Inclusion of cavitands and calix[4]arenes into a metallobridged para-(1H-imidazo[4,5-f][3,8]phenanthrolin-2-yl)-expanded calix[4]arene

Article abstract of DOI:10.1002/anie.200603180

(Figure Presented) A hunter hunted! A highly preorganized, deep metallocavitand of nanoscale dimensions containing rhenium atoms at the four corners can be readily synthesized from a simple formyl-substituted calix[4]arene and 3,8-phenanthroquinone. Unsub

Full text of DOI:10.1002/anie.200603180

Communications
DOI: 10.1002/anie.200603180
Inclusion Complexes
Inclusion of Cavitands and Calix[4]arenes into a Metallobridged
para-(1H-Imidazo[4,5-f][3,8]phenanthrolin-2-yl)-Expanded
Calix[4]arene**
Enrique Botana, Eric Da Silva, Jordi Benet-Buchholz, Pablo Ballester, and Javier de Mendoza*
Since Cram and co-workers first introduced cavitands, namely
bridged resorcin[4]arene hosts whose structure is preorgan-
ized in the absence of a guest,[1] in 1982, many enforced
cavities based on bowl-shaped resorcinarenes have been
reported. The concave
their conical shapes.[7] We report herein the synthesis of the
deep calixarene 1 and its tetrarhenium complex 1·Re4—the
first example of a metallobridged cavitand—and its binding
properties towards cavitands and calix[4]arenes (Scheme 1).
shapes of these constructs
result from either covalent
bonding[2,3] or self-assembly
mediated by hydrogen
bonds,[4] ion pairing,[5] or
metal coordination.[6]
However,
cavitand
structures not based on
resorcinarenes but on the
related calixarenes instead
are as yet unknown. Unlike
resorcinarenes, calixarenes
are difficult to bridge at
the wider rim, although
they benefit from the possi-
bility of deepening the cav-
ities, through the attach-
ment of large, flat aromatic
surfaces at the p-phenol
positions, while keeping
Scheme 1. Structure of metallobridged cavitand 1·Re4 and of the previously described deep calix[4]arene 2.
TFA=trifluoroacetic acid.
We previously reported the synthesis of 2, an expanded
calix[4]arene bearing the wide, coplanar 1H-phenanthro[9,10-
[*] Dr. E. Botana, Dr. E. Da Silva, Dr. J. Benet-Buchholz, Prof. P. Ballester,
Prof. J. de Mendoza
d]imidazol-2-yl aromatic surface at the para positions of the
wider rim.[8] It was shown that the overall conical shape of 2
can be partially stabilized by ion-paired bridges between the
vicinal imidazole moieties (such as 2·TFA4), which prevent
full collapse of the cavity (Scheme 1).[8]
Institute of Chemical Research of Catalonia (ICIQ)
43007 Tarragona (Spain)
Fax: (+34)977-920-226
E-mail: jmendoza@iciq.es
Homepage: http://www.iciq.es
The use of a 3,8-phenanthroline instead of the phenan-
threne moiety locates the heteroatoms at the corners of a
square with the 908 angles required for bridging with metal
ions with a preference for square planar or octahedral
coordination.[9] We selected {Re(CO)3Br} as the metal bridges
since highly stable tetranuclear square boxes based on
porphyrins have been reported for this metal core.[10]
The expanded 3,8-phenanthrolinoimidazolylcalix[4]arene
(1) was obtained in 62% yield by reaction of tetra-O-octyl
para-formylcalix[4]arene (6)[11] with eight equivalents of 3,8-
phenanthroline-5,6-dione (5) in the presence of an excess of
ammonium acetate in refluxing acetic acid (Scheme 2).[8] The
hitherto unknown quinone 5 was obtained in moderate yield
by cyclization of bisimine 3 under strongly acidic conditions
followed by oxidation of the resulting 2,7-diazaphenanthrene
(4)[12] under similar conditions as those reported for 1,10-
Dr. E. Botana, Prof. J. de Mendoza
Department of Organic Chemistry
Universidad Autónoma de Madrid, 28049 Madrid (Spain)
Prof. P. Ballester
Institució Catalana de Recerca i Estudis Avançats (ICREA)
Pg. Lluís Companys 23, 08010 Barcelona (Spain)
[**] This work was supported by the MCYT (projects BQU2002-03536
and CTQ2005-08989-C02/BQU), the ICIQ Foundation, Generalitat
de Catalunya, DURSI (project 2005SGR00108), and Consolider
Ingenio 2010 (Grant CSD2006-0003). Contracts from the “Personal
TØcnico de Apoyo” (E.B.) and “Torres-Quevedo” (E.D.S.) programs
are gratefully acknowledged. We thank Prof. Enrico Dalcanale
(University of Parma, Italy) for helpful discussions and samples of
the cavitand guests, and Eduardo Escudero (ICIQ) for the crystal-
structure measurements.
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
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Chemie
ca. 2.8 Š). The remaining hydrogen
atoms of the bridging water molecules
contact the disordered atoms at the
lower apical positions of the rhenium
ligands (H···X distances ca. 2.5 Š).
Additionally, these apical atoms inter-
act with identical positions on neighbor-
ing molecules which are inverted in
orientation (X···X contact distances
ca. 3.5 Š). Overall, the cavity shows a
local C4 symmetry which is broken by a
slight deformation in the pyramid shape
by two concave and two convex oppo-
site faces. In the hydrophobic region,
the octyl chains display, as expected,
large atomical displacement parameters
(ADPs), although they could be clearly
localized in their positions (Figure 1).
Scheme 2. Synthesis of calixarene 1.
phenanthroline.[13] Finally, the metallobridged cavitand 1·Re4
was formed in 80% yield from reaction of 1 with four
equivalents of [Re(CO)5Br] in refluxing tetrahydrofuran
(THF). The neutral rhenium complex exchanges two equa-
torial CO ligands for two vicinal pyridine rings on the
phenanthrolinoimidazole subunits, with formation of a fac-
{Re(CO)3Br} bridge at each corner of the structure.
1
The H NMR spectrum of 1 (in CDCl3 containing 2%
CH3OH) showed broad signals, which likely arise from the
slow interconversion of flexible conformers and prototropic
tautomers. However, addition of a small amount of trifluoro-
acetic acid (TFA) to a suspension in [D3]MeCN resulted in
solubilization and a color change from yellow to red-orange.
1
The H NMR spectrum of the protonated ligand displayed
well-resolved, sharp signals corresponding to a structured
ligand conformation, probably caused by the formation of
ionic TFA bridges between protonated imidazole and/or
phenanthroline rings (see Supporting Information).
The metallocavitand 1·Re4 was fully characterized by ESI-
MS as well as IR and NMR spectroscopy. The IR spectrum
showed the characteristic strong CO absorption bands of fac-
tricarbonylrhenium(I) complexes (at 2027, 1930, and
1879cm À1).[14] The 1H NMR spectrum (either recorded in
CDCl3 or [D8]THF) gave two distinct sets of signals for the
aromatic protons which were attributable to the presence of
stereoisomers at the rhenium centers.[15,16] The signals were
unequivocally assigned by a full set of 2D NMR experiments
(COSY, NOESY, and ROESY). Interestingly, water mole-
cules were found to bridge the vicinal imidazole rings.[17]
The proposed coordination of Re by phenanthroline
heteroatoms in solution, as well as the bridging of the
imidazole rings by water molecules, was fully confirmed in the
solid state. In the crystal structure[18,19] the four rhenium
atoms were located at the corners of an almost perfect square
(diagonal distances 16.0 and 16.7 Š; sides ca. 11.56 Š each)
(Figure 1). The compound crystallizes as a mixture of
stereoisomers about the apical positions of the bromine
atoms attached to the rhenium atoms (up and down). This
results in a positional disorder of the apical groups in the
refined structure. The well-localized bridging water molecules
are hydrogen bonded to the imidazole rings (O···N distances
Figure 1. ORTEP plot (thermal ellipsoids shown at 50% probability
level) of 1·Re4. Nonrelevant hydrogen atoms and solvent molecules
have been omitted for clarity.
The deep metallocavitands pack in parallel 2D layers of
alternating stacked pyramids (average distance between rings
ca. 3.2 Š), with the octyl tails pointing into the interlayer
space, in a membranelike arrangement (Figure 2). The tails
interdigitate pairwise, leaving cavities between two molecules
that are oriented in a face-to-face arrangement with respect to
their wider rims and at a distance of about 10 Š. All the
available space in these cavities is filled with partially
disordered nitromethane molecules (not shown in Figure 2).
In total, 9different positions of solvent molecules could be
localized and refined to give a total occupancy of 4.5
nitromethane molecules for each cavitand.
Simple molecular modeling studies[20] suggest that the
highly preorganized basketlike 1·Re4 molecule endowed with
a nanosized, deep, square pyramidal cavity could be an almost
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Communications
For the favorable cases (7–9 and
12) the fact that the proton chemical
shifts of 1·Re4 remain invariable after
the addition of more than one equiv-
alent of guest points to 1:1 stoichio-
metries and to stability constants for
the complexes that are too high to be
measured accurately by 1H NMR
spectroscopy. Consequently, binding
affinities were established by lumi-
nescence spectroscopy. Addition of
the guest (0 to 4.5 ” 10À4 m) to a
solution of 1·Re4 in THF (1.0 ”
10À5 m) resulted in a detectable modi-
fication of the luminescence spectra
(lexc = 340 nm).[21] The association
constants were calculated from non-
linear curve fitting of the dependence
of the normalized luminescence
intensity on the guest concentration
by using a 1:1 binding model.[22] The
calculated Ka values (quoted under
each formula in Figure 3) fully agree
with the qualitative observations
derived from the 1H NMR spectra.
Figure 2. Structure model showing two different orientations of the molecular layers in the crystal packing of
1·Re4.
ideal receptor for the complexation of molecules of comple-
mentary shape and size, such as calix[4]arenes or cavitands,
provided no steric hindrance is present at their lower rims.
Accordingly, we explored the interaction of 1·Re4 with several
of these molecular structures by 1H NMR spectroscopy. Thus,
addition of one equivalent of calixarenes 7–9 or cavitand 12 to
a 3.2 mm solution of 1·Re4 in [D8]THF caused dramatic
changes in the line shape and chemical shift values of the
proton signals of both the free host and the guest (Table 1). In
contrast, addition of one equivalent of calixarenes 10 or 11,
endowed with O-propyl substituents at the lower rim, or of
the methyl-substituted cavitand 13 to the host solution did not
produce any observable change in the proton spectra.
Calixarene guests 7–9, which lack substituents at the lower
rim, are strongly complexed by 1·Re4, whereas those endowed
with four or just two propyl groups (10 and 11, respectively)
did not show any binding or were only weakly bound.
Cavitands behaved similarly: whereas the highly preorgan-
ized, sterically unhindered guest 12 showed the highest
binding constant, the isomeric 13, with methyl groups at the
lower rim, was not recognized by the host.
The above data are consistent with the fitting of the guest
inside the deep metallocavitand host, driven by face-to-face
stacking interactions between the electron-rich guest and the
Table 1: 1H NMR chemical shifts Dd (ppm, dcomplexÀdhost/guest) of the host
1·Re4 and the guest (7–9 and 12) protons upon formation of a 1:1
complex.[a,b]
7
8
9
12
Host[c]
NH
Hc
Guest
OH
Hmeta
R1
Heq
Hax
Harom
Hout
Hin
+0.17
À0.62
+0.20
À0.79
+0.20
À0.32
+0.18
À0.84
À3.58
À0.68
À3.20
À0.80
n.d.[d]
À0.35
À0.28 (Hpara
>À2.25
>À2.25
)
+0.02 (tBu) À0.21 (CHO) À0.13 (Me)
>À2.50
>À2.50
À0.60
À0.60
À1.86
À4.45 (R2)
À3.11
À0.64
À0.24
Figure 3. Association constants Ka (mÀ1) of guests 7–13 with 1·Re4 in
THF measured by luminiscence (lexc =340 nm, lemission range=475–
650 nm). n.d.: not determined (changes in the luminescence of the
host on binding were obscured by the luminiscence of the added
guest).
[a] 1:1 1·Re4:guest mixture in [D8]THF. [b] No significant changes were
observed for guests 10, 11, and 13. [c] Some signals are split because of
the presence of stereoisomers (See Supporting Information for details).
[d] Signal not detected.
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Angewandte
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supported by computer calculations (Figure 4)[20] and NMR
data: protons pointing inside the host were dramatically
shifted upfield (by more than 3 ppm for some of the inner
protons at the bridging positions, Table 1).
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[12] a) T. J. Schwan, N. J. Miles, J. Heterocycl. Chem. 1982, 19, 1351 –
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1107 – 1109.
Figure 4. Top and side views of the optimized model of complex 12@
1·Re4. Receptor 1·Re4 is displayed in stick representation with a
transparent van der Waals radii surface except for the front wall (side
view). The octyl tails have been replaced by methyl groups for clarity.
Cavitand 12 is shown with a van der Waals radii surface.
[13] N. Margiotta, V. Bertolasi, F. Capitelli, L. Maresca, A. A. G. G.
Moliterni, F. Vizza, G. Natile, Inorg. Chim. Acta 2004, 357, 149–
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[14] J. L. Smithback, J. B. Helms, E. Schutte, M. Woessner, B. P.
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[15] Up to six stereoisomers (oooo, oooi, ooii, oioi, iiio, and iiii; i =
inwards, o = outwards) can be predicted if it is assumed that the
bromine atom is always located in an apical position relative to
the plane containing the four metal centers.
[16] No such mixtures were reported for porphyrin squares, since the
stereoisomers averaged on the NMR time scale as a result of free
rotation of the pyridine ligands: R. V. Slone, J. T. Hupp, Inorg.
Chem. 1997, 36, 5422 – 5423.
[17] This was clearly seen in the NOESY spectrum (contacts between
the bulk water signal and the Ha and Hd cavitand signals).
[18] CCDC-618949 contains 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.
Intermolecular NOE contacts observed between protons
Hb and Hc of the host and protons Hmeta and Hpara of guest 7, or
R1 (Me) protons of 12, also support the proposed geometry of
the complex (see Scheme 1 and Figure 3 for proton assign-
ment). Finally, the 7@1·Re4 inclusion complex was stable
enough to be detected by ESI-MS.
In summary, we have shown that a highly preorganized
metallocavitand 1·Re4 of nanoscopic dimensions can be
readily synthesized from a simple formyl-substituted calix[4]-
arene and 3,8-phenanthroquinone. Unsubstituted calix[4]ar-
enes and cavitands without substituents on the lower rim are
ideal guests for such a structure. Thus, for the first time, a
calixarene host becomes the guest. We are currently studying
an O-unsubstituted derivative of 1·Re4 that could self-
assemble into a continuous pile of bowl molecules. Also, the
use of the deep cavity of 1·Re4 for recognition and catalysis
studies is under active investigation.
[19] Single crystals were grown by slow evaporation of a CHCl3/
MeNO2 solution at RT. Data for 1·Re4 at 100 K:
C
129H135Br4N21O30Re4, 3524.02 gmolÀ1
¯
, triclinic, space group
Received: August 4, 2006
Published online: October 18, 2006
P1, a = 16.1122(19) Š, b = 23.443(3) Š, c = 23.654(3) Š, a =
113.546(3), b = 90.258(3), g = 99.928(3)8, V= 8041.1(16) Š3,
Z = 2, 1calcd = 1.455 MgmÀ3, R1 = 0.1256 (0.2172), wR2 = 0.3259
(0.3960), for 20154 reflections with I > 2s(I) (for 40618 reflec-
tions (Rint: 0.0966) with a measured total number of 100297
Keywords: calixarenes · cavitands · N ligands · rhenium ·
.
supramolecular chemistry
reflections), GOF on F2 = 1.045, largest diff. peak (hole) = 6.628
À3
(À3.193) eŠ
.
[20] CAChe WorkSystem Version 6.1.12.33. Fujitsu Limited.
[21] The deep calixarene 1 and the metallocavitand 1·Re4 are
luminescent, as are the formyl-substituted calixarenes 9 and
10, whereas the remaining calixarene and cavitand guests are
not. Addition of increasing amounts of guest to a solution of
1·Re4, keeping its concentration constant, caused an increase in
the intensity in the band at 550 nm.
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[22] SPECFIT, version 3.0.36, Spectrum Software Associates.
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