A novel switchable [2]rotaxane driven by light energy with Rhodamine B as a stopper

Article abstract of DOI:10.1016/j.tet.2015.04.105

Abstract Over the past few decades, bistable [2]rotaxanes have been extensively studied because of their applications in molecular switches. In this paper, a rotaxane molecule containing a dibenzo-24-crown-8 ring and Rhodamine B units was synthesized and characterized by ¹H NMR and HRMS. The Rhodamine B component allows the fluorophore fluorescence to be manipulated in alternate modes by varying the pH of the solution under irradiation. Because of the easy regulation and high sensitivity of the changes in fluorophore fluorescence, Rhodamine B [2]rotaxane can be used as a molecular switch, with different pH values as the input and changes in the fluorescence intensity as the output signals.

Full text of DOI:10.1016/j.tet.2015.04.105

Tetrahedron 71 (2015) 4116e4123
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
A novel switchable [2]rotaxane driven by light energy with
Rhodamine B as a stopper
,
Jiaxin Shi a c, Xiaowei Cao a, Xinlong Wang c, Xuemei Nie c, Baojing Zhou c,
,
b,
*
Xiaofeng Bao a , Jing Zhu
*
a Department of Biochemical Engineering, Nanjing University of Science & Technology, Chemical Engineering Building B308, 200 Xiaolingwei, Nanjing,
210094, PR China
b Department of Pharmacy, Nanjing University of Chinese Medicine, 138 Xianlin Dadao, Nanjing, 210023, PR China
c School of Chemical Engineering, Nanjing University of Science & Technology, Nanjing, 210094, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Over the past few decades, bistable [2]rotaxanes have been extensively studied because of their appli-
cations in molecular switches. In this paper, a rotaxane molecule containing a dibenzo-24-crown-8 ring
and Rhodamine B units was synthesized and characterized by 1H NMR and HRMS. The Rhodamine B
component allows the fluorophore fluorescence to be manipulated in alternate modes by varying the pH
of the solution under irradiation. Because of the easy regulation and high sensitivity of the changes in
fluorophore fluorescence, Rhodamine B [2]rotaxane can be used as a molecular switch, with different pH
values as the input and changes in the fluorescence intensity as the output signals.
Received 31 March 2015
Received in revised form 23 April 2015
Accepted 27 April 2015
Available online 1 May 2015
Keywords:
Rotaxane
Rhodamine B
Synthesis
Ó 2015 Elsevier Ltd. All rights reserved.
Fluorescence
Molecular switch
1. Introduction
that contain a fluorescent structure, such as cyclodextrins, 4-
morpholin-naphthalimide, and pyrene, have recently been used
Rotaxane, a supermolecular compound, is described as a mo-
lecular system in which a macrocycle threads a linear axle with two
bulky stoppers.1e4 The macrocycle controls the movement of the
ring along the dumbbell-shaped component and reversible mo-
lecular motion through changes in the relative positions of the
wheels between the two bulky stoppers.5,6 Because of their unique
structural architectures, rotaxanes have shown great promise in
a variety of applications, such as molecular sensors, molecular logic
gates,7,8 molecular switches,9,10 molecular electronic devices11,12
and drug delivery devices.13e15 These architectures consist of
beautiful interlocking structures and unique mobile features that
result from the high degree of freedom among the relatively in-
dependent rod and linear components. The shuttling motion of the
macrocycle in rotaxane allows for the development of sophisticated
supermolecular devices and materials.16e18
as a rotaxane cap to study the properties of these supermolecules
with electro-optical instruments and, in some cases, even with the
naked eye.23e25 These fluorescent rotaxanes are good models for
binary systems because of their variable and reversible fluores-
cence intensity (output signals), which is controlled by changing
the proper external stimuli (input signals).26e29 For example, using
the change in fluorescence as the input ensures that no waste
product forms while powering a rotaxane because there are no
chemical reactions or changes in the covalent structure.30e32 Light-
driven changes can be easily carried out in small spaces and re-
motely detected with low cost. These changes are also preferable to
other output signals because they are easily transformed into
fluorescent output signals, which respond very quickly. However, to
the best of our knowledge, there have been few reports on rotax-
anes, especially those containing a Rhodamine B moiety.33
Recently, supermolecules have been extensively studied for
application in the fields of functional molecules and molecular
switches, and rotaxanes are unique in that they fluoresce.19e22 Dyes
The design and synthesis of this interlocked molecule presents
a significant challenge. Various preparation methods for rotaxanes
are being actively pursued based on template-directed strategies
using supermolecular interactions, including hydrogen bond-
ing,34,35 hydrophobic effects,36e38 electrostatic interactions,39,40
coordination and ionic templates.38,39 In practice, however, the
use of catalysts or molecular sieves sometimes limits their
* Corresponding authors. E-mail addresses: baoxiaofeng@mail.njust.edu.cn (X.
Bao), zhujing1227@hotmail.com (J. Zhu).
http://dx.doi.org/10.1016/j.tet.2015.04.105
0040-4020/Ó 2015 Elsevier Ltd. All rights reserved.

J. Shi et al. / Tetrahedron 71 (2015) 4116e4123
4117
application, and finding a mild and efficient reaction suitable for
the synthesis of rotaxanes remains challenging. We previously re-
ported the synthesis of [2]rotaxane and [3]rotaxane by the DCC
coupling method.33,41e44 In this paper, we designed a novel [2]
rotaxane (Fig. 1) containing a fluorescence moiety, Rhodamine B, as
the bulky stopper. This novel fluorescent [2]rotaxane was effi-
ciently synthesized through the strong hydrogen interactions be-
tween the sec-ammonium salt axle and the crown ether wheel and
the esterification of alcohol with chloride without the help of
a catalyst. It was composed of dibenzo-24-crown-8(DB24C8) rings
interlocked through a dumbbell-shaped component and 2,2-
diphenylacetyl chloride as the other stopper unit. We pre-
dominantly focused on the states of the DB24C8 ring in response to
external stimuli after the synthesis of [2]rotaxane.
product was purified by flash chromatography on silica gel and
eluted with CH2Cl2/MeOH (v/v, 95:5) to yield compound 2 as
a white solid (6.45 g, 92%). 1H NMR (500 MHz, CDCl3, 298K):
d¼7.72
(s, 1H), 7.29e7.25 (m, 5H), 5.09 (s, 2H), 3.35 (t, J¼5.5 Hz, 2H), 2.92 (t,
J¼6.5 Hz, 2H) ppm.
2.3. Synthesis of Benzyl3-(30,60-bis(diethylamino)-3-oxospiro
[isoindoline-1,90exanth en]-2-yl)propanoate (3)
A solution of compound 2 (2.00 g, 10 mmol) and triethylamine
(1.5 mL, 10.8 mmol) dissolved in 20 mL of CH2Cl2 was added to
a solution of Rhodamine B (4.00 g, 8.3 mmol) and HOBt (1.2 g,
8.9 mmol) in 30 mL of CH2Cl2. After the reaction mixture was
stirred at room temperature for 12 h, the solution was filtered
through a pad of Celite and then dried under vacuum. The crude
mixture was purified by column chromatography using CH2Cl2/
MeOH (v/v, 98:2) as the eluent to give compound 3 (4.51 g, 90%) as
a bright-red solid. 1H NMR (500 MHz, acetone-d6/D2O, 298K):
d
¼7.94e7.92 (m, 1H), 7.58e7.56 (m, 2H), 7.36e7.29 (m, 5H),
7.03e7.01 (m, 1H), 6.43e6.39 (m, 6H), 4.98 (s, 2H), 3.45e3.37 (m,
10H), 2.30 (t, J¼7.75 Hz, 2H), 1.15 (t, J¼7.0 Hz, 12H) ppm. 13C NMR
(126 MHz, acetone- d6/D2O, 298 K):
d
¼171.6, 168.2, 153.9, 153.4,
148.9, 136.0, 132.5, 130.9, 128.9, 128.5, 128.2, 128.0, 123.8, 122.9,
108.3, 105.4, 98.2, 66.2, 65.0, 44.5, 35.9, 32.9, 29.8, 12.7 ppm. HRMS
(m/z): [MþH]þ found at 604.3180; calculated for C38H42N3Oþ4 ,
604.3170.
2.4. Synthesis of 3-(30,60-bis(diethylamino)-3-oxospiro[iso-
indoline-1,90-xanthen]-2- yl)propanal (4)
Fig. 1. The chemical structure of Rhodamine B [2]rotaxane.
Compound 3 (3.75 g, 5.84 mmol) was dissolved in 50 mL of
CH2Cl2, and the air was purged with nitrogen for 10e20 min in
a 100-mL dried round-bottom flask. The solution was cooled to
ꢁ80 ꢀC, treated with a solution of 1.2 M diisobutylaluminum hy-
dride (DIBAl) in toluene (7.5 mL, 8.76 mmol), and stirred at ꢁ80 ꢀC
for 2 h under nitrogen. Next, 15 mL of methanol was slowly added
to the reaction mixture sequentially, and then, the mixture was
stirred at room temperature for another 30 min. The crude mixture
was then taken to dryness under vacuum, and the residue was
extracted with CH2Cl2 (3ꢂ40 mL). The combined organic layer was
dried with MgSO4 after being concentrated under reduced pres-
sure. Flash chromatography (silica gel; hexane/EtOAc, v/v, 70:30) of
the residue yielded compound 4 as a white solid (1.421 g, 49%). 1H
2. Experimental
2.1. Materials and general methods
All reagents and organic solvents were of ACS grade or higher
and used without further purification. Unless otherwise noted, all
chemicals were purchased from J&K Scientific (Shanghai, China).
Reactions were performed under argon atmosphere with standard
Schlenk techniques. Thin-layer chromatography was performed on
a HAIYANG silica gel F254 plate, and the compounds were visualized
under UV light (
l
¼254 nm). Column chromatography was carried
out using HAIYANG silica gel (type: 200e300 mesh ZCX-2). 1H NMR
(500 MHz) and 13C NMR (126 MHz) spectra were recorded on an
Avance 500 spectrometer (Bruker; Billerica, MA, USA). The chem-
NMR (500 MHz, CDCl3, 298 K):
d
¼9.54 (s, 1H), 7.88e7.90 (m, 1H),
7.42e7.44 (m, 2H), 7.06e7.08 (m, 1H), 6.38e6.44 (m, 4H), 6.27e6.29
(m, 2H), 3.47 (t, J¼14.5 Hz, 2H), 3.32e3.36 (m, 8H), 2.35e2.38 (m,
2H), 1.17 (t, J¼14.0 Hz, 12H); 13C NMR (126 MHz, CDCl3, 298 K):
ical shifts are reported in
d units (parts per million) downfield
relative to the chemical shift of tetramethylsilane. The abbrevia-
tions br, s, d, t and m denote broad, singlet, doublet, triplet and
multiplet, respectively. Mass spectra were obtained on a Finnigan
TSQ Quantum LC/MS spectrometer. High-resolution mass spectra
(HRMS) were acquired with electron impact ionization on a dou-
ble-focusing high-resolution instrument (Autospec; Micromass
Inc.). UVevis and fluorescence spectra were obtained on a UV-3600
UVevis-NIR spectrophotometer (Shimadzu, Japan) and an Edin-
burgh FLS920 fluorescence spectrophotometer (Livingston, UK),
respectively, at room temperature.
d
¼201.2, 168.2, 153.7, 153.4, 148.9, 132.6, 131.0, 128.8, 128.1, 123.9,
122.8, 108.3, 105.2, 97.9, 65.0, 44.5, 42.65, 34.0, 12.7. HRMS (m/z):
[MþH]þ found at 498.2761; calculated for C31H36N3Oþ3 , 498.2751.
2.5. Synthesis of 30,60-bis(diethylamino)-2-(3-((5-
hydroxypentyl)amino)propyl)spiro [isoindoline-1,90-
xanthen]-3-one (5)
Compound 4 (700 mg, 1.41 mmol) was dissolved in 10 mL of
CH2Cl2, and then, 5-amino-1-pentanol (440
mL, 4.83 mmol) was
2.2. Synthesis of 3-(benzyloxy)-3-oxopropan-1-aminium
chloride (2)
added to the solution, followed by stirring of the resulting mixture
for 3.5 h. NaBH(OAc)3 (598 mg, 2.82 mmol) was added. After the
mixture was stirred overnight at room temperature, 5 mL of H2O
was added to the solution, and it was stirred for an additional
20 min. The crude mixture was then taken to dryness under vac-
uum, and the residue was extracted with CH2Cl2 (3ꢂ40 mL). The
combined organic layer was dried with MgSO4. After being con-
centrated under reduced pressure, the crude was purified on a silica
column with CH2Cl2/MeOH (v/v, 90:10) to yield compound 5
Hydrogen chloride was prepared by adding concentrated sul-
furic acid and sodium chloride to a solution of b-alanine (2.9 g,
32.5 mmol) in 20 mL of phenylmethanol, and the reaction mixture
was stirred at room temperature for 15 min. The reaction mixture
was stirred at 120 ꢀC for 12 min and then cooled to room temper-
ature. After removal of the solvent under vacuum, the crude

4118
J. Shi et al. / Tetrahedron 71 (2015) 4116e4123
(323 mg, 39%) as a white solid. 1H NMR (500 MHz, CDCl3, 298K):
35.47, 29.68, 27.92, 25.87, 24.87, 22.91, 14.10, 12.51 ppm. HRMS (m/
z): [M]þ found at 779.4551; calculated for C50H59N4Oþ4 , 779.4536.
HRMS (m/z): [M]ꢁ found at 144.9647; calculated for PFꢁ6 , 144.9642.
d¼7.95e7.83 (m, 1H), 7.56e7.30 (m, 2H), 7.28 (s, 1H), 7.17e6.95 (m,
4H), 6.39 (t, J¼5.4 Hz, 2H), 3.94e1.72 (m, 2H), 3.53e2.17 (m, 8H),
3.53e1.72 (m, 2H), 2.62 (t, J¼6.8 Hz, 2H), 2.55 (dt, J¼12.7, 6.6 Hz,
2H), 2.48 (t, J¼6.4 Hz, 1H), 1.90 (s, 4H), 1.68e1.52 (m, 2H), 1.52e1.18
(m, 2H), 1.18e1.01 (m, 12H). 13C NMR (126 MHz, CDCl3, 298K)
2.8. Synthesis of Rhodamine B [2]rotaxane
d
¼168.86, 153.48, 148.99, 132.43, 131.10, 128.75, 128.26, 123.95,
Compound 6 (100 mg, 0.1368 mmol) and DB24C8 (123 mg,
0.2736 mmol) were dissolved in 5 mL of CHCl3 and stirred in an ice-
salt bath for 2 h. Diphenylacetyl chloride (79 mg, 0.342 mmol) was
then added, and the mixture was stirred at ꢁ10 ꢀC for an additional
2 h. The reacting mixture was allowed to reach room temperature
and then stirred for 8 h. Three milliliters of H2O was then added to
the reaction mixture, and it was stirred for an additional 1 h. The
crude mixture was then extracted with CHCl3. The organic layer
was dried with MgSO4 and concentrated under vacuum. Chroma-
tography of the residue on a silica gel column eluted with CH2Cl2/
MeOH (v/v, 95:5) gave Rhodamine B [2]rotaxane as a red solid
(77 mg, 40% yield). HRMS (m/z): [M]þ found at 1227.6650; calcu-
lated for C74H91N4O12þ, 1227.6634.
122.90, 108.19, 105.41, 97.84, 77.85, 76.65, 76.35, 65.70, 65.08, 62.11,
48.62, 45.94, 44.45, 38.15, 36.84, 37.26, 36.90, 32.18, 28.30, 28.13,
27.20, 23.03, 12.66 ppm. HRMS (m/z): [MþH]þ found at 585.3811;
calculated for C36H49N4Oþ3 , 585.3805.
2.6. Synthesis of N-(3-(30, 60-bis(diethylamino)-3-oxospiro
[isoindoline-1,90-xanthen] -2-yl)propyl)-5-hydroxypentan-1-
aminium (6)
Two milliliters of 2 mol/L HCl (aq) was added to the solution of
compound 5 (300 mg, 0.513 mmol) in 10 mL of EtOH, and the
mixture was stirred at room temperature for 30 min. The solvent
was removed under vacuum to yield a red solid. The residue was
dissolved in 10 mL of CH2Cl2. A saturated NH4PF6 aqueous solution
was prepared in 1 mL of water and was added to the mixture. The
biphasic solution was stirred vigorously for 8 h until the solid had
dissolved into the organic layer. The reaction mixture was then
dried under vacuum, washed with DCM three times and purified on
a silica column with CH2Cl2/MeOH (v/v, 80:20) to yield compound 6
(285 mg, 76%) as a red solid. 1H NMR (500 MHz, CDCl3, 298K):
2.9. Computational studies
Computational studies were carried out to investigate the na-
ture conformation of Rhodamine B [2]rotaxane using the Gaussian
09 software package. The geometries of Rhodamine B [2]rotaxane
were optimized using ab initio HF and density functional theory
(DFT) calculations. The geometries were first optimized at the HF/3-
21G level. The resulting structures were further optimized by DFT
calculations using B3LYP with the 6-31G (d, p) basis sets.
d
¼7.92 (d, J¼6.9 Hz, 1H), 7.72e7.44 (m, 2H), 7.21 (d, J¼7.0 Hz, 1H),
6.41 (d, J¼2.4 Hz, 2H), 6.30 (dt, J¼8.9, 5.6 Hz, 4H), 3.87e3.62 (m,
2H), 3.52e3.29 (m, 8H), 3.25 (dd, J¼25.8, 19.8 Hz, 2H), 3.05 (t,
J¼7.2 Hz, 2H), 2.85e2.61 (m, 2H), 1.99e1.80 (m, 2H), 1.75e1.49 (m,
4H), 1.38 (d, J¼35.5 Hz, 2H), 1.19 (t, J¼7.0 Hz, 12H). 13C NMR
3. Results and discussion
(126 MHz, CDCl3, 298K):
d¼168.86, 153.48, 148.99, 132.43, 131.10,
3.1. Synthesis of Rhodamine B [2]rotaxane
128.75, 128.26, 123.95, 122.90, 108.19, 105.41, 97.84, 77.85, 76.65,
76.35, 65.70, 65.08, 62.11, 48.62, 45.94, 44.45, 38.15, 36.84, 37.26,
36.90, 32.18, 28.30, 28.13, 27.20, 23.03, 12.66 ppm. HRMS (m/z):
[M]þ found at 585.3813; calculated for C36H49N4Oþ3 , 585.3805.
HRMS (m/z): [M]ꢁ found at 144.9646; calculated for PFꢁ6 , 144.9642.
As shown in Fig. 1, synthetic rhodamine B [2]rotaxane contains
a dibenzo-24-crown-8 (DB24C8) ring that is interlocked onto
a dumbbell-shaped thread component around the sec -ammonium
binding site bearing a terminal fluorescent rhodamine B moiety as
a stopper. 2,2-diphenylacetyl chloride was used as the other bulky
terminal stopper. We divided the synthetic steps into three main
routes to obtain Rhodamine B [2]rotaxane, which will now be il-
lustrated in detail.
2.7. Synthesis of N-(3-(30,60-bis(diethylamino)-3-oxospiro
[isoindoline-1,90-xanthen]-2 -yl)propyl)-5-(2,2-
diphenylacetoxy)pentan-1-aminium (7)
As illustrated in Scheme 1, aldehyde 4 was first synthesized as
a standard substrate according to our previous report.30 Briefly,
compound 2 was prepared at 92% yield by treating compound 1
with 3-aminopropanoic acid and HCl gas at 120 ꢀC for 12 h, which
was followed by coupling with Rhodamine B in the presence of
DCC, HOBt, and TEA in CH2Cl2 at room temperature for 12 h to
obtain ester 3 in a 90% yield. Then, ester 3 was reduced by the slow
addition of diisobutylaluminum hydride in DCM at ꢁ80 ꢀC under
nitrogen for 2 h to provide aldehyde 4 in a 49% isolated yield.
The ammonium salt, compound 6, was prepared from com-
pound 4, as shown in Scheme 2. Specifically, the aldehyde 4 and 5-
amino-1-pentanol were added to a flask, and the obtained light-red
Schiff base was then reduced with NaBH(OAc)3 in MeOH in a 39%
isolated yield. Treatment of compound 5 with HCl gas in EtOH for
30 min afforded the 6-H-Cl salt. Anion exchange of 6-H-Cl in DCM
with a saturated aqueous solution of NH4PF6 afforded the sec
-ammonium salt, compound 6, in a 76% isolated yield as a pale red
solid.
Compound 6 (24 mg, 0.0328 mmol) was dissolved in 2 mL of
CH2Cl2 and stirred in an ice-cooled bath. Diphenylacetyl chloride
(11 mg, 0.0492 mmol) was then added, and the mixture was stirred
at 0 ꢀC for another 30 min. The reacting mixture was allowed to
reach to room temperature. After the mixture was stirred for 8 h,
the solvent was removed under vacuum; water (2 mL) was added,
and the mixture was extracted by CH2Cl2 (3ꢂ50 mL) and water
(30 mL). The organic layer was dried over anhydrous sodium sulfate
and then concentrated. The crude product was purified via column
chromatography with CH2Cl2/MeOH (v/v, 80:20) to give compound
7 (20 mg, 68%) as a purple solid. 1H NMR (500 MHz, CDCl3, 298K):
d
¼9.44 (s, 2H), 7.86 (d, J¼7.3 Hz, 1H), 7.59e7.42 (m, 2H), 7.38e7.28
(d, 8H), 7.25e7.20 (m, 1H), 7.09e7.13 (d, 1H), 6.38 (d, J¼2.5 Hz, 2H),
6.35 (dd, J¼33.2, 5.7 Hz, 2H), 886.30e6.20 (m, 2H), 5.04 (s, 1H), 4.18
(t, J¼6.4 Hz, 2H), 3.41e3.30 (m, 8H), 3.30e3.23 (m, 2H), 2.81e2.76
(m, 2H), 2.70e2.63 (m, 2H), 1.91e1.82 (m, 3H), 1.74e1.65 (m, 3H),
1.52e1.43 (m, 3H), 1.42e1.35 (m, 3H), 1.28e1.21 (m, 7H), 1.20e1.09
(m, 13H), 0.91e0.8 (m, 4H). 13C NMR (126 MHz, CDCl3, 298K):
The synthesis, molecular structure, and schematic representa-
tion of compound 7, Rhodamine B [2]rotaxane, are shown in
Scheme 3. This synthesis was based on the esterification reaction of
an alcohol with chloride without any catalyst. First, DB24C8 was
d
¼172.50, 169.89, 153.47, 149.18, 138.69, 135.70, 133.34, 130.20,
129.96, 128.58, 127.22, 125.81, 124.87, 124.80, 124.15, 122.94, 108.26,
104.08, 97.87, 77.26, 77.01, 76.75, 66.28, 64.66, 57.11, 48.03, 44.40,

J. Shi et al. / Tetrahedron 71 (2015) 4116e4123
4119
Scheme 1. The synthetic route for compound 4.
Scheme 2. The synthetic route for componud 6.
exposed to the compound 6 axle in DCM at ꢁ10 ꢀC for 2 h of in-
duced threading, which was followed by the addition of 2,2-
diphenylethanamine for another 2 h. The reacting mixture was
allowed to reach to room temperature and was then stirred for
another 8 h. This mixture was then purified by preparatory silica gel
chromatography, and Rhodamine B [2]rotaxane was isolated in
a 40% yield as a pale red solid. The product was characterized by 1H
NMR and HRMS (Fig. S1). Compound 7 was also synthesized and
isolated in a 68% yield by the same method without the addition of
DB24C8, and its structure was characterized by 1H NMR and HRMS
(Fig. S1), illustrating that this capping method uses mild reaction
conditions and simple steps.
(
Dd¼ꢁ0.470 ppm) due to the introduction of the 2,2-
diphenylethanamine unit. The single peak of proton 25 also dem-
onstrates the product of compound 7, indicating that this quick
blocking reaction method can be used to block rotaxane. When
DB24C8 interlocked on the thread of 7 to form [2]rotaxane, the
proton signals of 11 and 14 displayed slight chemical shifts from the
multiplet peaks centered at 1.899 and 1.481 ppm to singlet peaks
centered at 1.792 and 1.382 ppm, respectively (Dd¼0.107 and
0.099 ppm, respectively). These changes were due to the strong
hydrogen bond between DB24C8 and the secondary ammonium
salt and offer additional proof of this synthetic method’s ability to
synthesize [2]rotaxane. Moreover, all of the proton peaks belonging
to the macrocyclic DB24C8 (21, 22, 23, 24) appeared in Fig. 2d at
4.151, 3.912, 3.835 and 6.884 ppm, respectively, and moved
downfield significantly (Dd¼0.173, 0.199, 0.226, and 0.070 ppm,
respectively) because the macrocyclic ring was interlocked on the
dumbbell of 7 to form [2]rotaxane. The axle contained Rhodamine
B and 2,2-diphenylethanamine units as two bulky terminal stop-
pers to prevent unthreading, which further demonstrated that we
had successfully synthesized [2]rotaxane.
To verify the synthesis of Rhodamine B [2]rotaxane, the 1H NMR
spectra of compound DB24C8, compound 6, compound 7 and
Rhodamine B [2]rotaxane were compared, and all were in agree-
ment with their structures. The 1H NMR spectrum of compound 6 is
shown in Fig. 2a, along with the spectrum observed after the ad-
dition of the other stopper (Fig. 2b). Upfield shifts in protons 10, 12
and 16 (Dd¼0.109, 0.209 and 0.194 ppm, respectively) were ob-
served, as well as a significant downfield shift in proton 17

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J. Shi et al. / Tetrahedron 71 (2015) 4116e4123
Scheme 3. The synthetic route for Rhodamine B [2]rotaxane.
For a better understanding of the conformation of the Rhoda-
on TFA (Scheme 4), based on our previous reports. In addition, the
absorption peak at 546 nm rapidly increased with the addition of
TFA to the solution, and the fluorescence intensity of Rhodamine B
[2]rotaxane was enhanced to a moderate level after 6 equiv of TFA
were added to the solution.
mine B [2]rotaxane, its energy optimized structure was obtained
using Density functional theory (DFT) calculations with the B3LYP
method using 6-31þG(d,p) as the basis set. The lowest energy
structure of Rhodamine B [2]rotaxane was shown in Fig. 3, in-
dicating that the DB24C8 ring was located around the sec -am-
monium salt on the chain of the dumbbell of [2]rotaxane. These
results combined with the HRMS spectrum (Fig. 4) confirmed the
interlocking nature of Rhodamine B [2]rotaxane, which also in-
dicates that this ionic template can synthesize good models for
binary [2]rotaxane systems.
The UVevis spectra of the macrocycle movement around the
thread of compound 7 were compared by the addition of tri-
fluoroacetic acid (TFA) and triethylamine (TEA). Absorption spectra
of Rhodamine B [2]rotaxane were obtained upon titration with TFA
in MeOH. As shown in Fig. 5, when no TFA was added to the solution
containing [2]rotaxane, almost no absorbance above 546 nm could
be observed, and the spectra exhibited two characteristic peaks
belonging to Rhodamine B. However, a new strong absorbance
band centered at 546 nm was observed upon addition of TFA, and
this absorbance gradually increased with increasing TFA concen-
tration, resulting in a color change from colorless to light pink. This
indicates that Rhodamine B [2]rotaxane is a sensitive bistable
model for TFA in MeOH. This phenomenon is primarily ascribed to
the formation of the ring-opened amide form of Rhodamine B units
Having demonstrating the acid-based control over the posi-
tion of DB24C8 on the axle of compound 7, we also investigated
using the position of the rotaxane macrocycle as a molecular
switch in alkaline solution. The UVevis spectra of the solutions
containing Rhodamine B [2]rotaxane were observed with addi-
tion of TEA. The absorption changes for Rhodamine B [2]rotaxane
in acidic and basic solutions are shown in Fig. 6. There was al-
most no difference between the curves of Rhodamine B [2]
rotaxane and the solution with 10 equiv of TEA added. The curves
of TFA were significantly different from those of Rhodamine B [2]
rotaxane due to the ring-opened amide form of the Rhodamine B
unit in rotaxane. After 20 equiv of TEA was added to the solution,
this unit reverted back to its original state. The ring-opened
amide form must have transitioned to a spirocyclic amide form
after addition of TEA. However, the changes in the UVevis
spectra of Rhodamine B [2]rotaxane were very small in the acidic
and basic solutions, and do not clearly confirm the position of the
macrocyclic ring under different conditions. Further fluorescence
spectra were obtained in MeOH to study the migration of the
macrocyclic ring DB24C8.

J. Shi et al. / Tetrahedron 71 (2015) 4116e4123
4121
Fig. 2. Comparison of the 1H NMR spectra (500 MHz, CDCl3, 298K) of a), compound 6, b) compound 7, c) Rhodamine B [2]rotaxane, and d) DB24C8.
shows the appearance and increase in the emission peak of Rho-
damine B at 576 nm, which was accompanied by a slight red shift
upon addition of different volumes of TFA. These gradual changes
were observed upon addition of up to 6 equiv of TFA, after, which
the emission intensity remained unchanged. All of these data prove
that the ring-opened amide form of the Rhodamine B moiety was
formed in solution after the addition of TFA.
Fig. 8 displays the fluorescence spectra of Rhodamine B [2]
rotaxane alone, with 10 equiv of added TEA, and with 10 and
20 equiv of added TFA and TEA. Rhodamine B [2]rotaxane exhibited
stronger fluorescence (lex¼546 nm) at 576 nm than the other two
curves. A similar but much more apparent band at 576 nm was
observed upon titration with TEA. TEA can decrease the band at
576 nm. These changes in the fluorescence spectra can also be at-
tributed to the movement of the DB24C8 macrocycle from the
Rhodamine B unit towards the diphenylacetyl unit under irradia-
tion. However, titration with 20 equiv of TEA to the solution con-
taining Rhodamine B [2]rotaxane and 10 equiv of TFA resulted in
a comparatively smaller decrease at 576 nm than in the free
rotaxane solution. Overall, the DB24C8 ring could be shifted away
from the Rhodamine B unit towards the other side by the addition
of the solution under irradiation, and we monitored the location of
the macrocycle through the changes in the fluorescence spectra.
Hence, the relative position of the macrocycle on the thread was
affected by the pH of the solution. At the same time, the theoretical
basis for the synthesis of Rhodamine B [2]rotaxane confirms that
the original state of DB24C8 resides near the recognition site of the
Fig. 3. Snapshot of a Gaussian simulation of Rhodamine B [2]rotaxane, illustrating the
position of DB24C8 on the chain around the recognition site based on the in-
termolecular hydrogen bonding (line shown in Figure).
Changes in the fluorescence spectra of Rhodamine B [2]rotaxane
under different pH conditions in methanol further investigated the
movement of DB24C8 on the thread. These titration experiments
were performed under the same conditions as the UVevis experi-
ments. As in the fluorescence spectroscopy experiments, Fig. 7

4122
J. Shi et al. / Tetrahedron 71 (2015) 4116e4123
Fig. 4. HRMS of rhodamine B [2]rotaxane.
Fig. 6. UVevis spectra of: (a) Rhodamine B [2]rotaxane (10
m
M); (b) Rhodamine B [2]
M)þTFA (100 M);
M).
rotaxane (10 M); (c) Rhodamine B [2]rotaxane (10
m
M)þTEA (100
m
m
m
m
Fig. 5. UVevis spectra of Rhodamine [2]rotaxane (10 mM) upon addition of different
concentrations of trifluoroacetic acid (TFA). Inset: plot of the equivalent of TFA versus
absorbance intensity at 546 nm.
(d) Rhodamine B [2]rotaxane (10
m
M)þTEA (200
mM)þ TFA (100
4. Conclusions
In summary, we constructed a novel Rhodamine B [2]rotaxane
using a capping method that represents a new synthetic method to
produce fluorescent rotaxanes. This capping method uses mild
reaction conditions and simple steps and does not require a cata-
lyst. This work will promote the construction of rotaxane systems
and may lead to a wide range of applications. The effect of the
variable pH value was also evaluated as a molecular switch, and this
type of [2]rotaxane can serve as a model for molecular switches
driven by light. The DB24C8 ring could be stimulated to shift from
thread. When TEA was added to the solution, the secondary am-
monium salt lost an electron, which resulted in weaker hydrogen
bonding between the recognition sites and the DB24C8 ring and led
to the facile migration of the DB24C8 ring around Rhodamine B [2]
rotaxane under irradiation. The pH-induced movement of Rhoda-
mine B [2]rotaxane with TFA and TEA (input signals) under irra-
diation illustrates the application of this rotaxane as a molecular
switch based on fluorescence intensity (output signals).
Scheme 4. Proposed machanism for addition of TFA and TEA to Rhodamine B[2]rotaxane.

J. Shi et al. / Tetrahedron 71 (2015) 4116e4123
4123
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Acknowledgements
This research was supported by the National Natural Science
Foundation of China (81371616), the Research Fund for the Doctoral
Program of Higher Education of China (20133219120020) and the
Jiangsu Specially Sponsored Professorship for Dr. Jing Zhu.
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Supplementary data
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2015.04.105.