Tetraphenylethene-based tetracationic cyclophanes and their selective recognition for amino acids and adenosine derivatives in water

Article abstract of DOI:10.1039/c9cc00599d

Two new tetracationic cyclophanes 1 and 2 containing tetraphenylethene and bipyridinium moieties were synthesized via a two-step S_N2 reaction. These water-soluble cyclophanes with a cationic and hydrophobic cavity exhibited selective recognitio

Full text of DOI:10.1039/c9cc00599d

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January 2016 Pages 1–216
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Reactivity differences of Sc
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This manuscript is submitted on an exclusive basis:
Firstly, two new tetracationic cyclophanes 1-2 containing tetraphenylethene and bipyridinium
moieties were synthesized via two-step S 2 reaction
N
Secondly, the cyclic structure and cavity’s size of cyclophanes 1-2 were further confirmed by
single crystal X-ray analysis.
Thirdly, two cyclophanes showed fluorescence quenching effect on the fluorescence indicator
HPTS through π-π and electrostatic interactions with strong affinity in aqueous media. More
interestingly, 1 exhibited highly-selective recognition for tryptophan and ATP due to its proper
size of cavity and good water-solubility. We firmly believe these two cyclophanes could offer
new opportunities for detecting biological analytes (e.g. DNA) and constructing molecular knots
in supramolecular chemistry.
We are proud, therefore, to offer this manuscript for publication in Chemical Communications.

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Dear Dr Alexander Metherell:
Thank you for your email of Jan. 08, 2019 about our manuscript (CC-COM-12-2018-
10009) detailed below.
0
Title:
Tetraphenylethene-based tetracationic cyclophanes and their selective
recognition for amino acids and adenosine derivatives in water
Lin Cheng, Haiyang Zhang, Yunhong Dong, Yanxia Zhao, Yang Yu,
and Liping Cao*
Authors:
Please find below a complete transcription of the comments of the reviewers and our
response. We have carefully re-refined the X-ray files, and uploaded a version of the
manuscript with the relevant scientific changes highlighted to aid your examination of
the revisions. We very much hope that you'll find the paper in a suitable form for
publication in Chemical Communications. Look forward to your reply.
Sincerely,
Liping Cao
Herein, we answer the questions and indicate the changes in the revised manuscript.
=============================================================
Reviewer 1: Herein, Cao and co-authors reported synthesis of two new water-soluble
tetracationic cyclophanes 1-2 containing tetraphenylethene and bipyridinium moieties.
The water-soluble tetracationic cyclophanes show selective recognition for tryptophan
and ATP via electrostatic and π-π interactions in water. It’s an interesting work and the
investigation contents are original and data enrichment. I recommend it to be published
in Chemical Communications after minor revisions.
1
.Sensitivity is an important feature for chemosensor. Author should supply the
recognition sensitivity (i.e. LOD) of tetracationic cyclophane for ATP and Trp,
respectively.
Response: We have measured the sensitivity, and have rewritten the description about
-
the recognition sensitivity of 1•4Cl for ATP and Trp in the ESI, as follows: “ The
method of the recognition sensitivity: The recognition sensitivity (i.e. the detection

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limits) of host for guests were determined by UV-vis experiments in phosphate buffer
(10 mmol, pH=7.4). With different concentrations of 2 μLguests (Trp andATP) solution
-
(
0, 2, 4, 6, 8, 10 μmol) were added into 2.4 mL host (1•4Cl ) while keeping the host
concentration constant (10 μmol) in all the samples. And UV-vis absorption of host-
guest solution was measured after mixing homogeneously. Next, the difference △A
between the different host-guest mixtures and host of absorption values in a certain
wavelength was taken, and the linear fitting between △A and the corresponding guest
concentration can be conducted ([guest] as the x-axis, △A as the y-axis). When y=0,
the obtained x value is the detection limits of guest that the lowest concentration of the
-
guest can be detected by host. (page S28) ” The detection limit of 1•4Cl for ATP (1.89
μmol) and Trp (0.36 μmol) were determined by UV-vis experiments (Figures S36 and
S79) and calculated on the basis of the linear fitting between △A (i.e. the difference
between the different host-guest mixtures and host of absorption values in a certain
wavelength) and the corresponding guest concentration.
In text, we have added “Then, the limit of detection of the host 1 for Trp was calculated
as 0.36 μmol by UV-vis experiments (Figure S36). (page 3, the second paragraph) ”
and “In addition, the limit of detection of the host 1 for ATP was calculated as 1.89
μmol (Figure S79). (page 4, the first paragraph)”
2
. Author investigated the recognition property of tetracationic cyclophane for ATP and
1
Trp by H NMR and ITC, how is it reflected in the fluorescence intensity? Some
fluorescent spectra and photographs of tetracationic cyclophane with different amino
acids or adenosine derivatives should be supplied.
Response: In our case, 1-2 are non-emitted in water due to the photoinduced electron
transfer (PET) from TPE to bipyridinium units, so we can't use fluorescence
experiments to further verify the recognition properties of host and ATP or Trp.
3
. In order to make the results more realistic, the mass spectrum of the host-guest
complex should be provided.
Response: We performed the mass spectrum experiments of the host-guest complexes

Page 5 of 71
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in the ESI. (1) For the complex 1•HPTS, the peaks at 626.1466 (calcd. for 626.1405)
and 655.1273 (calcd. for 655.1198) were observed in the ESI-MS, which could be
-
+ 2+
-
+ 2+
attributed to the [1•HPTS-4Cl -2Na ] and [1•HPTS-3Cl -1Na ] , respectively
Figure S25). (2) For the complex 2•HPTS, the peaks at 753.7004 (calcd. for 753.6969)
(
-
+ 2+
could be attributed to the [2•HPTS-4Cl -2Na ] (Figure S26). (3) For the complex
•Trp, the peaks at 337.8140 (calcd. for 337.8098) and 524.2022 (calcd. for 524.1994)
1
3+
2+
could be attributed to the [1•Trp] and [1•Trp] , respectively (Figure S35). (4) For
the complex 1•ATP, the peaks at 650.6692 (calcd. for 650.6666) and 679.6466 (calcd.
for 679.6459) could be attributed to the [1•ATP-4Cl -1Na -1H ] and [1•ATP-3Cl--
-
+
+ 2+
+
2+
1
H ] , respectively (Figure S84). (5) For the complex 1•ADP, the peaks at 610.6829
(calcd. for 610.6834), 628.6739 (calcd. for 628.6718) and 639.6767 (calcd. for
-
+
+ 2+
-
+ 2+
6
39.6627) could be attributed to the [1•ADP-4Cl -1Na -1H ] , [1•ADP-3Cl -1Na ]
-
+ 2+
and [1•ADP-3Cl -1H ] , respectively (Figure S85). (6) For the complex 1•AMP, the
peaks at 559.7139 (calcd. for 559.7093) and 599.6963 (calcd. for 599.6796) could be
-
+ 2+
-
+ 2+
attributed to the [1•AMP-4Cl -2Na ] and [1•AMP-3Cl -1H ] , respectively (Figure
S86).
In text, we have added (1) “In addition, electrospray ionization mass spectrometry
(ESI-MS) confirmed the formation of 1:1 host-guest complex between 1-2 and HPTS,
respectively (Figures S25-26). (page 4, the third paragraph)”, (2) “Furthermore, ESI-
3+
2+
MS also observed the two- and three-charged peaks ([1•Trp] and [1•Trp] ), which
confirm the formation of 1:1 host-guest complex, respectively (Figure S35). (page 3,
the second paragraph)” and (3) “All ESI-MS spectra of 1•ATP, 1•ADP and 1•AMP
showed the formation of 1:1 host-guest complexes, respectively (Figure S84-86). (page
4
, the first paragraph)”
4
. Some related references on recognition of amino acids should be included:
Macromolecules, 2017, 50, 7863; Chem. Eur. J., 2018, 24, 777; Soft Matter, 2018, 14,
390.
8
Response: We have corrected reference [23] as follows: “Q. Lin, Y.-Q. Fan, P.-P. Mao,
L. Liu, J. Liu, Y.-M. Zhang, H. Yao, and T.-B. Wei, Chem. Eur. J., 2018, 24, 777-783.”

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Reviewer 2: By using a two-step reaction starting from tetraphenylethene and
bipyridine, cao and his tetracationic cyclophenes, and then they characterized and
determined the X-ray single crystal structures for the two new cyclophene hosts.
Furthermore, they studied host-guest interactions in water. The results revealed a
selective recognition for amino acids and adenosine derivatives (ATP) etc. through
electrostatic and π-π interactions in water. This work is well-done and the novel results
deserve the publication in RSC journal chem. commun. as it stands.
Response: No response.
Reviewer 3: This submission has details of the structures of the two cyclophane
compounds labelled by the authors as Cyclophane 1•4PF -
and Cyclophane 2•4PF -
6
6
None of these structures is well determined and while the gross non-H connectivities
may have been established the crystallographic work is not of an acceptable quality (see
below) and I cannot recommend acceptance in this present form. Rejection and perhaps
resubmission to a different journal after significant revisions is recommended.
-
Cyclophane 1•4PF
6
==================
1
.1.1 We see from the CIF that the SQUEEZE program was used to remove the
contributions of disordered solvent but we are nowhere told about this in text or ESI
material, although the authors have appended the CIF format output from PLATON
(generated as platon.sqf) to the CIF from which we see that the contributions of some
4
55 electrons were removed from the unit-cell contents.
-
And 2•4PF -
with the version of
Response: We have re-refined the structures 1•4PF
6
6
OLEX2 1.2. and ShelXL-2018/3 respectively, and we used the SQUEEZE subroutine in
the latest version (201118) of PLATON to remove severely disordered solvent
molecules from structure model of compound 1•4PF -
molecules co-crystallised in the unit cell of complex 1•4PF
electron density removed using the SQUEEZE subroutine implemented within the
. Four CH
Cl
and two CHCl
6
2
2
3
-, with the corresponding
6

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program PLATON (Ver. 201118). The above description has been added in the ESI, as
follows: “X-ray Crystal Structure Determination. Diffraction data for the complexes
-
-
1
•4PF
6
and 2•4PF
6
were performed on a Bruker D8 Venture photon II, at low
temperature (153 K) with graphite-monochromated Mo Kα radiation ( = 0.71073 Å).
4
An empirical absorption correction using SADABS was applied for all data. Both
2
structures were solved and refined to convergence on F for all independent reflections
5
6
by the full-matrix least squares method using SHELXL-2018/3 in OLEX2 1.2. All non-
hydrogen atoms, including those in disordered parts, were refined anisotropically. All
H-atoms were also included at calculated positions and refined as riders, with Uiso(H)
-, two PF
-
anions were found to be disordered and were modelled
=
1.2 Ueq. In 1•4PF
6
6
with two orientations having relative occupancies of 0.54:0.46 and 0.57:0.43 for the
two parts, separately. The geometries of the disordered parts were restrained to be
similar. The anisotropic displacement parameters of the disordered molecules in the
direction of the bonds were restrained to be equal with a standard uncertainty of 0.01
Å2. They were also restrained to have the same Uij components, with a standard
2
-, four CH
uncertainty of 0.04 Å . In 1•4PF
6
2
Cl
2
and two CHCl molecules co-
3
crystallized in each unit cell of complex 1•4PF -
, with the corresponding electron
6
densities removed using the SQUEEZE subroutine implemented within the software
7
program PLATON (Ver. 201118), and the resulting .fab file was processed with
OLEX2 1.2. using the ABIN instruction. Approximately 280 electron equivalents were
3
removed from the unit cell. The total void volume was 1804 Å indicated by PLATON,
equivalent to 25.38 % of the unit cell’s total volume. In 2•4PF
6
-, the PF -
anion was
6
found to be disordered and was modelled with two orientations having relative
occupancy of 0.55:0.45. The geometries of the disordered parts were restrained to be
similar. The anisotropic displacement parameters of the disordered molecules in the
direction of the bonds were restrained to be equal with a standard uncertainty of 0.01
Å2. They were also restrained to have the same Uij components, with a standard
2
uncertainty of 0.04 Å . There are 32 severely disordered Et
2
O molecules in crystal
2
•4PF
-, They were also removed by by the SQUEEZE subroutine in PLATON (Ver.
6

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2
01118) and the resulting .fab file was processed with OLEX2 1.2. using the ABIN
instruction. Approximately 1324 electron equivalents were removed from each unit cell.
3
The total void volume was 4070 Å indicated by PLATON, equivalent to 39.81 % of the
unit cell’s total volume. Crystallographic data and refinement details for 1•4PF -
and
6
-
are given in Table S1. CCDC 1870620 (1•4PF -
) and 1870621 (2•4PF -
2
•4PF
6
6
6
). These
data can be obtained free of charge from the Cambridge Crystallographic Data Centre
www.ccdc.cam.ac.uk/data_request/cif.(page S7)”
We have corrected reference [4-7] in the ESI, as follows:“4. G. M. Sheldrick, Program
SADABS: Area-Detector Absorption Correction, 1996, University of Göttingen,
Germany. 5. G. M. Sheldrick, Acta Crystallogr., Sect. C: Cryst. Struct. Chem. 2015,
C71, 3-8. 6. O. V. Dolomanov, L. J. Bourhis, R. J. Gildea, J. A. K. Howard and H.
Puschmann, J. Appl. Cryst. 2009, 42, 339-341. 7. A. L. Spek, Acta Cryst. 2015, C71, 9–
1
8. (page S8)”
1
.1.2 The contribution of any disordered solvent removed by the SQUEEZE process
should have been included in the overall formula, formula weight, density, F(000), etc.,
calculations reported in the crystal-data text and in the CIF. This should now be done
and we should also be explicitly told what (and the amount of) disordered solvent that
was removed from the Formula unit by the SQUEEZE process in the
_
platon_squeeze_details text of the revised CIF. A reference to the SQUEEZE process
should be in the reference list: - Spek, A. L. (2015). Acta Cryst. C71, 9–18
Response: The disordered solvent removed by the SQUEEZE have been included in the
overall formula, formula weight, density, F(000), etc. calculations reported in the
crystal-data text and in the CIF. The details of SQUEEZE were included in the
_
platon_squeeze_details text of the revised CIF. A reference to the SQUEEZE has been
added in the references list.
In text, we have corrected reference [21] as follows: “A. L. Spek, Acta Cryst. 2015, C71,
9
-18.”

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1
.1.3 It is also clear from the submitted CIF that the authors did not carry out the post-
squeeze refinement as required by the squeeze program. This is: - "Continue refinement
in the presence of the three files name_sq.ins, name_sq.hkl & name_sq.fab" as
produced by SQUEEZE.
Response: The solvent contribution to the structure factors was re-calculated with the
latest version of PLATON SQUEEZE (A. L. Spek, Acta Cryst. 2015, C71, 9–18.) and
the resulting .fab file was processed with SHELXL using the ABIN instruction. We have
submitted the full CIF files to the CCDC.
1
.1.4 Before this is done the authors must look very carefully at their pre-SQUEEZE
shelxl.ins file and consider why they have some 52 OMIT commands in that file. [Note
that it is usual to use the OMIT command only for very few low order reflections that
may have been obscured by the beam stop and not all reflections with poor Fo/Fc
agreements.]
Response: Most omitted commands have been deleted. Only reflection -2 0 2 was
omitted because it was obscured by the beam stop.
1
.1.5 If SQUEEZE had been correctly run there should have been no large positive
residual density as is found in this post-squeeze refinement (_refine_diff_density_max
.410).
Response: After re-perform SQUEEZE, no large positive residual density is left
2
(_refine_diff_density_max
0.880).
-
Cyclophane 2•4PF
6
==================
2
.1 Routine PLATON checks indicate that the Cmc2~1~space group has been wrongly
deduced and reports an excellent fit in the Cmca space group with some minor disorder
and the various component molecules having significant crystallographically imposed
symmetries about which we must be told. The refinement should be carefully redone in
the Cmca space group and the text revised as appropriate.
Response: The space group of compound 2•4PF -
Cmca space group by PLATON. The refinement based on space group Cmca was
has been changed from Cmc2(1) to
6

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redone. All disorder modeling and SQUEEZE operation details were included in the
revised crystallographic description.
Due to the disorder of ether molecules in the cavity of 2•4PF
it. In text, (1) Because we have re-refined the structures 1•4PF -
between two pyridinium rings in the bipyridinium moieties is converted from 44.3° to
4.4° (page 3, the second paragraph). (2) we have deleted the following sentence :“in
6
-, we rerefined and deleted
6
, the dihedral angle
4
which a diethyl ether molecule as guest is encapsulated. (page 3, the second paragraph)”
and the corresponding fig. 1(b) was modified. (3) In addition, we have rewritten in the
text, as follows: “At the same time, solvent molecules (e.g. MeCN, acetone, CH
2
Cl ,
2
-
CHCl
3
and Et
2
O) and PF
6
counter ions exist in the interspace of the framework
structure. (page 3, the last sentence of the second paragraph)”

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Journal Name
COMMUNICATION
Tetraphenylethene-based tetracationic cyclophanes and their
selective recognition for amino acids and adenosine derivatives
†
in water
Received 00th January 20xx,
Accepted 00th January 20xx
Lin Cheng,a,‡ Haiyang Zhang,a,‡ Yunhong Dong,a,b,‡ Yanxia Zhao, Yang Yu, and Liping Cao *
a
a
a,
DOI: 10.1039/x0xx00000x
www.rsc.org/
Two
tetraphenylethene and bipyridinium moieties were synthesized emission (AIE) luminogen has been widely applied to fabricate
via two-step S 2 reaction. These water-soluble cyclophanes with and construct fluorescent systems with carbohydrates, lipids,
new
tetracationic
cyclophanes
1-2
containing
Tetraphenylethene (TPE) as a typical aggregation-induced
N
a cationic and hydrophobic cavity exhibited selective recognition amino acids, proteins, enzymes, nucleic acids, and others.16 In
for amino acids (e.g. tryptophan) and adenosine derivatives (e.g. supramolecular chemistry, TPE derivatives have been also used
ATP) via electrostatic and π-π interactions in water.
as building block for the design and synthesis of macrocyclic
compounds or assemblies.17-19 For example, Zheng and co-
workers reported a series of TPE-based macrocycles and cages
Synthesis, recognition and self-assembly of supramolecular
hosts (e.g. clips, macrocycles, cages, and capsules) have played
an important role in the development of supramolecular
with AIE effect for functional applications, such as chiral
recognition,17a self-assembly,17b gas sorption,17c and TNT
1
chemistry. Several famous macrocyclic compounds, such as
detection.17d Stang and co-workers developed a series of pyridyl
2
cyclodextrin,3 calixarene,4 cucurbituril,5
crown ether,
TPE-based platinum(II) metallacycles18 and metallacages,19
6
7
cyclophane, and pillararene, have already attracted attention
from chemical community to explore the nature of molecular
which exhibited a high emission based on their AIE properties in
various solvents. Although several cationic cyclophane
derivatives have been effectively utilized for host–guest
complexation, the synthesis and host-guest study of water-
soluble cyclophanes that retain the recognition ability in aqueous
media still has been a huge challenge.20 Here we report the
interactions
and
construct
supramolecular
architectures/machines. Particularly, cationic cyclophanes with
various sizes, shapes, and functional groups has been widely
used, because of not only their unique electron-deficient cavity
for selectively binding guest molecules, but also their reduction-
synthesis and characterization of two cationic cyclophanes (1-2
)
8
oxidation property for electronic devices (e.g. semiconductor)
containing tetraphenylethene (TPE) and bipyridinium (BP)
moieties, which have a suitable cavity for selectively recognizing
amino acids (e.g. tryptophan) and adenosine derivatives (e.g.
ATP) in water.
9
and molecular machine (e.g. molecular shuttle and molecular
pump). The most famous one is Stoddart's ‘Blue Box’, as a
classic cationic cyclophane, which has milestone significance for
the synthesis and development of the new cationic
cyclophanes.10 It and its derivatives can form stable complexes
with a series of electron-rich guest molecules through non-
covalent bonds for the construction of many complicated
supramolecular structure, such as catenane,11 rotaxane,12 nano
conductive material,13 electrochemically switchable molecule,14
metal–organic framework (MOF),15 and so on.
a
Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of the
b
Ministry of Education, National Demonstration Center for Experimental
Chemistry Education, College of Chemistry and Materials Science, Northwest
University, Xi’an, 710069, P. R. China. E-mail: chcaoliping@nwu.edu.cn
†
Electronic Supplementary Information (ESI) available: Experimental details,
including synthesis, ITC, NMR, UV/vis, fluorescence, and crystal data in the cif
format (CCDC 1870620-1870621). For ESI and crystallographic data in CIF or
other electronic format see DOI: 10.1039/x0xx00000x
‡
Scheme 1. Synthesis of the cationic cyclophane derivatives 1 and 2.
These authors contributed equally.
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 1
Please do not adjust margins

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Page 12 of 71
COMMUNICATION
Journal Name
of this 2D nanotubular layer, neighboring 2 moleculesViferwoAmrtictlwe Oon1linDe
N
Cationic cyclophanes (1-2) were synthesized via two-step S 2
reactions as shown in Scheme 1 (see the Supporting Information): nanotubes contact with each other througDhOIC: 1−0H.10••3•9π/Ci9nCteCr0a0c5ti9o9nDs
) the first-step S 2 reaction between and dipyridine gives a C- (Figure S18). Finally, neighboring 2D nanotubular layers are stacked
shaped compound ( ) in 97% yield; 2) the second-step S
reaction between and corresponding dibromide compounds (
or ) achives a cyclic formation to give
1
N
3
4
N
2
parallelly to form a 3D nanotubular framework (Figure 1d). At the
4
3
same time, solvent molecules (e.g. MeCN, acetone, CH
2
Cl
2
, CHCl
3
-
-
5
1
-
2
with PF
6
as and Et
2
O) and PF
6
counter ions exist in the interspace of the
counterions in 35% and 42% yeild without chromatography, framework structure.21
respectively. Finally, 1-2 were transferred to their Cl form by
-
adding excess amount of tetrabutylammonium chloride in 90%
-
and 85% yield, respectivley.
1
-
2
with Cl as counterions showed
2
a good solubility of ~49.0 mM and ~3.4 mM in D O determined
by NMR, indicating their potential application for molecular
recognition in water (Figures S15-S16).
Fig. 2 (a) UV-vis and (b) fluorescence titration (λex= 365 nm) of HPTS (5μmol)
-
with gradual addition of 1•4Cl in water at 298K. The insets show a plot of
absorbance intensity at 403 nm and emission intensity at 514 nm versus the
-
equivalent of 1•4Cl . (c) UV-vis and (d) fluorescence titration (λex= 365 nm) of
HPTS (5μmol) with gradual addition of 2•4Cl in water at 298K. The insets show a
Fig. 1 The single-crystal X-ray structures of (a) a single molecule of
1
•4PF
6
-; (b) a
-
single molecule, (c) side view of the 2D nanotubular layer from the c axis, and (d)
plot of absorbance intensity at 403 nm and emission intensity at 514 nm versus the
equivalent of 2•4Cl .
-
-
perspective view of the 3D framework of
2
•4PF
6
from the b axis, respectively.
Colour code: C, grey; N, blue; H, white; O, red. Counter ions and solvent molecules
have been omitted for clarity; the atom-to-atom distances are showed here.
To explore the recognition ability of these cationic cyclophanes as
hosts, 1H NMR experiments between cyclophanes (1-2) and 8-
hydroxy-1,3,6-pyrene trisulfonate (HPTS) were first performed in
The cyclic structure and cavity’s size of cyclophanes 1-2 were
further confirmed by single crystal X-ray analysis (Figure 1). The X-
-
D
2
O or DMSO-d
6
. The host-guest recognition between 1-2 and HPTS
than in D O, because strong
ray-quality single crystals of cyclophane 1•4PF
6
were obtained by
was presented more clearly in DMSO-d
6
2
slow vapour diffusion of dichloromethane into an acetone solution of
-
electrostatic interactions between sulfonate groups and pyridinium
ring make the host-guest complex a poor solubility in water (Figures
S19-S23). As a result, NMR titration of 1-2 and HPTS confirmed the
1
•4PF
6
at room temperature. Cationic cyclophane 1 was found to
crystallise in monoclinic crystal system. The dihedral angle between
two pyridinium rings is about 44.4° in the bipyridinium moieties.
Interestingly, 1 possesses a trapezoid-like cavity with up, down, and
side lengths of about 5.8 Å, 9.6 Å, and 9.9 Å, respectively (Figures 1a
and S17). Furthermore, 1 exhibits a head-to-head and tail-to-tail
stacking pattern to form supramolecular framework structure (Figure
6
formation of 1:1 host-guest complexes in DMSO-d . For example,
when HPTS was added to the solution of 2, upfield shifts of the pyrene
resonances for HPTS were observed, indicating that the pyrene unit
of HPTS is totally encapsulated by the cavity of 2. Simultaneously, all
resonances (Ha-e) of 2 located around HPTS in the host-guest complex
exhibited upfield shifts, because of the shielding effect of π-electron-
S17). On the other hand, X-ray-quality single crystals of 2•4PF -
6
were
also obtained by slow vapour diffusion of diethyl ether into a solution
-
rich HPTS. In addition, the COSY and NOESY spectra showed a H2'-
of 2•4PF
6
in acetonitrile/acetone at room temperature. Cationic
Hb' inter-correlation between guest and host, indicating the inclusion
cyclophane 2 was crystallized in orthorhombic crystal system.
Because the middle part of bipyridinium units bent into the inside of
the cavity, 2 possesses a flat rectangle-like cavity with a length of
about 9.9 Å and widths of ~9.8 Å at two sides and ~9.0 Å at the center
6
complex between 2 and HPTS in the DMSO-d (Figure S24). In
addition, electrospray ionization mass spectrometry (ESI-MS)
confirmed the formation of 1:1 host-guest complex between 1-2 and
HPTS, respectively (Figures S25-26).
(
Figure 1b). Beyond the intriguing macrocyclic cavity described
Subsequently, the photophysical properties of HPTS and 1-2 were
analysed in water by fluorescence and UV-vis experiments. Like
Ramaih’s anthracene-based cyclophane, 1-2 are non-emitted in water
due to the photoinduced electron transfer (PET) from TPE to
bipyridinium units.22 As shown in Figure 2a, when 1 was successively
added to HPTS in water, the absorbance maxima at 403 nm decreased
and moved to 408 nm, indicating that the formation of the host-guest
complex. And there was a new peak at 430-510nm which may be
above, a 3D nanotubular framework stacked by 2 molecules is
revealed, that features 1D intrinsic nanotubes constructed by the
cavities of 2 along the b axis (Figure 1c-d). Firstly, 2 molecules are
aligned parallelly to form a 1D intrinsic nanotube, in which each 2
molecules are in register to one another to extend through a lattice
translation (~9.5 Å repeat) along the b axis. Secondly, neighboring 1D
nanotubes formed from 2 with a parallel arrangement form a 2D
nanotubular layer in the alternate pattern (Figure 1c). Close inspection
2
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•Trp with a
caused by the charge-transfer interaction between HPTS and the a 1:1 stoichiometry of the host-guest complex
bipyridinium units. As a result, a dramatic fluorescence quenching of moderate binding constant (K
1
View Article Online
3 -1
DOI: 10.1039/C9CC00599D
1
•Trp = 2.67 × 10 M ) in the
HPTS at 514 nm happened when 1.0 equiv. of 1 was added, which solution (Figures S29-S34). In addition, binding constant (K
could be contributed to the PET from HPTS to 1 based on the = 1.21 × 10 M ) and 1:1 stoichiometry of 1•Trp were also
1
•Trp
3
-1
formation of host-guest complex (Figure 2b). In addition, UV-vis and confirmed by ITC experiments (Figure 3b and Table 1).
fluorescence titration experiments between 1 and HPTS gave a 1:1 Furthermore, ESI-MS also observed the two- and three-charged
stoichiometry for the complex 1•HPTS. Similarly, UV-vis and peaks ([1 1•Trp] ), which confirmed the formation
•Trp]3+ and [
2+
fluorescence titration experiments of HPTS with 2 also established a of 1:1 host-guest complex, respectively (Figure S35). Then, the
:1 stoichiometry of the host-guest complex 2•HPTS (Figure 2c-d). limit of detection of the host for Trp was calculated as 0.36
Job plot using the UV-vis spectroscopy displayed a maximum at about μmol by UV-vis experiments (Figure S36).23 Similar but weak
.5, which supports a 1:1 binding stoichiometry for both complexes recognition behaviours were observed in the case of tyrosine,
Figure S28). Furthermore, isothermal titration calorimetry (ITC) data phenylalanine, aspartic acid, and cysteine with , however, their
also confirmed that a 1:1 binding stoichiometry and the strong binding association constants are too weak to be calculated by NMR or
1
1
0
(
1
8
-1
9
-1
(K1•HPTS = 4.88 × 10 M and K2•HPTS = 1.42 × 10 M ) facilitates these ITC (Figures S37-S41). In contrast, 2 showed weaker
stable host-guest complexes in water (Figure S29). Because of the interactions with all the amino acids on account of its too large
proper size of cavity, 2 exhibited a stronger binding affinity for HPTS cavity (Figures S56-S75). For arginine (Asn) and lysine (Leu) as
through π-π and electrostatic interactions. However, the utility of the basic amino acids, the α- and β-protons (H1’-H2’) of Asn/Leu
host-guest complexes (1•HPTS and 2•HPTS) as an on-off-on with 1-2 showed downfield shifts, indicating only electrostatic
fluorescent sensor is limited due to the too high binding constants interactions between the deprotonated carboxyl groups and
between 1-2 and HPTS.22
positive pyridinium groups played a main role (Figures S42-S43
and S62-S63).
1
Fig. 3 a) H NMR spectra (400MHz, 298 K, D
7
2
-
O, 10 mM phosphate buffer, pH =
-
.4) recorded for: i) 1•4Cl (0.4 mM); ii) 1•4Cl (0.4 mM) and Trp (0.4 mM); iii)
tryptophan (0.4 pmM) at 298K. b) ITC data for the titration of 1•4Cl (0.40 mM) in
-
the cell with a solution of Trp (16.0 mM) in the syringe in phosphate buffer (10
-
mM, pH = 7.4) at 298 K. 1•4Cl : tryptophan = 1:1. Here, primes (’) denote
resonances within the host-guest complexes.
Fig. 4 a) schematic representation of
O, 10 mM phosphate buffer, pH = 7.4) recorded for: b) ATP (0.4 mM); c)
1
•ATP; 1H NMR spectra (400MHz, 298 K,
-
D
2
1
•4Cl
To further explore the host-guest recognition of
1
-
2
in aqueous
-
(
0.4 mM) and ATP (0.4 mM); d) 1•4Cl (0.4 mM). Here, primes (’) denote
media, we decided to investigate the recognition ability of 1-2 resonances within the host-guest complexes.
for amino acids and nucleotides (e.g. ATP, ADP, and AMP).
Initially, the recognition between
1
-
2
and amino acids was
Next, adenosine derivatives (e.g. ATP, ADP, and AMP) as guests
O with phosphate buffer (Figures were investigated for 1-2 as hosts by NMR and ITC. In the H NMR
1
1
screened by H NMR in D
S30-S75). Interestingly,
2
1
exhibited
a
2
highly-selective spectrum of 1 with 1.0 equiv. of ATP in D O (phosphate buffer, pH =
recognition toward tryptophan (Trp), compared to other amino 7.4), proton resonances (H1’-H2’ and H6’-H7’) for adenine (ΔδH1’ = 1.50
acids (Figures 3 and S30). NMR spectra of the 1:1 mixture of
ppm and ΔδH2’ = 1.74 ppm) and ribose moieties (ΔδH7’ = 0.62 ppm) of
1
and Trp showed that all proton resonances (H1’-H7’) of Trp ATP were obviously shifted to upfield, compared to free ATP,
underwent upfield shifts (Δδ = 0.14-0.79 ppm), indicating Trp indicating that whole adenine and part of ribose moieties resided in
molecule is fully encapsulated into the cavity of
time, partial protons (Hd’-Hg’) of displayed upfield shifts (Δδ =
.04-0.33 ppm), which could be caused by π-electron shielding unit of 1, indicating adenine moiety of ATP was closer to the TPE unit
1
. At the same the cavity of 1 (Figure 4). In addition, NOESY spectra showed a H1’
-
1
Hh’-l’ inter-correlation between adenine moiety of ATP and the TPE
0
of the face-to-face oriented aromatic rings between the π- in the cavity of 1. The π-π interaction between adenine moiety of ATP
electron-rich indole moiety of Trp and π-electron-deficient and bipyridinium units of 1 also results in a shielding effect for proton
.15 Remarkably, compared with that of resonances (Hd’-He’) for the bipyridinium unit in 1. At the same time,
(Hb’) and
bipyridinium unit of
protons near the p-xylylene ring, the chemical shifts of the proton proton resonances for the p-xylylene (Ha’), bridged CH
d’-Hg’) near the TPE unit in
was larger, which indicated that neighboring pyridinium (Hc’) units in 1 were significant downshifted
Trp molecule was closer to the TPE unit in the cavity of
. Job (△δ = 0.29 ppm, 0.06 ppm, and 0.18 ppm, respectively), which
O (phosphate buffer, pH = 7.4) determined probably were caused by the electrostatic interactions between the
1
2
(
H
1
1
1
plot by H NMR in D
2
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Journal Name
triphosphate unit of ATP and the pyridinium near the p-xylylene ring
in 1 (Figure 4). Based on the above NMR data, the adenine moiety of
ATP molecule is closed to TPE in the cavity of 1, while triphosphate
unit prefers to p-xylylene and neighboring pyridinium rings, which is
consistent with the result of NOESY spectra (Figure S77). On the
Notes and references
View Article Online
DOI: 10.1039/C9CC00599D
1
F. Diederich, P. J. Stang and R. R. Tykwinski, Modern
Supramolecular Chemistry: Strategies for Macrocycle
Synthesis. Wiley-VCH Verlag GmbH Co. KGaA,
Weinheim, 2008
G. W. Gokel, W. M. Leevy and M. E. Weber, Chem. Rev., 2004,
04, 2723-2750.
&
.
2
other hand, the 1:1 host-guest stoichiometry and binding constant (K
a
1
4
-1
=
1.17 × 10 M ) were determined by ITC (Figure S78). In addition,
3
4
5
G. Chen and M. Jiang, Chem. Soc. Rev., 2011, 40, 2254-2266.
D.-S. Guo and Y. Liu, Chem. Soc. Rev., 2012, 41, 5907-5921.
J. Lagona, P. Mukhopadhyay, S. Chakrabarti and L. Isaacs,
Angew. Chem. Int. Ed., 2005, 44, 4844-4870.
the limit of detection of the host 1 for ATP was calculated as 1.89
μmol (Figure S79). Similarly, ADP and AMP were quantitatively
accommodated within cyclophane 1 to give 1:1 host-guest complexes
1
6
7
8
Z. Liu, S. K. M. Nalluri and J. F. Stoddart, Chem. Soc. Rev.,
by the H NMR and ITC. ADP and AMP were bound by 1 with
2
017, 46, 2459-2478.
3
-1
3
-1
moderate binding constants of 5.07 × 10 M and 1.09 ×10 M ,
respectively (Figures S80-S83). Compared the host-guest interactions
of three nucleotides with 1, their binding ability gradually strengthen,
accompanying with the increase of the number of phosphate (Tables
M. Xue, Y. Yang, X. Chi, Z. Zhang and F. Huang, Acc. Chem.
Res., 2012, 45, 1294-1308.
(a) M. T. Nguyen, M. D. Krzyaniak, M. Owczarek, D. P. Ferris,
M. R. Wasielewski and F. J. Stoddart, Angew. Chem. Int. Ed.,
2
017, 56, 5795-5800; (b) W. W. Porter, T. P. Vaid and A. L.
1
and S2). All ESI-MS spectra of 1•ATP, 1•ADP and 1•AMP showed
the formation of 1:1 host-guest complexes, respectively (Figure S84-
6). The results indicated that cyclophane 1 can selectively recognize
Rheingold, J. Am. Chem. Soc., 2005, 127, 16559-16566.
9
1
C. Cheng, P. R. McGonigal, S. T. Schneebeli, H. Li, N. A.
Vermeulen, C. Ke and J. F. Stoddart, Nat. Nanotech., 2015, 10
547-553.
0 (a) E. J. Dale, N. A. Vermeulen, M. Juríček, J. C. Barnes, R.
M. Young, M. R. Wasielewski and J. F. Stoddart, Acc. Chem.
Res., 2016, 49, 262-273; (b) H. Y. Gong, B. M. Rambo, E.
8
,
ATP molecule through both electrostatic and π-π interactions.
However, the weak binding behavior between 2 and adenosine
1
derivatives was confirmed by the H NMR and UV-vis (Figures S87-
S92), probably because the large cavity of 2 is not fit with adenine
ring.
Karnas, V. M. Lynch and J. L. Sessler, Nat Chem, 2010,
06-409; (c) H. Y. Gong, B. M. Rambo, E. Karnas, V. M.
Lynch, K. M. Keller and J. L. Sessler, J. Am. Chem. Soc., 2011,
33, 1526-1533.
2,
4
a
Table 1. Binding constants between 1-2 and guests
.
1
1
1
1 J. Sun, Z. Liu, W. G. Liu, Y. Wu, Y. Wang, J. C. Barnes, K. R.
Hermann, W. A. Goddard, III, M. R. Wasielewski and J. F.
Stoddart, J. Am. Chem. Soc., 2017, 139, 12704-12709.
2 A. Trabolsi, A. C. Fahrenbach, S. K. Dey, A. I. Share, D. C.
Friedman, S. Basu, T. B. Gasa, N. M. Khashab, S. Saha, I.
Aprahamian, H. A. Khatib, A. H. Flood and J. F. Stoddart,
Chem. Commun., 2010, 46, 871-873.
-
1
Host
Guest
HPTS
HPTS
Trp
ATP
ADP
AMP
Binding Constant (K
a
, M )
8
1
2
1
1
1
(4.88 ± 1.95) × 10
(1.42 ± 0.98) × 10
(1.21 ± 0.04) × 10
(1.17 ± 0.12) × 10
(5.07 ± 0.28) × 10
(1.09 ± 0.16) × 10
9
3
4
3
3
13 J. C. Barnes, E. J. Dale, A. Prokofjevs, A. Narayanan, I. C.
Gibbs-Hall, M. Juríček, C. L. Stern, A. A. Sarjeant, Y. Y.
Botros, S. I. Stupp and J. F. Stoddart, J. Am. Chem. Soc., 2015,
1
a
Determined by ITC.
1
37, 2392-2399.
In conclusion, we have designed and synthesized two new cationic
cyclophanes (1-2) containing tetraphenylethene and bipyridinium
moieties. Determined by their X-ray crystal structures, asymmetrical
1
4 C. Cheng, P. R. McGonigal, S. T. Schneebeli, H. Li, N. A.
Vermeulen, C. Ke and J. F. Stoddart, Nat. Nanotech., 2015, 10
547-553.
,
cyclophane 1 possesses a trapezoid-like and smaller cavity whereas 15 Q. Chen, J. Sun, P. Li, I. Hod, P. Z. Moghadam, Z. S. Kean, R.
Q. Snurr, J. T. Hupp, O. K. Farha and J. F. Stoddart, J. Am.
Chem. Soc., 2016, 138, 14242-14245.
6 J. Mei, N. L. C. Leung, R. T. K. Kwok, J. W. Y. Lam and B.
Z. Tang, Chem. Rev., 2015, 115, 11718-11940.
symmetrical cyclophane 2 possesses a flat rectangle-like and larger
cavity. Their host-guest behaviours have been investigated by H
NMR, UV-vis, fluorescence and ITC experiments. In aqueous media,
1
1
two cyclophanes have fluorescence quenching effect on the 17 (a) J. B. Xiong, H. T. Feng, J. P. Sun, W. Z. Xie, D. Yang, M.
fluorescence indicator HPTS when forming 1:1 host-guest complexes
H. Liu and Y. S. Zheng, J. Am. Chem. Soc., 2016, 138, 11469-
11472; (b) S. Song and Y. S. Zheng, Org. Lett., 2013, 15, 820-
8
9
through π-π and electrostatic interactions with strong affinity (10 ~10
8
23; (c) C. Zhang, Z. Wang, L. X. Tan, T. L. Zhai, S. Wang,
-
1
M ). More interestingly, 1 exhibited a highly-selective recognition for
B. Tan, Y. S. Zheng, X. L. Yang and H. B. Xu, Angew. Chem.,
Int. Ed., 2015, 54, 9244-9248.
tryptophan and ATP (~2 times to ADP, ~10 times to AMP) due to its
proper size of cavity and good water-solubility. We anticipate that this 18 X. Yan, H. Wang, C. E. Hauke, T. R. Cook, M. Wang, M. L.
kind of cationic cyclophane can also be synthesized and modified with
other functional linkers, affording the ability to tune the cavity, host-
guest and photophysical properties of these cationic macrocycles,
which may find utility in applications such as not only biosensor for
detecting biological analytes (e.g. DNA) but also supramolecular
building blocks for constructing molecular knots in near future.
This work was supported by National Natural Science
Foundation of China (21771145 and 21472149 to L.C.,
Saha, Z. Zhou, M. Zhang, X. Li, F. Huang and P. J. Stang, J.
Am. Chem. Soc., 2015, 137, 15276-15286
9 X. Yan, T. R. Cook, P. Wang, F. Huang and P. J. Stang, Nat.
Chem., 2015, 7, 342-348.
0 E. Persch, O. Dumele and F. Diederich, Angew. Chem., Int. Ed.,
2015, 54, 3290-3327.
21 A. L. Spek, Acta Cryst. 2015, C71, 9-18.
2 P. P. Neelakandan, M. Hariharan and D. Ramaiah, J. Am.
Chem. Soc., 2006, 128, 11334-11335.
3 Q. Lin, Y.-Q. Fan, P.-P. Mao, L. Liu, J. Liu, Y.-M. Zhang, H.
Yao, and T.-B. Wei, Chem. Eur. J., 2018, 24, 777-783.
1
2
2
2
21402151 to Y.Z.).
4
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TOC:
Tetracationic cyclophane 1 with a trapezoid-like cavity exhibited a highly-selective recognition for tryptophan and ATP through
electrostatic and π-π interaction in water.
This journal is © The Royal Society of Chemistry 20xx
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Page 16 of 71
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DOI: 10.1039/C9CC00599D
Tetraphenylethene-based tetracationic cyclophanes and their
selective recognition for amino acids and adenosine derivatives
in water
a,‡
a,‡
a,b,‡
a
a
Lin Cheng, Haiyang Zhang, Yunhong Dong,
Yanxia Zhao, Yang Yu, and
a,
Liping Cao *
aKey Laboratory of Synthetic and Natural Functional Molecule Chemistry of the Ministry of
b
Education, National Demonstration Center for Experimental Chemistry Education, College of
Chemistry and Materials Science, Northwest University, Xi’an, 710069, P. R. China. E-mail:
chcaoliping@nwu.edu.cn
Table of Contents
Pages
General experimental details
..….………
S2
Synthetic procedures and characterization data
……………… S3-S8
1
13
H and C NMR spectra and ESI-MS of new compounds
………… S9-S16
X-ray crystal structure of cyclophanes 1 and 2
………….….. S17-S19
NMR, UV-vis, Job’s plot, ITC and MS of 1-2 and HPTS………….….. S20-S25
NMR, MS, Job’s plot, and LOD experiments of 1 and tryptophan..S26-S29
NMR experiments of cyclophane 1 and amino acid
NMR experiments of cyclophane 2 and amino acid
………….….. S30-S38
………….….. S39-S48
NMR, ITC, MS, UV-vis experiments of 1-2 and ATP/ADP/AMP…….….. S49-S56
1

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ChemComm
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DOI: 10.1039/C9CC00599D
General Experimental Details.
Starting materials were purchased from commercial suppliers were used without further
1
2
3
purification. SI3 , SI6 , and 3 was prepared according to the published procedure.
Melting points were determined using XT-4 apparatus. IR spectra were recorded on a
−1
1
13
Bruker IFS 120HR spectrometer and were reported in cm . H and C NMR spectra
were done on a Bruker ascend spectrometer at 400MHz. UV-Vis spectra were measured
using an Agilent Cary-100 spectrophotometer. Fluorescence spectra were recorded on
a Horiba Fluorolog-3 spectrometer. Fluorescence decay profiles were recorded on a
Flsp920. Electron Spray Ionization (ESI) mass spectra were acquired by using a
UltiMate3000 electrospray instrument. Isothermal titration calorimetry (ITC) was
carried out using a VP-ITC (Malvern) at 25 ˚C, and computer fitting of the data were
performed using the VP-ITC analyze software. X-ray Crystal Structure was performed
on a Bruker D8 Venture photon II.
2

ChemComm
Page 18 of 71
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DOI: 10.1039/C9CC00599D
Synthetic Procedures and Characterization Data.
Compound SI3. To a solution of SI2 (2.02 g, 12 mmol) in dry THF (20 mL) was
added 6.2 mL of a 1.6 M solution of n-butyllithium in hexane at 0℃ under a N
2
atmosphere. The resulting orange-red solution was stirred for 30 min at that temperature.
Next, SI1 was dissolved in appropriate dry THF. This solution was added to the above
mixture slowly with a dropping funnel, and the reaction mixture was allowed to warm
to room temperature with stirring for 6 h. The reaction was quenched with addition of
an aqueous solution of saturated ammonium chloride and the organic layer was
extracted with CH
2
Cl (3 × 50 mL) and the combined organic layers were washed with
2
saturated brine solution and dried over anhydrous MgSO
4
. The solvent was evaporated
and the resulting crude alcohol (containing excess SI2) was subjected to acid catalyzed
dehydration as follows.
The crude alcohol was dissolved in about 80 mL of toluene in a 100 mL round flask
with the 4Å molecular sieve dehydration unit. A catalytic amount of p-toluenesulphonic
acid (342 mg, 1.8 mmol) was added and the mixture was refluxed for 5 h and cooled to
room temperature. The toluene layer was washed with 10% aqueous NaHCO
3
solution
(
3 × 25 mL) and dried over anhydrous MgSO and evaporated to afford the crude SI3.
4
The crude product was purified by a silica gel column chromatography using petroleum
3

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DOI: 10.1039/C9CC00599D
1
ether as eluent, and white solid of pure SI3 was obtained. The H NMR matches that
reported in the reported literature.1
Compound 3. Under a N
g, 8.4 mmol) and dibenzoyl peroxide (36 mg, 0.15 mmol) were added to CCl
The solution was heated to reflux for another 12 h. The mixture was cooled to room
temperature and filtered to remove suspension. Next, CH Cl (20 mL) was added to the
filtrate and then the solution was washed with water and brine, respectively, for three
times, it was dried over anhydrous Na SO , filtered and evaporated under vacuum to
2
atmosphere, compound SI3 (1.08 g, 3.0 mmol), NBS (1.18
4
(20 mL).
2
2
2
4
dryness. The residue was purified by a silica gel column chromatography using
petroleum/dichloromethane ether as eluent, and white solid of pure compound 3 was
obtained. The H NMR matches that reported in the reported literature.3
1
Compound 4. 4,4’-bipyridine (603 mg, 3.86 mmol) was dissolved in 20 mL of
CH
3
CN in a 50 mL round flask and the solution was brought to reflux. Next, compound
3
(200 mg, 0.39 mmol) was dissolved in 5 mL of acetonitrile. This solution was added
to the bipyridine refluxing solution slowly with a dropping funnel. Then the mixture
was refluxed for an additional 48 h. The precipitate formed was filtered and washed
with acetonitrile (3 × 35 mL), and compound 4 (yield: 97%) was obtained by dried in
-1
high vacuum. M.p. 170-171 °C. IR (KBr, cm ): 3128w, 3059w, 1637s, 1598w, 1404m,
1
1
8
7
1
1
216w, 1153w, 841s, 700w, 560s. H NMR (400 MHz, CD
3
CN): 8.85 (d, J = 5.7, 4H),
.72 (d, J = 6.6, 4H), 8.29 (d, J = 6.6, 4H), 7.77 (d, J = 5.7, 4H), 7.22 (d, J = 8.1, 4H),
1
3
.20-7.10 (m, 10H), 7.05-6.95 (m, 4H), 5.63 (s, 4H). C NMR (100 MHz, CD
55.5, 152.1, 145.8, 145.7, 144.1, 143.8, 142.0, 139.7, 132.9, 132.0, 131.7, 129.6, 128.8,
27.9, 127.1, 122.7, 64.6. MS (ESI): m/z 335.1552 ([4 - 2PF -]2+, calcd. for 335.1543)
-]+, calcd. for 815.2733).
3
CN):
6
and m/z 815.2676 ([4 - PF
6
Compound 1. (Approach 1) To a solution of compound 4 (200 mg, 0.28 mmol), 5
(55 mg, 0.28 mmol), and tetrabutylammonium iodide (TBAI, 21 mg, 0.20 mmol) in dry
4

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MeCN (100 mL) was heated at 85 °C for 72 h. Then the crude product was obtained by
centrifuge and was dried in high vacuum. The crude product was purified by anion
conversion in water. Next, pale yellow solid of pure 1·4PF -
by addition of an excess of NH PF . M.p. 233 -234 °C. IR (KBr, cm ): 3129w, 3058w,
925w, 2848w, 1636s, 1559w, 1504w, 1441m, 1216w, 1153m, 832vs, 700w, 637w,
(yield: 35%) was obtained
6
-1
4
6
2
5
1
59s. H NMR (100 MHz, CD CN): 8.92 (d, J = 7.0, 4H), 8.84 (d, J = 7.0, 4H), 8.24
3
(d, J = 7.0, 4H), 8.23 (d, J = 7.0, 4H), 7.63 (s, 4H), 7.20-7.10 (m, 6H), 7.09 (s, 8H),
1
3
7
1
1
.05-7.00 (m, 4H), 5.79 (s, 4H), 5.67 (s, 4H). C NMR (100 MHz, CD CN): 150.8,
3
46.5, 146.2, 145.4, 144.3, 143.8, 139.7, 136.7, 132.5, 132.4, 131.7, 131.5, 131.5, 129.0,
28.8, 128.5, 128.4, 127.8, 65.4, 65.2. MS (ESI): m/z 532.1521 ([1•4PF -
- 2PF ] ,
- 2+
6
6
calcd. for 532.1498). An excess of TBACl (205.66mg, 0.74mmol) was added to the
-
acetonitrile solution of 1•4Cl (100mg, 0.074 mmol) and stirred overnight at room
temperature. Thenthe mixture was centrifuged and washed twice with acetonitrile. Pure
-
1
•4Cl (61 mg, yield: 90%) was obtained by dried in high vacuum. M.p. 221-222 °C .
-1
IR (KBr, cm ): 3118w, 3041m, 1629s, 1551w, 1497w, 1443m, 1217w, 1156m, 791m,
1
7
4
59w, 691w, 628w. H NMR (400 MHz, D
2
O): 9.14 (d, J = 6.3, 4H), 9.00 (d, J = 6.3,
H), 8.37 (d, J = 6.3, 4H), 8.35 (d, J = 6.3, 4H), 7.67 (s, 4H), 7.25-7.05 (m, 18H), 5.92
1
3
(
s, 4H), 5.78 (s, 4H). C NMR (100 MHz, CD
3
OD): 151.2, 151.1, 147.2, 146.7, 146.1,
1
6
44.7, 143.9, 140.1, 137.3, 133.0, 132.0, 131.9, 129.2, 128.9, 128.8, 128.5, 128.0, 65.5,
5.4 (only 19 of the 20 resonances expected were observed).
Compound 2. To a solution of compound 4 (200 mg, 0.21 mmol), compound 3
(109 mg, 0.21 mmol), and tetrabutylammonium iodide (TBAI, 15.5 mg, 0.042 mmol)
in dry MeCN (100 mL) was heated at 85 °C for 72 h. Then the crude product was
obtained by centrifuge and was dried in high vacuum. The crude product was purified
-
by anion conversion in water. Next, light yellow solid of pure 2•4PF
obtained by addition of an excess of NH PF
056w, 2917w, 2856w, 1629s, 1559w, 1497w, 1443m, 1216w, 1153w, 838vs, 700m,
6
(yield: 42%) was
-1
4
6
. M.p. 252-253 °C. IR (KBr, cm ): 3121w,
3
6
1
29w, 559s. H NMR (400 MHz, CD
3
CN): 8.86 (d, J = 6.6, 8H), 8.29 (d, J = 6.6, 8H),
5

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1
3
7
1
.25-7.10 (m, 28H), 7.10-7.00 (m, 8H), 5.69 (s, 8H). C NMR (100 MHz, CD CN):
3
51.1, 146.3, 145.8, 144.3, 143.9, 139.7, 132.8, 131.6, 129.5, 128.8, 128.3, 127.9, 65.1
(
only 13 of the 14 resonances expected were observed). MS (ESI): m/z 659.2058
[2•4PF
-- 2PF -]2+, calcd. for 659.2045). An excess of TBACl (172.31mg, 0.62mmol)
(100mg, 0.062 mmol) and stirred
(
6
6
was added to the acetonitrile solution of 2•4PF -
6
overnight at room temperature. Then the mixture was centrifuged and washed twice
-
with acetonitrile. Pure 2•4Cl (62mg, yield: 85%) was obtained by dried in high vacuum.
-1
M.p. 275-276 °C. IR (KBr, cm ): 3118w, 3025w, 2917w, 2855w, 1628s, 1559w,
1
1
9
497w, 1442s, 1210w, 1155w, 790m, 759m, 698s, 628w. H NMR (400 MHz, CD
3
OD):
.01 (d, J = 6.9, 8H), 8.40 (d, J = 6.9, 8H), 7.25-7.15 (m, 28H), 7.15-7.05 (m, 8H), 5.76
1
3
(
s, 8H). C NMR (100 MHz, CD
3
OD): 151.6, 146.9, 146.6, 144.8, 144.0, 140.0, 133.4,
1
32.5, 132.1, 129.9, 129.0, 128.6, 128.1, 65.6.
Compound SI6. 4,4’-bipyridine (592 mg, 3.79 mmol) was dissolved in 10 mL of
CH CN in a 50 mL round flask and the solution was brought to reflux. Next, p-bis-
bromo-methyl) benzene (100 mg, 0.38 mmol) was dissolved in 5 mL of acetonitrile.
3
(
This solution was added to the bipyridine refluxing solution slowly with a dropping
funnel. Then the mixture was refluxed for an additional 24 h. The precipitate formed
was filtered and washed with acetonitrile (3 × 35 mL), and dried in high vacuum. The
1H NMR matches that reported in the literature.2
Compound 1. (Approach 2) To a solution of SI6 (200 mg, 0.28 mmol), 3 (55 mg,
0
.28 mmol), and tetrabutylammonium iodide (TBAI, 21 mg, 0.20 mmol) in dry MeCN
(100 mL) was heated at 85 °C for 72 h. Then the crude product was obtained by
centrifuge and was dried in high vacuum. The crude product was purified by anion
6

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(yield: 30%) was obtained by a
-
conversion in water. Next, yellow solid of pure 1•4PF
6
silica gel column chromatography using CH
eluent.
2
Cl
2
/saturated NH
4
PF solution (5:1) as
6
X-ray Crystal Structure Determination. Diffraction data for the complexes 1•4PF -
6
-
and 2•4PF were performed on a Bruker D8 Venture photon II, at low temperature (153
6
K) with graphite-monochromated Mo Kα radiation ( = 0.71073 Å). An empirical
4
absorption correction using SADABS was applied for all data. Both structures were
2
solved and refined to convergence on F for all independent reflections by the full-
5
6
matrix least squares method using SHELXL-2018/3 in OLEX2 1.2. All non-hydrogen
atoms, including those in disordered parts, were refined anisotropically. All H-atoms
were also included at calculated positions and refined as riders, with Uiso(H) = 1.2 Ueq
.
-, two PF
-
anions were found to be disordered and were modelled with two
In 1•4PF
6
6
orientations having relative occupancies of 0.54:0.46 and 0.57:0.43 for the two parts,
separately. The geometries of the disordered parts were restrained to be similar. The
anisotropic displacement parameters of the disordered molecules in the direction of the
2
bonds were restrained to be equal with a standard uncertainty of 0.01 Å . They were
also restrained to have the same Uij components, with a standard uncertainty of 0.04 Å2.
In 1•4PF
6
-, four CH
-, with the corresponding electron densities removed using the
2
Cl
2
and two CHCl molecules co-crystallized in each unit cell of
3
complex 1•4PF
6
SQUEEZE subroutine implemented within the software program PLATON (Ver.
7
2
01118), and the resulting .fab file was processed with OLEX2 1.2. using the ABIN
instruction. Approximately 280 electron equivalents were removed from the unit cell.
3
The total void volume was 1804 Å indicated by PLATON, equivalent to 25.38 % of
the unit cell’s total volume. In 2•4PF -
, the PF -
anion was found to be disordered and
6
6
was modelled with two orientations having relative occupancy of 0.55:0.45. The
geometries of the disordered parts were restrained to be similar. The anisotropic
displacement parameters of the disordered molecules in the direction of the bonds were
2
restrained to be equal with a standard uncertainty of 0.01 Å . They were also restrained
7

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2
to have the same Uij components, with a standard uncertainty of 0.04 Å . There are 32
severely disordered Et
2
O molecules in crystal 2•4PF -
, They were also removed by by
6
the SQUEEZE subroutine in PLATON (Ver. 201118) and the resulting .fab file was
processed with OLEX2 1.2. using the ABIN instruction. Approximately 1324 electron
equivalents were removed from each unit cell. The total void volume was 4070 Å3
indicated by PLATON, equivalent to 39.81 % of the unit cell’s total volume.
Crystallographic data and refinement details for 1•4PF -
S1. CCDC 1870620 (1•4PF ). These data can be obtained free
-) and 1870621 (2•4PF -
of charge from the Cambridge Crystallographic Data Centre
and 2•4PF -
are given in Table
6
6
6
6
www.ccdc.cam.ac.uk/data_request/cif.
References
1
. Moloy Banerjee, Susanna J. Emond, Sergey V. Lindeman, and Rajendra Rathore, J.
Org. Chem. 2007, 72, 8054-8061.
2
3
1
4
. Wolfram Geuder, Sibgfried Hunig, Adolf Suchy, Tetrahedron, 1986, 42, 1665-1677.
. Jin-Hua Wang, Hai-Tao Feng and Yan-Song Zheng, Chem. Commun. 2014, 50,
1407-11410.
. G. M. Sheldrick, Program SADABS: Area-Detector Absorption Correction, 1996,
University of Göttingen, Germany.
5
6
. G. M. Sheldrick, Acta Crystallogr., Sect. C: Cryst. Struct. Chem. 2015, C71, 3−8.
. O. V. Dolomanov, L. J. Bourhis, R. J. Gildea, J. A. K. Howard and H. Puschmann,
J. Appl. Cryst. 2009, 42, 339−341.
7
. A. L. Spek, Acta Cryst. 2015, C71, 9–18.
8

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Figure S1. H NMR spectrum recorded (400 MHz, D
O, RT) for 1•4Cl-.
1
2
Figure S2. C NMR spectrum recorded (400 MHz, CD
OD, RT) for 1•4Cl-.
1
3
3
9

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1
Figure S3. a) COSY and b) NOESY H NMR spectrum recorded (400 MHz, D O, 298
2
-
K) for 1•4Cl (2.0 mM).
1
CN, RT) for 1•4PF6-.
Figure S4. H NMR spectrum recorded (400 MHz, CD
3
10

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Figure S5. C NMR spectrum recorded (100 MHz, CD
CN, RT) for 1•4PF6-.
1
3
3
1
CN, RT) for 4•2PF6-.
Figure S6. H NMR spectrum recorded (400 MHz, CD
3
11

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Figure S7. C NMR spectrum recorded (100 MHz, CD
CN, RT) for 4•2PF6-.
1
3
3
1
O, RT) for 2•4Cl-.
Figure S8. H NMR spectrum recorded (400 MHz, D
2
12

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1
3
OD, RT) for 2•4Cl-
Figure S9. C NMR spectrum recorded (100 MHz, CD
3
.
1
CN, RT) for 2•4PF -
Figure S10. H NMR spectrum recorded (400 MHz, CD
3
6
.
13

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Figure S11. C NMR spectrum recorded (100 MHz, CD
CN, RT) for 2•4PF6-.
1
3
3
Figure S12. ESI-MS spectrum of 1•4PF -
in CH CN. Expansions confirm the expect
6
3
+
m/z spacing of 0.5 for the 2 ion.
14