close

Вход

Забыли?

вход по аккаунту

?

Molecules with Helical Structure How To Build a Molecular Spiral Staircase.

код для вставкиСкачать
Highlights
Helical Molecules and Aggregates
Molecules with Helical Structure: How To Build a
Molecular Spiral Staircase
Carsten Schmuck*
Keywords:
arenes · conformation analysis · foldamers ·
helical structures
Helical Compounds
Molecules with helical structure
have fascinated chemists for may years
now. Due to their nonplanar structure,
such molecules are inherently chiral and
exhibit interesting optical and electronic
properties. In principle, molecules with
such unusual topologies[1] can be synthesized through three different approaches: First, in rigid molecules steric
effects can be used to enforce a helical
structure. This is the case, for example,
in the long-known and well-studied
helicenes and their derivatives.[2] An
increasing ortho annulation of aromatic
ring systems first causes an increasing
steric interaction between the H atoms
on the terminal rings, leading to a nonplanar conformation. When the number
of annulated arenes further increases,
the terminal rings will overlap, giving
rise to a helical conformation. Second,
flexible molecules without any biased
conformation can also give rise to defined structures through stabilizing intramolecular noncovalent interactions.[3]
A classical example is the a helix found
in proteins, which is stabilized by intramolecular hydrogen bonds between the
amide groups of amino acid i and i + 4
within a linear peptide strand.[4] As a
result of the flexible nature of the
underlying molecule (the linear peptide
strand), helix formation in this case is a
dynamic equilibrium process. Therefore,
[*] Prof. Dr. C. Schmuck
Institut fr Organische Chemie
Universit#t Wrzburg
Am Hubland, 97074 Wrzburg (Germany)
Fax: (+ 49) 931-888-4625
E-mail: schmuck@chemie.uni-wuerzburg.
de
2448
stable helices are only formed from
a amino acids with chain lengths of
more than 10 amino acids. In shorter
chains the noncovalent interactions are
not strong enough to compensate for the
unfavorable entropy change associated
with the folding of the flexible molecule.[5] Third, helical structures can also
be formed through supramolecular interactions[6] of two or more molecules.
This is, for example, the case in DNA, in
which intermolecular hydrogen bonds
between two complementary base
strands give rise to the well-known
double-helical conformation.[7]
Even though these examples show
that molecular spiral staircases of various types have been well-known for a
long time,[8] especially in the last few
years a number of new compounds with
helical structures have been described.
We wish to present herein some examples that demonstrate the different ways
in which such helical structures can be
obtained: covalent synthesis of rigid
molecules, the folding of flexible molecules as a result of intramolecular interactions, and structure formation by
supramolecular complexation.
catalyzed cyclotrimerizations of a suitable
alkyne-substituted
arene
(Scheme 1). This alkyne 3 can be synthesized in good yields by palladiumcatalyzed coupling of iodoarenes 1 with
Me3Si-substituted alkyne 2. The nonyne
3 thus obtained undergoes cobalt-catalyzed cyclization to the [7]phenylene 4
with the simultaneous formation of nine
rings, six of which are formal cyclobutadiene units with an estimated strain
energy of 300 kcal mol 1. Even though
the yield of this reaction is only 2 %, this
synthesis represents a general approach,
which can also be used for the synthesis
of higher homologues such as [8]- and
[9]phenylene.[9b] These phenylenes are
orange solids with a helical structure
(Figure 1). According to 1H NMR stud-
Rigid Molecules with Helical
Structures
Vollhardt and co-workers recently
reported the synthesis of the first helical
phenylene.[9] [n]Phenylenes consist of n
alternating benzene rings fused to n 1
cyclobutadiene rings. Phenylenes with
n > 5 become helical and are thus chiral.
Phenylenes have a larger ring size than
the classical helicenes as a result of the
intermediate cyclobutadiene s spacer.
The synthesis involved multiple cobalt-
ies, this structure also predominates in
solution. The conformational stability of
the phenylenes is much lower than that
of the helicenes. Temperature-dependent NMR studies provide a barrier of
activation for the inversion of [7]phenylene of only 12.6 kcal mol 1. This is only
a third of the value of that of the
[7]helicene (41.7 kcal mol 1[2c]). Phenylenes are therefore much more flexible
than their smaller relatives. Accordingly,
an enantiomeric separation was thus far
not possible.
DOI: 10.1002/anie.200201625
Angew. Chem. Int. Ed. 2003, 42, 2448 – 2452
2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Figure 1. Structure of the helical [7]phenylene
4 in the solid state.
Angewandte
Chemie
per turn and an inner diameter of 10 A.
The overlap of the last two aromatic
rings in nonamer 8 within the helix can
be proven spectroscopically by NOE
interactions. According to these studies,
the helical conformation seems to be
predominant in solution. Even upon the
addition of 50 % DMSO to the solution
in chloroform, the helical structure is
still present, as the diagnostic NOE
interactions of the two overlapping
terminal rings can still be detected.
R
R
Scheme 1. Synthesis of the cyclization precursor 3 by palladium-catalyzed Sonogashira coupling
and its conversion into 4. R = DMTS = dimethylthexylsilyl.
R
An alternative approach to rigid
helical molecules represent the so-called
“Gel=nder” helical molecules (molecules whose structure resemble the
banisters of a spiral staircase) described
X
X
5
by V?gtle and co-workers.[10] These are
ortho-bridged terphenylenes such as 5,
in which the helical structure results
from steric interactions between the
substituents ortho to the biaryl axis.
Depending on the relative twist around
each of the two biaryl axes, these
molecules may exist in three different
stable conformations: two enantiomeric
chiral forms and one meso form. With
suitable substituents at the terphenylene, the conformational stability is
large enough that even an enantiomeric
separation is possible.
A new class of flexible molecules
that adopt a helical conformation as a
Angew. Chem. Int. Ed. 2003, 42, 2448 – 2452
O
H
R
O
N
O
H
N
H
O
N
O
N
O
O
R
O
R
3
O
R
O
N
H
N
O
R
R
O
O
O
H
N
R
R
O
O
N
O
H
para-substituted spacers
reduce the curvature
R
O
O
H
R
When para-aminobenzoic acid units
are incorporated as linear spacers into
the oligoamide, the diameter of the helix
should increase (see 7, Scheme 2). According to model calculations, the 21mer
9 (Figure 2), which consists of alternating meta- and para-connected building
blocks, should form a helix with an inner
diameter of 30 A. An exact experimental structure elucidation was so far not
possible. But again, in a spectroscopic
study of solutions in chloroform, NOE
interactions were detected, which suggest an interaction between the two ends
of the oligoamide strand and hence
indicate a helical conformation.
In contrast to the covalent helicenes
or phenylenes, the structure of such
R
O
O
H
N
3
H bonds fix
conformation
R
O
R
O
8
result of intramolecular interactions
along their backbone are the oligoamides of general type 6, which were
recently introduced by Gong et al.
(Scheme 2).[11] In these molecules, benzene rings are connected through amide
bonds placed meta to each other on each
benzene ring. Localized three-center
hydrogen bonds between the amide
hydrogen atom and alkoxy groups on
the benzene ring lead to a curved
conformation, which with increasing
length of the oligoamide leads to helix
formation. The nonamer 8 adopts, both
in the solid state and in chloroform
solution, a helical structure. As the
amide linkages are slightly curved towards the NH side, the backbone is
slightly opened up, leading to a helix
with approximately seven benzene rings
small helix
Flexible Molecules with a Helical
Secondary Structure
O
H
H
N
O
R
O
O
wide helix
R
R
O
O
O
R
6
7
Scheme 2. Intramolecular hydrogen bonds stabilize a conformation within the oligoamides 6
and 7 and induces helix formation.
www.angewandte.org
2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2449
Highlights
Figure 3. In the unfolded state (left), 10 contains both transoid and cisoid backbone conformations; in the helical conformation (right), only cisoid conformations occur.
Figure 2. The 21mer 9 adopts a helical conformation with a pore size of 30 @ according to
preliminary NOESY studies.
foldamers strongly depends on external
parameters. The conformation is based
on intramolecular noncovalent interactions, whose strength is determined also
by the surrounding factors such as the
nature and polarity of the solvent.[12]
Moore and Hill recently investigated
the influence of 30 different solvents on
the formation of helical structures in
TgO2C
H
CH3
6
TgO
TgO
CH3
H
TgO2C
6
Tg = (CH2CH2O)3CH3
pending on the solvent, nearly all helix
ratios from 0 (completely unfolded) to 1
(completely folded) can be found.
An opposite effect of the solvent can
be found in the oligopyridine amides 11
described by Lehn and co-workers
(Scheme 3). The conformation of these
oligomers, which are formed from alternating 2,6-diaminopyridine and 2,6-pyridinedicarboxylic acid units, is again
based on hydrogen bonds.[14] An intramolecular interaction between the
amide NH proton and the pyridine N
atom is responsible for the curved conformation necessary for helix formation.
The X-ray single-crystal structure
determination of 11 showed the presence of ellipsoid helices with an inner
diameter of 5.5 (n = 2) and 8 A (n = 4)
(Figure 4). The longest strand examined
so far, an undecamer (n = 4), already
extends to 21=2 helix turns. According to
NMR spectroscopic studies, these helices are also present in chloroform solution. In DMSO however, at least the
shorter oligomers do not adopt a helical
conformation. The intramolecular hydrogen bonds are broken in DMSO as a
result of competitive solvation of donor
and acceptor sites by the solvent. Hence,
Figure 4. Solid-state structure of heptamer 11
(n = 2).[14b]
the building blocks of the oligomer no
longer adopt any preferred conformations and no stable secondary structure
results.
Supramolecular helices
The oligoamide helices described by
Lehn and co-workers can also further
dimerize at higher concentrations, forming a stable double helix in solution.[14a, 15] Within the double helix, the
two oligomer strands are held together
by arene–arene interactions between
pyridine rings lying opposite each other.
As before, intramolecular hydrogen
bonds within each strand are responsible
for the curvature of the helix. The
formation of the double helix is accompanied by an unwinding of the individual helices, but the inner diameter of the
10
conformationally flexible oligo(m-phenylene ethynylene) foldamers 10.[13]
In this case, the intermolecular
forces that give rise to helix formation
are mainly hydrophobic or solvophobic
interactions. Hence, with increasing polarity of the solvent, the extent of helical
structures in the unfolded–folded conformational equilibrium increases, as
could be shown by UV and CD spectroscopy (Figure 3). Whereas in chloroform
mainly disordered random conformations predominate, a well-ordered helix
is formed in methanol which is characterized by a strong Cotton effect. De-
2450
H bonds fix
conformation
H
O
N
H
N
N
H
N
11
O
H2N
N
H
N
H
N
N
O
O
N
H
N
H
N
N
n
N
NH2
O
O
11
Scheme 3. Intramolecular hydrogen bonds within the oligopyridine 11 cause a curved conformation, which leads to helix formation in longer strands.
2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
Angew. Chem. Int. Ed. 2003, 42, 2448 – 2452
Angewandte
Chemie
Figure 5. Two helical single strands 11 dimerize to form a supramolecular double helix.
central pore is not significantly affected
(Figure 5).
The conformational behavior of
fused heterocycles can also be exploited
for helix formation, as shown by Lehn
and co-workers.[16] 2,2’-Bipyridines and
related heterocycles adopt a transoid
conformation, which is biased towards
helix formation in a similar way as the
intramolecular hydrogen-bonded oligoamides by Lehn and co-workers[14]
and Gong et al.[11] described above. In
this context, it was recently shown that
the use of naphthyridines instead of
pyridines results in an opening of the
structure, which allows now for the first
time the inclusion of other molecules
within the central pore of the helix[17]—a
first step towards helical channels. For
transoid conformation
Ar
N
N
N
N
N
n
N
Ar
N
N
N
N
12
Figure 6. Only the interaction with the cation
gives rise to the formation of a supramolecular helix from the oligomers 12.[17]
helices were observed. The formation
of such cation channels is also supported
by results from electrospray mass spectrometry and transmission electron microscopy.
As shown by Meijer and co-workers
in recent years, supramolecular polymers[18] may also adopt a helical superstructure as a result of specific noncovalent interactions between the individual monomers.[19] In the case of the
bifunctional ureido-s-triazine 13 (Figure 7), in addition to the hydrogen-bond
driven dimerization of the head groups,
p–p interactions between the aromatic
rings cause the formation of columnar
stacks. The chiral side chains further
induce a helicity of these stacks, as could
be shown by CD spectroscopy.
The examples presented herein
demonstrate the various possibilities
that exist today to obtain molecules
with a helical conformation: from the
synthesis of rigid molecules, in which
helix formation minimizes steric strain,
to flexible molecules with well-defined
secondary structures, to supramolecular
aggregates with a helical superstructure.
Whether new material properties are
associated with these molecules still has
to be determined.
Scheme 4. In oligomer 12 interactions between the adjacent heterocycles result in a
transoid conformation around the biaryl axis.
example, the naphthyridine pyrimidine
oligomer 12 (n = 2, Scheme 4) adopts a
conformation in solution (CDCl3/
CD3CN) that represents a single helical
turn. In the presence of alkali metal ions
such as Cs+, a supramolecular association of such individual helical springs
occurs, leading to long hollow tubes in
which, as the authors suggest, cations
are incorporated (Figure 6). It is only
this mutual interaction of two strands
with one cation that stabilizes these
supramolecular aggregates, as in the
absence of cations only monomeric
Angew. Chem. Int. Ed. 2003, 42, 2448 – 2452
[1] a) F. V?gtle, Reizvolle Molekle in der
Organischen Chemie, Teubner, Stuttgart, 1989; b) H. Hopf, Classics in Hydrocarbon Chemistry, Wiley-VCH,
Weinheim, 2000.
[2] a) K. P. Meurer, F. V?gtle, Top. Curr.
Chem. 1985, 127, 1; b) W. H. Laarhoven,
W. J. C. Prinsen, Top. Curr. Chem. 1984,
125, 63; c) R. H. Martin, Angew. Chem.
1974, 86, 727; Angew. Chem. Int. Ed.
Engl. 1974, 13, 649.
[3] D. J. Hill, M. J. Mio, R. B. Prince, T. S.
Hughes, J. S. Moore, Chem. Rev. 2001,
101, 3893 – 4011.
[4] For a review article on protein folding,
see: Acc. Chem. Res. 1998, 31, 697 – 773.
[5] A stabilization of such secondary structures is possible by using suitable templates or nonproteinogenic buildings
blocks such as b amino acids; for review
articles, see: a) J. S. Nowick, Acc. Chem.
Res. 1999, 32, 287 – 296; b) S. H. Gellman, Acc. Chem. Res. 1998, 31, 173 –
180; c) J. S. Nowick, E. M. Smith, M.
Pairish, Chem. Soc. Rev. 1996, 25, 401 –
415; d) J. P. Schneider, J. W. Kelly,
Chem. Rev. 1995, 95, 2169 – 2187.
[6] a) H. J. Schneider, A. Yatsimirsky, Principles and Methods in Supramolecular
Chemistry, Wiley, Chichester, 2000;
b) J. W. Steed, J. L. Atwood, Supramolecular Chemistry, Wiley, Chichester,
2000; c) J.-M. Lehn, Supramolecular
Chemistry; Concepts and Perspectives,
VCH, Weinheim, 1995; d) F. V?gtle,
Supramolecular Chemistry, Wiley, Chichester, 1991.
[7] W. Saenger, Principles of Nucleic Acid
Structure, Springer, New York, 1984.
[8] For reviews on older work, see: a) C.
Piguet, G. Bernardinelli, G. Hopfgartner, Chem. Rev. 1997, 97, 2005 – 2062;
b) A. E. Rowan, R. J. M. Nolte, Angew.
Chem. 1998, 110, 65 – 71; Angew. Chem.
Int. Ed. 1998, 37, 63 – 68; c) T. J. Katz,
Angew. Chem. 2000, 112, 1997 – 1999;
Angew. Chem. Int. Ed. 2000, 39, 1921 –
1923.
Figure 7. In supramolecular polymers of type 13, additional p–p interactions are responsible for
the formation of columnar stacks, which form a helix as a result of the chiral side chains.
www.angewandte.org
2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2451
Highlights
[9] a) S. Han, A. D. Bond, R. L. Disch, D.
Holmes, J. M. Schulmann, S. J. Teat,
K. P. C. Vollhardt, G. D. Whitener, Angew. Chem. 2002, 114, 3357 – 3361; Angew. Chem. Int. Ed. 2002, 41, 3223 –
3227; b) S. Han, D. R. Anderson, A. D.
Bond, H. V. Chu, R. L. Disch, D.
Holmes, J. M. Schulmann, S. J. Teat,
K. P. C. Vollhardt, G. D. Whitener, Angew. Chem. 2002, 114, 3361 – 3364; Angew. Chem. Int. Ed. 2002, 41, 3223 –
3230.
[10] B. Kiupel, C. Niederalt, M. Nieger, S.
Grimme, F. V?gtle; Angew. Chem. 1998,
110, 3206 – 3209; Angew. Chem. Int. Ed.
1998, 37, 3031 – 3034.
[11] B. Gong, H. Zeng, J. Zhu, L. Yua, Y.
Han, S. Cheng, M. Furukawa, R. D.
Parra, A. Y. Kovalevsky, J. L. Mills, E.
Skrzypczak-Jankun, S. Martinovic, R. D.
2452
[12]
[13]
[14]
[15]
[16]
2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Smith, C. Zheng, T. Szyperski, X. Zheng,
Proc. Natl. Acad. Sci. USA 2002, 99,
11 583 – 11 588.
a) G. A. Jeffrey, An Introduction to
Hydrogen Bonding, Oxford University
Press, New York, 1997; b) J. Israelachvili, Intermolecular and Surface Forces,
2nd ed., Academic Press, London, 1992.
D. J. Hill, J. S. Moore, Proc. Natl. Acad.
Sci. USA 2002, 99, 5053 – 5057.
a) V. Berl, I. Huc, R. G. Khoury, M. J.
Krische, J.-M. Lehn, Nature 2000, 407,
720 – 723; b) V. Berl, I. Huc, R. G.
Khoury, J.-M. Lehn, Chem. Eur. J.
2001, 7, 2798 – 2809.
V. Berl, I. Huc, R. G. Khoury, J.-M.
Lehn, Chem. Eur. J. 2001, 7, 2810 – 2820.
a) L. A. Cuccia, J.-M. Lehn, J.-C. Homo,
M. Schmutz, Angew. Chem. 2000, 112,
239 – 243; Angew. Chem. Int. Ed. 2000,
www.angewandte.org
38, 233 – 237; b) K. M. Gardinier, R. G.
Khoury, J.-M. Lehn, Chem. Eur. J. 2000,
6, 4124 – 4131.
[17] A. Petitjean, L. A. Cuccia, J.-M. Lehn,
H. Nierengarten, M. Schmutz, Angew.
Chem. 2002, 114, 1243 – 1246; Angew.
Chem. Int. Ed. 2002, 41, 1195 – 1198.
[18] For reviews, see: a) C. Schmuck, W.
Wienand, Angew. Chem. 2001, 113,
4493 – 4499; Angew. Chem. Int. Ed.
2001, 40, 4363 – 4369; b) D. C. Sherrington, K. A. Taskinen, Chem. Soc. Rev.
2001, 30, 83 – 93.
[19] a) L. Brunsveld, J. A. J. M. Vekemans,
J. H. K. K. Hirschberg, R. P. Sijbesma,
E. W. Meijer, Proc. Natl. Acad. Sci. USA
2002, 99, 4977 – 4982; b) R. P. Sijbesma,
E. W. Meijer, Chem. Commun. 2003, 5 –
16.
Angew. Chem. Int. Ed. 2003, 42, 2448 – 2452
Документ
Категория
Без категории
Просмотров
1
Размер файла
270 Кб
Теги
structure, molecular, helical, molecules, build, spiral, staircase
1/--страниц
Пожаловаться на содержимое документа