Directional Transportation of a Helic[6]arene along a Nonsymmetric Molecular Axle

Article abstract of DOI:10.1021/acs.joc.9b00229

Directional transportation of a helic[6]arene along a nonsymmetric molecular axle was achieved, which was easily performed in dichloromethane by a stopper reaction and subsequent addition of fluoride ions. In this system, the fluoride ions could act as a versatile stimulus to unidirectionally release the macrocycle that not only destroyed the host-guest interaction but also removed the silyl stopper.

Full text of DOI:10.1021/acs.joc.9b00229

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Note
Directional Transportation of a Helic[6]arene
Along a Nonsymmetric Molecular Axle
He-Ye Zhou, Ying Han, Qiang Shi, and Chuan-Feng Chen
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b00229 • Publication Date (Web): 22 Mar 2019
Downloaded from http://pubs.acs.org on March 22, 2019
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Directional Transportation of a Helic[6]arene Along a Nonsymmetric
Molecular Axle
a,b
,a,b
a,b
,a,b
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He-Ye Zhou, Ying Han,* Qiang Shi and Chuan-Feng Chen*
a
Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of
Molecular Recognition and Function, Institute of Chemistry, Chinese Academy of
Sciences, Beijing 100190, China.
b
University of Chinese Academy of Sciences, Beijing 100049, China.
ABSTRACT: Directional transportation of a helic[6]arene along a nonsymmetric
molecular axle was achieved, which was easily performed in dichloromethane by
stopper reaction and subsequent addition of fluoride ions. In this system, the fluoride
ions could act as a versatile stimulus to unidirectionally release the macrocycle that
not only destroyed the host-guest interaction, but also removed the silyl stopper.
In nature, the biomolecular machines and motors are capable of converting
energy into unidirectional transportation for their metabolic processes, such as cargo
1
2
3
delivery, cellular locomotion, and proteins synthesis. Inspired by these biological
4
processes, the artificial molecular machines (AMMs) have been designed and
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constructed for directional motion. And these system have been harnessed to perform
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special functions, such as sequence-specific peptide synthesis, surface
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functionalization and active transport. Mechanically interlocked molecules (MIMs),
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especially rotaxanes and catenanes, provide a perfect prototype to achieve directed
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motion at the molecular level. The directed transport in MIMs is that a ring exhibit a
directionally biased translational or circumrotational movement. For this purpose,
chemists have introduced ratchet mechanisms to MIMs, including energy ratchets and
11
information ratchets, which require precise molecular design to change the kinetic
12
energy barrier and energy well under the external stimulus. Leigh and co-workers
13
demonstrated rotary and linear molecular motor by utilizing chemical fuel. Stoddart
and co-workers reported the macrocycle directionally threaded and dethreaded along
1
4
an axle fueled by redox stimuli. Credi et al. also described the unidirectional transit
1
5
of a non-symmetric axle through a ring driven by photo stimuli. However,
developing additional means of controlling directional molecular motion remains
16
formidable challenge.
1
7
Previously, we have reported directional molecular transportation based on a
stopper-leaving rotaxane system, which provided a new strategy for construction of
directional transportation. In this system, the macrocycle was directionally released in
the presence of DBU after heating. Based on this strategy, we hope to develop a more
effective way to release the macrocycle from a rotaxane at a single versatile stimulus.
1
8
Recently, we report a new macrocyclic arene named helic[6]arenes (HA), which had
found applications in recognition of organic guests, switchable complexation and
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interlocked molecules. In particular, the complexation between HA and protonated
tertiary ammonium salts could be reversibly controlled by anions such as chloride ion
2
0
and fluoride ion. The latter was commonly used to remove silyl ether protecting
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groups. These facts encouraged us to design and construct directional macrocycle
transportation system controlled by fluoride ions.
Herein, we report a directional transportation of a helic[6]arene along a
nonsymmetric molecular axle (Figure 1). A semi-dumbbell axle containing protonated
tertiary ammonium as a central recognition site and tert-butyldiphenylsilyl group as
one of the stopper was designed and synthesized. HA was initially allowed to thread
onto the axle from the open side, affording a pseudorotaxane. Subsequently the
2
2
terminal OH group was covalently captured by the stoppering reaction, giving a
nonsymmetric [2]rotaxane. Then, the unidirectional dethreading process of HA was
triggered by addition of fluoride ions that not only destroyed the host-guest interaction,
but also removed the silyl stopper. The whole unidirectional threading and
dethreading process occurs easily in dichloromethane.
Figure 1. Cartoon representations of directional macrocycle transportation system.
As shown in Scheme 1, a semidumbbell axle G which incorporated protonated
tertiary ammonium as a binding site, bulkier tert-butyldiphenylsilyl at one side and a
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terminal hydroxyl group at the other side was designed and synthesized. Due to the
steric interaction, the threading process of HA exclusively occurred from the open
terminus of the axle. We firstly investigated the complexation between HA and G by
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H NMR spectroscopy. The H NMR spectrum of 1:1 solution of HA and G showed
an obvious difference compared to the spectra of the uncomplexed species, which
clearly demonstrated the formation of the complex (Figure S15). And the electrospray
ionization mass spectra (ESI-MS) also confirmed the formation of 1:1 complex
1
between HA and G (Figure S16). According to the H NMR spectroscopic titration
experiments, the association constant (K ) of the complex in CD Cl solution was
a
2
2
-1
23
determined to be 3317254 M using the nonlinear curve-fitting method.
Scheme 1. Synthesis of [2]Rotaxane R.
Based on the 1:1 complexation mode between HA and G, we obtained the
2]rotaxane R (Scheme 1). The macrocycle HA was firstly mixed with three equiv of
[
G in dry CH Cl for the formation of pseudorotaxane. To the above solution was then
2
2
added a catalytic amount of dibutyltin dilaurate (DBTDL) and slight excess bulky
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isocyanate stopper S. After the solution was stirred under room temperature for eight
hours, the [2]rotaxane R was isolated by column chromatography in a yield of 80% as
a white solid. Then the structure of R was identified by NMR spectroscopy. As shown
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in Figure 2a, the strong upfield shifts were observed for protons H in the ammonium
e
unit and the contiguous methylene protons H and H . Especially, the signal of proton
d
f
H appeared at
e
̶
0.80 ppm, implying that the ammonium unit was combined with
macrocycle. The ROESY spectrum of R in CD Cl showed clear cross peak between
2
2
the protons of HA and the protons related to the ammonium unit (Figure S14), firmly
supporting the host-guest interactions. Moreover, the HR-ESI mass spectrum of R
+
gave intense peak at m/z 1835.8037, corresponding to [R-BArF] (calcd. m/z
1835.8053).
1
Figure 2. H NMR spectra (500 MHz, 5 mM, 298 K, CD Cl ) of (a) R, (b) the
2
2
solution obtained after adding 3.6 equiv of TBAF to R, (c) HA.  denotes TBAF.
To promote the unidirectional dethreading process of HA we used fluoride ions.
They could be a strong hydrogen-bond acceptor that destroyed the host-guest
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interaction between HA and protonated tertiary ammonium. Subsequently, the silyl
stopper could be removed, giving rise to dethreading of helic[6]arene from the other
side. The unidirectional dethreading process was indeed verified through NMR and
mass spectrum. When 3.6 equiv of tetrabutylammonium fluoride (TBAF) were added
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into R in CD Cl , the H NMR spectra clearly displayed the separate components
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(Figure 2b). The proton signals of HA were consistent to those shown in Figure 2c.
And the signals of protons H , H and H related to the ammonium unit drastically
d
e
f
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shifted downfield owing to their disassociation with macrocycle. The F NMR
spectrum also revealed two additional signals that were different from free fluoride
ions in TBAF (Figure S19), which was in accordance with the dual role of fluoride
ions. Moreover, the atmospheric pressure chemical ionization mass spectra (APCI-MS)
also gave a strong peak at m/z 979.3985 corresponding to dethreaded helic[6]arene
+
[
HA+H] (calcd. m/z 979.3920), m/z 619.2944 corresponding to the detached axle
(calcd. m/z 619.2955) (Figure S20). These results unambiguously demonstrated that
HA was completely released from R in a directed path.
1
The H NMR kinetic experiments were carried out to investigate the rate of
macrocycle release in the presence of various amount of TBAF. The concentration
changes versus time (min) for dethreaded HA were recorded by the integrals of
proton signals of H (see Supporting Information). As shown in Figure 3, it was found
F
that 1.2 equiv of TBAF was enough to thoroughly release HA. With the increase of
concentration of TBAF, the rate of macrocycle release showed an increasing trend.
After 3.6 equiv of TBAF was added to R (5 mM, CD Cl ), the dethreading process of
2
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HA could be completed within a few minutes.
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Figure 3. The concentration of dethreaded HA with the time after the addition of 1.2
.6 equiv of TBAF to R (5 mM, CD Cl , 298 K).
̶
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Taking into consideration of the whole process, we could achieve the directional
transportation of a helic[6]arene along a nonsymmetric molecular axle. Moreover, the
whole process could be conducted in dichloromethane without isolating the rotaxane,
1
which was clearly demonstrated by H NMR spectra (Figure S29). This unidirectional
threading and dethreading process was a typical energy ratchet. An essential feature of
these systems is their ability to modulate both of the depths of energy wells and the
2
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heights of energy barriers. Firstly, HA was directionally combined with protonated
tertiary ammonium site to complex formation under thermodynamical control,
corresponding to the particles in the energy well (Figure 4). Then, HA was covalently
captured by stoppering the terminal primary hydroxyl group that prevents dethreading
for kinetic factors, corresponding to elevating the heights of energy barriers at the left
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side. When fluoride ions were added, the direction-biased movement was attained by
raising the energy well and synchronously lowering the energy barriers at the right
side.
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Figure 4. Chemical drawing and energy profiles of directional transportation of a
helic[6]arene along a nonsymmetric molecular axle through an energy ratchet
mechanism.
In conclusion, we have constructed a directional macrocycle transportation
system driven by stopper reaction and subsequent addition of fluoride ions. Fluoride
ions could act as a versatile stimulus to directionally release the helic[6]arene from a
rotaxane. HA was initially threaded onto a semidumbbell axle from the open side and
subsequently was covalently captured by stoppering reaction, affording to a
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nonsymmetric [2]rotaxane. The directional dethreading process of HA could be
triggered by the addition of fluoride ions without any additional intervention, which
destroyed the host-guest interaction and removed the silyl stopper. The dethreading
rate could be tuned by varying the amounts of TBAF. As a result, the directional
transportation of a helic[6]arene along a nonsymmetric molecular axle in
dichloromethane was achieved through an energy ratchet mechanism. We believe that
this system would not only provide a facile and effective way to molecular machines
with directional motion, but also find potential applications in design and construction
of functional materials.
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EXPERIMENTAL SECTION
General Information. All reagents were commercially available and used without
1
8b
25
further purification. Helic[6]arenes (HA),
(4-(aminomethyl)phenyl)methanol,
2
6
4
-((tert-butyldiphenylsilyl)oxy)benzaldehyde,
2
7
(
(4-isocyanatophenyl)methanetriyl)tribenzene were synthesized according to the
literature procedures.
4-(((4-((tert-Butyldiphenylsilyl)oxy)benzyl)amino)methyl)phenyl)methanol (1).
solution of (4-(aminomethyl)phenyl)methanol (0.21 g, 1.53 mmol) and
-((tert-butyldiphenylsilyl)oxy)benzaldehyde (0.55 g, 1.53 mmol) in 20 mL of
CH OH was stirred at room temperature for 4 h, and then was added 0.12 g (3.16
(
A
4
3
mmol) of NaBH in small portions. After the reaction mixture was stirred for 2 h,
4
water was slowly added to quench the reaction, and the mixture was partitioned
between water and CH Cl (80 mL). The organic extract was washed with water (20
2
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mL× 3), and then dried over anhydrous magnesium sulfate. The solvent was
evaporated, and the reside was purified by column chromatography (CH Cl /methanol
2
2
1
2
0:1 v/v) to afford compound 1 as colorless sticky oil (0.66 g, 90%). H NMR (300
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MHz, CDCl ) δ = 7.72–7.69 (m, 4H), 7.41–7.33 (m, 6H), 7.28–7.25 (m, 4H), 7.04 (d,
3
J = 8.1 Hz, 2H), 6.72 (d, J = 8.0 Hz, 2H), 4.64 (s, 2H), 3.73 (s, 2H), 3.64 (s, 2H), 1.09
1
3
1
(s, 9H). C{ H} NMR (125 MHz, CDCl ): δ = 154.6, 139.7, 139.4, 135.5, 133.0,
3
1
32.3, 129.8, 129.1, 128.4, 127.7, 127.1, 119.6, 65.1, 52.6, 52.4, 26.5, 19.5. HRMS
+
(
ESI) m/z: [M+H] Calcd for C H NO Si 482.2515; Found 482.2504.
3
1
36
2
(4-(((4-((tert-Butyldiphenylsilyl)oxy)benzyl)(methyl)amino)methyl)phenyl)methanol
2). Compound 1 (0.59 g, 1.23 mmol) and K CO (0.17 g, 1.23 mmol) were mixed in
(
2
3
acetone (20 mL). Then, iodomethane (0.1 mL, 1.62 mmol) was added and the mixture
was stirred at room temperature for 30 min. The reaction mixture was filtrated, and
the filtered cake was washed with CH Cl . The filtrate was collected and concentrated
2
2
under reduced pressure to give a residue, which was purified by silica-gel column
chromatography (CH Cl /methanol 40:1 v/v) to give compound 2 (0.53 g, 88%) as a
2
2
1
colorless oily liquid. H NMR (300 MHz, CDCl ) δ = 7.80–7.64 (m, 4H), 7.41–7.30
3
(m, 6H), 7.28–7.25 (m, 4H), 7.05 (d, J = 8.1 Hz, 2H), 6.71 (d, J = 8.0 Hz, 2H), 4.66 (s,
1
3
1
2
H), 3.45 (s, 2H), 3.37 (s, 2H), 2.11 (s, 3H), 1.09 (s, 9H). C{ H} NMR (125 MHz,
CDCl ) δ = 154.6, 139.5, 138.8, 135.5, 135.5, 133.0, 129.9, 129.8, 129.2, 128.8, 127.7,
3
+
127.0, 119.4, 115.5, 65.2, 61.3, 61.1, 42.0, 26.5, 19.5. HRMS (ESI) m/z: [M+H]
Calcd for C H NO Si 496.2672; Found 496.2661.
3
2
38
2
N-(4-((tert-Butyldiphenylsilyl)oxy)benzyl)-1-(4-(hydroxymethyl)phenyl)-N-methylmeth
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anaminium tetrakis(3,5-bis(trifluoromethyl)phenyl)borate (G). Trifluoroacetic acid
(
0.067 mL, 0.86 mmol) was added to the solution of 2 (0.40 g, 0.80 mmol) in CH Cl2
2
(20 mL). The solution was stirred at room temperature for 1 h, concentrated in vacuo
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to give a residue. Then the residue was dispersed in CH Cl /H O with sodium
2
2
2
tetrakis[3,5-bis(trifluoromethyl)phenyl] borate (NaBArF) (0.72 g, 0.81 mmol). After
the mixture had been stirred overnight, the organic layer was separated, washed with
water three times, and dried with anhydrous MgSO . The organic layer was
4
evaporated under vacuum to afford G (1.04 g, 95%) as a white solid. M.p.: 70–72 °C.
1
H NMR (300 MHz, CDCl ) δ = 7.83–7.67 (m, 12H), 7.57–7.55 (m, 6H), 7.50–7.40
3
(m, 6H), 7.32 (d, J = 7.9 Hz, 2H), 7.13 (d, J = 8.2 Hz, 2H), 6.96 (d, J = 8.1 Hz, 2H),
4.79 (s, 2H), 4.51–4.29 (m, 2H), 4.18–4.07 (m, 2H), 2.84 (d, J = 5.1 Hz, 3H), 1.14 (s,
1
3
1
9
H). C{ H} NMR (125 MHz, CDCl ) δ = 162.3, 158.5, 145.2, 135.4, 134.8, 131.8,
3
1
31.8, 131.7, 130.3, 130.3, 129.0, 128.9, 128.7, 128.7, 128.7, 128.5, 128.3, 127.9,
127.82, 125.8, 125.7, 123.5, 121.6, 121.3, 119.1, 117.5, 117.5, 117.4, 63.9, 61.5, 61.3,
+
4
0.3, 26.0, 19.2. HRMS (ESI) m/z: [M–BArF] Calcd for C H NO Si 496.2666;
32
38
2
Found 496.2665.
[2]Rotaxane (R). G (0.25 g, 0.18 mmol) and HA (0.06 g, 0.06 mmol) were dispersed
in dry CH Cl (2 mL). The mixture was stirred at room temperature for 4 h. Then
2
2
((4-isocyanatophenyl)methanetriyl)tribenzene (0.07 g, 0.19 mmol) and two drops of
dibutyltin dilaurate (DBTDL) were added into the above solution. The mixture was
further stirred at room temperature for 8 h, and then purified by column
chromatography (CH Cl ) to give R as white powder (0.13 g, 80%). M.p.: 170–
2
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172 °C. H NMR (500 MHz, CD Cl ) δ = 8.02–7.93 (m, 2H), 7.87–7.74 (m, 2H),
2
2
7
.79–7.66 (m, 9H), 7.66–7.51 (m, 9H), 7.49–7.35 (m, 6H), 7.35–7.13 (m, 25H), 7.03
(
d, J = 8.2 Hz, 1H), 7.01–6.87 (m, 8H), 6.57–6.55 (m, 3H), 6.49 (d, J = 7.5 Hz, 1H),
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6.43–6.41 (m, 3H), 6.25 (d, J = 7.6 Hz, 1H), 6.17 (d, J = 8.2 Hz, 1H), 5.94 (d, J = 8.2
Hz, 1H), 5.51–5.42 (m, 2H), 5.12–5.10 (m 3H), 5.04–5.03 (m, 3H), 3.68 (d, J = 3.0
Hz, 5H), 3.65 (s, 4H), 3.58–3.56 (m, 9H), 3.45 (s, 4H), 1.42–1.39 (m, 2H), 1.26–1.24
(
m, 10H), 1.02–1.00 (m, 1H), 0.95–0.77 (m, 3H), 0.74–0.69 (m, 1H), -0.79–-0.82 (m,
1
3
1
3
H). C{ H} NMR (125 MHz, CD Cl ) δ = 163.6, 163.3, 162.9, 162.5, 155.3, 155.2,
2 2
155.2, 155.2, 148.1, 146.4, 146.3, 146.2, 146.2, 146.2, 144.1, 139.1 138.9, 138.8,
38.7, 137.1, 137.0, 136.9, 136.9, 136.1, 133.2, 133.2, 133.1, 133.0, 132.4, 132.2,
132.0, 131.5, 130.6, 130.3, 130.3, 130.1, 130.0, 129.7, 129.7, 129.5, 129.5, 129.2,
1
1
1
28.9, 128.8, 128.6, 128.4, 128.3, 127.3, 127.2, 127.2, 127.2, 127.1, 127.0, 126.7,
26.6, 124.8, 124.6, 124.5, 122.7, 122.0, 121.9, 119.1, 118.8, 118.7, 109.5, 109.4,
109.1, 109.1, 67.1, 65.9, 61.6, 61.0, 60.4 57.7, 57.6, 57.4, 57.3, 54.2, 54.2, 35.3, 35.2,
+
3
1.0, 29.5, 29.4, 27.6, 27.5, 20.7, 20.6. HRMS (ESI) m/z: [M–BArF] Calcd for
C H N O Si 1835.8053; Found 1835.8037.
127 111
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ASSOCIATED CONTENT
Supporting Information
NMR and MS spectra of new compounds, determination of the association constants
of HA and G, NMR kinetic experiments for the dethreading process. The Supporting
Information is available free of charge on the ACS Publications website.
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AUTHOR INFORMATION
Corresponding Author
*
Email: cchen@iccas.ac.cn; hanying463@iccas.ac.cn
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Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
We thank the National Natural Science Foundation of China (21332008, 21772205,
21521002), and the Strategic Priority Research Program of CAS (XDB12010400) for
financial support.
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