Metallo-foldamers with backbone-coordinative oxime peptides: Control of secondary structures

Article abstract of DOI:10.1002/anie.201206968

A new series of square-planar Pd^II-mediated foldamers with mononuclear and dinuclear helix or (double) hairpin structures were constructed by novel backbonecoordinative oxime peptides. Some of these metallo-foldamers allow significant structura

Full text of DOI:10.1002/anie.201206968

Angewandte
Chemie
DOI: 10.1002/anie.201206968
Metallo-Foldamers
Metallo-Foldamers with Backbone-Coordinative Oxime Peptides:
Control of Secondary Structures**
Shohei Tashiro, Koji Matsuoka, Ai Minoda, and Mitsuhiko Shionoya*
Metal coordination is a powerful tool for constructing
biologically relevant structural motifs found in
nucleic acids, proteins, and polysaccharides. Pioneer-
ing work in the modeling of natural helices started
from helicates,[1,2] in which linear synthetic ligands
complex with several metal ions and form single- or
multi-stranded helical structures. As part of this
approach, DNA analogues featuring metal base
pairs have also been developed as semi-natural
helicates.[3] In these artificial helical complexes,
replacement of hydrogen bonds in natural helices
with metal coordination bonds is a key design concept
to construct more stable, diverse, dynamic, and
functional helicates based on the unique structures
and functions of metal ions.
To date, a variety of excellent peptide-based
synthetic foldable molecules “foldamers”[4–6] have
been designed and applied not only to vital related
functions,[7] but also to structure-dependent chemical
functions.[8] Thus, metal–peptide conjugates[9] have
great potential in terms of diverse conformation
libraries, dynamic features, and metal-based func-
tions. Herein, we report a novel type of metallo-
Figure 1. a) A conceptual scheme of this study. b) Syntheses of dipeptides, 2
and 3, and a tetrapeptide 4 from a protected oxime amino acid 1, and c) the
formation of mononuclear helical complexes, 5–7, and hairpin complexes, 8 and
9, and a dinuclear double-hairpin complex 10.
foldamer formed from a peptide mimic containing up to four
synthetic oxime amino acids (Figure 1). We envisaged that the
incorporation of a metal-coordinative oxime group into an
amino acid mimic would provide a peptide mimic with
multiple metal binding sites possibly leading to metal-
mediated secondary structures such as helices, hairpins,
turns, and sheets. In this study, we have demonstrated that
oxime–peptide complexes with up to two PdII ions form
folded structures such as helices, hairpins, and double-hair-
pins, as revealed by NMR and XRD analyses. Furthermore,
we found that they show conformation changes because of the
linkage isomerization upon addition of acids or bases.
binding site, and both C- and N-terminal parts have an a-
methylene group where one or two side chains may be
introduced as needed. The peptides can be synthesized
according to general liquid-phase methods without protecting
the oxime groups. In this study, we prepared two dipeptides 2
and 3[11] and one tetrapeptide 4 from monomeric 1 (Figure 1b
and Scheme S1 in the Supporting Information). It was
expected that the oxime nitrogen atoms and the O or N (as
NÀ) atoms of amide groups would take part in metal
coordination to provide some secondary folded structures
depending on the kind of metal ions and complexation
conditions. In view of the high Lewis acidity and greater
coordination space of square-planar coordination geometry,
PdII was selected as the first choice.
Upon complexation of the C-terminal, ester-protected
dipeptide 2 and Pd(OAc)2 in CD3CN, the formation of
a single product was confirmed by 1H NMR spectroscopy (see
Figure S27 in the Supporting Information). The disappear-
ance of two N-H signals suggests the complexation of both
carbamate and amide N-H moieties with deprotonation. The
large up-field shift of CH2 protons of the Cbz (benzylox-
ycarbonyl) group at the N-terminal, which is probably
because of the electronic influence from the neighboring
Our design concept is to incorporate an additional metal
binding site into the backbone of a synthetic amino acid as
a minimal structure of foldamers. A structurally robust oxime
group[2j,10] is the essential part of amino acid 1 as a metal
[*] Dr. S. Tashiro, K. Matsuoka, A. Minoda, Prof. Dr. M. Shionoya
Department of Chemistry, Graduate School of Science
The University of Tokyo
7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan)
E-mail: shionoya@chem.s.u-tokyo.ac.jp
[**] This study was supported by KAKENHI, the Japan Society for the
Promotion of Science and MEXT (Japan). We thank Dr. J.-L. Duprey
for his helpful discussion.
=
O C-N-Pd moiety, also supports the complexation at the
carbamate moiety. The formation of a mononuclear complex
was confirmed by electrospray ionization time-of-flight (ESI-
TOF) mass spectrometry (m/z 549.06 [Pd(HÀ22)·Na]+). The
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201206968.
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product was obtained as yellow crystals in 86% yield by
recrystallization from CHCl3/toluene. The single-crystal X-
ray analysis revealed the molecular structure of a neutral,
mononuclear complex Pd(HÀ22) (5) as shown in Figure 2a.
as determined by X-ray analysis (Figure 2b, left). In this
structure, two oxime nitrogen atoms and two deprotonated
amide nitrogen atoms at the C-terminal bind to a PdII ion to
form an N4 plane with two six-membered chelate rings, which
is different from metal complexes of natural peptide chains
forming only five-membered chelate rings. As the PdII ions in
6 and 7 are bound by the N-terminal and C-terminal of 3,
respectively, 6 and 7 have an isomeric relationship.
In the helical complexes 5–7, formed from 2 or 3, two
deprotonated N-H groups bind to the PdII centers as the trans
ligands. Coordination structures of such complexes are often
controllable by addition of acid and base.[9a,d] Indeed, com-
plexation of dipeptides 2 and 3 with Pd(CH3CN)4(BF4)2
containing BF4 anions instead of basic AcOÀ anions in
À
Pd(OAc)2 afforded alternative mononuclear complexes as
1
confirmed by H NMR spectroscopy (see Figures S27, S43 in
the Supporting Information) and ESI-TOF mass spectrome-
try (m/z 527.07 [Pd(HÀ12)]+ for 8 and 512.08 [Pd(HÀ13)]+ for
9). The molecular structure of 9 was determined by the X-ray
crystal analysis of [Pd(HÀ13)]BF4 which was isolated in 81%
yield (Figure 2c). In contrast to the helical complexes 5–7,
one carbonyl oxygen atom of the C-terminal of 9 binds to
a PdII ion to form a monocationic, square-planar complex,
which is regarded as a hairpin rather than a helix. Overall, the
common coordination structure of complexes 5–9 is an N-NÀ-
N tridentate coordination with two oxime nitrogen atoms and
one deprotonated amide nitrogen atom to form a helix or
a hairpin structure, in which the fourth intramolecular
coordination is influenced by the basicity of the counter
anions.
Figure 2. Chemical structures of 5–9 and crystal structures of a) N-
terminal helix 5, b) C-terminal helix 7, and c) hairpin 9.[17] Disordered
atoms in 5, one acetic acid molecule in 7, and disordered atoms and
one BF4À anion in 9 are omitted for clarity.
The reversible structural conversion between helix 5 and
hairpin 8 through intramolecular ligand exchange has been
clearly established upon treatment of acid or base
(Scheme 1).[12] When 2.6 equivalents of N,N,N’,N’-tetra-
The obtained structure contains one square-planar PdII ion
bound by two oxime and two deprotonated amide nitrogen
1
atoms as expected from its solution-phase H NMR spectra.
Notably, complex 5 has a one-roll helical structure because of
the overlap of both N- and C-terminals, leading to the
existence of enantiomeric pairs of P and M helices in the
crystal. Interconversion of both helical enantiomers in
1
solution appears to be fast on a H NMR timescale at room
temperature because of an absence of diastereotopic splitting
of the methylene protons of 5. The fast racemization of 5 is
consistent with the results of recent metallo-foldamers
reported by Fox and co-workers.[2m]
Scheme 1. Acid–base control of the fourth intramolecular coordination
with reversible interconversion between mononuclear complexes, 8
and 5.
In contrast to 2, the C-terminal, amide-protected dipep-
tide 3 afforded two different mononuclear species through
complexation with Pd(OAc)2 in CD3CN as confirmed by
1H NMR spectroscopy (a ratio of about 2.5:1, see Figure S34
in the Supporting Information) and ESI-TOF mass spectrom-
etry (m/z 534.06 [Pd(HÀ23)·Na]+). The major product, with
upfield shifted CH2 protons of the Cbz group, was assigned to
6, similarly to 5. In the minor product, complex 7, little
shifting of the CH2 of the Cbz group was observed and
therefore the most likely structure is that where the depro-
tonated C-terminal amide nitrogen binds to the PdII ion
(Figure 2b, right). Fortunately, complex 7 was crystallized
from CH3CN in 24% yield. As expected, the resulting
structure was a neutral, mononuclear complex Pd(HÀ23) (7)
methyl-1,8-naphthalenediamine (11) was added as a base to
a solution of cationic hairpin 8 in CD3CN, quantitative
formation of helix 5 was confirmed by 1H NMR spectroscopy.
This indicates that the N-terminal carbamate nitrogen atom
binds to the PdII ion with simultaneous deprotonation.
Conversely, addition of HBF4 to the solution of 5 resulted in
quantitative reverse conversion to hairpin 8 (see Figure S27 in
the Supporting Information). This reversible conversion
1
between 5 and 8 was found to be repeatable by H NMR
measurements in which 11 and HBF4 were alternately added
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to the regenerated 8 to achieve quantitative spectral trans-
formation (see Figure S62 in the Supporting Information).
This result demonstrates that the structural conversion of
PdII-mediated foldamers depends on the Lewis acidity of the
PdII ions used and the acid–base balance. Recently, helicity
inversion of mononuclear acyclic metal complexes through
acid–base control or anion addition have been reported by
Miyake and co-workers.[9k,13] In contrast, our approach would
lead to direct control of the secondary structure itself because
our metallo-foldamers can be elongated with multiple metal
ions that are structure-determining components.
For multinuclear higher-order structures, complexation of
a longer tetrapeptide 4 was subsequently examined. Upon
addition of three equivalents of Pd(CH3CN)4(BF4)2 to
a solution of 4 in [D6]DMSO, a single
formed in solution (Figure 3b).[12] On the other hand, other
long-range NOE signals (Hb-Hf) observed here are not
consistent with the distance observed in the X-ray structure
(8.4 ꢀ), indicating that the conformation of the Cbz part of
the N-terminal is flexible.
The structure of double hairpin 10 can be regarded as
a mixture of the structure of hairpin 8 and helix (therefore
chiral) 5 as mentioned above. If the N-H moiety of the N-
terminal carbamate in 10 is deprotonated and thereby binds
to PdII by replacing the middle amide carbonyl oxygen donor,
a repeating structure of a kind of two consecutive helices 5
would be formed (Scheme 2). Indeed, the addition of base 11
to a solution of 10 in [D6]DMSO gave rise to a new species 12
in which the N-H moiety of the N-terminal carbamate
product was found to form as shown by
1H NMR spectroscopy (see Fig-
ure S51). The unchanged signals of the
N-terminal carbamate N-H protons
suggest that this moiety does not bind
to PdII as observed with cationic hair-
pins 8 and 9. ESI-TOF mass spectro-
metric measurement supports the for-
mation of the dinuclear complex (m/z
Scheme 2. Acid–base control of the intramolecular coordination with reversible interconversion
between dinuclear complexes 10 and 12.
889.09 [Pd2(HÀ34)]+). The folded struc-
ture was eventually determined by
single-crystal X-ray analysis although
the data quality was not very high (Figure 3a).[14] As expected,
the resulting structure was a dinuclear, cationic complex
[Pd2(HÀ34)]BF4 (10) with a PdII-PdII distance of 5.98 ꢀ
bridged by a deprotonated amide bond (O and NÀ). While
the N-terminal PdII-centered structure with oxime-amide-
oxime-carbonyl coordination is similar to cationic hairpin 8,
the C-terminal structure with amide-oxime-amide-oxime
coordination is almost identical to neutral helix 5. As
a result, complex 10 adopts a double hairpin structure.[15]
To confirm the solution structure of 10, 1H and 13C NMR
spectra of 10 in [D6]DMSO were fully assigned with the aid of
appears to be deprotonated to bind PdII as suggested from
the large upfield shift of the CH2 signal of the Cbz group. This
behavior is comparable to the conversion from cationic
hairpin 8 to neutral helix 5. Similarly, species 12 was quanti-
tatively and reversibly converted to the initial structure 10 by
adding HBF4 (see Figure S63 in the Supporting Information).
The double hairpin 10 has a rigid structure due to the two PdII
centers being bridged by the middle amide group. However,
the resulting deprotonated 12, after intramolecular ligand
exchange, most likely can adopt a few, more flexible
conformational isomers such as a helix, sheet, or intramolec-
ularly stacked PdII complex (see Figures S66 and S67).
1
1H-1H COSY, NOESY, H-13C HSQC, and HMBC measure-
ments. In the NOESY spectrum, several long-range, inter-
strand NOEs (nuclear Overhauser effects) such as Hd-Hl, Hc-
Hl, and Hj-Hq were observed besides short-range, intrastrand
NOEs. This result suggests that a double-hairpin structure is
In summary, a new series of square-planar PdII-mediated
foldamers with mononuclear and dinuclear helix or (double)
hairpin structures were constructed by novel backbone-
coordinative oxime peptides. Some of these metallo-foldam-
ers allow significant structural interconversion between two
distinct structures through intramolecular ligand exchange
based on the acid–base balance. Metals with different Lewis
acidity and coordination geometry would modulate alterna-
tive, dynamically folded structures such as homo- and hetero-
multinuclear helices, hairpins, sheets, and their mixed ternary
structures thus leading to metal-based sensing functions.
Additionally, water-soluble oxime peptides without protect-
ing groups at both terminals[16] would provide their metallo-
foldamers with biological and bio-inspired functions such as
catalytic activities[9f,g] and specific binding to biopolymers.[2-
d,e,9c]
Figure 3. a) Crystal structure of the dÀinuclear double-hairpin complex
10.[17] Disordered atoms and one BF4 anion are omitted for clarity.
b) Observed NOE signals for 10 in NOESY measurement (500 MHz,
[D6]DMSO, 293 K) with distances calculated from the X-ray structure.
Received: August 28, 2012
Revised: October 2, 2012
Published online: November 14, 2012
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c) C. Dolain, V. Maurizot, I. Huc, Angew. Chem. 2003, 115,
2844 – 2846; Angew. Chem. Int. Ed. 2003, 42, 2738 – 2740; d) J.-
M. Suk, K.-S. Jeong, J. Am. Chem. Soc. 2008, 130, 11868 – 11869;
e) B. C. Gorske, J. R. Stringer, B. L. Bastian, S. A. Fowler, H. E.
Blackwell, J. Am. Chem. Soc. 2009, 131, 16555 – 16567; f) Y.
Zhao, Z. Zhong, J. Am. Chem. Soc. 2005, 127, 17894 – 17901;
g) R. M. Meudtner, S. Hecht, Angew. Chem. 2008, 120, 5004 –
5008; Angew. Chem. Int. Ed. 2008, 47, 4926 – 4930; h) E. Ohta,
H. Sato, S. Ando, A. Kosaka, T. Fukushima, D. Hashizume, M.
Yamasaki, K. Hasegawa, A. Muraoka, H. Ushiyama, K.
Yamashita, T. Aida, Nat. Chem. 2011, 3, 68 – 73.
Keywords: NMR spectroscopy · palladium · peptides ·
supramolecular chemistry · X-ray diffraction
.
[1] a) J.-M. Lehn, A. Rigault, J. Siegel, J. Harrowfield, B. Chevrier,
D. Moras, Proc. Natl. Acad. Sci. USA 1987, 84, 2565 – 2569;
b) E. C. Constable, Tetrahedron 1992, 48, 10013 – 10059; c) C.
Piguet, G. Bernardinelli, G. Hopfgartner, Chem. Rev. 1997, 97,
2005 – 2062; d) M. Albrecht, Chem. Rev. 2001, 101, 3457 – 3497.
[2] a) T. W. Bell, H. Jousselin, Nature 1994, 367, 441 – 444; b) M.
Albrecht, S. Kotila, Angew. Chem. 1995, 107, 2285 – 2287;
Angew. Chem. Int. Ed. Engl. 1995, 34, 2134 – 2137; c) R. B.
Prince, T. Okada, J. S. Moore, Angew. Chem. 1999, 111, 245 –
249; Angew. Chem. Int. Ed. 1999, 38, 233 – 236; d) M. J. Hannon,
V. Moreno, M. J. Prieto, E. Moldrheim, E. Sletten, I. Meister-
mann, C. J. Isaac, K. J. Sanders, A. Rodger, Angew. Chem. 2001,
113, 904 – 908; Angew. Chem. Int. Ed. 2001, 40, 880 – 884; e) S. E.
Howson, A. Bolhuis, V. Brabec, G. J. Clarkson, J. Malina, A.
Rodger, P. Scott, Nat. Chem. 2012, 4, 31 – 36; f) M. Barboiu, J.-M.
Lehn, Proc. Natl. Acad. Sci. USA 2002, 99, 5201 – 5206; g) V.
Amendola, L. Fabbrizzi, P. Pallavicini, E. Sartirana, A. Taglietti,
Inorg. Chem. 2003, 42, 1632 – 1636; h) N. Dalla Favera, L.
Guꢁnꢁe, G. Bernardinelli, C. Piguet, Dalton Trans. 2009, 7625 –
7638; i) L. Aboshyan-Sorgho, C. Besnard, P. Pattison, K. R.
Kittilstved, A. Aebischer, J.-C. G. Bꢂnzli, A. Hauser, C. Piguet,
Angew. Chem. 2011, 123, 4194 – 4198; Angew. Chem. Int. Ed.
2011, 50, 4108 – 4112; j) S. Akine, T. Taniguchi, T. Saiki, T.
Nabeshima, J. Am. Chem. Soc. 2005, 127, 540 – 541; k) S. Akine,
T. Shimada, H. Nagumo, T. Nabeshima, Dalton Trans. 2011, 40,
8507 – 8509; l) F. Zhang, S. Bai, G. P. A. Yap, V. Tarwade, J. M.
Fox, J. Am. Chem. Soc. 2005, 127, 10590 – 10599; m) Z. Dong,
R. J. Karpowicz, Jr., S. Bai, G. P. A. Yap, J. M. Fox, J. Am. Chem.
Soc. 2006, 128, 14242 – 14243; n) L. Bain, S. Bullock, L. Harding,
T. Riis-Johannessen, G. Midgley, C. R. Rice, M. Whitehead,
Chem. Commun. 2010, 46, 3496 – 3498.
[3] a) K. Tanaka, A. Tengeiji, T. Kato, N. Toyama, M. Shionoya,
Science 2003, 299, 1212 – 1213; b) K. Tanaka, G. H. Clever, Y.
Takezawa, Y. Yamada, C. Kaul, M. Shionoya, T. Carell, Nat.
Nanotechnol. 2006, 1, 190 – 194; c) Y. Takezawa, W. Maeda, K.
Tanaka, M. Shionoya, Angew. Chem. 2009, 121, 1101 – 1104;
Angew. Chem. Int. Ed. 2009, 48, 1081 – 1084; d) S. Liu, G. H.
Clever, Y. Takezawa, M. Kaneko, K. Tanaka, X. Guo, M.
Shionoya, Angew. Chem. 2011, 123, 9048 – 9052; Angew. Chem.
Int. Ed. 2011, 50, 8886 – 8890; e) S. Johannsen, N. Megger, D.
Bçhme, R. K. O. Sigel, J. Mꢂller, Nat. Chem. 2010, 2, 229 – 234.
[4] a) D. J. Hill, M. J. Mio, R. B. Prince, T. S. Hughes, J. S. Moore,
Chem. Rev. 2001, 101, 3893 – 4011; b) S. H. Gellman, Acc. Chem.
Res. 1998, 31, 173 – 180; c) C. M. Goodman, S. Choi, S. Shandler,
W. F. DeGrado, Nat. Chem. Biol. 2007, 3, 252 – 262; d) I. Huc,
Eur. J. Org. Chem. 2004, 17 – 29; e) G. Maayan, Eur. J. Org.
Chem. 2009, 5699 – 5710.
[7] a) S. J. Shandler, I. V. Korendovych, D. T. Moore, K. B. Smith-
Dupont, C. N. Streu, R. I. Litvinov, P. C. Billings, F. Gai, J. S.
Bennett, W. F. DeGrado, J. Am. Chem. Soc. 2011, 133, 12378 –
12381; b) A. D. Bautista, J. S. Appelbaum, C. J. Craig, J. Michel,
A. Schepartz, J. Am. Chem. Soc. 2010, 132, 2904 – 2906.
[8] a) W. C. Pomerantz, V. M. Yuwono, R. Drake, J. D. Hartgerink,
N. L. Abbott, S. H. Gellman, J. Am. Chem. Soc. 2011, 133,
13604 – 13613; b) M. M. Mꢂller, M. A. Windsor, W. C. Pomer-
antz, S. H. Gellman, D. Hilvert, Angew. Chem. 2009, 121, 940 –
943; Angew. Chem. Int. Ed. 2009, 48, 922 – 925; c) Y. Ferrand,
A. M. Kendhale, B. Kauffmann, A. Grꢁlard, C. Marie, V. Blot,
M. Pipelier, D. Dubreuil, I. Huc, J. Am. Chem. Soc. 2010, 132,
7858 – 7859.
[9] a) H. Sigel, R. B. Martin, Chem. Rev. 1982, 82, 385 – 426; b) E. W.
Wilson, Jr., R. B. Martin, Inorg. Chem. 1970, 9, 528 – 532;
c) E. C. Long, Acc. Chem. Res. 1999, 32, 827 – 836; d) E.
´
´
Łodyga-Chruscinska, Coord. Chem. Rev. 2011, 255, 1824 –
1833; e) M. R. Ghadiri, A. K. Fernholz, J. Am. Chem. Soc.
1990, 112, 9633 – 9635; f) B. V. Popp, Z. T. Ball, Chem. Sci. 2011,
2, 690 – 695; g) S. R. Gilbertson, S. E. Collibee, A. Agarkov, J.
Am. Chem. Soc. 2000, 122, 6522 – 6523; h) B. P. Gilmartin, K.
Ohr, R. L. McLaughlin, R. Koerner, M. E. Williams, J. Am.
Chem. Soc. 2005, 127, 9546 – 9555; i) P. Vairaprakash, H. Ueki, K.
Tashiro, O. M. Yaghi, J. Am. Chem. Soc. 2011, 133, 759 – 761;
j) J. P. Schneider, J. W. Kelly, J. Am. Chem. Soc. 1995, 117, 2533 –
2546; k) H. Miyake, H. Kamon, I. Miyahara, H. Sugimoto, H.
Tsukube, J. Am. Chem. Soc. 2008, 130, 792 – 793; l) H. Ishida, Y.
Maruyama, M. Kyakuno, Y. Kodera, T. Maeda, S. Oishi,
ChemBioChem 2006, 7, 1567 – 1570.
[10] a) S. Akine, T. Taniguchi, W. Dong, S. Masubuchi, T. Nabeshima,
J. Org. Chem. 2005, 70, 1704 – 1711; b) S. Akine, T. Nabeshima,
Dalton Trans. 2009, 10395 – 10408; c) J. Kalia, R. T. Raines,
Angew. Chem. 2008, 120, 7633 – 7636; Angew. Chem. Int. Ed.
2008, 47, 7523 – 7526.
[11] The single-crystal X-ray structural analysis of dipeptide 3
revealed the E form structure of the oxime bond and its 18-
helix conformation through hydrogen bonding in the solid state
(Figure S19).
[12] Although the carbonyl groups bind to PdII ions in the crystal
structure of 9, this carbonyl-bound structure appears not to be
the main species in the CD3CN solution because the chemical
shift of this carbonyl group of 9 in the 13C NMR spectrum was
almost the same as that of 5. Therefore, it is most likely that one
solvent molecule binds to PdII instead in the solution as shown in
Scheme 1. In contrast, the carbonyl-bound structure for 10 which
is shown in the crystal structure appears to be maintained as
a predominant conformation even in the [D6]DMSO solution as
judged from the results of NOESY analysis (Figure 3b) and
13C NMR measurements (see Figure S52).
[5] Examples for peptide-based foldamers: a) D. Seebach, M.
Overhand, F. N. M. Kꢂhnle, B. Martinoni, L. Oberer, U.
Hommel, H. Widmer, Helv. Chim. Acta 1996, 79, 913 – 941;
b) Y. Hamuro, S. J. Geib, A. D. Hamilton, J. Am. Chem. Soc.
1997, 119, 10587 – 10593; c) D. H. Appella, L. A. Christianson,
D. A. Klein, D. R. Powell, X. Huang, J. J. Barchi, Jr., S. H.
Gellman, Nature 1997, 387, 381 – 384; d) V. Berl, I. Huc, R. G.
Khoury, M. J. Krische, J.-M. Lehn, Nature 2000, 407, 720 – 723;
e) J. L. Goodman, E. J. Petersson, D. S. Daniels, J. X. Qiu, A.
Schepartz, J. Am. Chem. Soc. 2007, 129, 14746 – 14751; f) L.
Fischer, P. Claudon, N. Pendem, E. Miclet, C. Didierjean, E.
Ennifar, G. Guichard, Angew. Chem. 2010, 122, 1085 – 1088;
Angew. Chem. Int. Ed. 2010, 49, 1067 – 1070.
[13] a) H. Miyake, M. Hikita, M. Itazaki, H. Nakazawa, H. Sugimoto,
H. Tsukube, Chem. Eur. J. 2008, 14, 5393 – 5396; b) H. Miyake,
M. Ueda, S. Murota, H. Sugimoto, H. Tsukube, Chem. Commun.
2012, 48, 3721 – 3723.
[14] The origin of the low data quality of the diffraction data of 10
may come from the low quality of the crystal, which is a non-
merohedral twin. In the structural refinement, some restraints
[6] Examples for non-peptide foldamers: a) J. C. Nelson, J. G.
Saven, J. S. Moore, P. G. Wolynes, Science 1997, 277, 1793 –
1796; b) R. S. Lokey, B. L. Iverson, Nature 1995, 375, 303 – 305;
13126 www.angewandte.org
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for thermal parameters were used for several atoms in the main
residue. However, the NOESY measurement strongly supports
this folded structure.
transition-metal ions such as RhIII, CuII, and NiII. The details will
be reported elsewhere.
[17] CCDC 891133 (3), 891134 (5), 891135 (7), 891136 (9), and
891137 (10) contain 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.
[15] a) H. L. Schenck, S. H. Gellman, J. Am. Chem. Soc. 1998, 120,
4869 – 4870; b) H. Rapaport, G. Mçller, C. M. Knobler, T. R.
Jensen, K. Kjaer, L. Leiserowitz, D. A. Tirrell, J. Am. Chem. Soc.
2002, 124, 9342 – 9343.
[16] We have preliminarily synthesized water-soluble oxime peptides
and their metal complexes not only with PdII but also with other
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