Double-decked molecular crescents

Article abstract of DOI:10.1039/c0cc02465a

Molecules with a defined crescent shape have been generated from the folding or covalent locking of curved structural components connected together via multiple covalent tethers.

Full text of DOI:10.1039/c0cc02465a

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Double-decked molecular crescentsw
Li Lin,ab Jiaxin Zhang,ab Xiangxiang Wu,ab Guoxing Liang,ab Lan He*ab and Bing Gong*abc
Received 9th July 2010, Accepted 7th August 2010
DOI: 10.1039/c0cc02465a
Molecules with a defined crescent shape have been generated
from the folding or covalent locking of curved structural
components connected together via multiple covalent tethers.
Structures with well-defined conformations or shapes are
attracting wide attention in diverse fields because of their
unique features such as the presentation of functional groups
at specific location and with defined orientation, the creation
of edges and surfaces of different curvatures, and the formation
Scheme 1
of partially or fully enclosed cavities of tunable sizes and
properties.1 Besides, molecules with defined shapes also provide
building blocks for constructing larger architectures.2 For
PE segments connected via the maximum possible number of
both natural3 and designed4 systems, shape-defined structures
disulfide-containing linkers.
can be regarded as the result of restricted relative motion
Thus, compound 1a, 1b, or 1c was mixed with iodine
among structural components that associate via multipoint
(1 equiv.) in CH2Cl2 at room temperature.w After stirring for
interactions.5 Although defined arrangements of structural
4 hours, the reaction mixture was quenched with 10% aqueous
units via multipoint association are commonplace in Nature,
sodium thiosulfate and was washed with brine followed by the
the design of molecular structures and supramolecular
removal of solvent. In each case, examining the remaining
assemblies with similar controllability remains challenging.
solid residue by MALDI revealed a dominant species with a
Most known systems resulted from restricting the relative
mass corresponding to that of 2a, 2b, or 2c (Scheme 1).
motion between structural units, from the folding of
After being purified using column chromatography, products
biomacromolecules,6 and unnatural oligomers,7 to the formation
2a–c gave satisfactory analytical results.w
Each of compounds 2a–c consists of two curved PE
of supramolecular assemblies,8,9 relies on the presence of
multiple noncovalent interactions. Another strategy for
segments that are covalently tied together. The covalent
controlling the arrangement and orientation of structural units
tethers, consisting of disulfide and ethylene segments, should
involves the introduction of multiple covalent linkages that
render 2a–c sufficient, yet limited flexibility with interesting
hinder rotational and translational motions. We report herein
conformational implications. For example, like their fully
folded or covalently locked, double-decked molecular
rigidified, shape-persistent counterparts, these readily formed
crescents formed from the superposition of structural units
macrocycles may adopt an overall flat conformation that
enforced by covalent linkers.
contains an internal void enclosed by the two covalently linked
Building blocks represented by a general structure 1 were
crescent PE segments. Another possibility is that the two PE
designed. The tris(phenylene ethynylene) (PE) core of 1 consists
segments may interact intramolecularly, which, along with the
of a central meta-linked benzene ring flanked by two para-
flexible disulfide-containing linkers of these macrocycles,
linked residues, which results in a curved shape that is not
would lead to collapsed conformations devoid of any
compromised by the internal rotation of the PE unit.
internal voids.
Compounds 1a–c that share this PE core were first designed
Efforts were first made to grow single crystals suitable for
and prepared.w With their S-trityl groups, these compounds
analysis by X-ray crystallography. Single crystals of 2a were
will undergo reversible disulfide bond formation,10 leading to
obtained from CHCl3/CH3OH (10/1, v/v) by slow evaporation of
thermodynamically favorable products consisting of curved
solvent at room temperature.z In the solid state, compound 2a
adopts a folded conformation in which the two PE moieties are
a College of Chemistry, Beijing Normal University, Beijing 100875,
China
b State Key Laboratory of Applied Organic Chemistry, Lanzhou
University, Lanzhou 730000, China.
E-mail: helan1961@yahoo.com.cn; Tel: +86 10 5880 2076
c Department of Chemistry, University at Buffalo, State University of
New York, Buffalo, NY 14260, USA. E-mail: bgong@buffalo.edu;
Fax: +1 716 645 6963; Tel: +1 716 645 4307
w Electronic supplementary information (ESI) available: Synthetic
procedures; analytical data; NMR spectra; mass spectra. CCDC
784328–784329. For ESI and crystallographic data in CIF or other
electronic format see DOI: 10.1039/c0cc02465a
Fig. 1 The side and top views of the X-ray structure of 2a.
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parallel to each other, with an interplanar distance of about 3.5 A
that is typical of pꢁp stacking interaction (Fig. 1, left).
The covalently tied PE units stack on top of each other in a
nearly superposed way, with their concave and convex edges
being on the same side. As a result, the curved shape of the PE
units is translated into a double-decked crescent conformation
that is devoid of any internal cavity (Fig. 1, right).
with the shifts of protons 1 and 2 being the largest. The overall
upfield shifts of the aromatic protons of 2c were larger than
those of the corresponding protons of 2b, suggesting that the
amide groups of 2c helped enhance the stacking between the
PE segments, which probably led to a folded structure that is
more compact and thus more stable than those of 2a and 2b.
1H NMR spectra of 1c (from 0.02 mM to 20 mM) or 2c
(from 0.01 mM to 10 mM) recorded in CDCl3 revealed
insignificant change in the chemical shifts of the proton
signals,w indicating that the intermolecular aggregation of 1c
or 2c was insignificant within the concentration range
examined.
The folded conformation revealed by the crystal structure of
2a is the result of the interplay of the two covalent linkers and
the stacking interaction between the two PE segments. The
two covalent tethers serve to register the para-linked benzene
residues and at the same time, limit the degree of relative
rotational motion between the two PE segments. To engage in
stacking interaction, the doubly tethered PE segments of 2a
have no choice but to adopt a nearly superposed geometry, an
arrangement that is usually shunned by aromatic hydro-
carbons engaging in intermolecular stacking interaction due
to pꢁp electron repulsion.2
Thus, the folding of 2a–c results in double-decked crescents
because of the confinement imposed by their dual covalent
tethers and the noncovalent interaction between their PE
segments. Introducing additional covalent tethers should
further reduce the relative motion of the PE segments, leading
to a structure with further reduced conformational freedom.
Compound 1d was designed and prepared to test this possibility.
With each of its benzene residues carrying a side chain with a
terminal S-trityl group, compound 1d, upon treating with
iodine, was expected to form a product consisting of two PE
segments joined together via three disulfide-containing
covalent tethers. Indeed, examining the crude product from
the reaction of 1d and iodine using MALDI revealed a
dominant peak corresponding to the mass of a molecule
consisting of two triply tethered PE segments (Scheme 2).
In CDCl3, the 1H NMR signals of protons 1, 2, 3, and 4 of
2d (1 mM) showed significant upfield shifts of 0.25, 0.28, 0.19,
and 0.14 ppm, as compared to the corresponding protons of 1d
(2 mM), suggesting that the covalently tied PE units of 2d were
indeed undergoing stacking interaction. The upfield shifts
observed for 2d lie between those for 2b and 2c, which is
probably a reflection of the partial incompatibility between the
length of the covalent tethers and the optimum interplanar
distance needed for the pꢁp stacking interaction.
If the folded conformation of 2a also persists in solution,
1
compared to those of 1a or 1b, the H NMR signals of the
aromatic protons of 2a or 2b should show an upfield shift to
smaller d values due to the stacking of the two curved PE
segments.11 Such an expectation was confirmed by comparing
the 1H NMR spectra of 1b (2 mM) and 2b (1 mM) recorded in
CDCl3. Protons 1, 2, 3, and 4 of 2b exhibited noticeable upfield
shifts of 0.19, 0.23, 0.13 and 0.11 ppm, as compared to the
corresponding protons of 1b (see Scheme 1 for assignments of
protons).w The largest shifts were observed for protons 1 and 2
on the two central (meta-linked) benzene residues of 2b. If 2b
adopted an unfolded conformation in which these meta-linked
benzene residues were disposed in a transannular relationship,
the shifts of protons 1 and 2 should not be prominent.
Therefore, the observed upfield shifts, particularly those of
protons 1 and 2, are consistent with the two meta-linked
benzene residues being brought into close proximity when 2b
folds into a conformation similar to the one revealed by the
X-ray structure of 2a. The 1H NMR spectra of 1b and 2b
recorded at both high (40 mM and 20 mM, respectively) and
low (0.02 mM and 0.01 mM, respectively) concentrations in
CDCl3 revealed little change in the chemical shifts of all
proton signals.w The observed concentration-independence
of the 1H NMR signals indicated that the intermolecular
stacking was negligible under the conditions of the NMR
experiments.
The most likely conformation for the two curved PE
segments of 2d to stack is shown in Scheme 2, in which the
registration of the same type of benzene residues leads to a
covalently locked crescent. Aligning the two PE segments of 2d
in other geometry would be unfavorable because this would
Examining 2c using 1H NMR in CDCl3 provided additional
evidence that supports the above model as well as shows the
tunability of this system. Compound 2c carries two secondary
amide groups capable of engaging in hydrogen-bonding inter-
action. In a conformation similar to those of 2a and 2b, the
two amide groups of 2c should be brought into close proximity
and engage in favorable intramolecular H-bonding interac-
tion. The strength and directionality of H-bonding should
reinforce the alignment and stacking of the two PE segments.
In agreement with such an expectation, the signal of the amide
protons of 2c (1 mM) showed a large downfield shift of
0.83 ppm compared to that of the amide proton of 1c (2 mM).
As compared to the corresponding protons of compound 1c,
the aromatic protons 1, 2, 3, and 4 of 2c exhibited significant
upfield shifts of 0.32, 0.22, 0.21, and 0.24 ppm, respectively,w
Scheme 2
Fig. 2 The side and top views of the X-ray structure of 2d.
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not allow the formation of all three covalent tethers. Such a
prediction was confirmed by the solid-state structure of 2d.
Single crystals of 2d were obtained from a mixed solvent
containing DMF, CHCl3, and C2H5OC2H5 (1/1/4, v/v/v) by
slow evaporation of solvents at room temperature. The
solid-state structure of 2d (Fig. 2) reveals a double-decked
crescent in which the same type of benzene residues from two
PE segments are registered via the disulfide-containing tethers.
In the crystal structure of 2d, the two meta-linked benzene
residues sit on top of each other, in a face-to-face stacked
geometry and with an inter-planar distance of B3.6 A.
The para-linked residues from the two PE segments are
brought into close proximity but do not adopt a parallel-
stacked geometry. Instead, a roughly edge-to-face stacking
configuration commonly observed for aromatic interactions
was associated with the para-linked residues of 2d.
Notes and references
z Crystal data for 2a: C68H60O16S4, M = 1261.40, orthorhombic,
space group Pbcn, a = 16.300(3), b = 24.855(5), c = 15.010(3) A,
b = 901, V = 6081(2) A3, Z = 4, T = 173(2) K, m(Mo-Ka) = 0.228
mmꢁ1, 10 154 reflections measured (5370 unique, Rint = 0.0496).
R1[I
4 2s(I)] = 0.0751, wR2 =
0.1744 (F2, all data). 2d:
C62H46O12S6ꢂC2H5OC2H5, M = 1249.47, monoclinic, space group
P21/c, a = 7.6656(15), b = 27.416(6), c = 29.336(6) A, b = 92.51(3)1,
V = 6159(2) A3, Z = 4, T = 173(2) K, m(Mo-Ka) = 2.581 mmꢁ1
,
= 0.0703).
43 226 reflections measured (11 099 unique, Rint
R1[I 4 2s(I)] = 0.0765, wR2 = 0.2178 (F2, all data).
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This work was supported by the Changjiang Scholar
Program and the Cultivation Fund of the Key Scientific and
Technical Innovation Project, Ministry of Education of China
Grant 706009 (to BG), the NSFC Grant 20772012, RFDP
Grant 20070027038 and KNDCDP Grant 2009ZX09502-008
(to LH), and the US National Science Foundation Grant
CHE-0314577 (to BG), the Beijing Municipal Commission
of Education, and the Scientific Research Foundation of
Beijing Normal University (2009SC-1).
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