Self-assembly of a ternary architecture driven by cooperative Hg 2+ ion binding between cucurbit[7]uril and crown ether macrocyclic hosts

Article abstract of DOI:10.1039/c2cc33243d

A novel supramolecular assembly comprising CB[7], styrylpyridinium dye (1) and Hg²⁺ forms in aqueous solution based on the hydrophobic effect and metal-ligand and ion-dipole interactions. The binding of Hg²⁺ to 1·CB[7] displays positive cooperativity relative to 1 itself.

Full text of DOI:10.1039/c2cc33243d

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COMMUNICATION
Self-assembly of a ternary architecture driven by cooperative Hg2+ ion
binding between cucurbit[7]uril and crown ether macrocyclic hostsw
Ekaterina Chernikova,a Daria Berdnikova,a Yuri Fedorov,a Olga Fedorova,*a
Alexander Peregudova and Lyle Isaacs*b
Received 5th May 2012, Accepted 23rd May 2012
DOI: 10.1039/c2cc33243d
A novel supramolecular assembly comprising CB[7], styrylpyridinium
dye (1) and Hg2+ forms in aqueous solution based on the hydrophobic
effect and metal–ligand and ion–dipole interactions. The binding of
Hg2+ to 1ÁCB[7] displays positive cooperativity relative to 1 itself.
Nature relies on an intricate network of covalent reactions and
non-covalent interactions to produce higher order structure
and function. Among the processes driven by non-covalent
interactions (e.g. hydrogen bonds, electrostatic interactions,
hydrophobic effect) within natural systems those that display
high cooperativity are particularly prized.1 Systems that display
high cooperativity often display all-or-nothing assembly processes
which can be used as the basis of molecular switches or machines.2
Scheme 1 Chemical structure of CB[7], styrylpyridinium dye 1 and
Accordingly, much work has been directed toward understanding
the fundamentals of cooperative systems and their utilization to
create complex functional systems.
competititve ligand 2.
Notable cases where addition of metal ion to CB[n] host–guest
assemblies results in a distinct three component assembly
include Mohanty’s thioflavin TÁCB[7] and Pang’s squaraine
dyeÁCB[8] systems.6 We have been working toward marrying the
recognition properties of the CB[n] family with the outstanding
optical properties of styrylpyridinium dyes with an eye toward
creating stimuli (e.g. photochemical or metal ion) responsive
molecular machines.7 We choose styryl dyes for these studies
because of their intense absorption in an analytically favorable
region of the UV/Vis spectrum and the wide application for
optical detection in biological systems.8 Recently, we reported
host–guest complex formation of CB[7] with crown ether derived
cationic styryl and bis(styryl) dyes possessing pyridinium
moiety.7 In this paper, we exploit the combined ability of
electrostatically negative ureidyl CQO portal of CB[n]3,9 and
the dithia–dioxa–monoaza crown ether moiety of styryl dye 19 to
bind to Hg2+ ions to create a three component system that
displays positive cooperativity.
We, and others, have been studying the synthesis and
recognition properties of a class of molecular containers known
as cucurbit[n]urils (CB[n], Scheme 1).3 CB[n] are pumpkin-shaped
macrocycles comprising n glycoluril units connected by 2n
CH2-groups which feature two identical ureidyl carbonyl
portals.2 CB[n] compounds undergo high affinity, highly
selective interactions in water with cationic species (e.g. metal
cations and ammonium ions) at their portals and with hydro-
phobic species by inclusion in the inner cavity.3 Accordingly,
CB[n] compounds have been used as building blocks for the
creation of functional molecular systems like supramolecular
polymers, sensing ensembles, molecular machines, and drug
delivery systems.4
In most CB[n]-based systems, the presence of metal ions
reduces the binding affinity of host toward guest due to
competitive binding of metal ion at the ureidyl CQO portal
of CB[n] resulting in dissociation of the host–guest complex.5
To achieve this goal the N-methyl 4-styrylpyridinium dye
derivatized with dithia-dioxa-monoaza 15-crown-5 residue (1)
was synthesized according to the reported method.9 The binding
properties of 1 with CB[7] or Hg2+ ions were investigated in
aqueous solution by UV-Vis and NMR spectroscopy. The UV-Vis
spectrum of 1 in water (Fig. 1) is characterized by a very intense
long wavelength absorption band (LAB) centered at 456 nm
(e = 2.81 Â 104 MÀ1 cmÀ1). This band is assigned to an
efficient intramolecular charge transfer (ICT) process from the
donor nitrogen atom of the crown ether moiety to the acceptor
a A.N. Nesmeyanov Institute of Organoelement compounds,
Russian Academy of Sciences, 28 Vavilova st., 119991 Moscow,
Russian Federation. E-mail: fedorova@ineos.ac.ru;
Tel: +7 499 135 9253
b Department of Chemistry and Biochemistry, University of Maryland,
College Park, MD 20742, USA. E-mail: LIsaacs@umd.edu;
Fax: +1 301-314-9121; Tel: +1 301-405-1884
w Electronic supplementary information (ESI) available: Experimental
details of UV-Vis and NMR spectroscopy. See DOI: 10.1039/
c2cc33243d
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In order to confirm the cooperative character of the ternary
complex CB[7]ÁHg2+Á1 formation (Scheme 2) we measured
the relative stability constants of CB[7]ÁHg2+Á1 and 1ÁHg2+com-
plexes by competitive spectrophotometric titration with crown
ether 2 as competitor (ESIw). In both cases, increasing the
concentration of competitor 2 results in the displacement of
Hg2+ ions from the cavity of 1 and formation of the 2ÁHg2+
complex (Fig. 2). The displacement of Hg2+ ion from the
ternary CB[7]ÁHg2+Á1 complex requires a much larger excess
of competitor than the displacement of the same amount of
Hg2+ ions from the binary 1ÁHg2+ complex. The competitive
titration data showed that the ratio of the ternary complex
stability constant (CB[7]ÁHg2+Á1) to the binary complex
stability constant KB/KA is equal to 25, that is, Hg2+ affinity
for CB[7]Á1 is about 25 times greater than the Hg2+ affinity for
free 1. We attribute the dramatic increase in the binding of
CB[7]Á1 toward Hg2+ relative to free 1 to the formation of
CQOÁ Á ÁHg2+ coordination interactions between CB[7] and
Hg2+ in the CB[7]ÁHg2+Á1 complex. All the available evidence
establishes that the CB[7]ÁHg2+Á1 ternary complex forms with
positive cooperativity.
Fig. 1 UV-Vis spectra recorded (black lines) for a mixture of CB[7]
(100 mM) and 1 (20 mM) upon addition of Hg(ClO4)2 (0–240 mM).
The bold lines correspond to the spectra of: (1) free 1, (2) CB[7]Á1,
(3) 1ÁHg2+, and (4) CB[7]ÁHg2+Á1.
pyridinium ring. Addition of CB[7] to a solution of 1 results in
a moderate bathochromic shift (Dlmax = 26 nm) of the LAB,
which is diagnostic for inclusion of 1 in a less polar environment
(Fig. 1). The spectrophotometric titration data fits well to a 1 : 1
CB[7]Á7 binding model which allowed us to determine the associa-
tion constant for the CB[7]Á1 complex (log K = 5.36 Æ 0.02).
Separately, we added Hg2+ to a solution of 1 in water and observed
that the intensity of the absorption maximum of free 1 at 456 nm
gradually decreased along with the formation of a new band
centered at 346 nm (Fig. 1). The coordination of the Hg2+ ion to
styryl dye 1 decreases the electron-donating ability of the crown
ether residue which in turn makes the ICT process unfavorable
which results in a large blue shift (Dlmax = 110 nm) of the LAB.
The highly effective complexation of Hg2+ by 1 is achieved due
to formation of strong Hg2+Á Á ÁS interactions in the dithia-
dioxa-monoaza crown terminus of 1.9 It was not possible to
extract a value of Ka for the interaction between 1 and Hg2+
from this titration because the lack of well defined isosbestic
points (Fig. S8) suggests that the interaction model is complex
most likely due to Hg2+ hydrolysis in water.
To provide evidence of the three dimensional geometry of the
CB[7]ÁHg2+Á1 complex we performed 1H NMR spectroscopy
measurements of the various components and the complexes
(Fig. 3). The 1H NMR assignments were established by a
combination of 2D NMR techniques including COSY and
1
ROESY (ESIw). The H NMR spectra recorded for free 1 and
the CB[7]Á1 in D2O (Fig. 3b) show that the signals for the
Next, we examined the behaviour of the ternary system
comprising 1, CB[7], and Hg2+ ion in aqueous solution. For this
purpose, we measured the UV/Vis spectral changes of a solution
of 1 (20 mM) and CB[7] (100 mM, corresponding to 495%
complexation of 1) as the concentration of Hg2+ ions was
increased (Fig. 1). In sharp contrast to our related earlier work7 –
which showed competitive binding at the ureidyl CQO portals
of CB[7] and therefore complex dissociation upon addition of
metal ions (Mg2+, Ba2+, Zn2+, Cu2+) – the addition of an
excess of Hg2+ ions (up to 10 eq.) in the form of Hg(ClO4)2
does not lead to the appearance of the absorption spectra
characteristic of the individual components or the binary
complexes 1ÁHg2+ and CB[7]-Hg2+. We conclude that the addi-
tion of Hg2+ does not cause dissociation of CB[7]Á1 complex. On
the contrary, the addition of Hg2+ ions to solutions containing 1
and CB[7] results in a new absorption band centred at 361 nm,
which is ascribed to the formation of the CB[7]ÁHg2+Á1 ternary
complex. This band is red-shifted by 15 nm relative to the
absorption of the 1ÁHg2+ complex and substantially blue-shifted
by 95 and 121 nm with respect to the absorption of free dye 1 and
the CB[7]Á1 complex, respectively (Fig. 1).
Scheme 2 Schematic representation of the geometry of CB[7]Á1 and
CB[7]ÁHg2+Á1, and an MMFF minimized geometry of the ternary
complex CB[7]ÁHg2+Á1.
Fig. 2 Absorbance values recorded for the 1ÁHg2+ and CB[7]ÁHg2+Á1
complexes at 480 nm as a function of the concentration in competitor
2 in H2O ([1] = 2.0 Â 10À5 M; [CB[7]] = 1.0 Â 10À4 M; [Hg2+] =
1.0 Â 10À4 M, [2] = 0 –3.2 Â 10À4 M).
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Unfortunately, we were unable to obtain single crystals of
the CB[7]ÁHg2+Á1 complex that were suitable for X-ray
analysis. Nevertheless, the MMFF minimized geometry of
the CB[7]ÁHg2+Á1 complex (Scheme 2) is completely congruent
with the proposed structure.
In summary, we have demonstrated that mixtures of 1,
CB[7], and Hg2+ form ternary complex CB[7]ÁHg2+Á1 in a
process that displays substantial positive cooperativity. The
Hg2+ ion simultaneously coordinates to the ureidyl CQO
portals of CB[7] and the crown ether moiety of 1. Because the
geometry of the binary CB[7]Á1 binary and ternary CB[7]ÁHg2+Á1
complexes are similar, the addition of metal ion does not
involve a substantial shuttling motion of the components. It is
straightforward, however, to imagine that lengthening of the
linker between the styrylpyridinium and crown ether moieties
would result in complexes that would undergo shuttling
processes in response to the addition of metal ions. As such,
we believe that CB[7]Ástyrylpyridinium derived systems hold
promise as components of more complex molecular machines
and sensing systems that function in biologically relevant aqueous
media.
Fig. 3 1H NMR spectra (600 MHz, D2O) for: (a) 1 and Hg2+ (1.6 eq.),
(b) 1 and CB[7] (1.1 eq.), and (c) 1, CB[7] (1 eq.) and Hg2+ (1.3 eq.).
pyridinium (H2, H6, H3, H5), ethylene (H7, H8), and aromatic
(H10, H14) ring protons are significantly upfield shifted in the
CB[7]Á1 complex whereas the aromatic ring (H11, H13) protons
and CH2-groups (Ha–He) are downfield shifted. The direction
and magnitude of these shifts allowed us to deduce the geometry
of the complex based on the fact that the CB[7] cavity constitutes
a shielding region whereas the region just outside the portals
constitutes a deshielding region.10 We propose that the vinyl-
pyridinium unit of 1 is located inside the hydrophobic cavity of
CB[7] whereas the crown ether residue is outside the CB[7] cavity
in the CB[7]Á1 complex (Scheme 2).
This work was supported by the Russian Foundation for
Basic Research and a program of the Russian Academy of
Sciences (O.F.) and by the US National Science Foundation
(CHE-1110911 to L.I.).
The binding interactions between 1 and Hg2+ ions also can
1
be conveniently monitored by H NMR spectroscopy. Upon
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for the dithia–dioxa–monoaza crown moiety are significantly
broadened (Fig. 3a). This pattern of complexation-induced
chemical shifts can be attributed to the coordination of Hg2+
inside the crown ether ring of 1.
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1
The pattern of changes in the H NMR spectrum recorded
for solutions containing ternary complex CB[7]ÁHg2+Á1
(Fig. 3c) are similar to those observed for its binary constituents
(e.g. CB[7]Á1 and 1ÁHg2+). For example, the resonances for the
vinylpyridinium unit of 1 are upfield shifted by 0.32–0.57 ppm
relative to free 1 which is due to the shielding effect of the
CB[7] cavity. At the same time the resonances of the dithia-
dioxa-monoaza crown moiety (Ha–Hc) undergo downfield
shifts by 0.13–0.57 ppm and become distinctly separated. This
pattern of complexation induced shifts indicates that the
CB[7]ÁHg2+Á1 complex assumes the geometry shown in
Scheme 2. In this well-organized ternary complex, the components
are arranged in such a way that the Hg2+ ion is complexed by two
macrocycles, namely the cavity of crown ether and the one of the
oxygen portals of CB[7]. Simultaneously, the remote portal of CB[7]
interacts with the pyridinium unit of 1 by ion–dipole interactions.
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c
7258 Chem. Commun., 2012, 48, 7256–7258
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