Ion-pair recognition of amidinium salts by partially hydrogen-bonded heteroditopic cyclo[6]aramide

Article abstract of DOI:10.1039/c6ra08202e

Convergent heteroditopic cyclo[6]aramide demonstrates efficient ion-pair recognition of amidinium salts in 10% methanolic chloroform (>10⁴ M^-1) as confirmed by NMR and conductivity experiments. As predicted by density functional theo

Full text of DOI:10.1039/c6ra08202e

RSC Advances
View Article Online
View Journal | View Issue
PAPER
Ion-pair recognition of amidinium salts by partially
hydrogen-bonded heteroditopic cyclo[6]aramide†
Cite this: RSC Adv., 2016, 6, 39839
Shanshan Shi, Yumin Zhu, Xiaowei Li, Xiangyang Yuan, Teng Ma, Wen-Li Yuan,
*
Guo-Hong Tao, Wen Feng and Lihua Yuan
Convergent heteroditopic cyclo[6]aramide demonstrates efficient ion-pair recognition of amidinium salts
in 10% methanolic chloroform (>104 ꢀ1) as confirmed by NMR and conductivity experiments. As
M
predicted by density functional theory (DFT) method simulations, cyclo[6]aramide 1a is able to bind
amidinium salts G1–G5 with varying binding affinity in 1 : 1 stoichiometry through hydrogen bonding
interactions involving both anion-recognizing amide H-atoms and cation-binding amide carbonyl O-
atoms. Particularly, the binding affinities for G1, G2 and G3 are found to decrease with increasing the
size of substituents in the amidinium ion in the order of G1 > G2 > G3. Moreover, the association ability
for simultaneous binding of cationic and anionic guest species depends considerably on the counterions.
Among the four formamidinium salts (Clꢀ, Brꢀ, Iꢀ and BPh4ꢀ) examined, formamidinium chloride is best
encapsulated as a contact ion-pair species in the macrocycle. The reduced association constants with
increasing the size of counterions in the order of G1 > G6 > G7 > G4 underscore the importance of ion
paring in effecting the host–guest interaction. Comparative conductivity studies provide a convenient
approach to differentiate between contact and loose ion pairs for these amidinium complexes. This work
provides a rare example of binding biologically important types of amidinium cations as ion pairs by
a synthetic receptor.
Received 30th March 2016
Accepted 13th April 2016
DOI: 10.1039/c6ra08202e
www.rsc.org/advances
complexation of amidinium cation alone, other than binding
concomitantly both cationic species and its counteranion,
Introduction
which is widely known as ion-pair recognition. Ion-pair recog-
nition is considered as an efficient approach to enhance
binding affinities as shown by salt solubilisation, extraction and
membrane transport.5 Despite the realization of designed
molecules for coordinating zwitterionic amino acids and
peptides,6 complexation of biologically relevant amidinium ions
by synthetic receptors as ion pair in a convergent fashion is still
unknown. With widespread use of amidines and their salts,7
development of such ion-pair recognition systems may have
important implications for medicinal chemistry.
Hydrogen-bonded aromatic amide macrocycles8 have
received increasing attention because of their interesting host–
guest chemistry.9 Among them, cyclo[6]aramides, a class of
shape-persistent cyclic compounds with amide oxygen atoms
inwardly oriented,10 are of particular interest in their binding
affinity towards organic cations. Our recent work has revealed
the strong ability of these macrocycles to bind secondary
ammonium salts,11 diquat12 and tropylium.13 Their unique
host–guest chemistry is also revealed by their capability to
specically discriminate native arginine14 and to manipulate
liquid crystal properties.15 Interestingly, depletion of partial
hydrogen bonds leads to convergent heteroditopic cyclo[6]ara-
mides that have shown high association ability for intimate
organic ion pairs.16 The recent advance of ditopic receptors17
Recognition of amidinium cations by articial receptors has
been a subject of research interest for the last two decades1 due
to their importance in implementing biological functions in
DNA-binding and inhibitor drugs. For example, pentamidine
isethionate, which contains two amidinium residues, has been
widely used for the treatment of pneumocystosis, babesiosis,
trypanosomiasis, and leishmaniasis.2 However, very few
synthetic receptors are available so far for use in binding the
amidinium group.1,3 Among the very limited examples reported
up to 2003 and aerwards, only one recognition motif involves
the utilization of a highly preorganized multi pyridine-based
macrocycle.1 Therefore, the design and creation of new macro-
cyclic host–guest systems for amidinium complexation repre-
sents a great challenge, particularly when the development of
new receptor systems for amidinium ions4 has been untouched
by supramolecular scientists during the past decade. Further-
more, all articial receptors are only concerned with
College of Chemistry, Key Laboratory for Radiation Physics and Technology of Ministry
of Education, Institute of Nuclear Science and Technology, Sichuan University,
Chengdu 610064, China. E-mail: lhyuan@scu.edu.cn; Fax: +86-28-85418755; Tel:
+86-28-85412890
† Electronic supplementary information (ESI) available: Synthetic procedures,
characterization details, titration 1H NMR spectra and absorption spectral
traces. See DOI: 10.1039/c6ra08202e
This journal is © The Royal Society of Chemistry 2016
RSC Adv., 2016, 6, 39839–39845 | 39839

View Article Online
RSC Advances
Paper
aroused our intense interest to probe the possibility of binding
amidinium salt as ion pair by convergent H-bonded macro-
cycles. We report herein that heteroditopic cyclo[6]aramide 1a
(Fig. 1) is able to recognize a series of amidinium salts G1–G5
with varying binding affinity through hydrogen bonding (H-
bonding) interactions. Particularly, G1, G2 and G3 with
different steric hindrance in the central carbon of the cation are
bound as contact ion pair where the amidinium and chloride
are present essentially as one entity as evidenced by NMR and
conductivity experiments.
Fig. 2 Side (up) and top (down) views of optimized geometry of (a)
1b$G1 and (b) 1b$G2 at the RB3PW91/6-31G (d, p) level; all side chains
of 1a are replaced by methyl groups for simplicity (gray ¼ C, white ¼ H,
red ¼ O and blue ¼ N). The chloride anion is shown as a CPK model.
The dashed green lines indicate intermolecular H-bonds D–K with D ¼
Results and discussion
Density functional theory (DFT) calculation results
The feasibility of binding a contact ion-pair species amidinium
chloride is examined based on density functional theory (DFT)
method simulations of the complex system comprising cyclo[6]
aramide 1b and amidinium G1, G2. Our computational results
on the calculated binding energies reveal that G1 ts well in the
cavity of the host molecule (Fig. 2a and S37, ESI†). The chloride
anion is engaged in four H-bonds (H, I, J and K), three of which
are associated with the anion-binding cle formed by three H-
bond donors from the macrocycle (two amide NH and one
aromatic H) with the remaining charge-assisted H-bond formed
with the cationic NH group of G1. The ion-pair complexation is
further strongly stabilized by four charge-assisted H-bonds (D,
E, F, I). With this optimized conformation stabilized by coop-
erative H-bonding interactions, the amidinium chloride is
perfectly engulfed as a contact ion-pair species in the macro-
cycle. Computer simulations on G2 produce a similar result that
shows the acetamidinium chloride stays somewhat above the
macrocyclic platform due to the presence of additional methyl
substituent (Fig. 2b and S38, ESI†).
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
1.888 A, E ¼ 1.965 A, F ¼ 1.889 A, G ¼ 2.311 A, H ¼ 2.283 A, I ¼ 1.982 A,
0
0
0
0
ꢀ
ꢀ
ꢀ
0
ꢀ
ꢀ
J ¼ 2.308 A and K ¼ 2.464 A; D ¼ 1.976 A, E ¼ 1.911 A, F ¼ 2.114 A, G
0
0
0
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
¼ 2.202 A, H ¼ 2.360 A, I ¼ 2.040 A, J ¼ 2.295 A and K ¼ 2.581 A.
Ion-pair complexation studies
With the theoretical prediction for the stability of ion-pair
complex, ditopic cyclo[6]aramide 1a was synthesized via
a multi-step pathway (Scheme S1, ESI†).16 An acetylene chain
was incorporated to improve the solubility of the macrocycle.
Since G1 is very hygroscopic and not easy to handle in experi-
ments, guest G2 was tested rst for its binding ability with 1a.
The rst sign of binding with G2 as ion pair came from 1H NMR
experiments. Addition of one equivalent of G2 to a CDCl3
solution of 1a leads to the downeld shis in the signals arising
from amide and aromatic protons Hj, Hk, Hb and Hg on 1a by
1.39, 0.55, 0.20 and 0.27 ppm, respectively (Fig. 3).
This implies that both the cationic and anionic guests are
associated primarily with the cavity of this receptor.18 Particularly,
the substantial change of amide proton resonance (Dd ¼ 1.39
ppm for Hj) relative to other proton resonances strongly suggests
the H-bonding interaction of amide hydrogen with chloride
anion, and thus its residing in the core of the macrocycle.
Moreover, a binding constant of 6.08 ꢁ 103 Mꢀ1 in CDCl3–CD3OH
(v/v, 9 : 1) was obtained by tting the concentration-dependent
change of the chemical shis of proton 1a-Hd (Fig. 4 and Table 1).
Fig. 1 Chemical structures and proton designations of heteroditopic
cyclo[6]aramide 1 and amidinium salt G1–G7. Green and pink repre- Fig. 3 Partial 1H NMR spectra of (a) 1.0 mM cyclo[6]aramide 1a; (b) 1.0
sent chloride anion and amidinium cations, respectively.
mM cyclo[6]aramide 1a$G2 (400 MHz, CDCl3, 298 K).
39840 | RSC Adv., 2016, 6, 39839–39845
This journal is © The Royal Society of Chemistry 2016

View Article Online
Paper
RSC Advances
Fig. 5 FT-IR transform infrared spectra of cyclo[6]aramide 1a (a),
Fig. 4 Partial stacked 1H NMR spectra of cyclo[6]aramide 1a (1.0 mM) complex1a$G2 (b) and G2 (c).
titrated by G2 (0–2.0 equiv.) in (400 MHz, 9 : 1, CDCl3–CD3OD, 298 K).
complexation of G1 (Fig. S30 and S31, ESI†) and G3 (Fig. S32
and association and S33, ESI†). The method of Job's plot supplied information
Table
constants (Ka/Mꢀ1 c
TBACl) by 1a at 298 K
1
Electrical conductivity (s/mS cmꢀ1 a,b
for complexation of various guests (G1–G7 and
)
)
on the binding stoichiometry of 1a and G2 in solution. The
maximum absorbance in UV-vis spectra is observed at 0.5,
indicating a macrocycle–ion pair ratio of 1 : 1 in the complex
(Fig. 7). In fact, the stoichiometry of all host–guest complexes
was found to be 1 : 1 by the Job's plot method (Fig. S5, S17, S21
and S25, ESI†).
s/mS cmꢀ1
c
Guest
Ion pair
Guesta
Complexb
Ka /Mꢀ1
G1
G2
G3
G4
Contact
Contact
Contact
Loose
63.5
69.1
50.3
57.2
(5.98 ꢃ 0.89) ꢁ 104
(6.08 ꢃ 1.72) ꢁ 103
(4.08 ꢃ 0.73) ꢁ 103
Evidence in support of chloride ion binding in solution came
from the observation that the Ka value (ꢂ104 Mꢀ1) obtained by
77.2
68.5
333.1
351.2
67.8
311.8
319.4
55.6
(2.04 ꢃ 0.48) ꢁ 103 1H NMR titrations (Fig. 8) for G1 is larger by over one order of
magnitude than the value for G4 (ꢂ103 Mꢀ1) bearing a bulky
G5
Loose
(5.91 ꢃ 0.60) ꢁ 103
(1.45 ꢃ 0.58) ꢁ 104
(5.46 ꢃ 1.49) ꢁ 103
(3.81 ꢃ 0.83) ꢁ 102
G6
G7
TBACl
Contact
Contact
Loose
ꢀ
anion, BPh4 (Table 1). Thus, the small chloride anion greatly
78.4
66.8
enhances the complexation as compared to a larger anion,
indicating its essential contribution to the enhanced cation
binding via a positive cooperativity effect. In sharp contrast to
G1, TBACl, which shares the same anion but contains a large
tetrabutylammonium cation, is bound with a signicantly
lowered binding constant (ꢂ102 Mꢀ1). (Fig. S3–S24, ESI†). The
drastic reduction of the binding affinity in the presence of the
non-coordinated cationic species TBA or tetramethylammo-
nium,19 underscores the important cooperative action for ion
411.2
392.5
a
The electrical conductivity s values were obtained in CDCl3–CD3CN (v/
v, 1 : 1). The electrical conductivity s values were obtained in CDCl3–
CD3CN (v/v, 1 : 1). The association constant Ka values were obtained
b
c
by 1H NMR titration in CDCl3–CD3OD (v/v, 9 : 1).
The involvement of carbonyl oxygen atoms in forming
intermolecular hydrogen bonds was corroborated by the
infrared experiments of the complex prepared from a mixture of
1a and G1, G2, G3 in a molar ratio 1 : 1. The strong band at 1662
cmꢀ1 of n(C]O) in 1a shis to 1648 cmꢀ1 in the complex,
revealing a change of 14 cmꢀ1 from vibration of carbonyl
oxygen. On the other hand, the band of amidinium N–H
vibrations appears at 1699 cmꢀ1 in free G2 and merges into
a band at 1705 cmꢀ1 in the complex of 1a$G2 (Fig. 5), suggestive
of the interaction of aramide N–H with the oxygen atoms.
Similar results were obtained for the complexation of 1a$G1 and
1a$G3 (Fig. S34 and S35, ESI†).
+
paring of the formamidinium cation (HC(NH2)2 ) with the
chloride to retain its high binding affinity in the recognition
process. In addition, replacing the counterions of G1 with
halide anions (bromide and iodide) led to G6 and G7 with Ka
values in the decreasing order: G1 > G6 > G7 > G4 (Table 1,
Fig. S3–S11, ESI†). This indicates that a larger anion tends to
screw the anion out of the cavity, which in turn diminishes the
binding affinity of the complex. Among the four anions exam-
ined above, the smallest anion chloride is mostly likely to be
well accommodated in the cavity as ion pair. Results from
conductivity study are consistent with ion paring of chloride
(vide post). Unfortunately, all attempts to obtain suitable crys-
tals of 1a with amidinium salts failed. However, from 2D 1H
NMR experiments the information on the structure of the
complex can be retrieved. The NOESY spectrum of a solution
containing an equimolar mixture of 1a$G2 in CDCl3–CD3CN (v/
v, 1 : 1) shows correlations between the signals attributable to
the amidinium ion H1, H2 and aromatic protons Hk, Hg and Hb
Furthermore, results from the high resolution electrospray
ionization mass spectrometry (HRESI-MS) show a highly
intense fragment ion of [1a + G2 ꢀ Cl]+ at m/z ¼ 1685.1021 for
1a$G2 in the positive ion mode (Fig. 6a). Importantly, a peak at
m/z ¼ 1661.6003, corresponding to [1a + Cl]ꢀ, is observed in the
negative ion mode (Fig. 6b). This result indicates the binding of
chloride anion as ion pair in the complex and a 1 : 1 stoichi-
ometry. Similar results were obtained for the ion-pair
This journal is © The Royal Society of Chemistry 2016
RSC Adv., 2016, 6, 39839–39845 | 39841

View Article Online
RSC Advances
Paper
Fig. 8 Partial stacked 1H NMR spectra of cyclo[6]aramide 1a (1.0 mM)
titrated by G1 (0–2.0 equiv.) in (400 MHz, 9 : 1, CDCl3–CD3OD, 298 K).
Fig. 9 Expanded 2D NOESY spectra of 1 : 1 complex 1a$G2 showing
correlations between aromatic protons of 1a and (a) NH2 of G2 and (b)
CH3 of G2 (10 mM, 1 : 1, CDCl3–CD3CN, 400 MHz, 298 K).
Fig. 6 HRESI-MS spectra of an equimolar solution of 1a and G2 in
methanol in the positive ion mode (a) and negative ion mode (b).
protons of 1a and any protons of G2 are observed (Fig. S36,
ESI†). These ndings, combined with the facts above, strongly
support the residing of both cation and anion as contact ion
pair inside the cavity of the host molecule. In addition, the
binding affinities are found to decrease with increasing the size
of the substituent in the amidinium ion in the order of G1 > G2
> G3, reecting the decreased steric demands for efficient
complexation.
Conductometric studies for the intimacy of ion-pairs
Variation in conductivity of analytes is known to reect the
propensity of host–guest inclusion and ion-pair interaction in
solution,20 which can consequently be used to evaluate
the intimacy of ion pairs formed by the amidinium ion
and the anion. Therefore, conductivity experiments were
performed at 5 mM of the host 1a in CHCl3–CH3CN (v/v, 1 : 1) for
the complexes (Tables 1 and S10, ESI†). Di-n-butylammonium
Fig. 7 Job's plot for the complexation of 1a and G2 in CDCl3–CD3OD
(v/v, 9 : 1) based on the absorbance at 365 nm, indicating a 1 : 1 stoi-
chiometry. The total concentration is 3 ꢁ 10ꢀ4 M.
chloride
(DBACl)
and
di-n-butylammonium
hexa-
uorophosphate (DBAH), which are known to be contact ion pair
and loose (or separated) ion pair,21 respectively, are used as
a control. Their conductivity values were determined to be 63.4
and 594.5 mS cmꢀ1 respectively, revealing a tremendous differ-
ence in conductivity (Ds ¼ 531.1 mS cmꢀ1) between the contact
and loose ion pairs. Correspondingly, their complexes 1a$DBACl
of 1a (Fig. 9a). Meanwhile, two correlations are observed
between the signals of aromatic protons Hb, Hj and methyl
proton H3 on the amidinium ion (Fig. 9b). In contrast, no cross-
peaks associated with the interaction between exterior aromatic
39842 | RSC Adv., 2016, 6, 39839–39845
This journal is © The Royal Society of Chemistry 2016

View Article Online
Paper
RSC Advances
and 1a$DBAH also show a signicant difference in conductivity
(Ds ¼ 515.9 mS cmꢀ1). Interestingly, the crystal structure of
1a$DBACl in our previous work reveals contact ion-pair
complexation16 via hydrogen bonding where the distance
between one hydrogen of the charge-assisted H-bonds of the di-
n-butylammonium cation and the chloride anion measures
ꢀ
2.177 A. Therefore, the lower conductivity as observed for
1a$DBACl should point to the presence of a highly associated
species or a contact ion pair in solution, and conversely, the
higher conductivity should correspond to the formation of
a loose ion-pair. In these cases, the ion-pair behaviour of the
salts and complexes could be well distinguished by the differ-
ence of conductivity. It is envisioned that the simultaneous
complexation of both amidinium and chloride as contact ion
pair by the macrocyclic ditopic receptor would lead to low
conductivity. Indeed, upon complexation, G1–G3 offer
a conductivity value by ca. ve to six-fold lower than G4, and also
TBACl, a typical example of loose ion-pair22 (Table 1). These
comparative data indicate that amidinium salts with small
chloride are bound as contact ion pair in the cavity of 1a, while
1a$G4 having the large anion as the counterion is prone to exist
as loose ion pair. The extent to which the anion as contact ion
pair is bound inside the cavity is revealed by the increased
conductivity with increasing the size of anions in the order of G1
< G6 < G7. Formation of contact ion pair is particularly inter-
esting as this avoids the energetically unfavourable separation of
the two ions.23 Of particular relevance to biological molecules is
benzamidinium G3, a structural mimic of arginine and a potent
inhibitor.4 To the best of our knowledge, implementation of ion-
pair recognition of amidinium salts by synthetic receptors is still
unknown.
Fig. 11 Job's plot for the complexation of 1a and G5 in CDCl3–CD3OD
(v/v, 9 : 1) based on the absorbance at 365 nm, indicating a 1 : 1 stoi-
chiometry. The total concentration is 3 ꢁ 10ꢀ4 M.
macrocycle (Fig. S29, ESI†). However, the complex was found to
be present in 1 : 1 stoichiometry by both mass spectrometry
(MALDI-TOF) (Fig. 10) and the Job's plot method in solution
(Fig. 11), and its binding constant with host 1a was found to be
(5.91 ꢃ 0.60) ꢁ 103 Mꢀ1 (Fig. S26 and S27, ESI†). The close
conductivity values between the two complexes 1a$G5 and
1a$G4 (Table 1) indicate that PAM exists as loose ion-pair in
solution due to the bulky counterion. The decreased conduc-
tivity (Ds ¼ ꢀ31.8 mS cmꢀ1) of 1a$G5 as compared to the free
loose ion-pair of G5 is ascribed to the connement of the cation
in the macrocyclic lumen.
Pentamidine (PAM) isethionate (G5) is a bisamidinium salt
that has found extensive use against pneumonia and even for
AIDS therapy. Given its structural feature involving two benza-
midinium moieties in the molecule, the complexation of PAM
Conclusions
In summary, we have demonstrated a modular system based on
convergent heteroditopic cyclo[6]aramide for ion-pair recogni-
tion of amidinium chlorides. The association ability for simul-
taneous binding of cationic and anionic guest species depends
considerably on the counterions and the size of amidinium
ions. Comparative conductivity studies offer a convenient
methodology to discriminate between contact and loose ion
pairs for these amidinium complexes. Our ndings provide
a rare example of ion-pair recognition for formamidinium salts
and their kindred compounds by synthetic receptors. Further
work may lead to cycloaramide-based receptors for transport,
controlled release, and detection of these compounds.
1
by 1a was examined by H NMR spectroscopy. Signals for the
aromatic protons H7 and H8 (Dd ¼ +0.18 and ꢀ0.14 ppm) of G5
undergo downeld shis in CDCl3–CD3OD (v/v, 9 : 1), consis-
tent with its participation in forming the complex with the
Experimental
Materials and reagents
Compound 1 was synthesised following the reported proce-
dure.16 Dichloromethane, anhydrous Na2SO4 and anhydrous
Mg2SO4 were purchased from Chengdu Kelong Chemical
Factory. CH2Cl2 was dried over CaH2. Column chromatography
was carried out using silica gel (300–400 mesh). All other
solvents and chemicals used for the synthesis were of reagent
grade and used as received. The complex samples for ESI-MS
Fig. 10 MALDI-TOF spectrum of an equimolar solution CHCl3–
CH3OH (v/v, 9 : 1) of 1a and G5, showing the presence of 1 : 1 charge-
transfer complex [inset: experimental isotope distribution (blue) and
computer simulation (red)].
This journal is © The Royal Society of Chemistry 2016
RSC Adv., 2016, 6, 39839–39845 | 39843

View Article Online
RSC Advances
Paper
determination were prepared by mixing a CH3OH solution. Materials (SKLSSM201629), and Open Project of State Key
Solvents for extraction and chromatography were of reagent Laboratory of Structural Chemistry (20140013) for funding this
grade.
work.
Synthetic procedure of 1a
Notes and references
Pentamer 7 (300 mg, 0.20 mmol) was hydrogenated in the
presence of 20% Pd/C (60 mg) in CHCl3/CH3OH (80 mL, v/v ¼
5 : 1) for 10 h at 40 ꢄC. The solution was ltered in darkness as
fast as possible followed by immediate removal of the solvent.
The reduced diamine 8 was used for the immediate coupling
reaction. DMF (5 uL) was added to a suspension of 5-(prop-2-yn-
1-yloxy)isophthalic acid 10 (58 mg, 0.20 mmol) and oxalyl
chloride (87.5 mg, 0.70 mmol) in CH2Cl2. The mixture was
stirred for 40 min at room temperature. The solvent was evap-
orated and the resulting residue was dried in vacuum at room
temperature for 30 min. The acid chloride 11 thus obtained was
dissolved in CH2Cl2 (60 mL) and added dropwise to a mixture of
8 and Et3N (162 mg, 1.60 mmol) in CH2Cl2 (20 mL) at 0 ꢄC. The
solution was stirred under N2 for 7 h. The organic layer was
washed with water (20 mL ꢁ 3) and dried over anhydrous
Na2SO4 and ltered. The crude product was puried by chro-
matography on silica gel (CH2Cl2/MeOH ¼ 20 : 1) to provide the
1 T. W. Bell and V. J. Santora, J. Am. Chem. Soc., 1992, 114,
8300.
2 M. T. Cushion, P. D. Walzer, M. S. Collins, S. Rebholz,
J. J. Vanden Eynde, A. Mayence and T. L. Huang,
Antimicrob. Agents Chemother., 2004, 48, 4209.
¨
3 (a) T. Grawe, G. Schafer and T. Schrader, Org. Lett., 2003, 5,
1641; (b) S. Rudra and A. V. Eliseev, J. Am. Chem. Soc.,
1998, 120, 11543; (c) S. C. Zimmerman, Y. Wang,
P. Bharathi and J. S. Moore, J. Am. Chem. Soc., 1998, 120,
2172; (d) A. Kra and A. Reichert, Tetrahedron, 1999, 55,
3923; (e) A. Kra, L. Peters and H. R. Powell, Tetrahedron,
2002, 58, 3499.
4 T. Schrader and M. Maue, in Functional Synthetic Receptors,
ed. T. Schrader and A. D. Hamilton, Wiley, Weinheim,
2005, p. 111.
5 (a) J. Scheerder, J. P. M. van Duynhoven, J. F. J. Engbersen
and D. N. Reinhoudt, Angew. Chem., Int. Ed., 1996, 35,
1090; (b) P. D. Beer, P. Hopkins and J. McKinney, Chem.
Commun., 1999, 13, 1253; (c) S. G. Galbraith, P. G. Plieger
and P. A. Tasker, Chem. Commun., 2002, 22, 2662; (d)
P. R. Webber and P. D. Beer, Dalton Trans., 2003, 22, 2249;
(e) C. C. Tong, R. Quesada, J. L. Sessler and P. A. Gale,
Chem. Commun., 2008, 47, 6321; (f) P. A. Gale, Chem. Soc.
1
product 1a as a white solid (241 mg, 73%). HNMR (400 MHz,
CDCl3, 298 K) (ppm): 10.19 (s, 2H), 9.14 (s, 4H), 9.16 (s, 2H), 9.14
(s, 1H), 8.51 (d, 2H, J ¼ 12 Hz), 8.28 (s, 1H), 8.20 (s, 2H), 7.80 (s,
2H), 7.02 (d, 2H, J ¼ 8 Hz), 6.50 (s, 3H), 4.79 (s, 2H), 4.10 (d, 8H, J
¼ 10 Hz), 3.91 (d, 12H, J ¼ 16 Hz), 2.25 (t, 1H, J ¼ 4 Hz), 1.54–
1.26 (m, 74H), 0.94–0.86 (m, 24H); 13C NMR (101 MHz, CDCl3,
298 K): d 164.55, 163.18, 162.38, 159.92, 159.72, 153.40, 145.87,
135.19, 132.31, 124.98, 124.25, 122.13, 120.92, 118.95, 117.90,
117.81, 112.81, 94.58, 77.22, 72.45, 72.29, 55.89, 55.50, 38.52,
37.86, 31.87, 30.96, 30.35, 30.06, 29.72, 29.72, 29.59, 29.35,
29.08, 28.65, 26.72, 26.38, 23.44, 23.15, 23.09, 22.67, 14.13,
10.35, 10.32; MALDI-TOF MS (m/z) calcd for C97H136N6O15 [M +
Na]+ 1647.996, found [M + Na]+ 1647.900.
˜
´
Rev., 2010, 39, 3746; (g) S. K. Kim, G. I. Vargas-Zuniga,
B. P. Hay, N. J. Young, L. H. Delmau, C. Masselin,
C.-H. Lee, J. S. Kim, V. M. Lynch, B. A. Moyer and
J. L. Sessler, J. Am. Chem. Soc., 2012, 134, 1782; (h)
M. Yano, C. C. Tong, M. E. Light, F. P. Schmidtchen and
P. A. Gale, Org. Biomol. Chem., 2010, 8, 4356; (i)
X. D. Wang, S. Li, Y. F. Ao, Q. Q. Wang, Z. T. Huang and
D. X. Wang, Org. Biomol. Chem., 2016, 14, 330.
Instruments and apparatus
6 (a) M. A. Hossain and H.-J. Schneider, J. Am. Chem. Soc.,
1998, 120, 11208; (b) H. Tsukube, M. Wada, S. Shinoda and
H. Tamiaki, Chem. Commun., 1999, 11, 1007; (c) A. P. Silva,
1H and13C NMR spectra were recorded on Bruker AVANCE AV II-
400 MHz (1H: 400 MHz; 13C: 100 MHz) (Karlsruhe, Germany).
High resolution mass spectra (HR-MS) data were collected by
WATERS Q-TOF Premier (California, USA). UV-vis spectra were
measured by SHIMADZU UV-2450 (Tokyo, Japan). Chemical
shis are reported in d values in ppm using tetramethlysilane
(TMS). HR-MS data were obtained by WATERS Q-TOF Premier.
The geometry optimizations were carried out in gas phase by
employing the Gaussian09 program. Fourier transform infrared
(FT-IR) data were collected by a Thermo Nicolet NEXUS 670 FT-
IR spectrophotometer. MALDI-TOF MS spectra were recorded
on Bruker Autoex III MS spectrometer.
´
H. Nimala Gunaratne, E. Glenn and R. Pamela, Chem.
Commun., 1996, 18, 2191.
7 (a) T. Yu and R. G. Weiss, Green Chem., 2012, 14, 209; (b)
R. Talhout and J. B. Engberts, Org. Biomol. Chem., 2004, 2,
3071; (c) A. Clark, T. Hemmelgarn, L. Danziger-Isakov and
A. Teusink, Pediatr. Transplant., 2015, 19, 326; (d)
P. A. Nguewa, M. A. Fuertes, V. Cepeda, S. Iborra,
´
´
J. Carrion, B. Valladares, C. Alonso and J. M. Perez, Chem.
Biodiversity, 2005, 2, 1387.
8 For selected reviews, see: (a) D.-W. Zhang, X. Zhao, J.-L. Hou
and Z.-T. Li, Chem. Rev., 2012, 112, 5271; (b) K. Yamato,
M. Kline and B. Gong, Chem. Commun., 2012, 48, 12142; (c)
B. Gong and Z. F. Shao, Acc. Chem. Res., 2013, 46, 2856; (d)
H. L. Fu, Y. Liu and H. Q. Zeng, Chem. Commun., 2013, 49,
4127.
Acknowledgements
We are grateful to the National Natural Science Foundation of
China (21172158 and 21572143), the Doctoral Program of the
Ministry of Education of China (20130181110023), Open Project
of State Key Laboratory of Supramolecular Structure and
9 (a) A. R. Sanford, L. H. Yuan, W. Feng, K. Yamato,
R. A. Flowers and B. Gong, Chem. Commun., 2005, 37, 4720;
39844 | RSC Adv., 2016, 6, 39839–39845
This journal is © The Royal Society of Chemistry 2016

View Article Online
Paper
(b) Y. Liu, J. Shen, C. Sun, C. L. Ren and H. Q. Zeng, J. Am.
RSC Advances
B. A. Moyer, J. L. Sessler, W. S. Cho, D. Gross, G. W. Bates,
S. J. Brooks, M. E. Light and P. A. Gale, Angew. Chem., Int.
Ed., 2005, 117, 2593; (e) M. H. Filby, T. D. Humphries,
D. R. Turner, R. Kataky, J. Kruusma and J. W. Steed, Chem.
Commun., 2006, 2, 156; (f) J. W. Steed and J. L. Atwood, in
Supramolecular Chemistry, John Wiley Sons, Ltd, 2009, p.
285; (g) M. F. Ni, Y. F. Guan, L. Wu, C. Deng, X. Y. Hu,
J. L. Jiang, C. Lin and L. Y. Wang, Tetrahedron Lett., 2012,
53, 6409; (h) B. Qiao, A. Sengupta, Y. Liu, K. P. McDonald,
M. Pink, J. R. Anderson, K. Raghavachari and A. H. Flood,
J. Am. Chem. Soc., 2015, 137, 9746; (i) Y. Y. Fang,
X. Y. Yuan, L. Wu, Z. Y. Peng, W. Feng, N. Liu, D. G. Xu,
S. J. Li, A. Sengupta, P. K. Mohapatra and L. H. Yuan,
Chem. Commun., 2015, 51, 4263.
Chem. Soc., 2015, 137, 12055.
10 (a) L. H. Yuan, W. Feng, K. Yamato, A. R. Sanford, D. G. Xu,
H. Guo and B. Gong, J. Am. Chem. Soc., 2004, 126, 11120; (b)
W. Feng, K. Yamato, L. Q. Yang, J. S. Ferguson, L. J. Zhong,
S. L. Zou, L. H. Yuan, X. C. Zeng and B. Gong, J. Am. Chem.
Soc., 2009, 131, 2629; (c) Y. A. Yang, W. Feng and
L. H. Yuan, Chem. J. Chin. Univ., 2011, 32, 1950; (d)
Y. A. Yang, W. Feng, J. C. Hu, S. L. Zou, R. Z. Gao,
K. Yamato, M. Kline, Z. H. Cai, Y. Gao, Y. B. Wang,
Y. B. Li, Y. L. Yang, L. H. Yuan, X. C. Zeng and B. Gong, J.
Am. Chem. Soc., 2011, 133, 18590; (e) L. J. Zhong, L. Chen,
W. Feng, S. L. Zou, Y. Y. Yang, N. Liu and L. H. Yuan, J.
Inclusion Phenom. Macrocyclic Chem., 2012, 72, 367.
11 J. C. Hu, L. Chen, Y. Ren, P. C. Deng, X. W. Li, Y. J. Wang, 18 K. L. Zhu, S. J. Li, F. Wang and F. H. Huang, J. Org. Chem.,
Y. M. Jia, J. Luo, X. S. Yang, W. Feng and L. H. Yuan, Org.
Lett., 2013, 15, 4670.
12 M. Xu, L. Chen, Y. M. Jia, L. J. Mao, W. Feng, Y. Ren and
L. H. Yuan, Supramol. Chem., 2015, 27, 436.
13 L. Chen, Z. Y. Peng, S. Liu, X. W. Li, R. Z. Chen, Y. Ren,
W. Feng and L. H. Yuan, Org. Lett., 2015, 17, 5950.
14 Y. Z. He, M. Xu, R. Z. Gao, X. W. Li, F. X. Li, X. D. Wu,
D. G. Xu, H. Q. Zeng and L. H. Yuan, Angew. Chem., Int.
Ed., 2014, 53, 11834.
15 X. W. Li, B. Li, L. Chen, J. C. Hu, C. D. Wen, Q. D. Zheng,
L. X. Wu, H. Q. Zeng, B. Gong and L. H. Yuan, Angew.
Chem., Int. Ed., 2015, 54, 11147.
2009, 74, 1322.
19 M. D. Lankshear, A. R. Cowley and P. D. Beer, Chem.
Commun., 2006, 6, 612.
20 (a) Y. A. Gao, Z. H. Li, J. M. Du, B. X. Han, G. Z. Li, W. G. Hou,
D. Shen, L. Q. Zheng and G. Y. Zhang, Chem.–Eur. J., 2005,
11, 5875; (b) B. Datta and M. N. Roy, Phys. Chem. Liq.,
2015, 53, 574; (c) H. Shekaari and F. Jebali, Phys. Chem.
Liq., 2011, 49, 572.
21 (a) J. W. Jones and H. W. Gibson, J. Am. Chem. Soc., 2003,
125, 7001; (b) H. W. Gibson, J. W. Jones, L. N. Zakharov,
A. L. Rheingold and C. Slebodnick, Chem.–Eur. J., 2011, 17,
3192; (c) M. Montalti and L. Prodi, Chem. Commun., 1998,
14, 1461.
16 J. C. Hu, L. Chen, J. Shen, J. Luo, P. C. Deng, Y. Ren,
H. Q. Zeng, W. Feng and L. H. Yuan, Chem. Commun., 22 A. Arduini, E. Brindani, G. Giorgi, A. Pochini and A. Secchi, J.
2014, 50, 8024. Org. Chem., 2002, 67, 6188.
17 (a) A. J. McConnell and P. D. Beer, Angew. Chem., Int. Ed., 23 (a) J. M. Mahoney, A. M. Beatty and B. D. Smith, Inorg. Chem.,
2012, 51, 5052; (b) S. K. Kim and J. L. Sessler, Acc. Chem.
Res., 2014, 47, 2525; (c) S. K. Kim and J. L. Sessler, Chem.
Soc. Rev., 2010, 39, 3784; (d) R. Custelcean, L. H. Delmau,
2004, 43, 7617; (b) M. Cametti, M. Nissinen, A. Dalla Cort,
L. Mandolini and K. Rissanen, J. Am. Chem. Soc., 2005,
127, 3831.
This journal is © The Royal Society of Chemistry 2016
RSC Adv., 2016, 6, 39839–39845 | 39845