Self-Assembled Boronic Ester Cavitand Capsules with Various Bis(catechol) Linkers: Cavity-Expanded and Chiral Capsules

Article abstract of DOI:10.1002/chem.201501717

Two molecules of cavitand tetraboronic acid and four molecules of various bis(catechol) linkers self-assemble into capsules through the formation of eight dynamic boronic ester bonds. Each capsule has a different cavity size depending on the linker used, and shows particular guest encapsulation selectivity. A chiral capsule made up of the cavitand and a chiral bis(catechol) linker was also constructed. This capsule induces supramolecular chirality with respect to a prochiral biphenyl guest by diastereomeric encapsulation through the asymmetric suppression of rotation around the axis of the prochiral biphenyl moiety. Nanospace: Self-assembled boronic ester cavitand capsules (see scheme) show unique properties that depend on the characteristics of the bis(catechol) linkers.

Full text of DOI:10.1002/chem.201501717

DOI: 10.1002/chem.201501717
Full Paper
&
Cavitands |Hot Paper|
Self-Assembled Boronic Ester Cavitand Capsules with Various
Bis(catechol) Linkers: Cavity-Expanded and Chiral Capsules
Kento Tamaki,[a] Asumi Ishigami,[a] Yasutaka Tanaka,[b] Masamichi Yamanaka,[a] and
Kenji Kobayashi*[a]
Abstract: Two molecules of cavitand tetraboronic acid and
four molecules of various bis(catechol) linkers self-assemble
into capsules through the formation of eight dynamic bor-
onic ester bonds. Each capsule has a different cavity size de-
pending on the linker used, and shows particular guest en-
capsulation selectivity. A chiral capsule made up of the cavi-
tand and a chiral bis(catechol) linker was also constructed.
This capsule induces supramolecular chirality with respect to
a prochiral biphenyl guest by diastereomeric encapsulation
through the asymmetric suppression of rotation around the
axis of the prochiral biphenyl moiety.
Introduction
ble formation of boronic or boronate esters have been report-
ed recently.[11]
Supramolecular capsules, constructed by self-assembly of pre-
organized subunits, provide an isolated nanospace. Guest mol-
ecules confined in the nanospace often show unique proper-
ties that are not observed in their free forms. Calix[4]resorcinar-
ene cavitands are valuable subunits for covalent-bonded cap-
sules,[1] as well as self-assembled capsules under thermody-
namic control using noncovalent interactions, such as
hydrogen bonds,[2] metal-coordination bonds,[3] ionic interac-
tions,[4] and solvophobic interactions.[5] As an alternative strat-
egy, dynamic covalent chemistry offers great advantages in
supramolecular syntheses because dynamic covalent bonds
undergo reversible covalent bond-forming and bond-breaking
processes that are under thermodynamic control; namely, such
connections combine both the strength of covalent bonds and
the reversibility of noncovalent interactions.[6,7] The reversibility
of the imine bond-forming reaction in the presence of a catalyt-
ic amount of CF3CO2H[7b,8] or the disulfide bond-forming reac-
tion under redox buffer conditions[9] has been applied to cavi-
tand-based capsule synthesis. Boronic ester formation is anoth-
er reliable synthon for dynamic covalent chemistry.[10] The
merit of boronic ester formation is that there is no requirement
for the addition of external chemicals to the system. Capsule
syntheses using various types of subunits based on the reversi-
Chiral capsules are another interesting topic in supramolec-
ular nanospace chemistry. Chiral molecular recognition of a rac-
emic guest upon encapsulation in chiral capsules has been
studied extensively.[12–14] In a type of twisted capsule composed
of north and south hemispheres,[15] it is known that the equi-
librium between (P)- and (M)-twistomers can be controlled
either by the introduction of a chiral group onto a racemic
self-assembled capsule[14b] or by the encapsulation of a chiral
guest into a racemic self-assembled capsule.[16] Chiral induction
of a prochiral guest upon encapsulation in a chiral capsule
would also be important for supramolecular nanospace
chemistry because such an encapsulation design is related to
asymmetric capsular catalysts[17] and to the emergence of
novel stereoisomerisms.[18] Dynamic covalent-bonded chiral
capsules have been reported;[19] however, chiral encapsulation
in such capsules has not been studied so far, probably due to
the formidable challenges of molecular design.
Previously, we reported that two molecules of cavitand tetra-
boronic acid 1, as a polar aromatic cavity end, and four mole-
cules of 1,2-bis(3,4-dihydroxyphenyl)ethane E, as an equatorial
bis(catechol)-linker, self-assemble into capsule 12E4 through the
formation of eight dynamic boronic ester bonds (Figure 1a).[20]
Capsule 12E4 encapsulates a guest molecule, such as 4,4’-disub-
stituted-biphenyl derivatives, to form guest@12E4 in a selective
recognition event, wherein the guest substituents are oriented
to both aromatic cavity ends of 12E4 so as to maximize capsu-
le–guest interactions. If various bis(catechol) linkers are avail-
able for capsular assembly with 1 in place of E, this strategy
would endow the self-assembled boronic ester cavitand capsu-
le with an increased range of applications, such as a cavity-ex-
panded capsule[8b,11c,21,22] for larger guest encapsulation, or
a chiral capsule[19] for chiral sensing technology. Herein, we
report on cavity-expanded boronic ester cavitand capsules
self-assembled by 1 and various bis(catechol) linkers, which
[a] K. Tamaki, A. Ishigami, Prof. M. Yamanaka, Prof. K. Kobayashi
Department of Chemistry, Faculty of Science
Shizuoka University, 836 Ohya, Suruga-ku
Shizuoka 422-8529 (Japan)
E-mail: kobayashi.kenji.a@shizuoka.ac.jp
[b] Prof. Y. Tanaka
Department of Electronics and Materials Science
Faculty of Engineering, Shizuoka University
3-5-1 Johoku, Naka-ku, Hamamatsu 432-8561 (Japan)
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201501717.
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Supporting
Information).
In
a manner similar to the forma-
tion of capsule 12E4,[20] each
1H NMR
spectrum
showed
a highly symmetrical single spe-
cies and confirmed the disap-
pearance of the OH groups of
the units 1, P, B, and L, indicat-
ing quantitative formation of
capsules 12P4, 12B4, and 12L4, re-
spectively. Each capsule could be
isolated by reprecipitation from
benzene–hexane.
Guest encapsulation
Each capsule has
a different
cavity size that depends on the
linker used, and each encapsu-
lates one guest molecule in
C6D6, with particular guest en-
capsulation selectivity. The guest
encapsulation was slow and re-
quired approximately 0.5–1 day
to reach thermodynamic equili-
bration at room temperature.
The catalytic amount of water
that is inevitably present in C6D6
led to reversibility of the boronic
ester bond, partial capsule open-
ing, and guest encapsulation
within the capsules.[20b] Guest
molecules 2–11, which were
investigated here, are shown
in Figure 1c. Representative
Figure 1. a) Self-assembly of cavitand tetraboronic acid 1 and bis(catechol) linker E into capsule 12E4 and the mo-
lecular model of guest-encapsulating capsule 2@12E4.[20b] b) Bis(catechol) linkers P, B, and L, and their capsules
12P4, 12B4, and 12L4. c) Guest molecules 2–11 and 14 investigated in this study.
show particular guest encapsulation selectivity depending on
the capsule size. We also describe a chiral capsule, composed
of 1 and a chiral bis(catechol) linker, which expresses diastereo-
meric encapsulation selectivity with respect to a prochiral bi-
phenyl guest by asymmetric suppression of axial rotation of
the biphenyl moiety upon encapsulation.
1H NMR spectra of guests@capsules are shown in Figure 3 (for
other guests@capsules, see Figure S10–S21 in the Supporting
Information). The 1H NMR signals of encapsulated and free
guests were independently observed, and the signals of the
terminal methyl protons of functional groups of the encapsu-
lated guests were shifted upfield by 2.28–3.01 ppm relative to
those of free guests in C6D6, because of the ring-current effect
of the aromatic cavities of capsules. These results indicate that
the functional groups of all guests encapsulated within the
capsules are oriented toward the aromatic cavity ends of the
capsules, in a manner similar to guest@12E4.[20] The apparent
association constants (Kapp) of capsules 12P4, 12B4, and 12L4
with various guests in C6D6 at 258C,[25] and the changes in
1H NMR chemical shifts of the terminal methyl protons of the
functional groups in the guests@capsules relative to those of
the free guests (DdG =dencapsulated-guestÀdfree-guest) are summarized
in Table 1.
Results and Discussion
Capsule formation from cavitand tetraboronic acid and bis-
(catechol) linkers
We selected 1,3-bis(3,4-dihydroxyphenyl)propane (P),[23] 1,4-
bis(3,4-dihydroxyphenyl)butane (B),[23] and 1,4-bis[2-(3,4-dihy-
droxyphenyl)ethyl]benzene (L) (see the Supporting Informa-
tion), as flexible bis(catechol) linkers. The reaction for a 2:4
mixture of cavitand tetraboronic acid 1 with bis(catechol)
linker P, B, or L in CDCl3 at 508C produced the self-assembled
capsules 12P4, 12B4, and 12L4, respectively, quantitatively as
The encapsulation of 4,4’-diacetoxybiphenyl
2 in 12P4
showed Kapp =4.98”103 mÀ1 and DdG =À3.00 ppm, whereas
2@12E4 exhibited Kapp =1.26”106 mÀ1 and DdG =À2.85 ppm[20b]
(Table 1, entries 3 vs. 1, and Figure 3b vs. 3a). The smaller Kapp
and larger upfield shift of DdG of 2@12P4 compared with the
1
single species (Figure 1b).[24] The H NMR spectra of capsules
1
12P4, 12B4, and 12L4 in C6D6 are shown in Figure 2 (for H NMR
spectra of the compounds in CDCl3, see Figure S9 in the
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Table 1. Apparent association constants (Kapp) of capsules 12P4, 12B4, and
12L4 with guests, and the 1H NMR chemical shift changes (DdG) of
guest@capsule relative to free guests at the terminal methyl protons in
C6D6 at 298 K.
[a]
Entry
Capsule
Guest
Kapp [MÀ1
]
DdG [ppm][b]
À2.85
1[c]
2
3
4
5
6
7
8
12E4
12E4
12P4
12P4
12B4
12B4
12B4
12B4
12B4
12B4
12B4
12L4
12L4
12L4
2
3
2
3
2
3
4
5
6
7
8
9
10
11
1.26”106
ꢁ0
4.98”103
ꢁ0
À3.00
ꢁ0
2.45”105
1.38”104
1.53”103
4.31”103
4.20”102
4.48”103
4.18”106
2.05”105
8.59”103
À2.88
À2.89,[d] À2.89[e]
À2.89
9
À2.96,[d] À2.96[f]
À2.34
10
11
12
13
14
À2.28
À2.89, À2.83
À2.93,[d] À2.85[e]
À3.01, À2.92
[a] Kapp =[G@Capsule]/{[Capsule]f[G]f} or Kapp/Kapp-Standard ={[G@Capsule]
[GStandard]f}/{[GStandard@Capsule][G]f}. Errors are within 10%. [b] DdG =
dencapsulation-guestÀdfree-guest. [c] See ref. [20b]. The Kapp value was measured at
313 K. [d]Acetoxy group. [e] Ethoxy group. [f] Methyl group.
Figure 2. 1H NMR spectra (400 MHz, C6D6, 298 K) of a) 1 (heterogeneous);
b) P (heterogeneous); c) 12P4; d) B (heterogeneous); e) 12B4; f) L (heteroge-
neous); and g) 12L4. The signals marked ‘s’ are the satellite signals (13C-1H
coupling) of the residual solvent.
Kapp and DdG of 2@12E4 clearly indicate that the cavity size
(length) of 12P4 is slightly smaller than that of 12E4.[26,27] Linker
P is longer than E; however, this is not the case for the capsu-
les. In contrast to the anti-conformation of linker E in 12E4,[20b]
linker P would adopt a skew-conformation to form 12P4. There-
fore, the cavity size (length) of 12P4 is slightly smaller than that
of 12E4.
Capsules 12B4 and 12L4 possess more expanded cavities than
12E4 and can encapsulate larger guests that are inaccessible for
12E4 (Figure 1b and 1c). Capsule 12B4 encapsulates 4,4’-bis(p-
substituted-phenyl)acetylenes 3–5 (Table 1, entries 6–8, and
Figure 3c) and 4,4’’-disubstituted-p-terphenyls 6–8 (Table 1, en-
tries 9–11). Capsule 12L4 encapsulates 4-substituted-4’-(p-substi-
tuted-phenylethynyl)biphenyls 9–11 (Table 1, entries 12–14,
and Figure 3d), which are significantly larger in size than 3–8.
Thus, the cavity size (length) of capsules increases in the order
12P4 ꢀ12E4 <12B4 <12L4. In a manner similar to 12E4,[20b] capsu-
les 12B4 and 12L4 strictly discriminate between functional
groups of a guest. In a series of guests with a similar molecular
length, the Kapp values of guest@12B4 and guest@12L4 increased
in the order 5 (4,4’-OCH2CH3)<4 (4-OC(=O)CH3-4’-OCH2CH3)<
3 (4,4’-OC(=O)CH3), and 11 <10<9, respectively. This selectivi-
ty arises from a combination of CH···p interaction between the
terminal CH3 group of the guest and the electron-rich aromatic
cavity end of 12B4 and 12L4, and C=O···HC interaction between
the carbonyl oxygen atom of the acetoxy group of the guest
and the inner protons of the methylene-bridge rims (O-
CHinHout-O) of 12B4 and 12L4, which are observed in the X-ray
crystal structure of 2@12E4.[20b]
Figure 3. 1H NMR spectra (400 MHz, C6D6, 298 K) of representative guest@-
capsule: a) 2@12E4 ([12E4]=1 mm and [2]=2 mm); b) 2@12P4
([12P4]=2.5 mm and [2]=7.5 mm); c) 3@12B4 ([12B4]=1 mm and [3]=1 mm);
and d) 9@12L4 ([12L4]=1 mm and [9]=5 mm). AcO=Acetoxy signals of the
encapsulated guest.
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Chiral capsules and chiral induction of a prochiral biphenyl
guest upon encapsulation: a 1H NMR study
Chiral induction of a prochiral guest upon encapsulation in
a chiral capsule is important for supramolecular nanospace
chemistry, particularly with respect to asymmetric capsular cat-
alysts[17] and for the emergence of novel stereoisomerisms,[18]
as well as for chiral materials science.[28] 4,4’-Diacetoxy-2,2’-bis-
(methoxycarbonyl)biphenyl (12) is a prochiral molecule, but it
becomes chiral when rotation around the biphenyl axis is
asymmetrically suppressed by chiral steric factors that fix the
configuration of the biphenyl moiety asymmetrically.
We studied chiral induction of prochiral 12 upon encapsula-
tion within a chiral 12E4 capsule derivative. Thus, we synthe-
sized racemic 2,3-bis(3,4-dihydroxyphenyl)butane, which was
separated by HPLC with a chiral column into the correspond-
ing chiral (2R,3R)-form ER and its enantiomeric (2S,3S)-form ES
as chiral bis(catechol)ethane linkers (see the Supporting Infor-
mation). The absolute configurations of ER and ES were deter-
mined by comparing the observed and theoretical circular di-
chroism spectra (Figure 9a vs. 9b, see below). The reaction of
1 with chiral ER in a 2:4 ratio in CDCl3 at 508C produced the
Figure 5. 1H NMR spectra (400 MHz, C6D6, 298 K) of a) ER (heterogeneous);
b) 1 (heterogeneous); c) 12ER4; and d) the reaction mixture of 1 with racemic
ER and ES in a 2:2:2 ratio after heating in C6D6 at 508C for 12 h. The signals
marked ‘s’ are the satellite signals of the residual solvent.
Molecular models of 12E4[20a] and 12ER , calculated at the PM3
4
level, are shown in Figure 4b. Capsule 12E4, with anti-confor-
mation of linker E, exists in C6D6 as an interconvertible mixture
of (P)- and (M)-twistomers.[20b] In contrast, chiral capsule 12ER
4
self-assembled chiral capsule 12ER quantitatively (Figure 4a
tends to adopt a bent-anti-conformation of chiral linker ER,
with an average Ca-Cb-Cc-Cd torsion angle of 1558 to reduce
steric repulsion between the catechol and adjacent methyl
groups in ER, and this compound was calculated to produce
a (P)-twistomer with average dihedral angle of 658 between
the resorcinol and boronic ester rings (Figure 4b and 4c).
4
and 5). In a manner similar to the formation of capsule
12E4,[20a,b] the 1H NMR spectrum of the reaction mixture (Fig-
ure 5c and Figure S22 in the Supporting Information) indicated
the presence of a highly symmetrical single species and con-
firmed the disappearance of the OH groups of the constituent
units 1 and ER, indicating the quantitative formation of 12ER .
Thus, in the calculated model, the cavity size (length) of 12ER
4
4
Enantiomeric 12ES4 was synthesized similarly. In contrast, the re-
action of 1 with racemic ER and ES in a 2:2:2 ratio gave a com-
plex mixture without self-sorting of chiral linkers (Figure 5d).[29]
is approximately 0.4 Š smaller than that of 12E4.
Chiral capsule 12ER encapsulates guests 2 and 12 with
4
K
app =6.93”103 mÀ1 and DdG =À2.95 ppm (AcO group) for
[20a]
Figure 4. a) Formation of chiral capsules 12ER4 and 12ES . b) Molecular models of 12E4
and 12ER4, calculated at the PM3 level. c) Schematic representation of
4
conformations of E and ER in capsules.
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ing Information), respectively.
These Ka values were two orders
of magnitude smaller than those
of 2@12E4 and 12@12E4, and
these DdG values were shifted
more upfield by approximately
0.1 ppm than those of the AcO
groups of 2@12E4 and 12@12E4
(Table 2, entries 2 vs. 1 and 4 vs.
3). These results also support the
conclusion that the cavity size
(length) of 12ER is slightly small-
4
er than that of 12E4.
In contrast to 2@12ER , the
4
1H NMR signal of the AcO group
of 12@12ER appeared as two
4
sets of singlets (Figure 7c and 8).
Furthermore, the 1H NMR signal
of the CO2CH3 group of
12@12ER also appeared as two
4
sets of singlets at 3.40 ppm
Figure 6. a) Schematic representation of diastereomeric encapsulation of prochiral guests 12 and 13 in 12ER
.
4
(signal-a: DdG = +0.16) and
b) Molecular models of (R)-12@12ER and (S)-12@12ER4, calculated at the PM3 level.
4
Table 2. Comparison of Kapp, DdG, and de values between guest@12E4
and guest@12ER in C6D6 at 298 K.
4
[a]
Entry
Capsule
Guest
Kapp [MÀ1
]
DdG [ppm]
de [%][b]
1[c]
2
12E4
2
2
12
12
13
13
1.26”106
6.93”103
5.42”105
4.72”103
4.75”105
7.31”103
À2.85
12ER
À2.95
4
3[c]
4
12E4
12ER
12E4
12ER
À2.81
À2.92, À2.93
À2.79
15
54
4
5[c]
6
À2.90, À2.93
4
[a] Errors are within 10%. [b] de=diastereomeric excess for the encapsu-
lation. [c] See Ref. [20b]. The Kapp value was measured at 313 K.
Figure 7. 1H NMR spectra (400 MHz, C6D6, 298 K) of guest@12ER
4
([12ER4]=2.5 mm and [guest]=3.75 mm): a) 12ER alone; b) 2@12ER
;
4
4
c) 12@12ER4; and d) 13@12ER4. The signals marked ‘AcO’ are the acetoxy sig-
nals of the encapsulated guests. In (c), the signals marked with ‘a and b’
and ‘F’ indicate the CO2CH3 signals of the encapsulated and free 12, respec-
tively. The signals marked ‘s’ are the satellite signals of the residual solvent.
1
2@12ER
and Ka =4.72”103 mÀ1 and DdG =À2.92 and
Figure 8. Temperature dependence of the H NMR spectra (400 MHz) of
4
12@12ER ([12ER4]=2.5 mm and [12]=3.75 mm) in C6D6 at 25–708C in the
region of a) the CO2CH3 groups of the encapsulated and free 12 marked
with ‘a and b’ and ‘F’, respectively; and b) the AcO groups of the encapsu-
lated 12.
À2.93 ppm (AcO groups) for 12@12ER in C6D6 at 298 K
4
4
(Figure 6). The 1H NMR spectra of 2@12ER and 12@12ER are
4
4
shown in Figure 7b and 7c (Figure S23 and S24 in the Support-
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groups of the encapsulated and free 12, and b) the AcO
groups of encapsulated 12 are shown in Figure 8. Although
the two AcO signals of encapsulated 12 coalesced at 708C, the
two CO2CH3 signals (a and b) of encapsulated 12 did not coa-
lesce even at 708C, because the CO2CH3 groups of encapsulat-
ed 12 are placed on the chiral equatorial position of 12ER .[30] In
4
the 2D NOESY spectra of 12@12ER (Figure S26 in the Support-
4
ing Information), exchange cross-peaks between 12@12ER and
4
free 12 were not observed even at 708C, and the exchange
cross-peak between the CO2CH3 signals (a and b) of 12@12ER
4
was observed at 508C, but not at 258C. In marked contrast, ro-
tation around the axis of 12 within 12E4 was fast on the NMR
time-scale even at À608C in [D8]toluene, and in the 2D NOESY
spectra of 12@12E4, exchange cross-peaks between 12@12E4
and free 12 were observed at 508C, but not at 258C.[20b] These
results clearly indicate that rotation around the axis of 12
within 12ER as well as the exchange of 12 into and out of
4
12ER are much slower than those of 12@12E4. The diastereo-
4
meric excess (de) resulting from diastereomeric encapsulation
1
selectivity of 12@12ER based on the H NMR signal integration
4
ratios of the CO2CH3 signals (a and b) and of the two AcO sig-
nals was estimated to be 15%. Prochiral 4,4’-diacetoxy-2,2’-bis-
(octoxycarbonyl)biphenyl (13) was also encapsulated in 12ER
4
with Kapp =7.31”103 mÀ1 and DdG =À2.90 and À2.93 ppm
(AcO group) (Figure 7d and Table 2, entry 6). It is known that,
in contrast to 12@12E4, rotation around the axis of 13 within
[20b]
12E4 is inhibited at 258C in C6D6
because the CO2C8H17
groups of encapsulated 13 protrude from the equatorial win-
dows of 12E4. This is also the case for 13@12ER . Therefore, the
4
diastereomeric encapsulation selectivity of 13@12ER (de=
4
54%) was greater than that of 12@12ER . At this stage, it is not
4
easy to establish which enantiomer of (R)- or (S)-guest is more
favorably encapsulated in 12ER , and further studies are re-
4
quired in this regard.
Chiral induction of prochiral biphenyl guest: a CD study
Circular dichroism (CD) spectroscopy was used to examine fur-
ther the chiral induction of prochiral biphenyl guest upon en-
capsulation in chiral capsules 12ER and 12ES (Figure 9). The
4
4
chiral linkers ER and ES in THF showed CD spectra that were re-
ciprocal, and the UV/Vis absorption maxima of ER were ob-
served at 212–225 and 284 nm (Figure 9a). The CD signals cor-
responding to absorption at 212–225 nm were not definitive
because the shorter wavelength region below 220 nm over-
lapped with absorption by THF. Nevertheless, the split CD sig-
nals in the region were deduced from the theoretical CD calcu-
lated with TD-DFT at the B3LYP/6-31G(d,p) level (Figure 9a vs.
9b). The CD spectra of ER and ES also showed mirror image sig-
nals at 283 nm in addition to the split CD signals described
above. The CD signal at approximately 280 nm constitutes
a valuable CD probe that can be used to determine chiral in-
duction of the prochiral biphenyl guest (see below).
Figure 9. a) CD and UV/Vis spectra of ER and ES in THF at 258C (0.3 mm,
l=0.5 cm for CD and 1.0 cm for UV). b) Theoretical CD and UV/Vis spectra of
ER and ES, calculated with TD-DFT at the B3LYP/6-31G(d,p) level. c) CD and
UV/Vis spectra of 12ER4, 12ES , 12@12ER4, 12@12ES , and 12 in C6H6 at 258C
4
4
(l=0.5 cm for CD and 1.0 cm for UV): [12ER4]=[12ES ]=0.05 mm and
4
[12]=0.15 mm, i.e., [12@12ER4]+[12ER4]=0.05 mm in total and
[12@12ES ]+[12ES ]=0.05 mm in total.
4
4
3.04 ppm (signal-b: DdG =À0.20) relative to the signal of free
12, which resonates at 3.24 ppm. This result indicates that
chiral induction of prochiral 12 occurred upon encapsulation
in the chiral nanospace of 12ER through asymmetric suppres-
4
sion of rotation around the axis of the biphenyl moiety in 12;
The CD study of 12ER and 12@12ER was carried out in ben-
4
4
that is, diastereomeric complexes (R)-12@12ER and (S)-
zene to maintain guest encapsulation; therefore, it was not
possible to study the shorter wavelength region below
270 nm, which overlaps with the absorption of the solvent.
4
12@12ER were produced (Figure 6). The variable-temperature
4
1H NMR spectra of 12@12ER in the region of a) the CO2CH3
4
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The CD spectra of 12ER and 12ES in benzene (0.05 mm)
4
4
Conclusion
showed mirror image signals with CD maxima at 273 and
283 nm, and exhibited the same CD signs relative to those of
We have demonstrated the self-assembly of two molecules of
cavitand tetraboronic acid 1 and four molecules of various bis-
(catechol) linkers P, B, L, ER, and ES into capsules 12P4, 12B4,
12L4, 12ER , and 12ES , respectively, through the formation of
ER and ES, respectively (Figure 9c). The solution of 12@12ER for
4
the CD and UV/Vis measurements ([12ER ]=0.05 mm and
4
[12]=0.15 mm in C6H6, i.e., [12@12ER ]+[12ER ]=0.05 mm in
4
4
4
4
total) contains 12@12ER (38%), free 12ER (62%), and excess
eight dynamic boronic ester bonds. The following two features
are particularly noteworthy in this study. 1) Each capsule has
a different cavity size that depends on the linkers, and shows
particular guest encapsulation selectivity. Capsules 12B4 and
12L4, with more expanded cavity than previously reported 12E4,
were able to encapsulate larger guests such as 3 and 9, respec-
tively, which are inaccessible for 12E4. The capsules can also
clearly discriminate between functional groups of a guest.
2) Chiral capsules 12ER and 12ES induced supramolecular chir-
ality with respect to prochiral biphenyl guests 12 and 13 by
diastereomeric encapsulation through asymmetric suppression
or inhibition of rotation around the axis of the biphenyl
moiety of the guests upon encapsulation in the chiral nano-
space. Thus, the self-assembled boronic ester cavitand capsules
show unique properties that depend on the characteristics of
the bis(catechol) linkers. Further modifications of the bis(cate-
chol) linker and cavitand tetraboronic acid are expected to
endow this type of capsule with characteristics that should
help in the development of functional materials, which would
constitute an important advance in supramolecular nanospace
chemistry.
4
4
free 12, calculated based on the Kapp value. At wavelengths
longer than 270 nm, the UV/Vis absorption maxima of ER
(284 nm) in THF, and 12ER (281 nm), the solution containing
4
12@12ER (280 nm), and free 12 (289 nm) in benzene appeared
4
in a similar wavelength region (Figure 9c). Therefore, the
origin of the CD signals of 12@12ER is complex. The CD spec-
4
tra of a solution containing 12@12ER and 12@12ES showed
4
4
mirror image signals and exhibited the same CD signs relative
4
4
to those of 12ER and 12ES , respectively. Notably, 12@12ER and
4
4
4
12@12ES showed an approximate twofold increase in the CD
4
signal intensity at around 280 nm, compared with 12ER and
4
12ES , respectively (Figure 9c). In contrast, there was almost no
4
increase in the CD signal intensity of achiral-2@12ES relative to
4
that of 12ES (Figure 10a). These results strongly support the
4
Experimental Section
Typical procedure for capsule formation: capsule 12ER
4
A suspension of 1·OEt2 (50.0 mg, 42.4 mmol) and ER (23.3 mg,
84.9 mmol, 2 equiv) in CDCl3 (8.5 mL) was stirred at 508C for 12 h
1
under Ar. The H NMR spectrum of the resulting homogeneous so-
lution showed the quantitative formation of 12ER . After evapora-
4
tion of solvent, the residue was dried in vacuo at RT for 5 h. The re-
sulting solid was precipitated from benzene–hexane to give 12ER
4
(62.1 mg, 97% yield) as a white solid. 1H NMR (400 MHz, CDCl3,
298 K): d=7.37 (s, 8H; HD), 7.25 (s, 8H; Hc), 7.06 (d, J=7.8 Hz, 8H;
Ha), 6.70 (d, J=7.8 Hz, 8H; Hb), 5.72 (d, J=7.3 Hz, 8H; HB), 4.89 (t,
J=7.8 Hz, 8H; HC), 4.67 (d, J=7.3 Hz, 8H; HA), 3.04 (m, 8H; Hd),
2.30 (m, 16H), 1.25–1.55 (m, 80H), 1.21 (d, J=5.9 Hz, 24H; He),
0.92 ppm (t, J=6.8 Hz, 24H); 1H NMR (400 MHz, C6D6, 298 K): d=
7.69 (s, 8H; HD), 7.10 (s, 8H; Hc), 6.68 (d, J=7.8 Hz, 8H; Ha), 6.42 (d,
J=7.8 Hz, 8H; Hb), 5.55 (d, J=7.3 Hz, 8H; HB), 5.27 (t, J=7.8 Hz,
8H; HC), 4.64 (d, J=7.3 Hz, 8H; HA), 2.67 (m, 8H; Hd), 2.30 (m, 16H),
1.20–1.40 (m, 80H), 1.13 (d, J=4.4 Hz, 24H; He), 0.93 ppm (t, J=
6.8 Hz, 24H). The signal assignments are shown in Figure S22 in
the Supporting Information.
Figure 10. CD spectra of a) 12ES and 2@12ES4; and b) 12ER4, 12@12ER4, and
4
13@12ER in C6H6 at 258C (l=0.5 cm and [guest@chiral-capsule]+[chiral-cap-
4
sule]=0.05 mm in total and [guest]=0.15 mm).
idea of chiral induction of prochiral 12 upon encapsulation in
12ER and 12ES . The increase of the CD signal intensity of
4
4
12@12ER would arise from an exciton coupling between chiral
4
12 and 12ER , but not from a CD signal of chiral 12 alone, be-
4
cause the absorbance of 12 is much smaller than that of 12ER
4
(Figure 9c). Furthermore, 13@12ER showed an approximate Acknowledgements
4
threefold increase in the CD signal intensity at around 280 nm,
compared with that of 12ER (Figure 10b). This dramatic in-
We thank Daicel Corporation CPI Company for the chiral AY-H
4
crease in the CD signal intensity of 13@12ER compared with
column, Professor Toshiyuki Kan and Dr. Tomohiro Asakawa
(University of Shizuoka) for optical rotation measurements, and
Ayumi Oishi for experimental assistance. This work was sup-
ported in part by a Grant-in-Aid from JSPS (no. 25288034).
4
those of 12@12ER and 12ER arises from larger diastereomeric
4
4
encapsulation selectivity for 13@12ER (de=54%) than that for
4
1
12@12ER (de=15%), as mentioned in the H NMR study.
4
Chem. Eur. J. 2015, 21, 13714 – 13722
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147–183.
Keywords: cavitands · drug delivery · host–guest systems ·
self-assembly · supramolecular chemistry
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Chem. Eur. J. 2015, 21, 13714 – 13722
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[25] Large Kapp values of capsules with guests were estimated by competi-
tive encapsulation experiments with a standard guest. Details are given
in the Supporting Information.
size of 12P4. These results also support the conclusion that the cavity
size (length) of 12P4 is somewhat smaller than that of 12E4.
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[26] The guest length of 4,4’-bis(1-propynyl)biphenyl (14) (l=15.16 Š) is
longer than 2 (l=14.35 Š), where l=C···C atomic distance between the
terminal CH3 groups, calculated at the B3LYP/6-31G(d) level. It is known
that the 1-propynyl group as well as the acetoxy group is a good func-
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guest@12E4, the Kapp of 14@12E4 (Kapp =507mÀ1) was much smaller than
2@12E4 (Kapp =1.26”106 mÀ1), whereas the negative DdG value (upfield
shift value) of 14@12E4 (DdG =À3.18 ppm) was greater than 2@12E4
(DdG =À2.85 ppm).[20b] This result clearly indicates that the size of 14 is
closer to the cavity size of 12E4 than 2. In the present work, 14 was not
encapsulated in 12P4, because the size of 14 is too large for the cavity
Received: May 2, 2015
Published online on August 3, 2015
Chem. Eur. J. 2015, 21, 13714 – 13722
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ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim