Ex2box: Interdependent modes of binding in a two-nanometer-long synthetic receptor

Article abstract of DOI:10.1021/ja4052763

Incorporation of two biphenylene-bridged 4,4′-bipyridinium extended viologen units into a para-phenylene-based cyclophane results in a synthetic receptor that is ～2 nm long and adopts a box-like geometry. This cyclophane, Ex²Box⁴⁺, possesses the ability to form binary and ternary complexes with a myriad of guest molecules ranging from long π-electron-rich polycyclic aromatic hydrocarbons, such as tetracene, tetraphene, and chrysene, to π-electron-poor 2,6-dinitrotoluene, 1,2,4-trichlorobenzene, and both the 9,10- and 1,4-anthraquinone molecules. Moreover, Ex²Box⁴⁺ is capable of forming one-to-one complexes with polyether macrocycles that consist of two π-electron-rich dioxynaphthalene units, namely, 1,5-dinaphtho[38]crown-10. This type of broad molecular recognition is possible because the electronic constitution of Ex ²Box⁴⁺ is such that the pyridinium rings located at the ends of the cyclophane are electron-poor and prefer to enter into donor-acceptor interactions with π-electron-rich guests, while the middle of the cyclophane, consisting of the biphenylene spacer, is more electron-rich and can interact with π-electron-poor guests. In some cases, these different modes of binding can act in concert to generate one-to-one complexes which possess high stability constants in organic media. The binding affinity of Ex²Box⁴⁺ was investigated in the solid state by way of single-crystal X-ray diffraction and in solution by using UV-vis and NMR spectroscopy for 12 inclusion complexes consisting of the tetracationic cyclophane and the corresponding guests of different sizes, shapes, and electronic compositions. Additionally, density functional theory was carried out to elucidate the relative energetic differences between the different modes of binding of Ex²Box⁴⁺ with anthracene, 9,10-anthraquinone, and 1,4-anthraquinone in order to understand the degree with which each mode of binding contributes to the overall encapsulation of each guest.

Full text of DOI:10.1021/ja4052763

Article
pubs.acs.org/JACS
Ex2Box: Interdependent Modes of Binding in a Two-Nanometer-Long
Synthetic Receptor
Michal Jurícek,†,⊥ Jonathan C. Barnes,†,⊥ Edward J. Dale,† Wei-Guang Liu,§ Nathan L. Strutt,†
̌
Carson J. Bruns,† Nicolaas A. Vermeulen,† Kala C. Ghooray,† Amy A. Sarjeant,† Charlotte L. Stern,†
Youssry Y. Botros,‡,∥ William A. Goddard, III,*,§ and J. Fraser Stoddart*,†
†Department of Chemistry, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208, United States
‡Intel Laboratories, Building RNB-6-61, 2200 Mission College Boulevard, Santa Clara, California 95054, United States
∥National Center for Nano Technology Research, King Abdulaziz City for Science and Technology (KACST), P.O. Box 6086,
Riyadh 11442, Kingdom of Saudi Arabia
§Materials and Process Simulation Center, California Institute of Technology, 1200 East California Boulevard, Pasadena,
California 91125, United States
S
* Supporting Information
ABSTRACT: Incorporation of two biphenylene-bridged 4,4′-
bipyridinium extended viologen units into a para-phenylene-
based cyclophane results in a synthetic receptor that is ∼2 nm
long and adopts a box-like geometry. This cyclophane, Ex2Box4+,
possesses the ability to form binary and ternary complexes with a
myriad of guest molecules ranging from long π-electron-rich
polycyclic aromatic hydrocarbons, such as tetracene, tetraphene,
and chrysene, to π-electron-poor 2,6-dinitrotoluene, 1,2,4-
trichlorobenzene, and both the 9,10- and 1,4-anthraquinone
molecules. Moreover, Ex2Box4+ is capable of forming one-to-one
complexes with polyether macrocycles that consist of two π-electron-rich dioxynaphthalene units, namely, 1,5-dinaphtho[38]-
crown-10. This type of broad molecular recognition is possible because the electronic constitution of Ex2Box4+ is such that the
pyridinium rings located at the “ends” of the cyclophane are electron-poor and prefer to enter into donor−acceptor interactions
with π-electron-rich guests, while the “middle” of the cyclophane, consisting of the biphenylene spacer, is more electron-rich and
can interact with π-electron-poor guests. In some cases, these different modes of binding can act in concert to generate one-to-
one complexes which possess high stability constants in organic media. The binding affinity of Ex2Box4+ was investigated in the
solid state by way of single-crystal X-ray diffraction and in solution by using UV−vis and NMR spectroscopy for 12 inclusion
complexes consisting of the tetracationic cyclophane and the corresponding guests of different sizes, shapes, and electronic
compositions. Additionally, density functional theory was carried out to elucidate the relative energetic differences between the
different modes of binding of Ex2Box4+ with anthracene, 9,10-anthraquinone, and 1,4-anthraquinone in order to understand the
degree with which each mode of binding contributes to the overall encapsulation of each guest.
(CBPQT4+). Each of these receptors possesses specific
noncovalent modes of binding toward substrates either in the
form of (1) ion−dipole interactions, (2) hydrogen bonding, (3)
charge-transfer interactions, (4) chelation, and/or (5) con-
INTRODUCTION
Pedersen’s discovery1 of crown ethers2 and the subsequent
investigation of their ability to bind alkali and alkaline earth
metal cations opened the way for synthetic chemists to design
■
tributing hydrophobic effects. Typically speaking, however,
molecules that function as selective molecular receptors. His
most of these macrocycles are capable of binding only guests of
landmark paper was followed by seminal contributions from
Cram3 and Lehn4 who introduced more complex receptors
similar shape, size, and electronic constitution, that is, either
electron-rich or -poor. In order to craft a single macrocycle
with the objective of expanding the notion of molecular
capable of binding simultaneously a myriad of guests with
recognition beyond just the molecule. Their contributions to
host−guest5 and supramolecular6 chemistry, respectively, laid
different shapes and sizes, while also possessing multiple
pockets that function using different modes of recognition, a
the foundation upon which macrocyclic receptors have
assumed a litany of functions in chemistry.
large macrocycle consisting of a diverse electronic architec-
turemuch like that of an enzymeis required. Here, we
Some of the more commonly studied synthetic macrocycles,
apart from the crown ethers, are the cyclodextrins,7
cucurbiturils,8 calixarenes,9 pillararenes,10 porphyrins,11 and
Received: May 25, 2013
cyclophanes,12 such as cyclobis(paraquat-p-phenylene)13
© XXXX American Chemical Society
A
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Hz, 4H), 7.83−7.78 (AA′BB′, 8H), 7.57 (XX′ of AA′XX′, J = 6.2, 1.6
Hz, 4H). 13C NMR (125 MHz, CDCl3, ppm): δC 150.5, 147.8, 141.1,
137.6, 127.9, 127.7, 121.6.
DB·2PF6. α,α′-Dibromo-p-xylene (5.14 g, 19.5 mmol) was added to
a 1:1 mixture of CH2Cl2/MeCN (240 mL) in a round-bottomed
three-necked flask, and the resulting mixture was heated at 50 °C while
stirring until all of the solid material dissolved. Next, the temperature
of the oil bath was raised to 90 °C, and a suspension of Ex2BIPY (600
mg, 1.95 mmol) in MeCN (120 mL) was added in four aliquots slowly
over the course of 4 h. After heating under reflux for 24 h, the reaction
mixture was cooled to room temperature, and the yellow precipitate
was collected by filtration and washed with CH2Cl2. The yellow solid
was dissolved in cold (≤RT) MeOH (∼1 L) followed by the addition
of NH4PF6 (∼400 mg) and cold (≤RT) H2O (∼1 L), resulting in the
precipitation of pure DB·2PF6 (1.35 g, 72%) that was collected by
filtration as a yellowish solid. HRMS-ESI for DB·2PF6; calcd for
C38H31Br2F12N2P2: m/z = 821.0552 [M − PF6]+; found: 821.0551 [M
− PF6]+. 1H NMR (500 MHz, CD3CN, ppm): δH 8.76 (AA′ of
AA′XX′, J = 6.3 Hz, 4H), 8.33 (XX′ of AA′XX′, J = 6.3 Hz, 4H), 8.07
(AA′ of AA′BB′, J = 8.2 Hz, 4H), 8.01 (BB′ of AA′BB′, J = 8.1 Hz,
4H), 7.55 (AA′ of AA′BB′, J = 7.9 Hz, 4H), 7.46 (BB′ of AA′BB′, J =
7.8 Hz, 4H), 5.70 (s, 4H), 4.61 (s, 4H). 13C NMR (125 MHz,
CD3CN, ppm): δC 156.9, 145.3, 143.8, 141.1, 134.5, 134.3, 131.1,
130.3, 129.9, 129.3, 126.2, 64.1, 33.5.
Figure 1. (a) Structural formula of Ex2Box4+ (left) and stick
representation of the solid-state structure (right) for Ex2Box·4PF6.
(b) Electrostatic potential map (left) and its schematic representation
(right) for Ex2Box4+. Color code: red = relatively lower electron
density; and blue = relatively higher electron density. (c) HOMO
(left) and LUMO (right) electron density distributions for Ex2Box4+
obtained from DFT calculations.
Ex2Box·4PF6. A solution of DB·2PF6 (600 mg, 0.621 mmol),
Ex2BIPY (192 mg, 0.621 mmol), and the template pyrene (754 mg,
3.73 mmol) in dry MeCN (450 mL) was stirred at RT for 17 d. The
reaction was quenched by adding concentrated HCl (2−3 mL),
causing the crude product to precipitate from solution. The yellowish
precipitate was collected by filtration and dissolved in hot MeOH. The
crude Ex2Box·4PF6 was precipitated from solution by adding NH4PF6
(∼0.5 g) and an excess of H2O before being subjected to column
chromatography using silica gel and CH2Cl2/MeCN (1:1) and 0.25−
0.5% NH4PF6 in MeCN (w/v) as the eluents. Recrystallization in
MeCN on slow vapor diffusion of iPr2O yielded pure Ex2Box·4PF6
(87−104 mg, 10−12%) as a pale-yellow solid. HRMS-ESI of Ex2Box·
4PF6; calcd for C60H48F24N4P4: m/z = 1259.2799 [M − PF6]+,
557.1576 [M − 2PF6]2+; found: 1259.2792 [M − PF6]+, 557.1590 [M
report the design, synthesis, and versatile binding properties of
a large, globally rigid cyclophane, Ex2Box4+ (Figure 1),
comprised of two biphenylene-bridged bipyridinium units
also referred14 to as extended viologensthat is capable of
binding π-electron-rich and -poor guests, either as two
molecules simultaneously or in the form of long oligoacenes
such as tetracene, tetraphene, and chrysene.
1
− 2PF6]2+. H NMR (500 MHz, CD3CN, ppm): δH 8.74 (AA′ of
AA′XX′, J = 7.0 Hz, 8H), 8.18 (XX′ of AA′XX′, J = 6.9 Hz, 8H), 7.89
(AA′ of AA′BB′, J = 8.6 Hz, 8H), 7.84 (BB′ of AA′BB′, J = 8.6 Hz,
8H), 7.63 (s, 8H), 5.67 (s, 8H). 13C NMR (125 MHz, CD3CN, ppm):
δC 156.4, 144.8, 143.4, 137.0, 133.9, 131.0, 129.6, 129.1, 126.0, 64.5.
Crystal Parameters for Ex2Box·4PF6. [C60H48N4·(PF6)4]·
(MeCN)2. Colorless block (0.18 × 0.70 × 0.04 mm). Monoclinic,
P21/c, a = 20.278(8), b = 12.043(5), c = 14.511(7) Å, α = 90.000, β =
EXPERIMENTAL SECTION
■
The full experimental details are provided in the Supporting
Information. Below, the most important information is summarized
briefly.
1
1H NMR Titrations. H NMR (298 K, 600 MHz) titrations were
108.579(3), γ = 90.000°, V = 3358.9(3) Å3, Z = 2, T = 100.01 K, ρcalc
=
performed by adding small volumes of a concentrated guest solution/
suspension in either CD3CN or CDCl3 (depending on solubility) to a
solution of Ex2Box·4PF6 in CD3CN. Tetramethylsilane was used as a
reference. Significant upfield shifts of the 1H resonances for β, γ, and δ
protons were observed and used to determine the association
constants (Ka). The Ka values (M−1) were calculated using Dynafit,
a program that employs nonlinear least-squares regression on ligand−
receptor binding data.
1.470 g cm−3, μ = 2.042 mm−1. Of a total of 5570 reflections that were
collected, 5570 were unique. Final R1 = 0.0452 and wR2 = 0.1093.
CCDC Number: 913422.
Crystal Parameters for Ex2Box⊂(Anthracene)0. 5
·
4PF6(anthracene). [C60H48N4⊂(C14H10)0.5·(PF6)4]·(C14H10)·
(MeCN) . Yellow block (0.25 × 0.10 × 0.05 mm). Triclinic, P1, a
̅
2
= 10.061(3), b = 11.220(4), c = 21.754(7) Å, α = 77.931(18), β =
85.603(18), γ = 65.560(16)°, V = 2186.1(13) Å3, Z = 1, T = 100.03 K,
ρcalc = 1.333 g cm−3, μ = 0.184 mm−1. Of a total of 59 360 reflections
that were collected, 12 946 were unique. Final R1 = 0.0898 and wR2 =
0.2662. CCDC Number: 913425.
Ex2BIPY. A mixture of pyridin-4-ylboronic acid pinacol ester (10.0
g, 48.8 mmol), 4,4′-dibromo-1,1′-biphenyl (6.09 g, 19.5 mmol),
Pd(PPh3)4 (1.13 g, 0.970 mmol), Cs2CO3 (22.6 g, 117 mmol), and a
1:1 mixture of dry PhMe/DMF (500 mL) was heated to 130 °C under
Ar for 72 h before the hot reaction mixture was rendered acidic (pH
2−3) by adding dropwise concentrated HCl, which caused the crude
product to precipitate from solution. Then, the reaction mixture was
cooled to room temperature, filtered, and washed with CH2Cl2. The
solid was dispersed in H2O at 80 °C, and NaOH solution (10 M) was
added dropwise until the pH was ∼8−9, resulting in precipitation of
the desired product. The solid was filtered and washed with H2O,
dissolved in a 1:1 mixture of hot CHCl3/PhMe and filtered through
Celite. The filtrate was concentrated in vacuo, yielding pure Ex2BIPY
(4.2 g, 71%) as a white solid. HRMS-ESI for Ex2BIPY; calcd for
C22H16N2: m/z = 309.1386 [M + H]+; found: 309.1383 [M + H]+. 1H
NMR (500 MHz, CDCl3, ppm): δH 8.70 (AA′ of AA′XX′, J = 6.1, 1.6
Crystal Parameters for Ex2Box⊂Pyrene·4PF6(pyrene).
[C60H48N4⊂C16H10·(PF6)4]·(C16H10)·(MeCN)4. Yellow block (0.22
× 0.13 × 0.09 mm). Triclinic, P1, a = 10.280(3), b = 11.369(3), c =
̅
21.540(6) Å, α = 78.670(13), β = 84.909(13), γ = 64.499(13)°, V =
2227.88(11) Å3, Z = 1, T = 100.03 K, ρcalc = 1.471 g cm−3, μ = 0.190
mm−1. Of a total of 61 143 reflections that were collected, 12 838 were
unique. Final R1 = 0.0910 and wR2 = 0.2082. CCDC Number: 913426.
Crystal Parameters for Ex2Box⊂(Tetraphene)0. 5
4PF6(tetraphene)0.5. [C60H48N4⊂(C18H12)0.5·(PF6)4]·(C18H12)0.5
·
·
(MeCN) . Colorless block (0.11 × 0.08 × 0.04 mm). Triclinic, P1,
̅
3
a = 10.415(7), b = 11.339(9), c = 21.467(14) Å, α = 79.584(18), β =
85.427(13), γ = 65.790(2)°, V = 2274.0(3) Å3, Z = 1, T = 99.98 K, ρcalc
B
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a
Scheme 1. Two-Step Synthesis of Ex2Box·4PF6 Starting from Extended 4,4′-Bipyridine Ex2BIPY
a
Both the nontemplated and pyrene (6 equiv)-templated reaction of intermediate DB·4PF6 (1 equiv) with Ex2BIPY (1 equiv) in the second step
afforded the desired Ex2Box·4PF6 in similar 10−12% yields.
= 1.283 g cm−3, μ = 1.595 mm−1. Of a total of 14 610 reflections that
were collected, 7508 were unique. Final R1 = 0.1060 and wR2 = 0.3191.
CCDC Number: 936766.
Colorless block (0.11 × 0.08 × 0.04 mm). Triclinic, P1, a =
̅
10.4059(3), b = 11.3697(3), c = 21.2021(5) Å, α = 81.1853(12), β =
86.2716(13), γ = 64.9951(11)°, V = 2246.50(10) Å3, Z = 1, T =
100.03 K, ρcalc = 1.530 g cm−3, μ = 0.197 mm−1. Of a total of 90 082
reflections that were collected, 13 104 were unique. Final R1 = 0.1051
and wR2 = 0.2775. CCDC Number: 936770.
Crystal Parameters for Ex2Box⊂Chrysene·4PF6(chrysene).
[C60H48N4⊂C18H12·(PF6)4]·(C18H12)·(MeCN)4. Colorless block
(0.19 × 0.10 × 0.01 mm). Triclinic, P1, a = 10.480(4), b =
̅
Crystal Parameters for Ex2Box⊂(1,2,4-Trichlorobenzene)2·
4PF6(tetracene). [C60H48N4⊂(C6H3Cl3)2·(PF6)4]·(C18H12)·
11.349(5), c = 21.442(9) Å, α = 80.25(3), β = 86.77(3), γ =
64.519(2)°, V = 2268.6(17) Å3, Z = 1, T = 100.12 K, ρcalc = 1.483 g
cm−3, μ = 1.687 mm−1. Of a total of 14 871 reflections that were
collected, 7507 were unique. Final R1 = 0.0447 and wR2 = 0.1137.
CCDC Number: 936767.
(MeCN) . Yellow block (0.21 × 0.12 × 0.04 mm). Triclinic, P1, a
̅
4
= 10.779(3), b = 11.107(3), c = 21.133(5) Å, α = 81.978(10), β =
88.551(10), γ = 67.138(10)°, V = 2307.3(10) Å3, Z = 1, T = 99.99 K,
ρcalc = 1.555 g cm−3, μ = 3.257 mm−1. Of a total of 22 031 reflections
that were collected, 7769 were unique. Final R1 = 0.0435 and wR2 =
0.1208. CCDC Number: 913423.
Crystal Parameters for Ex2Box⊂Tetracene·4PF6(tetracene).
[C60H48N4⊂(C18H12)·(PF6)4]·(C18H12)·(MeCN)4. Orange block
(0.23 × 0.10 × 0.02 mm). Triclinic, P1, a = 10.480(3), b =
̅
11.384(3), c = 21.556(6) Å, α = 80.426(2), β = 86.407(17), γ =
63.302(16)°, V = 2265.29(11) Å3, Z = 1, T = 99.95 K, ρcalc = 1.448 g
cm−3, μ = 1.689 mm−1. Of a total of 14 958 reflections that were
collected, 7309 were unique. Final R1 = 0.0546 and wR2 = 0.1575.
CCDC Number: 913427.
Crystal Parameters for Ex2Box⊂(1,5-Dinaphtho[38]crown-
10)·4PF6. [C60H48N4⊂C36H44O10·(PF6)4]·(MeCN)8. Orange block
(0.47 × 0.13 × 0.08 mm). Triclinic, P1, a = 10.821(3), b = 13.528(3),
̅
c = 21.903(6) Å, α = 88.571(13), β = 86.429(12), γ = 72.761(11)°, V
= 3056.3(14) Å3, Z = 1, T = 99.98 K, ρcalc = 1.286 g cm−3, μ = 1.398
mm−1. Of a total of 24 907 reflections that were collected, 10 092 were
unique. Final R1 = 0.0562 and wR2 = 0.1607. CCDC Number: 913424.
Crystal Parameters for Ex2Box⊂(2,6-Dinitrotoluene)·4PF6.
[C60H48N4⊂C7H6N2O4·(PF6)4]. Colorless block (0.17 × 0.08 × 0.03
mm). Orthorhombic, Cmca, a = 14.443(6), b = 38.482(14), c =
12.120(4) Å, α = 90.000, β = 90.000, γ = 90.000°, V = 6735.9(4) Å3, Z
= 4, T = 99.99 K, ρcalc = 1.565 g cm−3, μ = 2.125 mm−1. Of a total of
13 160 reflections that were collected, 2799 were unique. Final R1 =
0.0791 and wR2 = 0.2195. CCDC Number: 913429.
RESULTS AND DISCUSSION
■
The chemical constitution of Ex2Box4+ (Figure 1a) is based on
the family of 1,4-phenylene-bridged 4,4′-bipyridiniums,14
referred to here as ExnBIPY2+ (n is the number of bridging
phenylene rings). In the case of Ex2Box4+, two pyridinium rings
are bridged by two (n = 2) phenylene ringsessentially a
biphenylene subunitto form Ex2BIPY2+, while two of these
subunits are bridged by two para-xylylene moieties to form a
tetracationic cyclophane which has a rectangular or box-like
geometry. From its solid-state structure (Figure 1a), its width of
6.8 Å, or 3.4 Å when considering the van der Waals radius, is
well suited13,15 to the accommodation of π-conjugated aromatic
guests, while its length of 18.9 Å allows a guest to be as long as
15.5 Å in relation to the van der Waals radii. In addition to this
vast cavity of almost 2 nm in length, the backbone of Ex2Box4+
is electronically nonuniform (Figure 1b), thus making it
possible to match the electronic constitutions of guests with
those of the receptor and exploit multiple modes of binding
with the aim of increasing the affinity of Ex2Box4+ toward a
particular guest. The electrostatic potential map (Figure 1b)
and the HOMO/LUMO electron density distribution (Figure
1c) of Ex2Box4+, obtained from density functional theory
(DFT) calculations, show that the biphenylene subunit in the
middle is more electronegative (the electron-rich region), while
Crystal Parameters for Ex2Box⊂(1,5-Dinitronaphthalene)·
4PF6. [C60H48N4⊂C10H6N2O4·(PF6)4]. Yellow block (0.19 × 0.16 ×
0.01 mm). Orthorhombic, Cmca, a = 14.913(6), b = 38.067(17), c =
12.106(5) Å, α = 90.000, β = 90.000, γ = 90.000°, V = 6872.8(5) Å3, Z
= 4, T = 100.01 K, ρcalc = 1.569 g cm−3, μ = 2.098 mm−1. Of a total of
13 018 reflections that were collected, 3017 were unique. Final R1 =
0.0422 and wR2 = 0.0994. CCDC Number: 936768.
Crystal Parameters for Ex2Box⊂(9,10-Anthraquinone)0.5
·
4PF6. [C60H48N4⊂(C14H10O2)0.5·(PF6)4]·MeCN. Yellow block (0.05
× 0.05 × 0.03 mm). Monoclinic, P21/c, a = 20.082(37), b = 12.103(4),
c = 14.458(6) Å, α = 90.000, β = 106.223(3), γ = 90.000°, V =
3374.2(2) Å3, Z = 2, T = 100.01 K, ρcalc = 1.528 g cm−3, μ = 2.068
mm−1. Of a total of 4115 reflections that were collected, 4115 were
unique. Final R1 = 0.0636 and wR2 = 0.1751. CCDC Number: 913430.
Crystal Parameters for Ex2Box⊂(1,4-Anthraquinone)·4PF6.
[C60H48N4⊂C14H8O2·(PF6)4]·(CHCl3)2. Yellow block (0.45 × 0.14 ×
0.12 mm). Monoclinic, P21/c, a = 9.790(4), b = 14.131(6), c =
27.617(12) Å, α = 90.000, β = 95.911(2), γ = 90.000°, V = 3800.4(3)
Å3, Z = 2, T = 100.0 K, ρcalc = 1.618 g cm−3, μ = 0.421 mm−1. Of a
total of 57 735 reflections that were collected, 11 430 were unique.
Final R1 = 0.0722 and wR2 = 0.2057. CCDC Number: 936769.
Crystal Parameters for Ex2Box⊂[1,4-Bis(3-methoxyphenyl)-
1H-1,2,3-triazole]·4PF6[1,4-Bis(3-methoxyphenyl)-1H-1,2,3-tri-
azole]. [C60H48N4⊂C16H15N3O2·(PF6)4]·(C16H15N3O2)·(MeCN)2.5.
C
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1
Figure 2. Structural formulas of the guests and the corresponding Ka values for binding inside Ex2Box4+ obtained by H NMR spectroscopy in
CD3CN (left) and the side-on (middle) and plan (right) views of the stick/space-filling representations of the solid-state superstructures of the
complexes of Ex2Box4+ with (a) anthracene, (b) pyrene, (c) tetraphene, (d) chrysene, and (e) tetracene. The hydrogen atoms, counterions, and
solvent molecules are omitted for the sake of clarity. Color code: green = all atoms of Ex2Box4+; and black = the carbon atoms of the aromatic core
of the guest. N.D. = not determined.
the pyridinium rings of Ex2Box4+ are more electropositive (the
electron-deficient region).
In order to probe the concerted modes of binding in
Ex2Box4+, various electron-rich polycyclic aromatic hydro-
carbon (PAH) guests were first investigated, and their
complexes with Ex2Box4+ were studied in the solid state
(XRD), in solution (1H NMR/CD3CN), and in silico. Single
crystals of the 1:1 complexes of five guestsanthracene,
pyrene, tetraphene, chrysene, and tetracenewith Ex2Box4+
were obtained by slow vapor diffusion of iPr2O into the
solution of the corresponding “1:1 complex” in MeCN, and the
XRD analysis (see Figure 2) of these crystals reveals the
binding diversity exhibited by Ex2Box4+.
Considering all five PAH guests investigated, each demon-
strates a different behavior in the solid state from that
observed15 in the case of ExBox4+. Instead of being aligned
along one side of the cyclophane, which would lead to charge-
transfer and van der Waals interactions, anthracene and pyrene
are positioned (Figure 2a,b, respectively) at angles of ∼45° and
90°, respectively, protruding from the cavity of Ex2Box4+. By
comparison,15 both anthracene and pyrene are almost fully
aligned along its long axis inside the cavity of ExBox4+. By
contrast, tetraphene, chrysene, and tetracene, which can overlap
with all four pyridinium rings of Ex2Box4+ and assist in charge-
transfer interactions on each end, are aligned (Figure 2c−e,
respectively) inside Ex2Box4+ but not inside ExBox4+ since the
length (11.3 Å, van der Waals) of the latter is not sufficient to
accommodate guests longer than anthracene (11.3 Å, van der
Waals). Out of the three, chrysene and tetracene are centered
Synthesis and Complex Formation. Ex2Box·4PF6 was
synthesized (Scheme 1) using a modified procedure (see the
Experimental Section) based on the preparation15 of its shorter
analogue, ExBox·4PF6. The synthesis was carried out by
treating the extended bipyridine (Ex2BIPY) with an excess of
α,α′-dibromo-p-xylene affording, after counterion exchange, the
hexafluorophosphate salt DB·2PF6. Subsequently, the cycliza-
tion step was performed by using Ex2BIPY and DB·2PF6 (in a
1:1 ratio) following two synthetic pathways: pyrene-templated
and nontemplated. Both methods led to the formation of the
desired product Ex2Box·4PF6 in comparable, 10−12%, yields. It
should be noted that these yields are lower than those
obtained15 for ExBox·4PF6, 19 and 42% yields for the
nontemplated and pyrene-templated procedures, respectively.
This result indicates that no templation of Ex2Box4+ occurs
using pyrene as the template, and the 10−12% yield merely
reflects the nontemplated pathway followed during the
cyclization step. The decrease in yield (from 19% to 10−
12%) for the nontemplated pathway when comparing ExBox4+
with Ex2Box4+ is most likely the result of the limited solubility
of Ex2BIPY in the reaction medium (MeCN). Full character-
izationNMR spectroscopy, HRMS, and XRDof Ex2Box·
4PF6 was carried out (see the Experimental Section for a full
synthetic description and characterization data for all the
precursors).
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anthracene and pyrene do not align inside Ex2Box4+ in the solid
state, a series of DFT calculations have been carried out using
anthracene as the model system.
Table 1. Binding Parameters of the Ex2Box4+⊂Guest
Complexes
binding parameters
DFT Calculations. In order to understand the relative
energetics which govern the mode of solid-state binding within
the elongated Ex2Box4+ cavity, the geometry of the
Ex2Box4+⊂anthracene complex in Figure 2a was optimized in
the Poisson−Boltzmann solvation model16 for MeCN (ε = 37.5
and R0 = 2.18 Å) at the level17 of M06-2X/6-311G with Jaguar
7.5 to calculate the relative energies (E) associated with moving
(Figure 3a) the anthracene guest over some distance (d) along
the length of the Ex2Box4+ cavity. After moving the guest,
relative to the host, the position of the anthracene center was
fixed, and both the host and guest were allowed to relax to find
the lowest-energy co-conformation of the 1:1 complex. Starting
from the crystal superstructure (Figure 3a; “crystal-like co-
conformation”), it is possible to calculate the relative energies
of the 1:1 complex as the anthracene guest is moved gradually
toward the center position (0.0 Å) of the cyclophane. As this
movement is enacted, a global energetic minimum, where the
guest is ∼2.5 Å away from the 0.0 Å position of Ex2Box4+, is
reached. This energy minimum occurs as a consequence of the
ideal overlap between one of the terminal benzenoid rings of
anthracene with the pyridinium rings of the host in addition to
the slipped π−π stacking interactions that occur between the
biphenylene bridges in the host with the remaining two
benzenoid rings of anthracene. Once the moving guest
molecule reaches the 0.0 Å position of the cyclophane, the
potential energy reaches a global maximum, indicating that the
donor−acceptor interactions near the pyridinium rings of the
cyclophane contribute the most in relation to the overall
binding of the 1:1 complex. If the anthracene guest is moved
beyond the 0.0 Å position to the other end of the cyclophane,
then the relative energy levels mirror, as expected, that of the
opposite end. Essentially, the co-conformation observed in the
solid state corresponds to the local minimum when the
semiorthogonal anthracene guest is allowed to overlap with the
π-electron-poor pyridinium rings of Ex2Box4+. This co-
conformation is 1.25 kcal mol−1 higher in energy than that of
the global minimum when the guest is mostly aligned with the
viologen subunits of Ex2Box4+. Thus, any π-electron-rich guest
that is incapable of overlapping with both of the π-electron-
poor pockets can only enter into favorable charge-transfer
interactions and polarization (interaction between a charge and
an induced dipole) at one of the ends of the cyclophane.18
In order to determine whether or not an electron-poor guest
can bind inside Ex2Box4+, a similar calculation (Figure 3b) for
the 1:1 complex of Ex2Box4+⊂9,10-anthraquinone reveals an
analogous mirror-like behavior between the relative energy
levels when the guest is positioned at either end of the
cyclophane. The difference in binding 9,10-anthraquinone
(9,10-AQ), however, lies in the fact that the central quinone
portion introduces a π-electron-poor region in the guest
molecule that forces the global minimum to exist ∼2.5 Å away
from the central 0.0 Å position (similar to anthracene) of
Ex2Box4+ and the next (local) minimum to exist ∼1.5 Å from
the central position. This co-conformation is different from that
observed computationally for anthracene and can be attributed
to favorable van der Waals interactionsand not charge-
transfer interactionsbetween Ex2Box4+ and 9,10-AQ.
a
d
e
guest
Ka/103 (M−1
)
E (kcal mol−1
)
ΔErel (kcal mol−1
)
anthracene
pyrene
0.237 0.026
0.172 0.009
1.46 0.32
6.36 2.5
−20.7
−
−
−
−25.8
−
−9.9
−
−
−
−14.7
−
tetraphene
chrysene
tetracene
DNT
b
−
0.022 0.010
0.042 0.021
0.463 0.018
0.825 0.106
0.836 0.013
DNN
−
−
9,10-AQ
1,4-AQ
BMPT
−21.4
−23.7
−
−
−
−10.3
−12.6
−
−
−
c
TCB
−
DN38C10
1.11 0.063
a
Determined by 1H NMR spectroscopy (CD3CN; CDCl3 for the
guests with limited solubility in CD3CN; all at 298 K). Binding
affinity could not be determined on account of solubility restrictions.
Binding affinity was too low for detection. Energy determined by
DFT calculations. Relative energy compared to the complex of
Ex2Box4+ with four MeCN molecules (E = −11.1 kcal mol−1)
determined by DFT calculations.
b
c
d
e
inside Ex2Box4+, while tetraphene is positioned closer to one
end of the cavity.
Binding studies in solution support the observations in the
solid state. By comparing the values of the binding affinities
1
(Table 1) for the five studied PAHs, obtained by H NMR
titration in CD3CN, anthracene and pyrene have significantly
lower Ka values (237 and 172 M−1, respectively) than those
(1.46 × 103 and 6.36 × 103 M−1, respectively) observed for
tetraphene and chrysene; the Ka value for tetracene could not
be determined because of solubility restrictions. The Ka values
for binding of anthracene and pyrene inside Ex2Box4+ are also
lower than those (883 and 7.16 × 103 M−1, respectively)
obtained with ExBox4+ and explain why no templation was
observed (Scheme 1) during the synthesis of Ex2Box·4PF6 by
using pyrene. These observations are in agreement with the fact
that only charge-transfer interactions on one end of the cavity
occur when anthracene and pyrene bind inside Ex2Box4+.
Moreover, the pyridinium rings in Ex2Box4+ are separated by
two relatively electron-rich phenylene rings, which decrease
their electron deficiency, and thus their affinities toward
electron-rich guests, when only one end of Ex2Box4+ can assist
in charge-transfer interactions. This hypothesis is further
supported by the fact that relatively weak charge-transfer
bands are observed (Figure S17) in the absorption spectra for
the complexes of Ex2Box4+ with anthracene and pyrene.
When comparing the binding affinities of tetraphene and
chrysene inside ExBox4+ and Ex2Box4+, the Ka values (1.46 ×
103 and 6.36 × 103 M−1, respectively) for Ex2Box4+ are higher
than those (914 and 2.32 × 103 M−1, respectively) for ExBox4+.
This significant increase in binding affinity, by a factor of ∼2,
can be attributed to the favorable alignment of the guests inside
Ex2Box4+, which is not possible in the case of ExBox4+, allowing
for more effective charge-transfer interactions. The smaller Ka
value (1.46 × 103 M−1) for the binding of tetraphene inside
Ex2Box4+ when compared with that (6.36 × 103 M−1) of
chrysene is possibly a result of the noncentered position of
tetraphene inside the cavity (Figure 2c) and/or different
solvophobic effects. To find a possible explanation as to why
When the guest molecule is changed from 9,10-AQ to the
constitutional isomer 1,4-AQ (Figure 3c)the only guest with
a net dipole moment (2.65 D as determined by gas-phase
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1,4-AQ overlaps simultaneously with the pyridinium rings of
Ex2Box4+. When the guest molecule is moved toward the center
0.0 Å position of the cyclophane, a global energy maximum is
obtained where the overlapping of the host−guest orbitals is
disfavored, presumably as a result of its losing the van der Waals
interactions between the terminal aromatic ring of the guest
with the pyridinium rings of the host and the dipole−
quadrupole interaction of the complex. As 1,4-AQ is moved
through the central cyclophane position, local minima are
observed at ∼0.5, 1.5, and 2.5 Å; these co-conformations,
however, remain significantly higher in energy relative to when
the quinone portion of the guest overlaps with the biphenylene
subunit of the cyclophane and the terminal aromatic ring of the
guest overlaps with the pyridinium rings of the cyclophane.
Figure 4 illustrates the plan and side-on views of the frontier
molecular orbitals of the 1:1 host−guest complexes of
Ex2Box4+⊂anthracene (a), Ex2Box4+⊂tetracene (b), and
Ex2Box4+⊂9,10-AQ (c). In the case of electron-rich anthracene
and tetracene, the HOMO resides on the guest molecule, while
the LUMO is located on the host, and the HOMO−LUMO
energy difference (ΔEHOMO−LUMO) of the complexes is 4.43 and
3.90 eV, respectively. The ΔEHOMO−LUMO for the anthracene
complex is greater than that for the tetracene complex on
account of anthracene possessing fewer π-electrons than
tetracene, resulting in a lower HOMO energy level. When
the guest is more electron-poor, as is the case with 9,10-AQ,
then the HOMO resides on the biphenylene subunit of
Ex2Box4+ and the LUMO on 9,10-AQ, and the ΔEHOMO−LUMO
is 5.18 eV. This energy difference is larger than those for
anthracene and tetracene, indicating that the affinity is not
based primarily on charge-transfer interactions, an observation
which is further supported by a complete lack of a charge-
transfer band in the absorption spectrum (Figure S17) of
Ex2Box4+⊂9,10-AQ. Thus, the binding affinity between
Ex2Box4+ and 9,10-AQ is attributed to the van der Waals
interactions, namely, intermolecular polarization.
Analysis (Figure 5a,b) of the frontier molecular orbitals
between Ex2Box4+ and 1,4-AQ demonstrates a similar result to
that observed in the case of 9,10-AQ, where the HOMO resides
on Ex2Box4+ and the LUMO is located on 9,10-AQ. The
ΔEHOMO−LUMO gap is 5.17 eV, resulting once again in the lack
of a charge-transfer band in the absorption spectrum of the 1:1
complex. These data suggest that the binding observed between
Ex2Box4+ and 1,4-AQ also occurs on account of favorable
electrostatic and other van der Waals interactions. Rotating
(Figure 5c) 1,4-AQ inside the cavity of Ex2Box4+ so that the
quinone portion overlaps with the pyridinium rings of the
cyclophane in preference to the biphenylene subunit results in
the loss of the dipole−quadrupole interaction, which increases
the energy of the complex by 3.8 kcal mol−1.
These computational results suggest that the complexation of
an electron-rich guest inside the cavity of Ex2Box4+ favors a co-
conformation which maximizes its orbital overlap with the
pyridinium rings on account of favorable charge-transfer
interactions, while the binding of an electron-poor guest
prefers to adopt a co-conformation which maximizes favorable
van der Waals interactions. A comparison of these different
modes of binding was made by calculating the complexation
energies (Table 1) for the four complexes to find that the
strengths increase in the following order: anthracene (−9.9 kcal
mol−1), 9,10-AQ (−10.3 kcal mol−1), 1,4-AQ (−12.6 kcal
mol−1), and tetracene (−14.7 kcal mol−1). Although 9,10-AQ
and 1,4-AQ capitalize on the electrostatic and other van der
Figure 3. Optimized superstructures of the complexes (a)
Ex2Box4+⊂anthracene, (b) Ex2Box4+⊂9,10-AQ, and (c)
Ex2Box4+⊂1,4-AQ and the relative energies (E) associated with the
different potential binding motifs were explored using DFT at the
M06-2X/6-311G level. After moving the guest molecule some distance
(d/Å) along the length of the viologen subunit of Ex2Box4+, the center
position of the guest molecule was fixed relative to the center position
of the cyclophane, and both the host and guest were allowed to relax
to find the lowest-energy co-conformation of the 1:1 complex.
calculations)the symmetry of the relative energy levels
between the two halves of the cyclophane, not surprisingly, is
lost. In this particular case, the global energy minimum occurs
when the guest molecule capitalizes on the favorable dipole−
quadrupole (electrostatic) interactions between the guest and
the host, in addition to the interactions between the electron-
poor quinone portion of the guest with the biphenylene
subunits of the cyclophane, while the terminal aromatic ring of
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Figure 4. Plan and side-on views of the frontier molecular orbitals of the 1:1 host−guest complexes of (a) Ex2Box4+⊂anthracene, (b)
Ex2Box4+⊂tetracene, and (c) Ex2Box4+⊂9,10-AQ. In each case, the yellow and green colored orbitals represent the HOMO, and the red and blue
colored orbitals represent the LUMO of the 1:1 complexes. The HOMO−LUMO energy difference (ΔEHOMO−LUMO) of each complex is also
provided (right).
Figure 5. Plan views of the frontier molecular orbitals of the 1:1 complex of Ex2Box4+⊂1,4-AQ (a,b). The yellow and green colored orbitals
represent the HOMO, and the red and blue colored orbitals represent the LUMO of the 1:1 complex. The energy values (eV) for the first and
second HOMO/LUMO levels are provided to the right of the orbital figures in (a) and (b). The relative energy difference associated with the
rotation (c) of 1,4-AQ inside the cavity of Ex2Box4+ is demonstrated; it is an action, which results in the overlap of the electron-poor quinone
portion of the guest with one set of pyridinium rings of the cyclophane. This co-conformation is 3.8 kcal mol−1 higher relative to the initial position,
which started with the quinone portion of the guest overlapping with the biphenylene subunit of the host.
Waals interactions, these calculations predict higher binding
affinities for these guests compared to anthracene, an
observation which demonstrates that the accumulation of
multiple weak interactions can result in higher binding affinities
over fewer and weakened charge-transfer interactions. The
highest value, in the case of tetracene, is in agreement with its
predicted high affinity for Ex2Box4+ based on the smallest
ΔEHOMO−LUMO, since the molecule is long enough to reach
both ends of the viologen subunits of the host.
In line with the results obtained from the DFT calculations
(Figures 3−5), the importance of interactions other than
charge-transfer becomes evident (Figure 6) experimentally
when Ex2Box4+ is cocrystallized with π-electron-poor guests,
namely, 2,6-dinitrotoluene (DNT), 1,5-dinitronapththalene
(DNN), 9,10-AQ, and 1,4-AQ. Three out of four electron-
deficient guests (specifically, DNT, DNN, and 9,10-AQ)
crystallized as inclusion complexes wherein the guests reside
(Figure 6a−c, respectively) in the middle of the Ex2Box4+
cavity and overlap optimally with the relatively electron-rich
biphenylene subunits of the cyclophane. In the case of 1,4-AQ,
the guest is positioned (Figure 6d) at one end, or in the
“pocket”, of the Ex2Box4+ cavity such that the naphthalene
subunit maximizes its overlap with the pyridinium rings and the
quinone subunit overlaps with the biphenylene bridge. The
position and orientation of 1,4-AQ inside Ex2Box4+ are in a
close agreement (Figure 3c) with the DFT prediction. In the
case of 9,10-AQ, the guest resides in the middle of the
cyclophane, which is, according (Figure 3b) to the DFT results,
one of the local energy minima. The global-minimum co-
conformation for 9,10-AQ occurs when it is aligned at one end
of the cyclophane in a similar fashion to both anthracene and
1,4-AQ.
Comparing Complex Stabilities. The relatively low Ka
values (Figure 6a−d, Table 1) for electron-deficient guests
support the theory that the charge-transfer interactions are not
present when an electron-deficient guest binds inside Ex2Box4+;
this observation supports the results obtained from DFT
calculations. The Ka values of the electron-deficient guests
become larger as the size of the aromatic core increases,
indicating the growing significance of the van der Waals
interactions inside Ex2Box4+ in the case of these guests. The
smallest one-ring guest, DNT, has a Ka value of 22 M−1, while
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1
Figure 6. Structural formulas of the guests and the corresponding Ka values for binding inside Ex2Box4+ obtained by H NMR spectroscopy in
CD3CN (left) and the side-on (middle) and plan (right) views of the stick/space-filling representations of the solid-state superstructures of the
complexes of Ex2Box4+ with (a) DNT, (b) DNN, (c) 9,10-AQ, (d) 1,4-AQ, and (e) BMPT. The hydrogen atoms, counterions, and solvent
molecules are omitted for the sake of clarity. Color code: green = all atoms of Ex2Box4+; black = the carbon atoms of the aromatic core of the guest;
yellow = electron-deficient substituents/subunits (NO2, CO, N−NN); and red = electron-rich substituents (OMe).
9,10-AQ and 1,4-AQ have the Ka values of 463 and 825 M−1,
respectively. In summary, it can be concluded that various van
der Waals interactions, such as ion−dipole, dipole−dipole, and/
or favorable orbital overlaps,19−21 are the main contributors to
the binding affinities of these guests.
showing an increase in yields in tune with the greater binding
affinity (463 and 836 M−1, respectively) of the template.
The alignment of the larger guests, such as, tetraphene,
chrysene, and BMPT, inside Ex2Box4+ is also observed in
solution (CD3CN) as indicated by 1H NMR spectroscopy. The
1H NMR spectra of the 1:1 complexes of Ex2Box4+ with
chrysene and BMPT are shown in Figure 7. Both complexes
display upfield shifts for the signals corresponding to the β, γ,
and δ protons of Ex2Box4+ and all of the signals for the protons
of the guests, in addition to a small downfield shift for the
resonances associated with the para-xylylene (C6H4) protons of
Ex2Box4+. This effect is caused by π-electron shielding of the
face-to-face oriented aromatic rings, which occurs upon
complexation. The signals for the α and CH2 protons of
Ex2Box4+ display very little or no movements in their 1H NMR
spectra since these protons are located in the pockets of
Ex2Box4+ and are therefore not affected significantly by the
shielding effect of the aromatic guests. This behavior is in good
agreement with the inclusion of the guests inside the cavity of
Ex2Box4+.
The difference in the chemical shifts for the individual proton
signals (H1−H6) of bound and unbound chrysene was
investigated, and the results are in agreement (Figure 7b)
with the fully aligned orientation (Figure 2d) of the guest inside
Ex2Box4+. All six proton signals display upfield change in
chemical shift because of the π-electron shielding of the face-to-
face oriented aromatic rings. Protons H2−H4 are additionally
shielded by the para-xylylene rings at each end of the
cyclophane. Of the three protons H2−H4, proton H3 should
The results obtained (Figures 3 and 6, respectively) from the
binding studies of both π-electron-rich and -poor guests inside
Ex2Box4+ indicate that a Ka value larger than 103 M−1 can be
achieved with the assistance of either the charge-transfer
interactions occurring simultaneously at each end of the
cyclophane (tetraphene and chrysene) or favorable van der
Waals interactions (1,4-AQ). In further support of this theory,
1,4-bis(3-methoxyphenyl)-1H-1,2,3-triazole (BMPT) was de-
signed and synthesized, and its binding properties inside
Ex2Box4+ were investigated (Figure 6e) in the solid state and in
solution. BMPT is nearly linear, possessing two electron-rich 3-
methoxyphenyl rings on either side of the electron-deficient
1H-1,2,3-triazole (triazole) ring in the middle. The electronic
structure of BMPT can, therefore, assist in charge-transfer
interactions at each end of the cyclophane and favorable van
der Waals interaction in the middle. As hypothesized, the Ka
value of BMPT is almost 103 (836 M−1), and the guest is fully
aligned (Figure 6e) inside the cavity of Ex2Box4+ in the solid
state.
As both 9,10-AQ and BMPT show good solubility in MeCN
and their Ka values were higher than that of pyrene, they were
tested as templates in the last step of the synthesis of Ex2Box·
4PF6. The isolated yields for Ex2Box·4PF6 when using 9,10-AQ
and BMPT as the templates were 15% and 20%, respectively,
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The ability of Ex2Box4+ to accommodate (i) two guests or
(ii) two subunits of a single macrocycle inside its cavity is
illustrated in Figure 8. The solid-state superstructures of a one-
ring guest, 1,2,4-trichlorobenzene (TCB, Figure 8a), and a two-
ring guest, 1,5-dinaphtho[38]crown-10 (DN38C10, Figure 8b)
were obtained from X-ray crystallographic analysis of the single
crystals of the corresponding complexes. Single crystals of the
complex of Ex2Box4+ with two TCB molecules were obtained
quite unintentionally while attempting to grow crystals of the
complex of Ex2Box4+ and tetracene, where TCB was present as
the solvent! The solid-state superstructure (Figure 8a) shows
that Ex2Box4+, in contrast to ExBox4+, has enough space to
encapsulate two guests; the two TCB molecules inside the
cavity are in close contact yet are not held together by
hydrogen bonds (Figure 8a, highlighted in blue). DN38C10
provides an example (Figure 8b) in which two dioxynaph-
thalene units within the same molecule allow for an even more
effective binding inside Ex2Box4+. Each dioxynaphthalene unit
is positioned as close as possible to the electron-deficient
pyridinium rings on each side to allow for the maximum
charge-transfer overlap, which is the predominant mode of
binding in Ex2Box4+. The fact that the Ka value (1.11 × 103
M−1) for DN38C10 is higher than those for anthracene and
pyrene by an order of magnitude and is comparable to the
values for anthracene and pyrene bound inside ExBox4+
demonstrates yet again that two charge-transfer interactions
within a 1:1 complex are required to observe binding on the
order of 103.
By comparing the extent (Figure 7d) of the shielding effect
for protons H1−H3 of DN38C10, one can determine the
preferred mode of binding in solution. For example, the signal
for the H3 protons of DN38C10 is shifted upfield by 0.22 ppm
when comparing it with that for the unbound guest, while the
resonance for the H1 protons is shifted by only 0.03 ppm and
the signal for the H2 protons by 0.11 ppm. These observations
imply the close-to-perpendicular orientation of the naphthalene
units of DN38C10 inside Ex2Box4+ (the shielding effect
decreases as the distance between the proton and cavity
increases) and are in agreement with the mode of binding
observed (Figure 8b) in the solid state.
CONCLUSIONS
■
We have shown that Ex2Box4+ is capable of binding both π-
electron-rich (predominantly charge-transfer interactions) and
-poor (predominantly van der Waals interactions) guests on
account of their electronic interplay with the host’s pyridinium
moieties, separated by biphenylene subunits. Such versatility in
a large synthetic host, combined with a simple design, has many
potential advantages. Not only is it possible for Ex2Box4+ to
form ternary complexes with two small guests, as demonstrated
in the case of 1,2,4-trichlorobenzene, but it is also possible to
bind strongly large macrocyclic polyethers such as
dinaphtho[38]crown-10 on account of the presence of two
covalently linked π-electron-rich subunits in the form of
dioxynaphthalene moieties. This recognition could be partic-
ularly useful in the realm of the template directed,22 stepwise
synthesis of topologically challenging molecular knots. Since
the length of Ex2Box4+ is almost 2 nm, it can potentially
encapsulate graphene nanoribbons23 that are as wide as four
fused ringsthe length of tetracenefor the purposes of
nanoribbon exfoliation. Moreover, when converted to the
water-soluble chloride salt, Ex2Box·4Cl may be able to serve as
a phase-transfer catalyst for both π-electron-rich and -poor
Figure 7. Partial 1H NMR spectra of (a) Ex2Box4+ and its 1:1
complexes with (b) chrysene, (c) BMPT, and (d) DN38C10 recorded
in CD3CN (containing ∼10% of CDCl3 (b,d) for the purposes of
solubility) at 298 K on a 600 MHz spectrometer. The 1H NMR
spectrum (black) of the unbound guest in CD3CN is shown above the
1H NMR spectrum of the 1:1 complex (green for the Ex2Box4+ and
black for the bound-guest signals) in (b−d).
be shielded the most since it resides near the center of the para-
xylylene ring. The observed differences in the chemical shifts
for each proton follow exactly this predicted order: (i) 0.34
ppm for proton H3, (ii) 0.25−2.26 ppm for protons H2 and H4,
and (iii) 0.20−0.22 ppm for protons H1, H5, and H6. Similar
behavior was observed (Figure 7c) in the case of BMPT.
According to the fully aligned orientation (Figure 6e) of the
guest inside Ex2Box4+, protons H2 and H3 in BMPT should
display the largest upfield shifts. Indeed, a difference in
chemical shifts of 1.15 and 1.11 ppm was observed for protons
H2 and H3, respectively, while all other protons displayed
upfield change in chemical shift in the range of 0.38−0.52 ppm.
I
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Figure 8. Structural formulas of the guests (left) and the side-on (middle) and plan (right) views of the stick/space-filling representations of the
solid-state superstructures of the complexes of Ex2Box4+ with (a) TCB and (b) DN38C10. The hydrogen atoms, counterions, and solvent molecules
are omitted for the sake of clarity. Color code: green = all atoms of Ex2Box4+; black = the carbon atoms of the aromatic core of the guest; yellow =
the chlorine atom; and red = the polyether chain.
guests that are insoluble in aqueous environments. By taking
advantage of the synergistic nature of Ex2Box4+, guests of
varying sizes and electronic compositions can be matched so as
to exploit multifarious interactions. Gaining a more fundamen-
tal understanding of synergistic binding modes in synthetic
receptors could make it possible one day to mimic the unrivaled
affinity and specificity that is characteristic of the enzyme−
substrate relationship.
supported by a National Defense Science and Engineering
Graduate Fellowship (32 CFR 168a) from the Department of
Defense (DoD) and gratefully acknowledges receipt of a Ryan
Fellowship from the NU International Institute for Nano-
technology (IIN). E.J.D., N.L.S., and C.J.B. are supported by a
Graduate Research Fellowship (GRF) from the National
Science Foundation (NSF).
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■
ASSOCIATED CONTENT
* Supporting Information
■
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Detailed synthetic procedures and characterization (NMR and
HRMS) data for all compounds, crystallographic and
spectroscopic (NMR, CV, and UV−vis) characterization for
Ex2Box·4PF6 and the corresponding inclusion complexes. This
material is available free of charge via the Internet at http://
pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
wag@wag.caltech.edu; stoddart@northwestern.edu
■
Author Contributions
⊥M.J. and J.C.B. contributed equally.
Notes
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ACKNOWLEDGMENTS
■
The data reported are tabulated in the Supporting Information
and the crystallographic parameters of each single crystal were
deposited into the Cambridge Crystallographic Data Centre
(CCDC). The research at Northwestern University (NU) was
enabled by the National Center for Nano Technology Research
at the King Abdulaziz City for Science and Technology
(KACST) in Saudi Arabia. The authors thank Dr. Turki S. Al-
Saud and Dr. Nezar H. Khdary at KACST for their interest in
this research. J.F.S. is supported by the Non-Equilibrium
Energy Research Center (NERC), which is an Energy Frontier
Research Center (EFRC) funded by the U.S. Department of
Energy, Office of Basic Energy Sciences (DOE-BES) under
award DESC0000989. M.J. gratefully acknowledges The
Netherlands Organization for Scientific Research (NWO) and
the Marie Curie Cofund Action (Rubicon Fellowship). J.C.B. is
J
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