New scaffolds for supramolecular chemistry: Upper-rim fully tethered 5-methyleneureido-5′-methyl-2,2′-bipyridyl cyclodextrins

Article abstract of DOI:10.1002/1521-3765(20020603)8:11<2438::AID-CHEM2438>3.0.CO;2-A

Seven upper-rim fully tethered cyclodextrins (URFT-CDs) have been synthesised in a good average coupling yield using the one-step "phosphine imide" approach and their metal complexation behaviour with lanthanides and transition metals was explored. We observed that the A-TE-E light conversion process (antennae effect) occurs in the URFT-CD lanthanide complexes. A molecular redox switch based on the corresponding iron complexes is also reported. A reversible intramolecular translocation of the Fe^II and Fe^III ions, between two distinct binding cavities has been monitored spectroscopically and achieved by chemical triggering. Finally, a negative allosteric control of ion recognition through the formation of a CD pseudocryptand is discussed.

Full text of DOI:10.1002/1521-3765(20020603)8:11<2438::AID-CHEM2438>3.0.CO;2-A

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FULL PAPER
New Scaffolds for Supramolecular Chemistry: Upper-Rim Fully Tethered
5-Methyleneureido-5'-methyl-2,2'-bipyridyl Cyclodextrins
Romain Heck, Florence Dumarcay, and Alain Marsura*[a]
Abstract: Seven upper-rim fully tethered cyclodextrins (URFT-CDs) have been
synthesised in a good average coupling yield using the one-step ™phosphine imide∫
approach and their metal complexation behaviour with lanthanides and transition
metals was explored. We observed that the A-TE-E light conversion process
(antennae effect) occurs in the URFT-CD lanthanide complexes. A molecular redox
Keywords: allosterism ¥ 2,2'-bipyri-
dine
¥ cyclodextrins ¥ molecular
switch based on the corresponding iron complexes is also reported. A reversible
intramolecular translocation of the FeII and FeIII ions, between two distinct binding
cavities has been monitored spectroscopically and achieved by chemical triggering.
Finally, a negative allosteric control of ion recognition through the formation of a CD
pseudocryptand is discussed.
devices ¥ molecular switches
Introduction
Results and Discussion
Cyclodextrins (CDs), a class of oligosaccharides with six,
seven or eight d-glucose units linked by a-1,4-glycosidic
bonds, are well known to accommodate various guest
molecules into their hydrophobic cavity in aqueous solution.[1]
The natural cyclodextrins are themselves of great interest as
molecular hosts, but much of their utility in supramolecular
chemistry is derived from their structural modification. From
another point of view, natural CDs may be viewed as
molecular scaffolds on which functional groups and other
substituents of increasing sophistication can be assembled
with controlled geometry. Thus, metallocyclodextrins, rotax-
anes, catenanes or surface monolayers of these modified
cyclodextrins are now accessible.[2] Here, metallocyclodex-
trins are considered as coordination compounds or metal
complexes in which the modified CD acts as a ligand platform.
The majority of metallocyclodextrins are formed from
functionalised CDs which incorporate one or more metal
ion coordinating groups of varying degrees of complexity.[3] In
the following discussion, some of these CDs are presented
along with their more interesting properties.
The new devices introduced here are based on upper-rim bis-
heterocyclic (2,2'-bipyridyl) fully functionalised CDs, which
accommodate one single or two different metal ions in their
internal ™hard∫ binding cavity and external ™soft∫ binding
cavity, leading to lanthanide and transition metal complexes
(Figure 1).
The present work describes these molecular devices with
respect to the nature of the complexing ions involved.
CH3
CH3
CH3
CH3
CH3
CH3
N
CH3
N
N
N
N
N
N
"Soft" binding cavity
N
N
N
N
N
N
HN
HN
NH
O
HN
NH
O
O
O
HN
HN
HN
NH
"Hard" binding cavity
Hydrophobic cavity
NH
NH
O
O
N
O
NH
[OH]14
[a] Prof. A. Marsura, R. Heck, F. Dumarcay
¬
Unite Mixte de Recherches CNRS
= "Soft" and "borderline" metals: Cu2+, Co2+, Ni2+, Zn2+, Fe2+, Cu+
= "Hard" metals: Eu3+, Tb3+, Fe3+...
¬
¬
Structure et Reactivite
des Systemes Moleculaires Complexes
¡
¬
¬
¬
Universite Henri Poincare, Nancy 1
5 rue A. Lebrun, B.P. 403, 54001 Nancy Cedex (France)
Fax :(‡33)383179057
Figure 1. Schematic representation of an upper-rim fully tethered CD
binuclear complex with ™hard∫ and ™soft∫ binding cavities.
E-mail: alain.marsura@pharma.u-nancy.fr
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2438 2445
Synthesis of the devices re-
quired the preparation of the
hexakis to octakis azido-cyclo-
dextrins 4 9,[4, 5] and their con-
H
H
N
N
R
N3
n = 6, 7, 8
PPh3 / CO2
RT / DMF
R NH2
O
n = 6, 7, 8
densation with 5-methylamino-
5'-methyl-2,2'-bipyridine (3) or
R1
R1
n = 12, 14, 16
n = 12, 14, 16
n-propylamine, using the so
called ™phosphine imide∫ one-
pot reaction,[6 7] to give directly
4 - 6: R1
7 - 9: R1 = OMe
=
3: R =
= Bpy 10: R = [Bpy]6 ; R1 = [OH]12
H2C
CH3-CH2-CH2
OH
N
N
[Bpy]7
[OH]
14
11: R =
; R1
=
=
= Pr
12: R = [Bpy]8 ; R1
[OH]16
the URFT-CDs 10 16 in mod-
; R1 = [OMe]12
erate to good yields (30 60%)
(Scheme 1). This reaction has
13: R = [Bpy]6
14: R = [Bpy]7 ; R1 = [OMe]14
also been extended to other
heterocycles such as 2,2'-bithia-
zole[8a] and thiourea derivatives,
15: R = [Bpy]8 ; R1
=
=
[OMe]16
16: R =
; R1
[Pr]7
[OH]
14
Scheme 1. Synthesis of URFT-CDs 10 16.
using carbon disulphide in
place of carbon dioxide as re-
agent and solvent.[8b] Recently, we published the scope and
limitations of this methodology, allowing the synthesis of
symmetrical versus unsymmetrical cyclodextrin carbodi-
imides under mild conditions, or isocyanates of complex and
sensitive molecules without the use of hazardous reagent (e.g.
phosgene).[9a]
(propyl substituents). The 1H NMR spectra (e.g. for com-
pound 14) recorded in solution (10À2 m) and in two solvents
(e.g. MeOH and DMSO), exhibited broad and unresolved
resonance signals (like a polymer) in both the regions
expected for cyclodextrins and bipyridines and therefore
their assignment was rendered uncertain. In our opinion, this
phenomenon may be interpreted in terms of polymeric-like
aggregates formed by self-organisation of the polyaromatic
cyclodextrins in solution. Broadening of signals disappeared
at the highest dilution (10À4 m in MeOH), indicating a
dissociation of the proposed aggregates, but no evidence of
a characterised dimer could be ascertained. This effect was
not observed with DMSO. Nevertheless, the integration ratio
(6:1) observed between the aromatic part and a broad singlet
at d ˆ 5.10, attributed to H(1) of CD, and the ratio (3:1)
observed between the methyl singlet of bipyridines at d ˆ 2.40
and the same CD H(1) singlet, were consistent with the
assigned per-substitution. Broadening of signals was not found
in alkyl derivative 16, and thus proton resonances could easily
be assigned. Owing to the limit of ligand solubility, the carbon
NMR signal-to-noise ratios were improved by recording the
Cp-MAS NMR spectrum. Spectra of 14 and its EuIII complex
17 are shown in Figure 3. The NMR spectrum of ligand 14 in
the solid phase was correlated to those in solution and clearly
All new compounds were characterised by FTIR, NMR,
CpMAS-NMR, MALDI-FTICR-MS, UV/Vis spectroscopies
1
and elemental analysis. The spectroscopic FTIR, H NMR,
13C NMR and MS data were all in agreement with the
assigned structures. As expected, the IR spectra exhibited
strong characteristic frequencies for the carbonyl urea func-
tions nCO NH at around 1650 cmÀ1, and intense aromatic double
À
bonds nC at around 1550 cmÀ1 that corresponded to the
ˆ
C
bipyridine units. Characteristic 13C NMR spectra of 10 16 in
solution (DMSO) indicated that the C2 ligand symmetry was
À
À
conserved. Signals corresponding to NH CO NH carbonyl
carbons at d ˆ 156 160, and intense sharp signals corre-
sponding to the bipyridyl carbons at d ˆ 155 120 were
detected. Analyses of the 13C NMR spectra, revealed that
the glycosyl carbon signals of the upper-rim persubstituted
bipyridyl compounds (e.g. compound 14 in Figure 2) were
highly broadened and of lower intensities than the aromatics.
This effect was not found under the same conditions with 16
Figure 2. 13C CpMAS NMR spectrum (8 KHz) and SPT of odd carbons (left) and 13C NMR spectrum in solution (right) of ligand 14.
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A. Marsura et al.
FULL PAPER
hydrogen bonds between urea functions.[9a] Preliminary
computations (molecular mechanics) with 11, suggest a spatial
™tubular∫ organisation of the ligand (Figure 4).[9b] The mo-
lecular geometry of 11 was optimised using the DISCOV-
ER III programme of INSIGHT II (Biosym/MSI) and the
AMBER force field. Minimisation was performed at 298 K
using ™steepest descent∫. ™Conjugate gradients∫ and ™New-
ton Raphson∫ methods were then applied to complete the
minimisation which converged for a maximum derivative of
0.01 kcalmolÀ1 ä or for 1000 steps of 1 ps. However, in the
absence of full molecular dynamics computations, or other
information such as X-ray analyses, one should treat these
preliminary results with care.
Treatment of 14 and 16 with EuCl3 ¥ 6H2O afforded the
complexes 17 and 18 in 71 and 90% yield, respectively. These
were obtained as pink powders, by diffusion of diethyl ether
into a methanol solution of 14 and 16 at room tempera-
ture. The europium complex of 16 was characterised
by positive mode MALDI FTICR-MS which had the desired
Figure 3. 13C CpMAS NMR spectra of (a) ligand 14 and (b) [EuIII(14)]
complex 17.
‡
mononuclear complex with an ion peak [16 ꢀ EuIII,Cl2] at
m/z 1946 (36%), accompanied by characteristic frag-
ments [16 ꢀ EuIII,Cl]2‡, [16 ꢀ EuIII]3‡, and [16 ꢀ EuIII
À
3‡
À
À
propyl NH CO] at m/z 1911 (45%), 1876 (40%) and
1790, respectively. Recent papers have reported efficient
antennae effects for EuIII or TbIII complexes of b-cyclo-
dextrins bearing amino carboxylates[3c] or ureido cyclam
derivatives.[10] In a recent paper, our group presented pre-
liminary results on luminescence properties and an efficient
antennae effect (A-TE-E) of Eu3‡ and Tb3‡ complexes of
ligand 11.[11] The luminescence excitation of [11 ꢀ EuIIICl]À at
288 nm, and of [16 ꢀ LbIII,PF6)]À at 280 nm, cause standard
exhibited the best signal-to-noise ratios, particularly for the
carbons signals of glucosyl units and the urea carbonyl. The
lack of bipyridine carbon signals on complexation with the
Eu3‡ ion, confirms that the bypyridine units are not involved.
Positive mode FABMS showed the presence of the desired
compound with a base peak at m/z 2705 corresponding to
‡
‡
[11‡H] , accompanied by a fragment [M À bipyridyl] at m/z
‡
2522. It should be noted that characterisation of the [M‡H]
ion was obtained only in the case of the lower-rim unsub-
stituted b-CD derivatives. This
result was attributed to the
greater stability of the b-CD
core towards ionisation, rela-
tive to a- and g-CDs or their
methylated derivatives. With
these last cases, the cyclodex-
trin cores are probably broken
first and give a set of oligomeric
fragments as observed in the
mass spectra of polymers. It
should be noted that so far, all
attempts to characterise this
family of ligands by ESMS have
failed. Elemental analyses were
consistent with the presence of
an additional number of asso-
ciated water molecules owing
to cyclodextrin hydration.
From a conformational point
of view, previous results ob-
tained with
a ureido-cyclam
ligand family by molecular dy-
namics computations, indicated
that the molecules adopted a
spatial ™calix∫ form, which es-
sentially arises from the pres-
ence of strong intramolecular
Figure 4. Ball-and-stick structure of ligand 11 [printed from the Insight II molecular modelling program and
obtained by molecular mechanics minimization at 298 K, until a maximum derivative of 0.01 kcalmolÀ1 ä (done
with AMBER force field and DISCOVER III, program from (Biosym/MSI)].
2440
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Upper-Rim Fully Tethered Cyclodextrins
2438 2445
emission of the EuIII and TbIII lanthanide ions by an
absorption energy transfer emission light conversion proc-
ess. Thus, the transitions corresponding to 5D0 7Fj (EuIII) and
5D4 7Fj (TbIII) are observed (Figure 5). Lifetime measure-
ments recorded in the time resolved mode for the two
complexes gave: t ˆ 0.7 ms and 3.5 ms for the [11 ꢀ EuIIICl]À
and [16 ꢀ LbIII,PF6)]À complexes, respectively. This antennae
effect also occurs with all the investigated ligands 10 16 and
an extensive study of their steady-state photophysical proper-
ties will be described in a forthcoming paper.
Cation complexation–UV/Vis absorption spectra: As shown
in Figure 1, upper-rim fully substituted bipyridyl-ureido-CDs
10 15 accommodate two potential complexation sites inside
their structures and one in 16 (the internal, hydrophobic
cavity of the CD core is not taken into account). In this
section, the cation complexation behaviour of two represen-
tative ligands [11 (non-methylated) and 14 (lower-rim per-
methylated)] is illustrated by UV/Vis spectroscopy; the
results were similar for other molecules except 16 (owing to
a lack of the bipyridine units). Titrations of the ligands 10 16
with lanthanides (Eu3‡, Tb3‡, Sm3‡ and Dy3‡) and other
™hard∫ HSAB-classified cations (e.g. Fe3‡) followed by ™soft∫
or ™borderline∫ metals were monitored by UV/Vis spectros-
copy.
The electronic spectra of the free ligands 10 15 were
recorded in MeOH and had two absorption maxima in the
UV region at lmax ˆ 250 nm and 284 288 nm (p p* and n
p* of bipyridines and urea carbonyl). Molar extinction
coefficients of 55080 110830molÀ1 LÀ1 cmÀ1 were obtained
for the bipyridyl derivatives; these gave an estimated
extinction average of about 12500molÀ1 LÀ1 cmÀ1 per bipyr-
idine unit which is in the expected range of values measured
for 2,2-bipyridine. In the case of the propyl derivative 16, the
absorption maximum was at lmax ˆ 260 nm with a molar
extinction coefficient of 603molÀ1 LÀ1 cmÀ1 as a result of the
urea-carbonyl chromophores.
Figure 6. Spectrophotometric titration of 11 (c ˆ 1.0  10À5 molLÀ1) in
MeOH with TbCl3 ¥ 6H2O; Tb3‡ ˆ 0.2 2 equiv.
plexes of 10 16 had a stoichiometry of 1:1 and this was also
confirmed by plasma torch titration of EuIII in 17 (see
Experimental Section). A stability constant of 6.02 Â 105 mÀ1
[11]
was calculated for the [11 ꢀ EuIIICl]À complex.
In these
complexes, lanthanides or ™hard∫ metals are coordinated to
the urea carbonyl oxygen atoms; this is in accordance with
their coordination preference observed in our previous results
obtained with 11,[12] MALDI-FTMS of 18, and literature
reports.[13]
Titration of 14 by FeIII was an exception because in this case
two isobestic points were determined: one, with 1 equivalent
and the second with 2 equivalents of FeIII added to the ligand,
indicating a new [(Fe)2(14)] binuclear complex [2M:1L]
formation (Figure 7). Looking at the absorbance evolution,
coordination with bipyridine units could be excluded and
formation of a stable, six-coordinate complex is suggested[14]
in which the CD lower-rim methyl ether oxygen atoms of 14
act as a crown ether macrocycle ™hard∫ binding cavity.[15] This
effect was not observed in the presence of an excess of
lanthanide ions.
The titrations of 10 15 by lanthanides (Figure 6) had an
isobestic point at 305 nm, a slight red shift of the 288 nm
absorption to 292 nm and appearance of a LMCT band at
320 nm owing to efficient metal coordination and according to
conformational changes occurring in the ligands. The com-
In contrast, titrations of the free ligands 10 15 by addition
of ™borderline∫ or ™soft∫ metals (CoII, NiII, FeII, CuII and CuI)
gave another isobestic point at 292 nm, along with a strong red
shift (and a hyperchromic effect) of the 288 nm absorption
band to 305 nm (Figure 8). The complexes had a stoichiom-
etry of 1:1. In the case of FeII, a
new MLCT band at lmax ˆ 520 nm
was observed, along with the
appearance of the characteristic
purple [FeII-bipyridyl] complex
colour.
Addition of transition metals
(e.g. CuI) to the mononuclear
lanthanide complex, reveals a sec-
ond isobestic point at 308 nm,
with a new strong red-shift of the
292 nm absorption maximum to
310 nm and a hyperchromic effect
as result of the second metal
coordination and conformational
Figure 5. a) Excitation and emission spectra of [Tb(16)(PF6)]À (c ˆ 1.06 mmolLÀ1); b) emission spectrum of
[Eu(11)(Cl)]À (c ˆ 2.65  10À6 molLÀ1) in MeOH at 300 K.
change occurring in the complex
(Figure 9). The resulting new
Chem. Eur. J. 2002, 8, No. 11
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