A flexible dibenzo-O4S2-macrocycle: twist-and-squeeze type metal binding via synergic action of metal-ligand and metal-π interactions

Article abstract of DOI:10.1016/j.tetlet.2007.09.157

A 21-membered O₄S₂-donor-macrocycle (L) incorporating a dibenzo-subunit was synthesized. From the reaction of L with AgPF₆, an endo-type 1:1 complex [AgL]PF₆ (1) was obtained. On complexation, the conformation o

Full text of DOI:10.1016/j.tetlet.2007.09.157

Available online at www.sciencedirect.com
Tetrahedron Letters 48 (2007) 8464–8467
A flexible dibenzo-O S -macrocycle: twist-and-squeeze
4
2
type metal binding via synergic action of metal–ligand
and metal–p interactions
Hyun Jee Kim, Il Yoon, So Young Lee, Joobeom Seo and Shim Sung Lee*
Department of Chemistry (BK21) and Research Institute of Natural Science, Gyeongsang National University,
Jinju 660-701, South Korea
Received 31 August 2007; revised 20 September 2007; accepted 27 September 2007
Available online 29 September 2007
Abstract—A 21-membered O
4
S
2
-donor-macrocycle (L) incorporating a dibenzo-subunit was synthesized. From the reaction of L
(1) was obtained. On complexation, the conformation of L changes dramatically
with AgPF , an endo-type 1:1 complex [AgL]PF
6
6
due to metal–ligand coordination as well as p-interactions between the metal and the dibenzo-subunit from L. This unique change in
configuration showing a twist-and-squeeze type process illustrates how large flexible ligands stabilize complexes through
conformational changes.
Ó 2007 Elsevier Ltd. All rights reserved.
Biological receptor molecules have structures that are
far from rigid, and thus, the folding or twisting of the
complexation that binds guests less strongly due to the
flexible nature of the host (entropy penalty) is ideal as,
for example, sensors and carriers in the event that
reaction sequences such as ‘bind-detect’ or ‘transport-
1
receptor upon itself has become of increasing interest.
2
3
As examples, valinomycin and nonactin, natural selec-
+
7
tive ionophores for K , are able to fold in upon them-
release’ are needed. Hydrogen-bonding, p–p stacking,
8
,9
selves to produce an approximately octahedral array.
In the area of artificial receptor systems, the conforma-
tions of crown-type macrocyclic compounds adjust their
conformations as required for optimum binding of cat-
and cation–p interaction are important interactions
that stabilize the resulting metallosupramolecules
including macrocyclic complexes. These stabilizing
forces also affect the transport properties of the related
complexes with respect to solvent extraction and
4
ions of various sizes.
7
membrane transport. Thus, the structure of a flexible
Macrocyclic complexes fall into three categories based
on the positioning of the metal cation relative to the do-
nor atoms in the cavity of macrocycle. The first category
includes the complexes in which the cation fits properly
in the cavity of macrocycle. In the second category, the
cation is too large to fit into the cavity, and therefore,
lies above the cavity of macrocycle. In the last category,
the cavity of macrocycle is larger than the cation and
usually no solid complex is isolated due to the low reac-
tivity. Very rarely, however, the large macrocycle wraps
macrocycle with such multiple contacts (or interactions)
holds great potential for the development of receptors or
ionophores in transport systems.
It is difficult to predict the real structure of macrocyclic
complexes with multiple contacts. In fact, the larger
dibenzo-30-crown-10 offers a bent conformation accom-
+
modating K ion in a three dimensional configuration
which is quite different from smaller macrocycle ana-
5
logs. Some calixarene derivatives form stable complexes
5
6
10
around the cation or encloses two cations in the cavity.
with metal ions through multiple contacts. Apart from
In few cases in which one cation is in the center of the
cavity, the host macrocycle becomes somewhat distorted
to accommodate the small cation. In fact, this kind of
the oxygen-bearing crown-type macrocycles, thia- or
thiaoxa-macrocycles frequently show stable products
1
1
with soft metal ions. We therefore focused our atten-
tion on stabilization of the thiaoxa-macrocyclic com-
plexes by multiple contacts. With such considerations
in mind, we explored the possibility of generating soft
metal coordination products with multiple contacts
*
Corresponding author. Tel.: +82 55 751 6021; fax: +82 55 753
614; e-mail: sslee@gnu.ac.kr
7
0040-4039/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.09.157

H. J. Kim et al. / Tetrahedron Letters 48 (2007) 8464–8467
8465
through the modification of the crown units. Our
approach involved the attachment of aromatic groups
and S/O mixed donors into the large macrocyclic unit.
Herein, we present the synthesis and structural charac-
terization of the flexible dibenzo-O S -macrocycle L
O3–C–C–O4 70.0(3), and S2–C–C–O4 179.9(2)°]. Two
sulfur donors tend to be as far apart as possible
˚
(S1ꢀ ꢀ ꢀS2 9.474 A), forcing the shape of the ring cavity
into an ellipsoid.
4
2
and its complex, highlighting the unusual behavior of
the ligand in stabilizing the complex.
Complex 1 crystallized in a 1:1 complex of formula
[AgL]PF (Fig. 2). A colorless precipitate was obtained
6
1
5
from L and AgPF6 in dichloromethane/methanol.
L was synthesized in a four-step reaction (Scheme 1).
Dialdehyde 2 was obtained by the reaction of salicylal-
dehyde with dibromopropane. The reduction of 2 with
sodium borohydride afforded dialcohol 3. Chlorination
of 3 with thionyl chloride yielded dichloride precursor
Single-crystals of 1 suitable for X-ray analysis were
obtained by slow evaporation. Ag atom in 1 is in the
cavity forming an endo-dentate environment. Upon
silver(I) binding, L undergoes considerable conforma-
tional interconversional rearrangement. It is noteworthy
that a conformational change in a 21-membered ring is
achieved mainly by altering a single torsion angle
around S2–C–C–O4, changing from anti- [179.9(2)°] to
gauche-form [61.1(2)°]. In other words, the fragmental
interconversion followed by twisting of the ring
rendered the sulfur donors pointing inward and, conse-
quently, all donors become a part of the complexation.
The Ag atom is four-coordinated with the S O donor
1
2
4
.
L was obtained by coupling reaction for macro-
0
cyclization from dichloride
4
and 2,2 -(ethylene-
dioxy)diethanthiol in the presence of Cs CO under
2
3
1
3
high dilution condition in reasonable yield (47%).
1
13
The H and C NMR spectra together with elemental
analysis and mass spectral data were clearly in agree-
ment with the proposed structure.
2
2
The structure of L was also characterized in the solid
state by single-crystal X-ray crystallography (Fig. 1).
Crystals of L were obtained by slow evaporation from
the solution of methanol. Without exception, oxygen
atoms are oriented in an endo-dentate fashion, while
set, in which each donor is located at the four corners
of the least-square plane within 0.13 A deviation. The
˚
S–Ag–S bite angle [147.2(3)°] is considerably large due
˚
to the additional interactions of Agꢀ ꢀ ꢀO1 [3.370(2) A]
˚
and Agꢀ ꢀ ꢀO2 [3.389(2) A]. Interestingly, 1 adopts a
1
1f–j,14
sulfur atoms are positioned exo-dentate.
Two
three-dimensional conformation because of the highly
twisted structure that L adopts upon complexation. By
comparing the dihedral angles between two aromatic
rings in free L [12.8(1)°] and in its silver(I) complex 1
[73.2(1)°], we observe what resembles a twist-and-
squeeze conformation. In fact, inspection of the folded
structure of 1 reveals the additional interactions between
the silver atom and the aromatic p-system [Agꢀ ꢀ ꢀC4
aromatic rings and ether linkage O1–C–C–C–O2 are
unfolded forming a dihedral angle of 12.83°. Mean-
while, the other aliphatic segment S1–C–C–O3–C–C–
O4–C–C–S2 is slightly bent due to its flexible nature
and torsion angles between donor atoms show a
gauche–gauche–anti arrangement [S1–C–C–O3 70.9(2),
3
.166(3), Agꢀ ꢀ ꢀC9 3.127(3), Agꢀ ꢀ ꢀC18 3.251(3), and
˚
Agꢀ ꢀ ꢀC23 3.254(3) A]. Each silver to carbon interaction
is at the short end of the range of literature values for
˚
9
the silver–p interaction (3.1–3.7 A). It is conceivable
that a combination of silver(I) coordination with the
2
S O donor set and the pair g -type p-interactions would
2
2
lead to the unique molecular folding that occurs upon
complexation with the flexible ligand L. With respect
to anion coordination ability, the preferred 3D structure
ꢁ
of 1 is also due to the weak affinity of PF6 ion toward
the silver(I) center, allowing the approach of the dibenzo
group to form the twist-and-squeeze structure. The affin-
ity of silver(I) toward L in 1:1 ratio was also observed by
Scheme 1. Synthesis of L.
+
ESI-mass measurement: [AgL] (m/z 541.9). Recently,
we were able to elucidate and visualize the stabilization
of the disilver(I) complex of calix[4]-bis-thiacrown by
the chopsticks-type p-coordination process by compar-
ing the dihedral angles of two opposite aromatic rings
1
0g
of 1,3-alternate calix[4] units upon complexation. To
the best of our knowledge, 1:1 endo-type complexes of
large mixed-donor macrocycles, in which the ligand is
distorted in a similar manner, have not been reported.
For comparison with this in solution, NMR titration
was carried out for the parallel system in CD CN
3
(
Fig. 3). The signals of the six methylene (H1 ) and
ꢁ6
the aromatic (Ha–d) protons in L were well resolved
and identified. The titration curves [plotting Dd (ppm)
vs added equivalents of silver(I)] for each proton clearly
Figure 1. Crystal structure of L; (a) front view (ORTEP drawing) and
(b) side view (stick drawing).

8466
H. J. Kim et al. / Tetrahedron Letters 48 (2007) 8464–8467
6
Figure 2. Crystal structures of L (left, ORTEP drawing) and its silver(I) complex 1, [AgL]PF (right, ball-stick drawing); noncoordinating anions are
˚
omitted for clarity. Selected bond lengths [A] and angles [°]: Ag–S1 2.478(1), Ag–S2 2.468(1), S2–Ag–S1 147.2(3), Ag–O3 2.606(2), Ag–O4 2.661(2),
O1–Ag–O2 58.7(1), S1–Ag–O3 75.1(1), S2–Ag–O4 74.4(1).
+
show an inflection point at mole ratio (Ag /L) of 1.0,
indicating the stoichiometry for the formation of the
complex is 1:1 in solution, which is the same as that of
the solid state. However, the titration curves were very
sharp, and consequently, the stability constant was too
1
6
high to be calculated using the EQNMR least-square
nonlinear fitting procedure. The order of magnitude of
the chemical shift variation for the aliphatic region is
H4 (Dd: 0.337 ppm) ꢂ H
(0.105 ppm) > H3, H6
2
(
0.072–0.076 ppm) > H (0.040 ppm) > H (0.026 ppm).
5
1
Upon complexation, silver(I) causes a much larger
downfield shift for the H peak than for those of H ,
4
1
H , H , and H . Thus, silver(I) appears to be more
2
5
6
strongly coordinated by S donors, while the O donors
interact with the silver(I) relatively weakly, once again
as in the solid state. For almost all of the aromatic
proton signals, the silver(I)-induced shifts (Dd: 0.009–
0
.084 ppm) and 1:1 break point were also observed
due to the Ag–p interactions. Notably, all the NMR
data in Figure 3 agree with the binding mode in the solid
state, suggesting that structure 1 is also retained in
solution.
In summary, we have described the synthesis of a
2
1-membered dibenzo-O S macrocycle with a flexible
4 2
nature. We have determined the structural characteris-
tics of its silver(I) complexation in both the solid and
solution states. These results clearly indicate that a
synergic cooperation of multiple contacts results in a
flexible macrocycle with the highly organized structure.
Thus, the conformational flexibility and aromatic sub-
units of larger macrocyles offer another potential design
tool for engineering new receptors with preprogrammed
properties.
Supplementary crystallographic data associated to L
and 1 have been deposited at the Cambridge Crystallo-
graphic Data Centre, CCDC Nos. 645648 and 645645.
Copies of the data can be obtained free of charge on
application to CCDC, 12 Union road, Cambridge CB2
1
1
EZ, UK (fax: +44 1223 336 033; e-mail: deposit@ccdc.
Figure 3. (a) Aliphatic region of H NMR spectra of L by stepwise
1
addition of AgPF
AgPF in CD CN.
6
and (b) the H NMR titration curves for L with
cam.ac.uk), or electronically via www.ccdc.cam.ac.uk/
data_request/cif.
6
3

H. J. Kim et al. / Tetrahedron Letters 48 (2007) 8464–8467
8467
Acknowledgment
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This work was supported by a Korea Research Founda-
tion (2006-311-C00364).
8, 1641; (g) Seo, J.; Song, M. R.; Lee, J.-E.; Lee, S. Y.;
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1
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were dissolved in DMF (1000 mL) in a 3-L round-bottom
0
flask. 2,2 -(Ethylenedioxy)diethanthiol (2.23 g, 12.3 mmol)
0
and 2,2 -(propyleneoxy)bis(benzyl chloride) (4.0 g,
1
2.3 mmol) were dissolved in DMF (30 mL) and this
6
solution was added to a 50-mL glass syringe. Under a
nitrogen atmosphere, the contents of the syringe was
ꢁ
1
added dropwise (a rate of 0.6 mL h ) into a DMF
solution of Cs CO at 45–50 °C for 50 h. The reaction
2
3
mixture was kept for a further 10 h with rapid stirring,
allowed to cool to room temperature, then filtered. The
filtrate was evaporated and the residue was partitioned
between water and dichloromethane. The aqueous phase
was separated and extracted with two further portions of
dichloromethane. The combined organic phases were
dried with anhydrous sodium sulfate and then evaporated
to dryness. Flash column chromatography on silica gel
using 10% ethyl acetate/n-hexane as the eluent led to the
isolation of L as a colorless crystalline product in 47%
yield. Mp 67–70 °C. C H O S (434.61): Anal. Calcd: C,
1
1801; (d) Habata, Y.; Seo, J.; Otawa, S.; Osaka, F.;
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Kuroda-Sowa, T.; Maekawa, M.; Suenaga, Y.; Maeno, N.
1
2
3
30
4 2
6
3.56; H, 6.96; S, 14.76. Found: C, 63.72; H, 7.10; S, 14.64.
J. Am. Chem. Soc. 1999, 121, 4968.
IR (KBr) 2861, 1607, 1496, 1460, 1243, 1123, 1104, 1047,
ꢁ
1 1
1
0. (a) Ungaro, R.; Casnati, A.; Ugozzoli, F.; Pochini, A.;
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1
6
3
014, 755 cm . H NMR (300 MHz, CDCl ): d = 7.34–
3
.87 (m, 8H, Ar), 4.23 (t, 4H, OCH ), 3.83 (s, 4H, ArCH ),
2
2
.53 (t, 4H, SCH
CH
C NMR (75 MHz, CDCl
2
CH
2
O), 3.48 (s, 4H, OCH
2
CH
CH
) 156.46, 130.65, 128.27,
2
O), 2.64
2
O) ppm.
(
t, 4H, SCH
2
2
O), 2.39 (m, 2H, OCH
2
CH
2
1
3
3
1
2
27.54, 120.95, 111.35, 71.08, 70.37, 64.99, 30.99, 30.30,
9.37 ppm. ESI-MS m/z 435.7 (MH ).
+
(
1
9
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1
1
1
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1
1
09, 4328.
5. Complex 1: Mp (decomp.) >225 °C. [AgL]PF : Anal.
6
1
1. (a) Janzen, D. E.; Mehne, L. F.; VanDerveer, D. G.;
Grant, G. J. Inorg. Chem. 2005, 44, 8182; (b) Vetrichelvan,
M.; Lai, Y.-H.; Mok, K. F. Eur. J. Inorg. Chem. 2004,
Calcd: C, 40.18; H, 4.40; S, 9.33. Found: C, 40.27; H, 4.67;
S, 9.40. IR (KBr) 2877, 1597, 1496, 1471, 1455, 1294, 1243,
ꢁ
ꢁ
1
1
112, 992, 842 ðPF Þ, 755, 559 cm . ESI-MS m/z 541.9
6
+
2
086; (c) Contu, F.; Dermartin, F.; Devillanova, F. A.;
Garau, A.; Isaia, F.; Lippolis, V.; Salis, A.; Verani, G. J.
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[AgL] .
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