days, all of the diffraction
peaks of the sample agreed with the simulated PXRD pattern
of T2 (Figure 2S in the Supporting Information). This result
indicates that the helical transition of T2 is induced by
protonation. No solubility phenomenon was observed during
the transformation owing to the low solubility of S1 and T2 in
water; therefore, the whole process can be regarded as a
water-mediated solid-state conversion.
The direct evidence for the transformation between the
two kinds of helical structures comes from powder X-ray
diffraction (PXRD) analyses (Figure 3b). The PXRD pattern
of the original sample S1 shows excellent agreement with the
simulated pattern obtained from the single-crystal structure
data. After the original sample was immersed in distilled
The transformation process between single- and triple-
helical structures can also be further identified based on IR
spectral analysis. As shown in Figure 4, the as-synthesized
sample S1 exhibits a strong peak at 1692 cmÀ1 that can be
=
assigned to the antisymmetric C O stretching vibration of the
hydrogen-bonded carboxylic acid dimer,[15a] corresponding
Angew. Chem. Int. Ed. 2011, 50, 1149 –1153
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
1151

Communications
Incomplete fading of the vibration band at 1720 cmÀ1 together
with long transformation time suggest that the transformation
from triple helix T2 to single helix S1 is more difficult to
realize than that from S1 to T2. In fact, although a complete
transformation is easy to achieve in hydrothermal condition,
the transformation from T2 to S1 at room temperature is not
always successful in several repeated experiments, which is
quite different from that from S1 to T2. The appearance of an
intermediate state during protonation should be mainly
responsible for this predicament. The carboxyl group as a
typical functional group is essential for the biological activity
of the protein; it has been suggested that the carboxylic acid
hydrogen bonds play a crucial role in the mechanism of HIV
protease.[16] The different transformation pathways (Figure 5)
observed in the winding/unwinding of the present system
clearly demonstrate the complexity of protonation phenom-
ena and the decisive effect of hydrogen bond orientation on
supramolecular conformations.
Figure 4. The transformation of S1 into T2 in water as observed by IR
spectroscopy. a) as-synthesized S1; b) immersion for 1 day; c) immer-
sion for 3 days; d) as-synthesized T2. The peaks marked with asterisks
undergo significant changes during the transformation process.
well to the structural analysis results. Upon immersing the
sample into water, the intensity of this vibration band
gradually decreased, and eventually evolved into a shoulder
as observed in the spectrum of T2. Other vibration bands
underwent small position shifts or fading, reaching an agree-
ment with those in T2 after immersion for three days. In
contrast, a decrease in the intensity of the band around
1690 cmÀ1 and the presence of carboxylate symmetric
1383 cmÀ1 (ns COOÀ) band[15] in T2 indicates different pro-
tonated forms between two kinds of crystals. After the
treatment with perchloric acid for two days, an intense new
band at 1720 cmÀ1 (corresponding to the carboxylic acid
without dimerization) can be clearly observed, suggesting the
formation of an intermediate state during the transformation
of T2. This result is in accordance with the PXRD observa-
tion. After 12 days, the intensity of the band at 1720 cmÀ1
decreased considerably, whilst the band at 1692 cmÀ1 became
dominant, accompanied with the general profile resembling
that of S1 (Figure 3S in the Supporting Information).
In conclusion, we have presented the unique self-assembly
of the single- and triple-stranded helices driven by hydrogen-
bonding interactions based on a flexible viologen carboxylic
derivative. The pH-triggered transformation of two helical
conformations can be achieved by a water-mediated solid-
state phase conversion by different pathways, which demon-
strates an important role of protonation in the helical
transition by manipulating hydrogen bonding modes between
the carboxyl groups. Attractively, this pH-dependent con-
formational conversion is accompanied by a visual fluores-
cence change. These results provide not only a valuable
insight into the mechanism for the construction and con-
version of helical structures, but also a promising approach to
the development of supramolecular systems undergoing
structural changes induced by external stimuli, and pH-
sensitive materials.
Received: September 8, 2010
Published online: December 22, 2010
Figure 5. Illustration of the helix transformation between S1 and T2 regulated by protonation/deprotonation through water-mediated solid-state
conversion at room temperature.
1152
www.angewandte.org
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2011, 50, 1149 –1153

[10] a) J. J. Jiang, S. R. Zheng, Y. Liu, M. Pan, W. Wang, C. Y. Su,
Inorg. Chem. 2008, 47, 10692 – 10699; b) J. C. Jin, Y. Y. Wang, P.
Liu, R. T. Liu, C. Ren, Q. Z. Shi, Cryst. Growth Des. 2010, 10,
2029 – 2032; c) G. Blay, I. Fernꢁndez, J. Pedro, R. Ruiz-Garcꢂa,
M. C. Muꢃoz, J. Cano, R. Carrasco, Eur. J. Org. Chem. 2003,
1627 – 1630; d) V. Maurizot, C. Dolain, Y. Leydet, J.-M. Lꢄger, P.
Guionneau, I. Huc, J. Am. Chem. Soc. 2004, 126, 10049 – 10052.
[11] a) H. Katagiri, Y. Tanaka, Y. Furusho, E. Yashima, Angew.
Chem. 2007, 119, 2487 – 2491; Angew. Chem. Int. Ed. 2007, 46,
2435 – 2439; b) A. K. Das, D. Haldar, R. P. Hegde, N. Shamala,
A. Banerjee, Chem. Commun. 2005, 1836 – 1838; c) M. P. Light-
foot, F. S. Mair, R. G. Pritchard, J. E. Warren, Chem. Commun.
1999, 1945 – 1946; d) X. Ouyang, F. W. Fowler, J. W. Lauher,
J. Am. Chem. Soc. 2003, 125, 12400 – 12401; e) M. Albrecht, Top.
Curr. Chem. 2004, 248, 105 – 139, and references therein.
[12] a) E. Lager, J. Z. Liu, A. Aguilar-Aguilar, B. Z. Tang, E. Peꢃa-
Cabrera, J. Org. Chem. 2009, 74, 2053 – 2058; b) Y. Sato, M.
Morimoto, H. Segawa, T. Shimidzu, J. Phys. Chem. 1995, 99, 35 –
39; c) R. G. Hu, E. Lager, A. Aguilar-Aguilar, J. Z. Liu, J. W. Y.
Lam, H. H. Y. Sung, I. D. Williams, Y. C. Zhong, K. S. Wong, E.
Peꢃa-Cabrera, B. Z. Tang, J. Phys. Chem. C 2009, 113, 15845 –
15853; d) L. N. Zhu, C. Zhong, Z. Y. Liu, C. L. Yang, J. G. Qin,
Chem. Commun. 2010, 46, 6666 – 6668.
Keywords: fluorescence · helical structures · hydrogen bonds ·
structural transformations · viologen
.
[1] a) E. Yashima, K. Maeda, H. Iida, Y. Furusho, K. Nagai, Chem.
Rev. 2009, 109, 6102 – 6211; b) E. Yashima, K. Maeda, Y.
Furusho, Acc. Chem. Res. 2008, 41, 1166 – 1180; c) D. Haldar,
C. Schmuck, Chem. Soc. Rev. 2009, 38, 363 – 371.
[2] a) S. Chakraborty, S. Sharma, P. K. Maiti, Y. Krishnan, Nucleic
Acids Res. 2009, 37, 2810 – 2817; b) G. Z. Yuan, C. F. Zhu, Y. Liu,
W. M. Xuan, Y. Cui, J. Am. Chem. Soc. 2009, 131, 10452 – 10460;
c) T. Yamada, Y. Nagata, M. Suginome, Chem. Commun. 2010,
46, 4914 – 4916; d) H. Sugiura, R. Amemiya, M. Yamaguchi,
Chem. Asian J. 2008, 3, 244 – 260; e) E. Kolomiets, V. Berl, J.-M.
Lehn, Chem. Eur. J. 2007, 13, 5466 – 5479; f) H.-J. Kim, E. Lee,
H.-s. Park, M. Lee, J. Am. Chem. Soc. 2007, 129, 10994 – 10995.
[3] a) Y. Ferrand, A. M. Kendhale, J. Garric, B. Kauffmann, I. Huc,
Angew. Chem. 2010, 122, 1822 – 1825; Angew. Chem. Int. Ed.
2010, 49, 1778 – 1781; b) H. Ito, Y. Furusho, T. Hasegawa, E.
Yashima, J. Am. Chem. Soc. 2008, 130, 14008 – 14015; c) H.
Yamada, K. Maeda, E. Yashima, Chem. Eur. J. 2009, 15, 6794 –
6798; d) Y. Furusho, E. Yashima, J. Polym. Sci. Part A 2009, 47,
5195 – 5207; e) M. Ikeda, S. Haraguchi, M. Numata, S. Shinkai,
Chem. Asian J. 2007, 2, 1290 – 1298.
[13] a) R. Ballardini, A. Credi, M. T. Gandolfi, C. Giansante, G.
Marconi, S. Silvi, M. Venturi, Inorg. Chim. Acta 2007, 360, 1072 –
1082; b) J. Peon, X. Tan, J. D. Hoerner, C. Xia, Y. F. Luk, B.
Kohler, J. Phys. Chem. A 2001, 105, 5768 – 5777, and references
therein.
[14] H. Y. Li, Z. G. Chi, B. J. Xu, X. Q. Zhang, Z. Y. Yang, X. F. Li,
S. W. Liu, Y. Zhang, J. R. Xu, J. Mater. Chem. 2010, 20, 6103 –
6110.
[4] K. Miwa, Y. Furusho, E. Yashima, Nat. Chem. 2010, 2, 444 – 449.
[5] a) H. Goto, Y. Furusho, E. Yashima, J. Am. Chem. Soc. 2007,
129, 109 – 112; b) J. G. Kennemur, J. B. Clark IV, G. L. Tian,
B. M. Novak, Macromolecules 2010, 43, 1867 – 1873.
[6] K.-i. Haruna, H. Iida, K. Tanabe, S.-i. Nishimoto, Org. Biomol.
Chem. 2008, 6, 1613 – 1617.
[7] a) H. Goto, Y. Furusho, E, Yashima, Chem. Commun. 2009,
1650 – 1652; b) C. Dolain, V. Maurizot, I. Huc, Angew. Chem.
2003, 115, 2844 – 2846; Angew. Chem. Int. Ed. 2003, 42, 2738 –
2740; c) E. Kolomiets, V. Berl, I. Odriozola, A.-M. Stadler, N.
Kyritsakas, J.-M. Lehn, Chem. Commun. 2003, 2868 – 2869.
[8] H. Goto, Y. Furusho, K. Miwa, E. Yashima, J. Am. Chem. Soc.
2009, 131, 4710 – 4719.
[15] a) D. Lin-Vien, N. B. Colthup, W. G. Fately, J. G. Grasselli, The
Handbook of Infrared and Raman Characteristic Frequencies of
Organic Molecules, Academic Press, Sandiego, 1991, p. 137 –
141; b) Md. K. Nazeeruddin, R. Humphry-Baker, P. Liska, M.
Grꢅtzel, J. Phys. Chem. B 2003, 107, 8981 – 8987.
[16] a) Y. Kiso, H. Matsumoto, S. Yamaguchi, T. Kimura, Lett. Pept.
Sci. 1999, 6, 275 – 281; b) A. Brik, C.-H. Wong, Org. Biomol.
Chem. 2003, 1, 5 – 14.
[9] M. C. Etter, Acc. Chem. Res. 1990, 23, 120 – 126.
Angew. Chem. Int. Ed. 2011, 50, 1149 –1153
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
1153