Design and synthesis of self-included pillar[5]arene-based bis-[1]rotaxanes

Article abstract of DOI:10.1016/j.cclet.2018.10.014

Two strategies for the design of new pillar[5]arene-based mechanically self-interlocked molecules (MSMs) are reported here. The first strategy is based on the construction of an intermediate pseudo[1]rotaxane followed by the desired bis-[1]rotaxane. The o

Full text of DOI:10.1016/j.cclet.2018.10.014

Accepted Manuscript
Title: Design and synthesis of self-included
pillar[5]arene-based bis-[1]rotaxanes
Authors: Mengjun Wang, Xusheng Du, Huasheng Tian, Qiong
Jia, Rong Deng, Yahan Cui, Chunyu Wang, Kamel Meguellati
PII:
DOI:
Reference:
S1001-8417(18)30401-7
https://doi.org/10.1016/j.cclet.2018.10.014
CCLET 4678
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Chinese Chemical Letters
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15-8-2018
8-10-2018
15-10-2018
Please cite this article as: Wang M, Du X, Tian H, Jia Q, Deng R,
Cui Y, Wang C, Meguellati K, Design and synthesis of self-included
pillar[5]arene-based bis-[1]rotaxanes, Chinese Chemical Letters (2018),
https://doi.org/10.1016/j.cclet.2018.10.014
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Original article
Design and synthesis of self-included pillar[5]arene-based bis-[1]rotaxanes
Mengjun Wang a, Xusheng Du a, Huasheng Tian a, Qiong Jia a, Rong Deng a, Yahan Cui a, Chunyu Wang
b,* chunyu@jlu.edu.cn, Kamel Meguellatia,* 0000-0003-4560-9461 kamel_m@jlu.edu.cn
aInternational Joint Research Laboratory of Nano-Micro Architecture Chemistry (NMAC), College of
Chemistry, Jilin University, Changchun 130012, China
bState Key Laboratory of Supramolecular Structure and Materials, Jilin University, Changchun 130012,
China
*
Corresponding authors.
Graphical abstract
fx1
Two strategies for the design of new pillar[5]arene-based mechanically self-interlocked molecules (MSMs) are reported here. The first strategy is
based on the construction of an intermediate pseudo[1]rotaxane followed by the desired bis-[1]rotaxane. The other one is
based on the construction of the desired bis-[1]rotaxane directly via a condensation reaction through host-guest interactions
between a mono-functionalized pillar[5]arene and the axle. This compound has interesting self-assembly properties in methanol and some extended
applications of this compound will be reported in the near future.
ABSTRACT
Two strategies for the design of new pillar[5]arene-based mechanically self-interlocked molecules (MSMs) are reported here. The first strategy is
based on the construction of an intermediate pseudo[1]rotaxane followed by the desired bis-[1]rotaxane. The other one is
based on the construction of the desired bis-[1]rotaxane directly via a condensation reaction through host-guest interactions
between a mono-functionalized pillar[5]arene and the axle. The newly synthesized bis-[1]rotaxane BR was characterized by 1H NMR, 13C NMR,
2D NMRs (1H-13C HSQC, 1H-1H COSY and NOESY) and LC-ESI-MS, which indicated compound BR displayed an self-interlocked structure in
CDCl3. Surprisingly, the results of SEM, TEM and DLS showed that the compound BR could assemble into spherical nanoparticles in MeOH.
Keywords: Pillar[5]arene; Bis-[1]rotaxane; Host–guest interactions; Supramolecular architectures; Self-
assembly
Supramolecular chemistry [1] has become an important field of research with the emergence of crown
ether [2] as the first synthesized macrocyclic host, and has attracted more scientists for its broad
applications in nanoscience [3], material science [4] and biology science [5], etc. Mechanically interlocked
molecules (MIMs) [6] have been broadly studied in supramolecular chemistry and led to the emergence of
special structures such as rotaxanes [7,8], catenanes [9], molecular shuttles [10] and switches [11], which
made them gradually applicable for the design of molecular machines [12], chemical probes [13] and drug
delivery [14]. Among MIMs, rotaxanes have been intensively studied owing to the classical topological
structure composed of a linear axle and a threaded macrocycle interconnected by non-covalent interactions
such as cation-π interactions, metal-ligand interactions, C-H···π interactions, hydrogen-bonding
interactions and so on. As a promising perspective of rotaxanes, (pseudo)[1]rotaxanes [15,16], where the
axle is linked and self-included to the macrocycle, are becoming of great interest in the field of MIMs.
However, there have been only a few reported strategies for the design of bis-[1]rotaxanes due to the
difficulties of their synthetic routes and characterizations.
Pillar[5]arene [17], first reported in 2008 by Tomoki Ogoshi, with pillar-like structure consisting of five
1,4-dimethoxybenzene linked by methylene bridges at their 2,5-positions, is a popular macrocycle along
with crown ether, cyclodextrin [18], cucurbituril [19], cyclophane and calixarene [20]. Because of their
electron-rich cavity, symmetrical pillar-like shape and easy modification of the rims, pillar[n]arene has
been widely used as an emerging host in the fields of chemistry [21–24], biology [25] and materials [26–
32]. With the development of modified pillar[n]arenes including hydrophobic, hydrophilic and amphiphilic
pillar[n]arenes, their applications have been extended to molecular machines [33], adsorption materials
[34], catalysis [35], drug delivery [36] and so on. They tend to be attractive for the construction of bistable
pseudo[1]rotaxanes, [1]rotaxanes and bis-[1]rotaxanes. For example, Tomoki Ogoshi et al. reported the
synthesis of a mono-guest functionalized pillar[5]arene-based pseudo[1]rotaxane with different
architectures (dethreaded structure in acetone and self-interlocked structure in CDCl3) [37]. Wang et al.
reported a pillar[5]arene-based interlocked pseudo[1]catenane and pseudo[1]rotaxane by a condensation
reaction (one included diamino alkane and an acid-functionalized pillar[5]arene, and the other one included

diisocyanate and amine-functionalized pillar[5]arene), which displayed different conformers responsive to
solvents and guests [38]. Yang et al. reported a mono-functionalized pillar[5]arene bearing an imidazolium
moiety that formed stable pseudo[1]rotaxane even at high concentration in chloroform [39]. Xue et al.
reported an efficient method to fabricate pillar[5]arene-based [1]rotaxane with the contribution of C-H···π
interactions and ion-pair interactions [40].
In 2017, our group designed an efficient strategy for the synthesis of pillar[5]arene-based
pseudo[1]rotaxane by amide formation between a monoester-functionalized pillar[5]arene and
dialkylamine [41]. Herein, we designed two different kinds of routes to fabricate the desired pillar[5]arene-
based bis-[1]rotaxane, one route involves the construction of a stable pseudo[1]rotaxane followed by a
click reaction at the terminal group of the axle leading to the desired bis-[1]rotaxane; the other route
involved a linear bis-amino containing moiety which was threaded by an acid-functionalized pillararene
from the two ending sides for the obtention of the targeted bis-[1]rotaxanes.
The synthetic routes of pillar[5]arene-based mechanically self-interlocked molecules (MSMs) are
illustrated in Scheme 1 Scheme 1. It showed two synthetic routes for the preparation of BR, route 1 and
route 2. Route 1 involves the construction of a pseudo[3]rotaxane through host–guest interactions by
interacting an electron-rich pillar[5]arene and a triazole-based guest in chloroform. The solution was
stirred at room temperature for 12░h, then dicyclohexylcarbodiimide (DCC) and 4-dimethylaminepyridine
(DMAP) were added to the solution, and the solution was stirred at room temperature for an additional
24░h. After purification using column chromatography, the expected BR was successfully obtained. Route
2 involves the formation of a self-included pseudo[1]rotaxane followed by the preparation of the final
product by a click reaction between pseudo[1]rotaxane h and 1,4-bis(2-propynyloxy)benzene. The
compounds h and BR were fully characterized by 1H NMR, 13C NMR, 2D NMRs including 1H-13C HSQC
NMR, 1H-1H COSY NMR, 1H-1H NOESY NMR and LC-ESI-MS.
Fig. 1 Fig. 1 represents the 1H NMR spectrum of BR in CDCl3 with a few protons below 0░ppm. From the
1H-1H COSY NMR spectrum of compound BR, we can emphasize that these protons were attributed to the
protons Hl-p of BR with upfield shifts due to the anisotropic interactions of the corresponding -CH2- with
the electronic cloud of the aromatic cavity (Δδ = -1.20 to -3.27), indicating that BR might be self-included
at this point. Due to the deshielding effect caused by the self-inclusion, the signals of protons Hh-i
displayed a downfield shift (Δδ = +0.13 and +0.53). The analysis and results of the 2D NOESY NMR
spectrum of BR (Fig. 2 Fig. 2) showed unequivocal correlation peaks between Hl-p (the signals of alkyl
chain protons) with the aromatic protons (Hb) and methylene protons (Hg) of BR. The similar correlation
peaks were also observed in the NOESY spectrum of h (Fig. S17 in Supporting information). Thus, we
concluded to a self-included structure for BR. Mass spectrometry (MALDI-TOF-MS) also confirmed of
the right compound. In the mass spectrum of BR (Fig. S21 in Supporting infornation), a base peak at m/z
2181.60 (100%) corresponding to [M+2Na-H]+ was observed. The comparative NMR and mass studies led
us to conclude to a self-interlocked structure for BR.
Since pillar[5]arene has highly symmetrical and rigid pillar architecture, we anticipated the potential self-
assembly of BR in some solvents. BR was dissolved in various solvents and sonicated for 30░min, then
the morphology of the aggregates were investigated by scanning electronic microscopy (SEM), dynamic
light scattering (DLS) and transmission electron microscopy (TEM). The results of SEM showed that BR
could assemble into polydisperse nanoparticles in MeOH at 6.2░×░10-4 mol/L (Fig. 3 Fig. 3a). However,
the size controllable morphologies in other solvents were not found (Fig. S26 in Supporting information).
The TEM studies showed that the nanospheres were formed in methanol and displayed a dark core
surrounded by a light corona and accompanied by a small percentage of coalescence. Furthermore, the
dynamic light scattering (DLS) result showed that the spherical nanostructures in methanol have an
average diameter of 700-800░nm. All these results demonstrated that BR could self-assemble into
polydisperse spherical nanostructures in methanol with punctual coalescence. We hypothesized that the
solvent played an important role in the assembly process where the solubility and the polarity of the
solvent play a pivotal role. Xi and co-workers reported that higher-polarity solvents lead to stronger
interactions, giving rise to more favorable aggregations [42,43]. Herein, when BR was dissolved in various
solvents (CH2Cl2, DMF, CH3OH and DMSO with increasing polarity), polydisperse and organized

nanoparticles only existed in CH3OH, due to the poor solubility in DMF and DMSO, and the lower
polarity of CH2Cl2. We also suspected that the O–H···O interactions between methanol and the carbonyl
group (C░=░O) of pillar[5]arene were favorable to the formation of spherical structures. On the other
hand, as pillar[5]arenes have pillar-like structure, each 1,4-dimethoxybenzene may interact with the
neighboring 1,4-dimethoxybenzene of the adjacent pillar[5]arene by π···π stacking interactions which lead
to a self-assembled structure in some specific solvents. The synthesized mechanism of aggregation in
MeOH is illustrated in Fig. 3c. These studies indicated that the solvent effect, the network of hydrogen
bonding and π···π stacking synergistically control the self-assembly process and final morphologies.
In conclusion, we developed two different strategies for the synthesis of a novel self-interlocked
pillar[5]arene-based bis-[1]rotaxane. Meanwhile, the results of TEM, SEM and DLS measurements
showed that BR tend to assemble into a spherical morphology with a dark core, where the driving forces of
the self-assembly are the intermolecular non-covalent interactions and the solvation. Our current efforts are
focused on the synthesis of novel MSMs and the extension of their potential applications of this new
nanomaterial in the near future.
Acknowledgment
Commented [SR1]: Have we correctly interpreted the following
funding source(s) and country names you cited in your article:
College of Chemistry at Jilin University?
We thank NMAC, College of Chemistry at Jilin University for financial support.
Appendix A Supplementary data
Supplementary material related to this article can be found, in the online version, at
doi:10.1016/j.cclet.2018.10.014.
Appendix B [{(Appendix A)}] Supplementary data
The following is Supplementary data to this article:
mmc1
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Scheme 1 Synthetic procedure of compound BR via two different synthetic routes, route I and II.
Fig. 1 1H NMR spectrum (600░MHz, 298░K, CDCl3) of compound BR.
Fig. 2 Partial 2D NOESY NMR spectrum of compound BR.
Fig. 3 Self-assembly of BR into nanoparticles in methanol. (a) SEM data of BR aggregates (6.2░×░10-4 mol/L). (b) TEM images of
BR self-assemblies. (c) DLS data of BR aggregates. (d) Schematic illustration of the self-assembly mechanism of BR in methanol.