Dual-Cavity Basket Promotes Encapsulation in Water in an Allosteric Fashion

Article abstract of DOI:10.1021/jacs.5b06041

We prepared dual-cavity basket 1 to carry six (S)-alanine residues at the entrance of its two juxtaposed cavities (289 ?³). With the assistance of ¹H NMR spectroscopy and calorimetry, we found that 1 could trap a single molecule of 4 (K₁ = 1.45 ± 0.40 × 10⁴ M^-1, ITC), akin in size (241 ?³) and polar characteristics to nerve agent VX (289 ?³). The results of density functional theory calculations (DFT, M06-2X/6-31G?) and experiments (¹H NMR spectroscopy) suggest that the negative homotropic allosterism arises from the guest forming C-H···π contacts with all three of the aromatic walls of the occupied basket's cavity. In response, the other cavity increases its size and turns rigid to prevent the formation of the ternary complex. A smaller guest 6 (180 ?³), akin in size and polar characteristics to soman (186 ?³), was also found to bind to dual-cavity 1, although giving both binary [16] and ternary [1-6₂] complexes (K₁ = 7910 M^-1 and K₂ = 2374 M^-1, ¹H NMR spectroscopy). In this case, the computational and experimental (¹H NMR spectroscopy) results suggest that only two aromatic walls of the occupied basket's cavity form C-H···π contacts with the guest to render the singly occupied host flexible enough to undergo additional structural changes necessary for receiving another guest molecule. The structural adaptivity of dual-cavity baskets of type 1 is unique and important for designing multivalent hosts capable of effectively sequestering targeted guests in an allosteric manner to give stable supramolecular polymers.

Full text of DOI:10.1021/jacs.5b06041

Article
pubs.acs.org/JACS
Dual-Cavity Basket Promotes Encapsulation in Water in an Allosteric
Fashion
Shigui Chen, Makoto Yamasaki, Shane Polen, Judith Gallucci, Christopher M. Hadad,
and Jovica D. Badjic*
́
Department of Chemistry and Biochemistry, The Ohio State University, 100 West 18th Avenue, Columbus, Ohio 43210, United
States
S
* Supporting Information
ABSTRACT: We prepared dual-cavity basket 1 to carry six (S)-alanine residues at the entrance
1
of its two juxtaposed cavities (289 Å3). With the assistance of H NMR spectroscopy and
calorimetry, we found that 1 could trap a single molecule of 4 (K1 = 1.45 0.40 × 104 M−1,
ITC), akin in size (241 Å3) and polar characteristics to nerve agent VX (289 Å3). The results of
density functional theory calculations (DFT, M06-2X/6-31G*) and experiments (1H NMR
spectroscopy) suggest that the negative homotropic allosterism arises from the guest forming
C−H···π contacts with all three of the aromatic walls of the occupied basket’s cavity. In response,
the other cavity increases its size and turns rigid to prevent the formation of the ternary complex.
A smaller guest 6 (180 Å3), akin in size and polar characteristics to soman (186 Å3), was also
found to bind to dual-cavity 1, although giving both binary [1⊂6] and ternary [1⊂62] complexes
1
(K1 = 7910 M−1 and K2 = 2374 M−1, H NMR spectroscopy). In this case, the computational
and experimental (1H NMR spectroscopy) results suggest that only two aromatic walls of the
occupied basket’s cavity form C−H···π contacts with the guest to render the singly occupied host
flexible enough to undergo additional structural changes necessary for receiving another guest
molecule. The structural adaptivity of dual-cavity baskets of type 1 is unique and important for designing multivalent hosts
capable of effectively sequestering targeted guests in an allosteric manner to give stable supramolecular polymers.
therefore permit tuning “on/off” response of the host,17 i.e.,
INTRODUCTION
■
rapid population switch from mainly bound to unbound or
Developing prophylactic measures1 for the effective removal of
active to inactive structures, and could be of interest for
organophosphorus (OP) nerve agents of G and V type as well
developing switchable18 and selective sensors19/catalysts20
as detection of their minute quantities is important for
capable of effectively detecting/degrading OP nerve agents.
preventing the act of terrorism and chemical warfare.2
In line with this, we hereby describe our findings about
Currently, the unambiguous detection of toxic OP substances
characterizing the operation of dual-cavity basket 1 (Figure 1A)
relies on nonportable analytical instrumentation,3 while
in water.13 This multivalent host21 is chiral, with two juxtaposed
developing effective measures for their rapid detection and
cavities and six alanine amino acids at the entrance for the
degradation is still a focus of many research efforts.4 Indeed,
solubility in water. Furthermore, the conformational flexibility
there are elegant examples of synthetic and biological molecules
of the framework of 1 is critical for tuning the size of the
capable of detecting5 and degrading nerve agents.6 Chemo-
cavities (V ≈ 240 Å3,22 Figure 1B)11c and therefore
sensors and catalysts often lack chemo/stereoselectivity7 for
accommodating guests23 in an allosteric fashion.17
exclusively “picking” desired OPs among other compounds.
The sensing problem could, perhaps, be addressed with the
RESULTS AND DISCUSSION
application of pattern recognition methods;8 however, for
■
Basket 1 was prepared via Pd(OAc)2 promoted homocoupling
of three bicyclic dibromoalkenes 2, each possessing two (S)-
alanine amino acids (Figure 1A, see also Scheme S1).13 The
cyclotrimerization of a synthetic precursor of 2 (Scheme S1),
however, gave dual-cavity host 313 akin in shape to basket 1.
Interestingly, single crystal of dual-cavity 3 was obtained by a
slow evaporation of a solution of this molecule in CH3OH/
CDCl3 (Figure 1C, see also Figure S10). The unit cell contains
pairs of C1 symmetric 3, with two baskets perpendicular to each
catalysis, one could envision a great utility of molecular
encapsulation.9 Accordingly, we posit10 that understanding the
fundamentals of OP recognition is important for advancing the
field. We therefore used molecular baskets equipped with
amino acids or amphiphilic groups at the rim for encapsulating
OPs.10,11 The binding of OP guests is, for such monovalent
hosts, described with hyperbolic binding isotherms whereby the
complexation event occurs over a broad range of guest
concentrations.12 In the case of multivalent baskets,13 however,
the complexation of monovalent guests ought to occur in
stages14 with the binding isotherm turning sigmoidal if a strong
positive cooperativity ensues.15 The positive allosterism16 shall
Received: June 17, 2015
© XXXX American Chemical Society
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Figure 1. (A) Dual-cavity 1 is obtained from 2 by palladium acetate promoted cyclotrimerization.13 1H NMR spectrum (500 MHz, 298.0 K) of 1
(1.0 mM) in D2O. (B) Van der Waals surface of 1 (MMFFs, Spartan). (C) Solid-state structure of dual-cavity basket 3 (see also Figure S10).
other forming π−π stacking contacts (Figure 1C).24 For one of
the baskets, the difference in the averaged length between
centroids of its three side aromatics, comprising two juxtaposed
cavities, is Δd = 0.5 Å; for another basket, however, Δd is
smaller and equal to 0.1 Å. Evidently, the framework of dual-
cavity 3 is flexible enough to, in the solid-state, adjust the size of
its concave clefts.23 Disordered solvent molecules were difficult
to locate in the electron density maps, yet some clearly occupy
the inner space of 3. Due to disorder, some carbon and oxygen
atoms were isotropically refined contributing to a large R factor.
Dual-cavity 1 was soluble in water showing a single set of 1H
NMR resonances (Figure 1A) corresponding to D3 symmetric
1. A rather broad line width indicates an aggregation11a of this
bolaamphiphilic host,25 yet there was no change in the signal
for 0.1−5.0 mM solutions of 1 (Figure S3). Importantly, the
radius of energy-minimized 1 (MMFFs, Spartan, Figure 1B) is
estimated to be 1 nm.11d
For studying the encapsulation characteristics of 1, we first
selected adamantane derivative 4. Importantly, the volume of
this guest (241 Å3) as well as its C−H “decorated” hydrophobic
moiety (see Figure 2C) resemble the nerve agent VX (289
Å3).10 An incremental addition of the standard solution of 4
1
(60.0 mM) to 1 (0.61 mM) in water was monitored with H
NMR spectroscopy (600 MHz, Figure 2A; see also Figure S4).
A large upfield shift of all proton resonances of 4 suggested the
formation of an encapsulation complex, with guest’s protons
being magnetically shielded by the host’s aromatics (Figure
2A). The method of continuous variation (Figure 2B) indicated
that a 1:1, but not 1:2, complex dominates in solution: the bell-
shaped curve peaks at equimolar (ca. 0.5) host−guest ratio.27 In
1
1
results of H NMR diffusion ordered spectroscopy (DOSY)
fact, the nonlinear least-squares fitting of H NMR titration
measurements26 of 1 in D2O revealed that the apparent
diffusion coefficient stayed practically constant (Dapp = 1.8−1.9
× 10−10 m2/s, 298.0 K) across a 0.5−5.0 mM concentration
range. The hydrodynamic radii (RH = 1.3−1.4 nm)
corresponding to such diffusion mobility may suggest the
existence of monomeric host or stable aggregates since the
data to a 1:1 stoichiometric model gave the association constant
K1 = 2.2−4.1 × 103 M−1 (R2 = 0.99 with 10% of the standard
fitting error; Figure 2A).28 The encapsulation was subsequently
monitored with isothermal titration calorimetry (ITC, Figure
S5), corroborating the exclusive formation of [1⊂4] and
providing thermodynamic data pertaining to the host−guest
B
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Figure 2. (A) Nonlinear least-squares analysis of Hh−Hk binding isotherms pertaining to the formation of [1⊂4] (298.0 K) gave the association
constant K1 = 2.2−4.1 × 103 M−1 (R2 = 0.99 with 10% of the standard fitting error; SigmaPlot). (B) The Job plot corresponding to the formation of
1
[1⊂4] was obtained using H NMR chemical shifts of signals corresponding to guest 4 ([1]0 + [4]0 = 0.4 mM). (C) A stick representation of
energy-minimized [5⊂4] (DFT, M06-2X/6-31G*) in water showing the guest forming C−H···π contacts with all three aromatic walls of the host’s
one cavity to alter the size of both cavities. Energy-minimized structures of VX (289 Å3) and 4 (241 Å3), showing their van der Waals surfaces and
also depicting a number of C−H groups protruding from the hydrophobic part of each molecule.
Figure 3. (A) Stick representation of energy-minimized model compound 5 (DFT, B3LYP/6-31G*) showing dihedral angles c1 (blue, top) and c2
(red, bottom). When one torsion is fixed (χ1) to a particular value, the energy optimization shows that another dihedral (χ2) changes
correspondingly (B) as well as the total energy of the system (C).
event. The binding (K1 = 1.45 0.40 × 104 M−1, R2 = 0.95;
Figure S5) is driven by entropy (TΔS° = 6.6 0.3 kcal/mol,
298.0 K) while the change in enthalpy is positive (ΔH° = 0.96
0.01 kcal/mol); we reason that an apparent discrepancy
between the results of NMR and ITC binding studies is likely
due to (a) the fitting of the NMR data to the chemical shift of
guest protons in the experiment in which the guest is added to
the host28 and (b) rather poor signal-to-noise ratio and a
broadening of proton resonances. Apparently, the classical
hydrophobic effect29 and therefore a desolvation of primarily
hydrophobic regions of the host/guest pair are driving the
formation of the noncovalent complex.11b The degree of
perturbation of 1H NMR signals of 4, characterizing its
entrapment (Figure 2A), is in line with this interpretation. That
is to say, the 1H resonances corresponding to nuclei Hh/Hi/Hj/
Hk within the adamantane moiety in 4 are shielded to a greater
degree (Δδ = 1.1−1.6 ppm, Figure 2A) than those of He/Hf/Hj
within the pyridinium group (Δδ = 0.1−0.5 ppm, Figure 2A). It
C
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1
Figure 4. (A, B) H NMR chemical shifts (600 MHz) of resonances corresponding to protons of 6 as its solution (31.3 mM) was incrementally
added to dual-cavity 1 (0.5 mM) in D2O at 298.0 K. (C) The Job plot describing to the formation of ternary [1⊂62] was obtained using 1H NMR
chemical shifts of signals corresponding to guest 6 ([1]0 + [6]0 = 0.4 mM).27 (D) Nonlinear least-squares analysis of binding isotherms pertaining
the formation of [1⊂6]/[1⊂62] gave association constants K1 and K2 for two subsequent binding events.32 Energy-minimized structures of guest 6
and soman (MMFFs, Spartan), showing their van der Waals surfaces and polar/nonpolar zones.
follows that more hydrophobic adamantane in the guest is
residing in the arene-based cavity of the host. Why does
negative homotropic allosterism30 take place with the
predominant formation of [1⊂4] and absence of [1⊂42]? To
address this question, we first used density functional theory
(DFT, B3LYP/6-31G*)31 to study the conformational
dynamics of the framework of model dual-cavity 5 (Figure
3A). The concave portion of this host is the same as in basket 1,
although it is lacking six negatively charged carboxylate groups
to facilitate the computational studies: the carboxylates serve to
improve the solubility of dual-cavity 1 and are hypothesized to
play a minor role in the recognition occurring in polar water
environment. Top and bottom torsions χ1 and χ2 (Figure 3A)
within 5 depict the size of the juxtaposed cavities and are
identical for the energy-minimized host (χ1 and χ2 = 120°).
When the top torsion χ1 was, however, constrained to a
particular value and the energy minimization conducted, the
bottom torsion χ2 would undergo a correlated change following
a linear dependence (Figure 3B). Thus, “squeezing” the top
cavity (reducing χ1) causes an expansion of the bottom one
(increasing χ2) and vice versa (Figure 3B). The total host’s
energy E as a function of χ1 fits a cubic polynomial (Figure 3C),
with a relatively small energy fluctuation (dE/dχ1 → 0) about
the energy minimum (χ1 = 120°, Figure 3C). The framework of
model 5, akin to 1, is flexible23 with 1.7 kcal/mol needed to
“squeeze” the top cavity by Δχ1 = 4° and thereby bring three
imide nitrogen atoms on top to dN/N = 9.0 Å while concurrently
separating those at the bottom to dN/N = 10.1 Å (Figure 3C)!
Then, we used M06-2X/6-31G*33 calculations to examine the
encapsulation of 4 inside the cavity of model basket 5. The
most stable coconformation34 (carcerisomer)35 of [5⊂4]
comprises an adamantane moiety holding against all three of
the host’s aromatic walls by forming numerous C−H···π
contacts (d(C−H···Csp2 < 3.05 Å, Figure 2C).36 In this way,
the occupied cavity becomes contracted (dN/N = 9.1 Å, Figure
2C) while concurrently the vacant one increases its size (dN/N
=
9.8 Å, Figure 2C). Since the adamantane group in 4 is also
occupying the cavity of 1, we presume that the same type of
conformational change is taking place with the experimentally
examined [1⊂4] complex. It follows that the observed negative
homotropic allosterism, and the absence of [1⊂42], arises from
dual-cavity 1 requiring all three of its aromatic walls, within one
cavity (Figure 2C), to interact with the guest. As this cavity is
reducing its size, in an induced-fit fashion,37 the other one
becomes bigger and incapable of forming sufficient number of
C−H···π contacts to stay occupied. In fact, the computed
binding energies (M06-2X/6-31G*) for the formation of
[5⊂4] (ΔE = −15.44 kcal/mol, Table S3) and [5⊂42] (ΔE
= −11.65 kcal/mol, Table S3), in implicit water solvent, suggest
a greater stability of the binary complex: to retain numerous
C−H···π contacts, one of the cavities is in [5⊂42] still more
(dN/N = 9.1 Å, Figure S11) contracted than the other (dN/N
=
9.4 Å, Figure S11). The effective formation of ternary [5⊂42]
requires for the “cups” to be similar in size, which clearly comes
at the energetic cost of straining the basket’s framework. In
general, when the dual-cavity basket is forming a “tight” 1:1
complex with the involvement of all three aromatic walls from
one of its “cups”, binding of a second identical guest is not to be
expected. Finally, preorganized complex [1⊂4]38 could elicit a
selective encapsulation of more sizable and complementary
molecules of interest11 to give a stable ternary complex39 or
even more elaborate assemblies.17
To additionally examine the allosteric operation of 1, we
studied the encapsulation of phenylpyridinium guest 6 (180 Å3,
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Figure 4) akin in size and polar characteristics to nerve agent
soman (186 Å3);10 note that these two molecules possess polar
and nonpolar zones of a comparable size (Figure 4). The
hypothesis was that less sizable compound 6 would form fewer
contacts24 with 1, which could possibly give rise to ternary
[1⊂62] complex. An incremental addition of the standard
solution of 6 (31.3 mM) to 1 (0.5 mM) in D2O was monitored
1
with H NMR spectroscopy (Figure 4A,B, see also Figure S6).
An upfield shift of all of the guest’s resonances is in line with an
inclusion of 6 in the cavity of 1. In fact, the Job plot is indicative
of the formation of ternary [1⊂62] complex with the parabola
peaking at approximate 1:2 host/guest ratio (0.67, Figure 4C).
A greater upfield perturbation (on average) of resonances Hg/
He/Hf (Δδ = 0.7−1.3 ppm, Figure 4A) than those of Hh/Hi/Hj
(Δδ = 0.5−0.8 ppm, Figure 4B) suggests the predominant
disposition of pyridinium moiety inside the aromatic cavity of 1.
In fact, the complexation-induced shift of He resonance is by far
the greatest (1.30 ppm), with this proton of the guest
embedded in the cavity of 1 more deeply than the others. A
Figure 5. Stick representation of energy-minimized [5⊂6] (DFT,
M06-2X/6-31G*) showing the guest forming C−H···π contacts with
the bottom benzene ring and back aromatic wall of the host in addition
to π−π stacking contacts with the aromatic group on the left. One
aromatic wall in the top cavity (green) is practically not interacting
with the guest.
1
small change in the chemical shift of H NMR resonances of
the host (Figure S6), however, prevented us from quantifying
two consecutive binding events K1 and K2. In line with it, the
calorimetry measurements (ITC) were giving scattered data
points due to a small heat of complexation (Figure S7), while
the electronic spectrum of 1 was practically unperturbed upon
the complex formation (Figure S8). Accordingly, we decided to
contacts with all three of its aromatic walls. As a result, the
other cavity changes its size and turns rigid to prevent
additional encapsulation leading to negative homotropic
allosterism. If the targeted guest is smaller, however, it interacts
with only one or two aromatic walls of the basket’s cavity to
render the singly occupied host flexible enough to undergo
additional structural changes necessary for receiving another
guest molecule of the same type. The structural adaptivity of
dual-cavity baskets of type 1 is unique42 and important for
designing multivalent hosts capable of effectively sequestering
targeted nerve agents in an allosteric fashion and via
hydrophobic effect, to eventually give stable supramolecular
polymers41 in water. The work in our laboratories continues
toward achieving such goals.
1
complete a “reverse” H NMR titration with an incremental
addition of the standard solution of host 1 (4.0 mM) to guest 6
(0.25 mM) in D2O (Figure 4D, see also Figure S9). Nonlinear
least-squares analysis of binding isotherms (Figure 4D),32 to
2:1 stoichiometric model, was satisfactory (cov fit = 0.0003)32
with K1 = 7910 M−1 corresponding to the stability of [1⊂6]
and K2 = 2374 M−1 describing the formation of [1⊂62]; the
fitting of the data was initiated with the ratio of variables K1/K2,
originally set to 4:1. Since the ratio of two consecutive
association constants is K1/K2 = 3.3, and smaller than 4, the
binding is positively cooperative albeit close to the statistical
one.40 The origin of the effect is, at present, difficult to
computationally/experimentally elucidate yet our preliminary
studies of dual-cavity 1 complexing a dimeric form of
compound 6 indicate the formation of supramolecular
polymers41 to vindicate the binding analysis. The computa-
tional study of model complex [5⊂6] (M06-2X/6-31G*, Figure
5)33 shows guest 6 positioning its pyridinium group against one
of the basket’s aromatic walls at centroid-to-centroid distance of
3.7 Å.24 Furthermore, C−H···π interactions36b with the bottom
benzene ring and two side aromatic walls hold the guest
molecule in its place (Figure 5). If two aromatic walls are in
[1⊂6] restrained, then one aromatic wall remains “discon-
nected” (shown as green for model [5⊂6], Figure 5). This
particular unit of the host is conformationally more flexible, and
it ought to be able to adjust in response to another guest to
allow for the formation of ternary complex. In brief, singly
occupied [1⊂6] comprises a more adaptable organic framework
capable of accommodating another guest of the same type and
giving [1⊂62]!
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/jacs.5b06041.
■
S
Crystallographic data (CIF)
Additional details of the experimental and computational
protocols (PDF)
AUTHOR INFORMATION
Corresponding Author
*badjic@chemistry.ohio-state.edu
■
Funding
The experimental portion of this work was financially
supported with funds obtained from the U.S. National Science
Foundation (CHE-1305179). The computational part was
financially supported with funds obtained from the Department
of Defense, Defense Threat Reduction Agency (HDTRA1-11-
1-0042). Computational support from the Ohio Super-
computer Center is gratefully acknowledged.
Notes
CONCLUSION
■
The authors declare no competing financial interest.
In conclusion, dual-cavity 1 (V ≈ 240 Å3) is a modular,
adaptable, and chiral host capable of trapping guests, akin in
size and polarity to nerve agents (186−289 Å3), in water via
hydrophobic effect. When a guest molecule effectively
populates one cavity of 1, it forms C−H···π noncovalent
REFERENCES
■
(1) Raushel, F. M. Nature 2011, 469, 310−311.
(2) Kim, K.; Tsay, O. G.; Atwood, D. A.; Churchill, D. G. Chem. Rev.
2011, 111, 5345−5403.
E
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Journal of the American Chemical Society
Article
(3) Cordell, R. L.; Willis, K. A.; Wyche, K. P.; Blake, R. S.; Ellis, A.
M.; Monks, P. S. Anal. Chem. 2007, 79, 8359−8366.
(4) Smith, B. M. Chem. Soc. Rev. 2008, 37, 470−478.
(5) (a) Ajami, D.; Rebek, J. Org. Biomol. Chem. 2013, 11, 3936−3942.
(b) Chen, S.; Cashman, J. R. Adv. Mol. Toxicol. 2013, 7, 207−233.
(6) Mondloch, J. E.; Katz, M. J.; Isley, W. C., III; Ghosh, P.; Liao, P.;
Bury, W.; Wagner, G. W.; Hall, M. G.; De Coste, J. B.; Peterson, G.
W.; Snurr, R. Q.; Cramer, C. J.; Hupp, J. T.; Farha, O. K. Nat. Mater.
2015, 14, 512−516.
(35) Timmerman, P.; Verboom, W.; van Veggel, F. C. J. M.; van
Duynhoven, J. P. M.; Reinhoudt, D. N. Angew. Chem. 1994, 106,
2437−2440.
(36) (a) Nishio, M.; Umezawa, Y.; Fantini, J.; Weiss, M. S.;
Chakrabarti, P. Phys. Chem. Chem. Phys. 2014, 16, 12648−12683.
(b) Ruan, Y.; Peterson, P. W.; Hadad, C. M.; Badjic, J. D. Chem.
Commun. 2014, 50, 9086−9089.
(37) (a) Hiraoka, S.; Harano, K.; Nakamura, T.; Shiro, M.; Shionoya,
M. Angew. Chem., Int. Ed. 2009, 48, 7006−7009. (b) Corbett, P. T.;
Tong, L. H.; Sanders, J. K. M.; Otto, S. J. Am. Chem. Soc. 2005, 127,
8902−8903.
(38) Wittenberg, J. B.; Isaacs, L. Supramol. Chem. Mol. Nanomater.
2012, 1, 25−43.
(39) Thordarson, P.; Coumans, R. G. E.; Elemans, J. A. A.;
Thomassen, P. J.; Visser, J.; Rowan, A. E.; Nolte, R. J. M. Angew.
Chem., Int. Ed. 2004, 43, 4755−4759.
(7) Benschop, H. P.; De Jong, L. P. A. Acc. Chem. Res. 1988, 21, 368−
374.
(8) Askim, J. R.; Mahmoudi, M.; Suslick, K. S. Chem. Soc. Rev. 2013,
42, 8649−8682.
(9) Chulvi, K.; Gavina, P.; Costero, A. M.; Gil, S.; Parra, M.; Gotor,
R.; Royo, S.; Martinez-Manez, R.; Sancenon, F.; Vivancos, J.-L. Chem.
Commun. 2012, 48, 10105−10107.
(40) Badjic, J. D.; Nelson, A.; Cantrill, S. J.; Turnbull, W. B.;
Stoddart, J. F. Acc. Chem. Res. 2005, 38, 723−732.
(41) Aida, T.; Meijer, E. W.; Stupp, S. I. Science 2012, 335, 813−817.
(42) Kao, M.-T.; Chen, J.-H.; Chu, Y.-Y.; Tseng, K.-P.; Hsu, C.-H.;
Wong, K.-T.; Chang, C.-W.; Hsu, C.-P.; Liu, Y.-H. Org. Lett. 2011, 13,
1714−1717.
(10) Ruan, Y.; Taha, H. A.; Yoder, R. J.; Maslak, V.; Hadad, C. M.;
Badjic, J. D. J. Phys. Chem. B 2013, 117, 3240−3249.
(11) (a) Chen, S.; Ruan, Y.; Brown, J. D.; Gallucci, J.; Maslak, V.;
Hadad, C. M.; Badjic, J. D. J. Am. Chem. Soc. 2013, 135, 14964−14967.
(b) Chen, S.; Ruan, Y.; Brown, J. D.; Hadad, C. M.; Badjic, J. D. J. Am.
Chem. Soc. 2014, 136, 17337−17342. (c) Ruan, Y.; Chen, S.; Brown, J.
D.; Hadad, C. M.; Badjic, J. D. Org. Lett. 2015, 17, 852−855. (d) Ruan,
Y.; Dalkilic, E.; Peterson, P. W.; Pandit, A.; Dastan, A.; Brown, J. D.;
Polen, S. M.; Hadad, C. M.; Badjic, J. D. Chem. - Eur. J. 2014, 20,
4251−4256.
(12) Riddle, J. A.; Jiang, X.; Lee, D. Analyst 2008, 133, 417−422.
(13) Hermann, K.; Sardini, S.; Ruan, Y.; Yoder, R. J.; Chakraborty,
M.; Vyas, S.; Hadad, C. M.; Badjic, J. D. J. Org. Chem. 2013, 78, 2984−
2991.
(14) Ercolani, G. J. Am. Chem. Soc. 2003, 125, 16097−16103.
(15) Hunter, C. A.; Anderson, H. L. Angew. Chem., Int. Ed. 2009, 48,
7488−7499.
(16) Perlmutter-Hayman, B. Acc. Chem. Res. 1986, 19, 90−96.
(17) Takeuchi, M.; Ikeda, M.; Sugasaki, A.; Shinkai, S. Acc. Chem. Res.
2001, 34, 865−873.
(18) Ramsay, W. J.; Nitschke, J. R. J. Am. Chem. Soc. 2014, 136,
7038−7043.
(19) (a) Zhu, L.; Anslyn, E. V. Angew. Chem., Int. Ed. 2006, 45,
1190−1196. (b) Saha, I.; Lee, J. H.; Hwang, H.; Kim, T. S.; Lee, C.-H.
Chem. Commun. 2015, 51, 5679−5682.
(20) Gianneschi, N. C.; Bertin, P. A.; Nguyen, S. T.; Mirkin, C. A.;
Zakharov, L. N.; Rheingold, A. L. J. Am. Chem. Soc. 2003, 125, 10508−
10509.
(21) Mammen, M.; Choi, S.-K.; Whitesides, G. M. Angew. Chem., Int.
Ed. 1998, 37, 2754−2794.
(22) Voss, N. R.; Gerstein, M. Nucleic Acids Res. 2010, 38, W555−
W562.
(23) Venugopalan, P.; Buergi, H.-B.; Frank, N. L.; Baldridge, K. K.;
Siegel, J. S. Tetrahedron Lett. 1995, 36, 2419−2422.
(24) Meyer, E. A.; Castellano, R. K.; Diederich, F. Angew. Chem., Int.
Ed. 2003, 42, 4120.
(25) Yu, G.; Jie, K.; Huang, F. Chem. Rev. 2015, 115, 7240.
(26) Cohen, Y.; Avram, L.; Frish, L. Angew. Chem., Int. Ed. 2005, 44,
520−554.
(27) Hirose, K. Anal. Methods Supramol. Chem. 2007, 17−54.
(28) Frontiers in Supramolecular Organic Chemistry and Photo-
chemistry; Schneider, H. J., Duerr, H., Eds.; VCH: Weinheim, 1991.
(29) Gibb, B. C. Chemosensors 2011, 3−18.
(30) (a) Thordarson, P.; Bijsterveld, E. J. A.; Elemans, J. A. A. W.;
Kasak, P.; Nolte, R. J. M.; Rowan, A. E. J. Am. Chem. Soc. 2003, 125,
1186−1187. (b) Nabeshima, T.; Yoshihira, Y.; Saiki, T.; Akine, S.;
Horn, E. J. Am. Chem. Soc. 2003, 125, 28−29.
(31) Lee, C.; Yang, W.; Parr, R. G. Phys. Rev. B: Condens. Matter
Mater. Phys. 1988, 37, 785−789.
(32) Thordarson, P. Chem. Soc. Rev. 2011, 40, 1305−1323.
(33) Zhao, Y.; Truhlar, D. G. Theor. Chem. Acc. 2008, 120, 215−241.
(34) Badjic, J. D.; Balzani, V.; Credi, A.; Lowe, J. N.; Silvi, S.;
Stoddart, J. F. Chem. - Eur. J. 2004, 10, 1926−1935.
F
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