Host-guest interaction of rotaxane assembly through selective detection of ferric ion: Insight into hemin sensing and switching with sodium ascorbate

Article abstract of DOI:10.1016/j.dyepig.2016.03.049

A mechanically interlocked host rotaxane was synthesized by incorporation of tetraphenylethylene and phenanthroimidazole units in the axle to exhibit significant emission bands and demonstrate host-guest interactions via its topologically constrained cavi

Full text of DOI:10.1016/j.dyepig.2016.03.049

Accepted Manuscript
Host-guest interaction of rotaxane assembly through selective detection of ferric ion:
Insight into hemin sensing and switching with sodium ascorbate
Tarun Shukla, Atul Kumar Dwivedi, Reguram Arumugaperumal, Chien-Min Lin, San-
Yuan Chen, Hong-Cheu Lin
PII:
S0143-7208(16)30118-8
10.1016/j.dyepig.2016.03.049
DYPI 5174
DOI:
Reference:
To appear in: Dyes and Pigments
Received Date: 15 January 2016
Revised Date: 27 March 2016
Accepted Date: 28 March 2016
Please cite this article as: Shukla T, Dwivedi AK, Arumugaperumal R, Lin C-M, Chen S-Y, Lin H-
C, Host-guest interaction of rotaxane assembly through selective detection of ferric ion: Insight into
hemin sensing and switching with sodium ascorbate, Dyes and Pigments (2016), doi: 10.1016/
j.dyepig.2016.03.049.
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to
our customers we are providing this early version of the manuscript. The manuscript will undergo
copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please
note that during the production process errors may be discovered which could affect the content, and all
legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT
Host-Guest Interaction of Rotaxane Assembly through Selective Detection of
Ferric Ion: Insight into Hemin Sensing and Switching with Sodium Ascorbate
Tarun Shukla, Atul Kumar Dwivedi, Reguram Arumugaperumal, Chien-Min Lin, San-Yuan
Chen, and Hong-Cheu Lin*
Department of Materials Science and Engineering, National Chiao Tung University, Hsinchu,
Taiwan
E-mail: linhc@mail.nctu.edu.tw
Abstract:
A
mechanically interlocked host rotaxane was synthesized by incorporation of
tetraphenylethylene and phenanthroimidazole units in the axle to exhibit significant emission
bands and demonstrate host-guest interactions via its topologically constrained cavity, and thus
to induce a significant and selective fluorescence quenching of rotaxane towards ferric ion
3
+
3+
(
Fe ). The quenching efficiencies of rotaxane with both ferric ion (Fe ) and bio-molecular
Hemin (containing ferric ion) were investigated to compare the sensitivities of rotaxane for ferric
ion and bio-molecular Hemin. The present study could probe host-guest interactions of rotaxane
3
+
with ferric ion (Fe ) and Hemin as well as monitoring the biological conversion of Hemin to
Heme in presence of sodium ascorbate (as a reducing agent), where the reduced non-toxic Heme
could be generated from the toxic form of Hemin.
1

ACCEPTED MANUSCRIPT
Keywords: rotaxane • tetraphenylethylene • aggregation induced emission • host-guest
interaction • ferric ion
1
. Introduction
Mechanically interlocked architecture molecules with topologically constrained ring structures
through non-covalent linkages have attracted much attention from several research groups during
last few decades. The excellent molecular recognition of mechanically interlocked systems are
significantly offered by various guest and host molecules [1]. Recently, the self-motivated
behavior of mechanically interlocked molecules (MIMs) have played a crucial role for vital
developments in nanotechnological applications [2], including molecular memory [3],
mechanical actuators [4], and drug delivery vehicles [5]. The properties of molecular switches
and machines associated with MIMs are pronounced to control the dynamics of MIMs in the
presence of external stimuli, which have been well studied and established in recent research [6].
Based on the aforementioned concept, some specific optical (perylene bisimides) [7] or
electrochemical (ferrocene) [8-9] receptor groups have been frequently employed. Once
incorporated into interlocked molecules, these receptor groups have specific signal transduction
properties and prominent selectivities towards sensing guest species [10-12]. Therefore, the
design and construction of MIMs with specific groups [13] can provide an excellent platform
towards probing the host-guest interactions for specific molecular recognitions [14-19]. Due to
external stimuli, MIMs binding with cations are capable of showing different emission colours or
intensity changes [20-26]. In addition, host-guest sensors based on fluorometric changes have
received much attention due to their potential applications in environmental science, chemistry,
biology, and medicine [27-30]. The challenges of developing unique water-soluble structures
2

ACCEPTED MANUSCRIPT
have been reported recently based on molecular switches in aqueous solution [31-34], where
most biological applications are possible via supramolecular chemistry [35,36].
The photophysical phenomena of luminogenic compounds originated from host-guest
complexation and aggregation induced emission (AIE) are non-emissive when soluble in good
solvents but become highly emissive as aggregated species in poor, which have been studied and
investigated over last decade [37,38]. Many aromatic compounds and dyes have the ability to
exhibit AIE including hexaphenylsilone, anthracene, and pyrrole derivatives [39], owing to the
restriction of intramolecular motions (RIM). Presently, tetraphenylethylene (TPE) is one of the
most favorite units due to its extraordinary AIE behaviour [40-43]. Therefore, several reports
have demonstrated the utilization of AIE in a variety of fields, such as chemical sensors [44],
stress sensors [45], explosive detections [46], and biosensors [47]. Importantly, a fluorescent
sensor based on the phenanthroimidazole (PIZ) unit with a less intense emission in contrast to
the aggregated TPE unit has been reported [48]. Therefore, the combination of TPE and PIZ
units were finely tuned for fluorescence emissions towards selective analytes.
Herein, the synthesis of rotaxane R1 incorporated with TPE and PIZ units as axle components
was accomplished via the conventional metal template method [49]. Interestingly, the AIE
behavior of the designed R1 was visualized with bright blue emissions in semi-aqueous solutions
of DMSO with high water content. However, the emission band from the PIZ unit of R1 (i.e., no
AIE phenomenum) was observed in pure and semi-aqueous (with low water contents) DMSO
3
+
solutions. Interestingly, the presence of Fe ion quenched the fluorescence of both TPE and PIZ
chromophoric units in semi-aqueous conditions selectively by means of host-guest interactions
3
+
into the topologically constrained cavity of R1. Moreover, the selectivity of Fe in the cavity of
3

ACCEPTED MANUSCRIPT
R1 was further visualized as fluorescence quenching with ferric ion containing biomolecular
Hemin with an enhanced sensitivity, where the quenching efficiency was measured by the extent
of AIE from the TPE as well as the fluorescence of PIZ. However, the fluorescence emission of
R1 in a system with a lower water content was proportionally enhanced in the presence of the
antioxidant sodium ascorbate and thus to signify the existence of Heme as a result of conversion
of Hemin to Heme [50]. Such a conversion could be probed by the generation of optical events in
R1. This study represents the first example of significant interactions of a macromolecular
rotaxane with cyclic ferriprotoporphyrin IX, along with probing the transformation of Hemin
3
+
2+
(
containing ferric ion Fe ) into Heme (containing ferrous ion Fe ) by means of an antioxidant
(sodium ascorbate).
2
2
. Experimental Section
.1 Materials
All reagents and most solvents were purchased from Aldrich Chemicals and used without further
purification. Solvents were degassed by freeze/thaw/pump cycle technique, and tetrahydrofuran
(
THF), chloroform (CHCl ), dichloromethane (DCM), acetonitrile (MeCN), and N,N-
3
dimethylformamide (DMF) were dried prior to use. All reactions were carried out under nitrogen
atmosphere. The following compounds, including 2,7-dibromophenanthrene-9,10-dione [49], 3-
(
2-bromoethoxy)phenol [49], 2,6 bis(bromomethyl)pyridine [51], 4-(1,2,2-triphenylvinyl)phenol
52], and macrocycle Pd-complex (MCC) [52], were prepared according to the literature
[
procedures.
2
.2 Characterization
4

ACCEPTED MANUSCRIPT
1
NMR spectra were recorded on Varian Inova 400 and Bruker DRX-300 Avance series ( H: 300,
1
3
4
00, MHz; C: 100 and 75 MHz) at 298 K. The chemical shifts were reported in parts per
1
13
million (ppm) from low to high fields and referenced to residual solvents ( H and C, CDCl δ =
3
7
.26 ppm and δ = 77.23 ppm; DMSO-d δ = 2.49 ppm and δ = 39.56 ppm, respectively). All
6
values of coupling constant (J) were reported in Hertz (Hz). The standard abbreviations of
multiplicities were used as follows: s = singlet, d = doublet, t = triplet, m = multiplet, br = broad.
In addition, UV-Vis spectra in different solvents were obtained by a Jasco UV600
spectrophotometer using 1 cm quartz cuvette. Fluorescence measurements were performed with
HITACHI 4000 Series Spectrophotometer. PL emission and excitation spectra were collected
(slit: 5 nm,10 nm, PMT voltage: 650 V, 450 V, scan limit: 1200 nm/min) for the detector
response and the lamp output. Elemental analyses were conducted on HERAEUS CHN-OS
RAPID elemental analyser. High resolution mass spectroscopic (HRMS) measurements were
performed using Bruker Daltonics Flex Series ESI mass via a buffer solution of α-cyano-4-
hydroxycinnamic acid (CHC). Thin layer chromatographies (chromatographies were performed
on Merck silica gel under pressure using TLC) were performed on glass plates coated with silica
6
0 F24 (Merck). The plates were visualized using ultra-violet light (256 nm) and developed
using an iodine chamber.
2
.3 Synthesis
{
5,10-Dibromo-2-(4-(prop-2-yn-1-yloxy)phenyl)-3a,11b-dihydro-1H-phenanthro[9,10-
d]imidazole} (1): A mixture of 2,7-dibromophenanthrene-9,10-dione (2.0 g, 5.50 mmol), 4-
prop-2-yn-1-yloxy) benzaldehyde (2.2 g, 13.77 mmol), and ammonium acetate (6.36 g, 82.63
(
mmol) in acetic acid (40 mL) was refluxed overnight. After completion of the reaction, the
5

ACCEPTED MANUSCRIPT
reaction mixture was cooled to room temperature and poured into water (500 mL). The resulting
precipitate material was filtered, and washed with water and hexane sequentially. The material
was dried overnight under vacuum at room temperature. The crude compound was crystallized
from ethanol to give the target compound as a colourless solid material (2.6 g, 93%). mp: > 195
0
1
C. H NMR (400 MHz, DMSO-d , 298 K) δ (ppm): 13.30 (s, 1H, NH), 8.64-8.56 (m, 4H, ArH),
6
8
.178 (dd, J = 8.8 Hz, 2H), 7.64 (d, J = 8.8 Hz, 2H), 7.18 (dd, J = 8.8 Hz, 2H), 4.90 (s, 2H), 3.61
1
3
(
s, 1H). C NMR (100 MHz, CDCl
3
, 298 K), δ (ppm): 158.7, 150.3, 136.9, 128.2, 126.5, 124.4,
1
23.6, 121.2, 115.6, 79.4, 78.9, 56.0, 40.5, 40.3, 40.1, 39.9, 39.7, 39.4, 39.2.
{5,10-Dibromo-1-hexyl-2-(4-(prop-2-yn-1-yloxy)phenyl)-3a,11b-dihydro-1H
phenanthro[9,10-d]imidazole} (2): To a solution of compound 1 (2.5 g, 4.9 mmol) and K CO
2
3
(2.04 g, 14.82 mmol) in DMF (10 mL), iodohexane (2.19 mL, 14.82 mmol) was added and
heated at 70ºC. After 6 h, the reaction mixture was poured into ice water (100 mL) and extracted
with EtOAc (150 mL). The isolated organic layer was washed with brine (250 mL), and then
concentrated under vacuum. Then, the crude residue was subjected to column chromatography
0
(
silica gel, EtOAc / hexane: 1/4) to give a colourless solid (2.8 g, 95%). mp: > 180 C. IR (KBr,
-1
1
cm ): 3306, 3085, 2976, 2901 (propargyl), 2855, 2141, 1660, 1555, 1400, 1310, 1251, 1115. H
NMR (400 MHz, DMSO-d , 298 K) δ (ppm): 8.85 (d, J = 2.4 Hz, 1H), 8.41 (d, J = 6.4 Hz, 1H),
6
8
.30 (d, J = 8.8 Hz, 1H), 8.18 (s, 1H), 7.64 (d, J = 8.4 Hz, 2H), 7.61 (t, J = 8.8 Hz, 2H), 7.14 (d,
J = 8.4 Hz, 2H), 4.78 (s, 2H), 4.42 (t, J = 7.6 Hz, 2H), 2.58 (s, 1H), 1.87 (t, J = 7.6 Hz, 2H),
1
3
1
1
3
5
.29-1.24 (m, 6H), 0.84 (t, J = 6.0 Hz, 3H). C NMR (100 MHz, CDCl , 298 K) δ (ppm): 158.6,
3
52.9, 137.4, 131.2, 128.6, 125.1, 124.4, 123.2, 1231.2, 115.2, 78.1, 76.7, 75.9, 55.9, 46.7, 31.0,
+
0.1, 26.0, 22.4, 13.9. HRMS (ESI) (m/z): [M+H] calcd for C30
H27Br
N
2 2
O, 589.0485, found:
91.0466.
6

ACCEPTED MANUSCRIPT
{3-(2-Azidoethoxy)phenol} (3): To a solution of 3-(2-bromoethoxy)phenol (2.5 g, 11.62 mmol)
in DMF (20 mL), the sodium azide (1.51 g, 23.25 mmol) was added and then the reaction
mixture was heated at 65ºC overnight. After the completion of reaction, the reaction mixture was
poured into ice water (100 mL) and extracted with EtOAc (350 mL). The organic layer was dried
over MgSO and then the solvent was evaporated under vacuum. The crude residue was purified
4
by column chromatography (silica gel, EtOAc / hexane: 1/1) to afford a transparent oil (1.8 g,
0
1
8
6
6%). mp: > 60 C. H NMR (400 MHz, DMSO-d
.53-6.43 (m, 3H), 4.02(t, J = 4.8 Hz, 2H), 3.50 (t, J = 5.2 Hz, 2H). C NMR (100 MHz,
, 298 K) δ (ppm): 159.4, 156.9, 130.4, 108.7, 106.8, 102.4, 66.9, 50.0.
6
, 298 K) δ (ppm): 7.13 (t, J = 8.0 Hz, 1H),
1
3
CDCl
3
{2-((3-(2-Azidoethoxy)phenoxy)methyl)-6-(bromomethyl)pyridine} (4):
A
mixture of
compound 3 (1.5 g, 8.37 mmol), 2,6 bis(bromomethyl)pyridine (2.19 g, 8.37 mmol), and K CO
2
3
(
3.4 g, 25.13 mmol) in MeCN (30 mL) ware heated at 70 ºC to react for 5 h. Then, MeCN was
removed by evaporation under vacuum and the crude was purified by column chromatography
silica gel, EtOAc/hexane: 4/1). The desired compound was obtained as a colourless solid (1.25
(
0
1
g, 41%). mp: > 65 C. H NMR (400 MHz, DMSO-d
6
, 298K) δ (ppm): 7.17 (t, J = 8.0 Hz, 1H),
.45 (d, J = 8.0 Hz, 1H), 7.43 (d, J = 8.0 Hz, 1H),7.19 (t, J = 8.0 Hz, 1H), 6.60 (dd, J = 10.0 Hz,
H, J = 7.6 Hz, 1H), 6.58 (t, J = 2.4 Hz, 1H), 6.54 (dd, J = 10.0 Hz, 1H J = 8.0 Hz, 1H), 5.17 (s,
7
1
2
2
3
1
3
H), 4.57 (s, 2H), 4.11 (t, J = 5.2 Hz, 2H), 3.57 (t, J = 4.8 H, 2H). C NMR (100 MHz, CDCl ,
3
98 K) δ (ppm): 159.5, 159.4, 157.2, 156.2, 137.8, 130.1, 122.3, 120.5, 107.6, 107.4, 101.9, 50.1,
3.6.
{2-((3-(2-Azidoethoxy)phenoxy)methyl)-6-(4-(1,2,2triphenylvinyl)phenoxy)methyl)pyridine
(5): To a solution of 4-(1,2,2-triphenylvinyl)phenol (0.76 g, 2.20 mmol) and compound 4 (0.80
7

ACCEPTED MANUSCRIPT
2 3
g, 2.20 mmol) in MeCN (20 mL), K CO (1.52 g, 11.04 mmol) was added. The reaction mixture
was heated at 70 ºC to react overnight. After completion of the reaction, the mixture was filtered
and the organic layer was concentrated under vacuum. The crude was purified by column
chromatography (silica gel, EtOAc/hexane: 4/1), and the desired compound was obtained as a
0
-1
colourless solid (1.1 g, 79%). mp: > 135 C. IR (KBr, cm ): 3115, 3020, 2935, 2865, 2108
(
azide), 1598, 1351, 1202. NMR (400 MHz, DMSO-d , 298 K) δ (ppm): 7.75 (t, J = 8.0 Hz, 1H),
6
7
6
1
4
1
7
6
.45 (q, J = 7.6 Hz, 2H), 7.21 (t, J = 8.0 Hz, 1H) 7.13-7.01 (m, 15H), 6.973 (d, J = 6.8 Hz, 2H),
.75 (d, J = 6.8 Hz, 2H), 6.64 (d, J = 2.4 Hz, 1H), 6.61 (q, J = 4.8 Hz, 1H), 6.56 (dd, J = 2.4 Hz,
H, J = 2.0 Hz, 1H), 5.20 (d, J = 5.2 Hz, 2H), 5.13 (s, 2H), 4.13 (t, J = 4.8 Hz, 2H), 3.58 (t, J =
1
3
.8 Hz, 2H). C NMR (100 MHz, CDCl , 298 K) δ (ppm): 159.6, 159.4, 156.9, 156.7, 156.6,
3
43.9, 143.8, 140.3, 136.6, 131.3, 127.6, 126.2, 120.2, 120.1, 114.7, 113.9, 107.6, 107.3, 102.0,
+
0.5, 70.4, 66.9, 50.1. HRMS (ESI) (m/z): [M+H] calcd for C H N O , 631.2704, found:
4
1
35
4
3
31.2705.
5
2
,10-Dibromo-1-hexyl-2-(4-((1-(2-(3-((6-((4-(1,2,2-triphenylvinyl)phenoxy)methyl)pyridin-
-yl)methoxy)phenoxy)ethyl)-1H-1,2,3-triazol-4-yl)methoxy)phenyl)-1H-phenanthro[9,10-
d] imidazole (S1): The solution of compound 2 (0.18 g, 0.30 mmol) and compound 5 (0.20 g,
.31 mmol) in THF/water (10 mL/5 mL) was degassed with nitrogen for 5 min. Then, CuSO4
0.057 g, 0.31 mmol) and sodium ascorbate (0.19 g, 0.63 mmol) were added sequentially, and the
0
(
color change was observed. The reaction mixture was stirred at room temperature for 12 h, then
the solution was concentrated from the reaction mixture and diluted with a mixed solvent of
CH
2
Cl
2
(100 mL) and ammonium hydroxide solution (20 mL). The solution was stirred for 1 h at
Cl was separated and concentrated under
room temperature, then the organic layer in CH
2
2
vacuum. The desired product was isolated from 1.5% MeOH in DCM as a pale yellow solid
8

ACCEPTED MANUSCRIPT
0
-1
(
0.29 g, 75%). mp: > 115 C. IR (KBr, cm ): 3132, 3045, 3030, 2958, 2888, 1667, 1552, 1458,
1
1
254, 1458, 1253, 1092. H NMR (400 MHz, DMSO-d , 298 K) δ (ppm): 8.90 (s, 1H), 8.55 (d, J
6
=
8.8 Hz, 1H), 8.41 (d, J = 8.8 Hz, 1H), 8.30 (s, 1H), 7.85 (s, 1H), 7.72-7.63 (m, 5H), 7.41 (d, J =
7
6
2
.6 Hz, 2H), 7.26 (s, 1H), 7.19 (d, J = 8.8 Hz, 2H), 7.11-6.99 (m, 15H), 6.72 (d, J = 8.4 Hz, 2H),
.61 (d, J = 8.4 Hz, 2H), 6.57 (d, J = 8.4 Hz, 1H), 6.56 (s, 1H), 6.50 (d, J = 8.4 Hz, 1H), 5.32 (s,
H), 5.15 (d, J = 6.4 Hz, 2H), 4.78 (t, J = 5.2 Hz, 2H), 4.49 (t, J = 7.6 Hz, 2H), 4.36 (t, J = 5.2
Hz, 2H), 1.91 (t, J = 7.2 Hz , 2H), 1.26 (s, 8H) 0.88-0.82 (m, 3H).
1
3
C NMR (100 MHz, CDCl , 298 K) δ (ppm): 159.6, 159.3, 158.9, 156.8, 156.7, 156.4, 153.1,
3
1
7
43.9, 143.8, 140.3, 136.6, 128.7, 127.0, 125.5,123.4, 120.1, 113.9, 107.8, 107.2, 102.1, 70.5,
0.3,66.2, 62.0, 49.8, 46.8, 31.0, 30.2, 29.6, 29.3, 26.0, 22.6, 22.4, 14.1, 13.9. HRMS (ESI)
+
(
m/z): [M+H] calcd for C H Br N O 1219.3121, found: 1221.3090.
71
61
2
6
4,
Pseudorotaxane (6): To a solution of macrocycle Pd-complex (MCC) (0.811 g, 1.26 mmol) in
CHCl /MeCN (15/5 mL), compound 5 (0.80 g, 1.26 mmol, 1eq) was added and stirred to react at
3
room temperature for 5 h. The solution was evaporated under reduced pressure and the crude
residue was purified by column chromatography (silica gel, 0.5% MeOH in DCM). The desired
0
-1
product was isolated as a yellow solid (0.85 g, 52%). mp: > 170 C. IR (KBr, cm ): 3643, 3429,
1
3
207, 3057, 2953, 2108 (azide), 1618, 1361, 1171. H NMR (400 MHz, DMSO-d , 298 K) δ
6
(
ppm): 8.13 (t, J = 8.0 Hz, 1H), 7.91 (q, J = 14.8 Hz, 4H), 7.63 (d, J = 8.0 Hz, 1H), 7.47 (d , J =
.0 Hz, 1H), 7.27 (q, J = 11.6 Hz, 2H), 7.15-6.99 (m, 15H), 6.72 (d, J = 8.0 Hz, 1H), 6.84 (dd, J
6.4 Hz, 1H, J = 2.4 Hz, 1H), 6.62–6.58 (m, 2H), 6.29 (d, J = 8.0 Hz, 4H), 6.16 (d, J = 8.0 Hz,
H), 5.37 (s, 2H), 4.66 (d, J = 14.4 Hz, 2H), 4.41 (s, 2H), 4.17 (t, J = 4.8 Hz, 2H), 3.63-3.38 (m,
8
=
4
1
1
3
8H), 2.03 (m, 2H). C NMR (100 MHz, CDCl , 298 K) δ (ppm): 171.26, 159.4, 158.5, 157.6,
3
9

ACCEPTED MANUSCRIPT
1
1
57.3, 155.1, 152.7, 144.0, 143.7, 140.8, 136.9,131.4, 130.4, 127.5, 125.1, 122.3, 122.2, 114.4,
14.4, 108.1, 107.8, 102.4, 70.69, 69.51, 69.29, 68.0, 67.14, 67.12, 50.13, 49.57. HRMS (ESI)
+
(
m/z): [M+H] calcd for C H N O Pd, 1271.5599, found: 1283.5189.
70
65
7
10
Metalated rotaxane (Pd-complex) (7): A solution of compound 6 (0.50 g, 0.39 mmol) and
compound 2 (0.23 g, 0.39 mmol) in THF/H O (15 mL/5 mL) was degassed with nitrogen for 5
2
4
min, and then CuSO (0.062 g, 0.39 mmol) and sodium ascorbate (0.15 g, 0.786 mmol) were
added sequentially to observe the color change. Then, the reaction mixture was stirred at room
temperature for 12 h. After this time the solvent was evaporated from the reaction mixture, and
the crude was diluted with DCM (100 mL)/ammonium hydroxide solution (20 mL) and stirred
for half an hour at room temperature. Then organic layer was isolated and concentrated under
vacuum. The crude product was purified by column chromatography (silica gel, 2% MeOH in
DCM). The crude product was isolated as a yellow solid (0.56 g) which was used in the next
0
-1
step of the reaction without further purification. mp: > 175 C. IR (KBr, cm ): 3078, 3052, 2977,
+
2
917, 2862, 1770, 1675, 1603, 1494, 1397, 1261. HRMS (ESI) (m/z): [M+H] calcd for
C
100 2 9
H91Br N O11Pd, 1858.4312, found: 1860.4327.
Final rotaxane R1: To a solution of crude compound 7 (0.40 g, 0.21 mmol) dissolved in CHCl3
10 mL), a solution of KCN (0.21 g, 3.23 mmol) dissolved in MeOH (5 mL) was added. The
(
reaction mixture was stirred at room temperature for 2 h, and then the solvent was evaporated
under vacuum. The crude residue was purified by column chromatography (silica gel, 2.5%
MeOH in DCM). The desired product was isolated as a colourless solid (0.32 g, 86%). mp: > 120
0
-1
C. IR (KBr, cm ): 3465, 3355, 3075, 3015, 2958, 2842, 1677, 1574, 1495, 1391, 1252, 1102.
1
H NMR (400 MHz, DMSO-d , 298 K) δ (ppm): 9.28 (t, J = 6.0 Hz, 2H), 8.84 (d, J = 2 Hz, 1H),
6
1
0

ACCEPTED MANUSCRIPT
8
1
7
6
1
1
.55 (d, J = 9.2 Hz, 1H), 8.41 (t, J = 9.2 Hz, 2H), 8.31 (d, J = 1.6 Hz, 1H), 8.00 (t, J = 8.0 Hz,
H), 7.86 (s, 1H), 7.66 (q, J = 15.2 Hz, 3H), 7.58 (d, J = 7.6 Hz, 2H), 7.25 (d, J = 7.4 Hz, 1H),
.23 (d, J = 7.8 Hz, 1H), 7.13-6.98 (m, 19H), 6.89 (d, J = 8.4 Hz, 2H), 6.63 (d, J = 8.0 Hz, 4H),
.54 (d, J = 8.0 Hz, 2H), 6.45 (t, J = 10.4 Hz, 2H), 6.30 (d, J = 8.0 Hz, 4H), 6.19 (d, J = 2.8 Hz,
H), 5.03 (s, 2H), 4.78 (s, 2H), 4.57-4.53 (m, 2H), 4.47 (t, J = 7.6 Hz, 2H), 4.37 (dd, J = 6.4 Hz,
H, J = 5.6 Hz, 1H), 4.29 (dd, J = 5.6 Hz, 1H, J = 6.4 Hz, 1H), 4.02 (t, J = 5.6 Hz, 2H), 3.84 (d,
J = 4.4 Hz, 2H), 3.73 (d, J = 3.6 Hz, 4H), 3.68 (d, J = 4.8 Hz, 4H), 3.63-3.60 (m, 4H), 2.25 (d, J
1
3
=
7.2 Hz, 2H), 1.92 (t, J = 7.6 Hz, 2H), 1.28-1.25 (m, 8H), 0.87-0.85 (m, 3H). C NMR (100
MHz, CDCl
3
, 298 K) δ (ppm): 163.5, 158.9, 155.6, 153.1, 149.1, 143.8, 143.3, 138.6, 136.6,
1
4
28.8, 127.5, 125.9, 124.4, 120.3, 114.9, 113.7, 107.6, 106.8, 101.8, 70.7, 69.2, 67.1, 65.6, 61.7,
+
9.3, 46.9, 42.5, 31.4, 30.2, 29.6, 29.3, 26.0, 22.6, 22.4, 14.1, 13.9. HRMS (ESI) (m/z): [M+H]
calcd for C H Br N O , 1754.5440, found: 1756.5599. Anal. Calcd for C H Br N O (%):
1
00 94
2
9
11
100 93
2
9
11
C, 68.37; H, 5.34; N, 7.18. Found (%): C, 67.85; H, 5.95; N, 6.45.
3
. Results and Discussion
Synthetic Strategy and Photo-Physical Properties of Rotaxane (R1).
Herein, we report the synthesis of the target mechanically interlocked rotaxane R1 based on
square planar Pd (II) complex strategy, as shown in Scheme 1. Acccording to our previous
4
9
report, the control axle S1 was synthesized by following Scheme 1(a). With the treatment of
TPE azide terminated compound 5 in the presence of 4-(1,2,2-triphenylvinyl)phenol macro-cycle
(Pd-complex) MCC, a predominantly self-complexing pseudorotaxane 6 was produced by the
replacement of the acetonitrile segment from MCC in chloroform.
Scheme 1
1
1

ACCEPTED MANUSCRIPT
Using a stoppering strategy, Pd-metalated rotaxane 7 was prepared through the well-known click
reaction between pseudorotaxane 6 and PIZ alkyne 2. Subsequently, through the treatment of Pd-
metalated rotaxane 7 with potassium cyanide to remove Pd metal, the target rotaxane R1 was
obtained with an excellent yield of 86% as shown in scheme 1 and displayed a good solubility in
most organic solvents.
As most of the biological as well as environmental significant analytes are present in water, we
were interested in evaluating the AIE phenomena from TPE and the maximum fluorescence
emission from PIZ in the presence of various compositions of semi-aqueous solutions (in water
and DMSO solvents). HEPES is a zwitterionic buffering agent to control the pH values within
7
.2-7.4. Herein, the HEPES buffer solution was used for the UV-vis and PL experiments to
maintain the pH value of 7.4. The UV-vis absorption and PL spectra of R1 (25 µM) in different
semi-aqueous solutions (in water and DMSO solvents), HEPES (pH 7.4, 10 mM) are displayed
in Figure 1.
Figure 1
As shown in Figure 1a, the designed rotaxane R1 (25 µM) displayed an absorption pattern in
DMSO solvent with well resolved absorption bands centered at 266 nm. As illustrated in Figure
1
b, the corresponding emission peak of the photoluminescence (PL) spectra in DMSO is
centered at 401 nm and is related to PIZ fluorophore. Due to the complete solubility in pure
DMSO, R1 was found to be non-fluorescent and absent of AIE, where R1 was in the non-
aggregated state of TPE with free rotations of conjugated rings about single bonds. DMSO along
with various compositions of water were subjected to investigations concerning the significant
variations in emission as well as absorption intensities. An unaltered emission related to PIZ
1
2

ACCEPTED MANUSCRIPT
fluorophore was appeared with 10% water without AIE. It was observed that more than 20% of
water up to 80% was able to generate a bright blue AIE centered at 470 nm as shown in Figure
1
b. Moreover, the PL emission of R1 (25 µM) related to TPE was found to be 65 times higher
than that of PIZ. The absorption pattern in the presence of high percentages of water was found
to be broadened and unrelaxed. The hetero-atoms ‘N’ and ‘O’ in the topologically constrained
cavity of designed interlocked host rotaxane R1 were proposed to facilitate the host-guest
interactions. An analyte of particular interest could be chelated with R1 through the specific
transduction capabilities associated with appended TPE and PIZ groups We were more interested
in investigating the interactions of guests captured by the macrocylic cavity and the variations of
host-guest interactions to affect photophysical properties of R1 in two solution media, such as
(1) with a lower content of water (10%), where AIE from TPE would be ineffective and thus to
transduct the photophysical change solely from PIZ. Therefore, the non-aggregated state of R1
will be dominant and (2) with a higher content of water (80%), where AIE from TPE would be
prominent and the transduction could be obtained with a bright blue emission (the aggregated
state). Host-guest interactions were subjected to cations as well as anions in our study, due to
their efficient perturbation capabilities in the micro-environment of the host probes. Therefore,
2
+
2+
2+
2+
2+
2+
2+
various alkali as well as transition metal ions, such as Fe , Ni , Pb , Cu , Hg , Sn , Co ,
2
+
2+
2+
2+
2+
2+
3+
3+
3+
3+
−
−
Zn , Cd , Mn , Mg , Ca , Se , Ru , Fe , Al , Cr , and various anions such as F , Cl ,
−
−
−
−
2−
−
−
Br , I , OH , SCN , HPO , H PO , and CN ions were chosen to study the chelation ability in
4
2
4
the cavity of R1. Our preliminary investigations were based on the significant changes in the
emission of R1 in the presence of various metal ions. Because fluorescence is considered to be a
highly sensitive optical technique towards prominent changes, to probe the detection of lower
concentrations of guest analytes with a lower detection limit is required in nano-molar regime.
1
3

ACCEPTED MANUSCRIPT
Figure 2
Primarily, the non-aggregated state of R1 (25 µM) was derived with a less content (10% vol.) of
aqueous solution, HEPES (pH 7.4, 10 mM) in DMSO and thus a solution medium with 9:1 vol.
ratio (DMSO:H O) was prepared to monitor the host-guest interaction event. R1 (25 µM) in the
2
aqueous HEPES solution displayed an emission band intensity centered at 401 nm upon
excitation at 350 nm. Upon the addition of various metal ions from 0 to 35 µM in R1, variations
in the PL emission maxima are shown in Figure 2a. The UV-vis. absorption spectra of R1 (25
3
+
µM) revealed the sign of aggregations as the increment (2.5 eq.) of the concentration for Fe ion
35 µM) and a developed band (375 nm) of R1 in Figure 2b is the confirmation of the internal
(
3
+
charge transfer mechanism of R1 with Fe ion. The fluorescence emission of R1 (25 µM) was
2
+
2+
2+
2+
almost unaffected in the presence of most alkali and transition metal ions Fe , Ni , Pb , Cu ,
2
+
2+
2+
2+
2+
2+
2+
2+
2+
3+
3+
3+
3+
Hg , Sn , Co , Zn , Cd , Mn , Mg , Ca , Se , Ru , Fe , Al , Cr even at their 35 µM
concentrations in Figure 2a.
3
+
However, the addition of Fe from 0-30 µM significantly quenched the fluorescence of R1 (25
µM). Our observations show significant fluorescence quenching with a huge red shift of (35 nm)
3
+
in presence of Fe ion within the concentration range from 0 to 30 ꢀM, and that was leveled off
over concentrations of 25 µM and thus a less intense and highly red-shifted emission band was
3
+
observed in Figure 2c. Moreover, the fluorescence quenching of R1 towards Fe ion was found
to be 30-fold within the investigated concentration range. The decreasing emission band patterns
3
+
of R1 (25 µM) in the presence of Fe (0-30 µM) were plotted as shown in Figure 2c.
3
+
At lower concentrations of Fe ion up to 16 µM, the fluorescence quenching behavior of R1 was
found to be linear. While at higher concentrations up to 25 µM, the linearity was lost and
1
4

ACCEPTED MANUSCRIPT
resulted in a nonlinear behaviour, signifying the possibility of a static quenching as shown in the
3
+
inset of Figure 2c. The efficiency of fluorescence quenching of R1 in the presence of Fe ion,
over the linear region was concluded in terms of Stern–Volmer constant and compared.
I /I = 1 + K [Q] ……………… (i)
0
sv
0
In above equation (i), where I and I are fluorescence intensities in the absence and presence of
the quencher, respectively, Ksv is the Stern–Volmer constant and the value of Ksv of an artificial
assay indicates the sensitivity of the probe towards the analyte, and [Q] is the quencher
3
+
concentration. The K value for R1 (25 µM) in the presence of Fe ion (35 µM) was found to
sv
5
-1
3+
be 1.39 × 10 M . The high K value of R1 towards Fe ion further confirmed that R1 is a
sv
3
+
selective and sensitive probe for sensing Fe ion in a semi-aqueous medium. The corresponding
3
+
absorption patterns of R1 (25 µM) in the presence of Fe ion (0-35 µM) within the investigated
concentration range revealed broadened and unresolved absorption spectra. Comparably, the
absorption patterns of R1 were visualized in the presence of water without metal ions, which
signified an aggregated state of R1. Interestingly, one broad band centered around 375 nm was
observed as shown in Figure 2c, which may be attributed to the charge transfer band in the
3
+
presence of Fe ion.
3
+
However, as the control axle S1 (25 µM) was treated with Fe ion (0-35 µM) as shown in Figure
(d), the fluorescence quenching patterns of S1 were similar but smaller than those of R1.
Furthermore, as shown in Figure S10, S1 (25 µM) was mixed with macrocycle MC (25 µM) in a
2
3
+
molar ratio of 1:1 (in contrast to R1) and treated with Fe (0-75 µM) ion. The combination of S1
3
+
and MC prohibited the fluorescence quenching alteration at the higher concentration of Fe ion.
1
5

ACCEPTED MANUSCRIPT
3
+
These experiments clarified that only R1 is the most sensitive and selective probe towards Fe
ion.
Tunable Aggregation of Rotaxane (R1).
The aggregated state of R1 (25 µM), derived from the high content (80% vol.) of aq., HEPES
buffer (pH 7.4,10 mM), was subjected to monitor the host-guest interaction event. In such a
solvent composition, R1 displayed an AIE band from TPE, centered at 470 nm, upon the
excitation at 350 nm as shown in Figure S6 (b). Under these conditions, a bright blue emission
from R1 was clearly visible under UV light due to a high emission as shown in Figure S6 (c).
Furthermore, significant changes in AIE were investigated in the presence of various metal ions.
The fluorescence emission of R1 was found to be almost unaffected in the presence of various
alkali and transition metal ions even at the concentration of 100 ꢀM as shown in Figure S6 (a).
3
+
However, a significant fluorescence quenching towards Fe ion within a concentration ranging
from 0 to 100 ꢀM was observed and the quenching levelled off at 110 µM concentration in
Figure S6 (b). The decreasing fluorescence intensity patterns of R1 (25 µM) in the presence of
3
+
Fe (0-100 µM) were found to be linear at lower concentrations as shown in the inset of Figure
3
+
S6 (b). However, at higher concentrations of Fe ion (4 eq.) the linearity was lost and the plot
became nonlinear indicating the possibility of a static type of quenching. The efficiency of the
3
+
fluorescence quenching of R1 in the presence of Fe ion was determined over the linear region
of the plot by generating a Stern–Volmer plot as described earlier. The obtained Ksv value was
5
-1
found to be 0.37 × 10 M .
1
6

ACCEPTED MANUSCRIPT
Time-Correlated Single Photon Counting (TCSPC) experiment:
The fluorescence quenching mechanism in non-aggregated (10% aq., HEPES pH 7.4, 10 mM
buffer) as well as aggregated (80% aq., HEPES pH 7.4, 10 mM buffer) state of R1 (25 µM)
3
+
stages in DMSO with Fe (30 µM and 100 µM) was confirmed by carrying out the time-
correlated single photon counting (TCSPC) experiments with a nanosecond excitation as shown
in Figure 3 and S7.
Figure 3
Table 1
The TCSPC data displayed unmodified biexponential decay patterns of R1 (25 µM) in the
3
+
absence and presence of Fe ion in semi-aqueous conditions As shown in Table 1, the concluded
lifetime values for R1 in the non-aggregated (10% aq.) and aggregated states (80% aq) of R1
{
(τ , 1.78 ns, 13.23%), (τ , 0.24 ns, 86.77%)} and {(τ , 4.70 ns, 48.34%), (τ , 1.40 ns, 51.66%)},
1 2 1 2
3
+
respectively. It was found to be almost unaffected upon the interaction with Fe {(τ , 0.83 ns,
1
4
7.97%), (τ , 0.13 ns, 52.03%)} and {(τ , 5.05 ns, 41.90%), (τ , 1.76 ns, 58.10%)}, respectively.
2 1 2
The unaffected life time values and decay patterns in both cases clearly indicated the occurrence
of a static type of quenching, and thus R1 formed a non-fluorescent ground state and stable
3
+
complex [R1+Fe ] under our experimental conditions.
1
H NMR Measurements.
1
The binding mode was also concluded by H NMR titrations of R1 in acetone-d solvent in the
6
3
+
3+
presence of Fe ion from 0 to 1.0 eq. as shown in Figure 4. Upon the addition of Fe ion with
various increasing concentrations in R1, amide protons (*) of cavity were found to be shifted
1
7

ACCEPTED MANUSCRIPT
upfield and the pyridyl proton (17,19) of axle shifted downfield. The further gradual addition of
3
+
Fe ion almost diminished the intensity of the proton peak (*). Such an up-field shift of amide
3
+
protons are attributed to the capture of Fe in the cavity and thus to enhance the N-H bond in the
amide region. Therefore, the NMR titrations clearly indicated a stoichiometric ratio of 1:1
3
+
3+
between R1 and Fe ion for complex [R1+Fe ].
Figure 4
3
+
In addition, as the axle S1 was treated with Fe ion up to 0-1.0 eq. in Figure S1 of the
supporting information, no proton shifts were observed. These results revealed that R1 is
3
+
responsible for Fe ion interaction due to its H-bonded constrained cavity.
Biomolecule (Hemin) Interactions with Rotaxane (R1). Since the sensor selectivity of R1
3
+
towards ferric ion (Fe ) has been verified in the previous study, both biological species Hemin
3
+
2+
(
containing ferric ion Fe ) and Heme (containing ferrous ion Fe ) are introduced to our
investigation of potential biological applications. Hemin can be reduced by antioxidant (sodium
ascorbate) [53]. Inspired by such quenching phenomena of R1 in non-aggregated state (10% aq.,
HEPES pH 7.4, 10 mM buffer) and aggregated state (80% aq., HEPES pH 7.4, 10 mM buffer),
we were more interested in the sensing capability of R1 for real small biomolecule (Hemin)
3
+
containing ferric ion (Fe ). Therefore, we further performed the fluorescence quenching
experiments in the presence of Hemin in both conditions of low-fluorescent non-aggregated and
high-fluorescent aggregated states for R1 in the solvent media of 10% and 80% water content.
The related PL responses of R1 towards Hemin in non-aggregated and aggregated states are
shown in Figures 5 and S8, respectively.
Figure 5
1
8

ACCEPTED MANUSCRIPT
Upon the addition of Hemin (0-13 µM), into non-aggregated R1 (25 µM) solution (with aq. 10%
vol., in DMSO), we found a significant quenching of the initial emission band centered at 401
nm into two emission bands centered at 380 and 439 nm. Figure 5. However, as demonstrated in
Figure S8 considerable quenching of the initial emission band of aggregated R1 (with aq. 80%
vol. in DMSO), centered at 470 nm shifted to the emission band centered at 465 nm in the
presence of Hemin (0-50 µM). The quenching efficiencies of Hemin in the non- aggregated as
well as aggregated states of R1 were concluded (in terms of Stern-Volmer constant) in terms of
5
-1
5
-1
K
sv values to be 2.80 × 10 M and 0.9 × 10 M , respectively. Therefore, the quenching
5
-1
efficiency of R1 towards Hemin (Ksv = 2.80 × 10 M ) was found to be superior over that
3
+
5
-1
towards Fe ion (K = 1.39×10 M ) and thus to signify a higher sensitivity of R1 towards
sv
Hemin.
Time-Correlated Single Photon Counting (TCSPC) experiments. Furthermore, time-
correlated single photon counting (TCSPC) spectra of R1 (25 µM) in the absence and presence
of Hemin in 10% aq., HEPES pH 7.4, 10 mM in DMSO are illustrated in Figure 6, which were
analyzed to demonstrate a biexponential decay pattern.
Figure 6
Table 2
As shown in Table 2, the lifetime values obtained for R1 in the absence and presence of Hemin
are summarized as {(τ , 1.78 ns, 13.23%), (τ , 0.24 ns, 86.72%)} and {(τ , 1.31 ns, 11.59%), (τ ,
1
2
1
2
0
.22 ns, 88.41%)}, respectively. However, the decay patterns of R1 in the absence and presence
3
+
of Hemin displayed less overlapped behaviour in contrast to Fe ion (see Figure 3), indicating
some interactions of R1 with Hemin. The overlapped behavior of R1 in the absence and presence
1
9

ACCEPTED MANUSCRIPT
3
+
3+
of Fe ion suggested that Fe ion formed a non-fluorescent ground state and stable complex
3
+
3+
[
R1+Fe ] due to the smaller size of Fe ion compared with Hemin.
1
H NMR Measurements.
1
Interaction of R1 with Hemin was further investigated by H NMR titrations of R1 with Hemin
in DMSO-d
6
solvent. As shown in Figure 7, when R1 (1eq.) solution was titrated with various
concentrations (0-1.0 eq.) of Hemin, slight upfield shifts for amidic protons (*) inside the cavity
3
+
of R1 were noted following a similar trend to that of Fe ion revealed in Figure 4. However,
3
+
smaller upfield shifts of R1 were observed with the titration of Hemin as compared with Fe
3
+
ion. These results suggested that stronger interactions of R1 with Fe ion were due to the easier
3
+
capture of Fe ion inside the cavity of R1, but the weaker cavity interactions of R1 with Hemin
3
+
were attributed to the steric hindrance of central metal ion (Fe ) coordinated with a larger size
Hemin. Our preliminary investigations revealed moderate photophysical alterations in R1 with
Hemin and thus to indicate the occurrence of certain interactions.
Figure 7
2
+
Since porphyrins of Heme with Fe ion are generally planar in their 6-coordinated geometry, 5-
3
+
coordinated Hemin leads Fe ion out of the central hole towards the 5th ligand, exhibiting some
perturbation of the porphyrin core Therefore, we believe that the porphyrin core in Hemin
3
+
assisted the availability of ferric ion for R1 cavity. A close proximity of R1 and Fe ion of
Hemin have induced some visualized spectroscopic alterations in R1. Regardless of no such
3
+
strong interactions as R1 complexed with Fe ion, the existence of a close proximity of R1 and
ferric ion of Hemin was further verified based on TCSPS data and NMR titration results.
2
0

ACCEPTED MANUSCRIPT
3
+
As we notice that the ferric ion (Fe ) in the active center of Hemin can be converted to another
2
+
iron metal ion form, i.e., the ferrous ion (Fe ), leading to the formation of non-toxic Heme,
which can be achieved by means of utilizing some biologically significant reducing agents, such
as glutathione and sodium ascorbate. Therefore, we further expanded our analysis by
incorporating tripeptide glutathione (GSH) and sodium ascorbate in our experiments. Both non-
aggregated (10% aq. vol in DMSO) and aggregated (80% aq. vol. in DMSO) states of R1 (25
µM) as well as Hemin with concentrations of 13 and 50 µM, respectively, were subjected to
monitor the interactions with reducing agents under physiological conditions.
Figure 8
According to the previous results, the responses of R1 towards Hemin in both non-aggregated
and aggregated states with different water contents (10% as well 80% of aq. solutions,
respectively) were quenched due to the formation of non-fluorescent complex R1-Hemin.
Moreover, upon the addition of various amounts of sodium ascorbate (0-8 mM) in complex R1-
Hemin, a significant increase in emission band centered at 475 nm was observed in the non-
aggregated state (10% aq. in DMSO) of Fig 8, but the quenched emission band of R1-Hemin was
unchanged in the aggregated state (80% aq. in DMSO). However, upon the addition of GSH, our
experiments did not reveal any significant changes in the quenched emission band of complex
R1-Hemin in both non-aggregated and aggregated states. Upon the addition of sodium ascorbate
in Figure 8, complex R1-Hemin demonstrates a gradual increase in the PL intensity centered at
4
75 nm in the non-aggregated state (10% aq. in DMSO), where the emission enhancement was
leveled off (with 50% recovery of initial emission intensity for R1) at 7 mM of sodium
ascorbate, which was found to be similar to the AIE band position but with less intensity. By
2
1

ACCEPTED MANUSCRIPT
means of biologically significant reducing agents, such as sodium ascorbate, the reduction form
of non-toxic Heme could be induced from the toxic form of Hemin.
4
. Conclusions
In conclusion, the mechanically interlocked host rotaxane R1 with terminal groups of TPE and
PIZ units was successively constructed through the method of Pd complexation, click reaction,
and removal of Pd metal by potassium cyanide. Both TPE and PIZ stopper units were used in
rotaxane R1 to possess aggregation induced emission (AIE) and low controllable fluorescence
with different water contents in DMSO, respectively. The emission of rotaxane R1 by PIZ as
3
+
well as TPE both exhibited significant signal quenching through the interaction of Fe in the
cavity of R1, and thus the host-guest interactions of both non-aggregated and aggregated states
3
+
of R1 were verified. Moreover, the interactions of R1 towards Fe ion in both semi-aqueous
states resulted in a static type of quenching and a non-fluorescent ground state of complex
3
+
[
R1+Fe ], as define by the Time-Resolved Photoluminescence (TRPL) studies. In addition, the
3
+
NMR titrations also indicated a stoichiometric ratio of 1:1 between R1 and Fe ion for complex
3
+
[
R1+Fe ]. The quenching efficiency of R1 towards Hemin was found to be superior over that
3
+
towards Fe ion and thus to signify a higher sensitivity of R1 towards Hemin. The variations of
PL emission intensities observed from PIZ in the R1 (10% aq. in DMSO) could be finely tuned
in the presence of the biological reducing agent (i.e., sodium ascorbate), where the enhancement
of the red-shifted emission band indicated the formation of Heme from Hemin. Finally, the
reduced form of non-toxic Heme could be produced from the toxic form, Hemin, by means of
biologically significant reducing agents.
Acknowledgement
2
2

ACCEPTED MANUSCRIPT
Financial support of this project was provided by the Ministry of Science and Technology
(MOST) through MOST 103- 2113-M-009-018-MY3.
References
[1] Fang L, Olson MA, Benı´tez D, Tkatchouck E, Goddard III WA, Stoddart JF. Mechanically
bonded macromolecules. Chem Soc Rev 2010;39:17–29.
[2] Ma X, Tian H. Bright functional rotaxanes. Chem Soc Rev 2010;39:70–80.
[3] Zhang W, DeIonno E, Dichtel WR, Fang L, Trabolsi A, Olsen J-C, Benı´tez D, Heath JR,
Stoddart JF. A solid-state switch containing an electrochemically switchable bistable poly[n]
rotaxane. J Mater Chem 2011;21:1487–95.
[4] Browne WR, Feringa BL. Making molecular machines work. Nat Nanotechnol 2006;1:25–
3
5.
[5] Coti KK, Belowich ME, Liong M, Ambrogio MW, Lau YA, Khatib HA, Zink JI, Khashab
NM, Stoddart JF. Mechanised nanoparticles for drug delivery. Nanoscale 2009;1:16–39.
[6] Dongen SFMV, Cantekin S, Elemans JAW, Nolte RJM. Functional interlocked systems.
Chem Soc Rev 2014;43:99–122.
[7] Li H, Li X, Cao Z-Q, Qu D-H, Ågren H, Tian H. A switchable bis-branched [1]rotaxane
featuring dual-mode molecular motions and tunable molecular aggregation. ACS Appl Mater
Interfaces 2014;6:18921–29.
[8] Li H, Zhang H, Zhang Q, Zhang Q-W, Qu D-H. A switchable ferrocene-based [1]rotaxane
with an electrochemical signal output. Org Lett 2012;14:5900–903.
2
3

ACCEPTED MANUSCRIPT
[9] Liu L, Wang Q, Chang, M, Hu X-Y, Jiang J, Wang L. A ferrocene-functionalized bistable [2]
rotaxane with switchable fluorescence. Asian J Org Chem 2015;4:221–5.
[10] Langton MJ, Beer PD. Rotaxane and catenane host structures for sensing charged guest
species. Acc Chem Res 2014;47:1935−49.
[11] Lee H, Kim EJ, Ahn J, Noh TH, Jung O-S. Anion effects on formation of
metallacyclodimeric silver(I) complexes as a solvent reservoir. J Mol Struct 2012;1010:111–5.
[12] Arumugaperumal R, Srinivasadesikan V, Raju MVR, Lin M-C, Shukla T, Singh R, Lin H-
−
C, Acid/Base and H PO4 controllable high-contrast optical molecular switches with a novel
2
BODIPY functionalized [2]rotaxane. ACS Appl Mater Interfaces 2015;7:26491–503.
[13] Suzaki Y, Osakada K. Formation, dynamic behavior, and chemical transformation of Pt
complexes with a rotaxane-like structure. Chem Asian J 2006;1:331–43.
[14] Caballero A, Zapata F, Beer PD. Interlocked host molecule for anion recognition and
sensing. Coord Chem Rev 2013;257:2434–55.
[15] Rebilly J-N, Hessani A, Colasson B, Reinaud O. A versatile strategy for appending a single
functional group to a multifunctional host through host–guest covalent-capture. Org Biomol
Chem 2014;12:7780–5.
[16] Chen Y-J, Yang S-C, Tsai C-C, Chang K-C, Chuang W-H, Chu W-L, Kovalev V, Chung
W-S. Anthryl-1,2,4-oxadiazole-substituted calix[4]arenes as highly selective fluorescent
3
+
chemodosimeters for Fe . Chem Asian J 2015;10:1025–34.
2
4

ACCEPTED MANUSCRIPT
[17] Kim EJ, Ahn J, Lee H, Noh TH, Jung, O-S. Synthesis, structures, and ligating ability of 4-
tert-butyl calix[n]arene (iso) nicotinoylate. Tetrahedron Lett 2012;53:1240–4.
[18] Lee H, Noh TH, Jung O-S. A ball-joint-type host–guest system that consists of
conglomerate helical metallacyclophanes. Angew Chem Int Ed 2013;52:11790–5.
[19] Suzaki Y, Taira T, Osakada K, Physical gels based on supramolecular gelators, including
host–guest complexes and pseudorotaxanes. J Mater Chem 2011;21:930–8.
[20] Ajayaghosh A. Chemistry of squaraine-derived materials: Near-IR dyes, low band gap
systems, and cation sensors. Acc Chem Res 2005;38:449–59.
[21] Lee S, Yuen KKY, Jolliffe KA, Yoon J. Fluorescent and colorimetric chemosensors for
pyrophosphate. Chem Soc Rev 2015;44:1749−62.
[22] Lee HN, Xu Z, Kim SK, Swamy KMK, Kim Y, Kim S-J, Yoon J. Pyrophosphate-selective
fluorescent chemosensor at physiological pH:ꢁ Formation of a unique excimer upon addition of
pyrophosphate. J Am Chem Soc 2007;129:3828−29.
[23] Lee M, Jo S, Lee D, Xu Z, Yoon J. A new naphthalimide derivative as a selective
fluorescent and colorimetric sensor for fluoride, cyanide and CO . Dyes Pigm 2015;120:288−92.
2
[24] Song NR, Moon JH, Choi J, Jun EJ, Kim Y, Kim S-J, Lee JY, Yoon J. Cyclic
-
benzobisimidazolium derivative for the selective fluorescent recognition of HSO via a
4
combination of C-H hydrogen bonds and charge interactions. Chem Sci 2013;4:1765−71.
2
5

ACCEPTED MANUSCRIPT
[25] Colasson B, Save M, Milko P, Roithová J, Schröder D, Reinaud O. A ditopic calix[6]arene
ligand with N-methylimidazole and 1,2,3-triazole substituents:ꢁ Synthesis and coordination with
Zn(II) cations. Org Lett 2007;9:4987−90.
[26] Hu Y, Liu Y, Kim G, Jun EJ, Swamy KMK, Kim Y, Kim SJ, Yoon J. Pyrene based
fluorescent probes for detecting endogenous zinc ions in live cells. Dyes Pigm 2015;113:372−7.
[27] Lakowicz JR. Topics in fluorescence spectroscopy: Probe design and chemical sensing,
Vol. 4; Plenum Press; New York;1994.
[28] Park S, Kim W, Swamy KMK, Lee HY, Jung JY, Kim G, Kim Y, Kim S-J , Yoon J.
Rhodamine hydrazone derivatives bearing thiophene group as fluorescent chemosensors for
2
+
Hg . Dyes Pigm 2013;99:323−8.
[29] Poul NL, Mest YL, Jabin I, Reinaud O. Supramolecular modeling of mono-copper enzyme
active sites with calix[6]arene-based funnel complexes. Acc Chem Res 2015;48:2097−106.
[30] Zhang R, Yuan Y, Liang J, Kwok RTK, Zhu Q, Feng G, Geng J, Tang BZ, Liu B.
Fluorogen−peptide conjugates with tunable aggregation-induced emission characteristics for
bioprobe design. ACS Appl Mater Interfaces 2014;6:14302−10.
[31] Grunder S, McGrier PL, Whalley AC, Boyle MM, Stern C, Stoddart JF. A water-soluble
pH-triggered molecular switch. J Am Chem Soc 2013;135:17691−94.
[32] Maurin A, Varatharajan S, Colasson B, Reinaud O. A water-soluble calix[4]arene-based
ligand for the selective linear coordination and stabilization of copper(I) ion in aerobic
conditions. Org Lett 2014;16:5426−29.
2
6

ACCEPTED MANUSCRIPT
[33] Li H, Fahrenbach AC, Coskun A, Zhu Z, Zhao Y, Botros YY, Sauvage JP, Stoddart JF. A
light-stimulated molecular switch driven by radical–radical interactions in water. Angew Chem
Int Ed 2011;50:6782−88.
[34] Fang L, Basu S, Sue CH, Fahrenbach AC, Stoddart JF. Syntheses and dynamics of donor-
acceptor [2] catenanes in water. J Am Chem Soc 2011;133:396−9.
[35] Coskun A, Spruell JM, Barin G, Dichtel WR, Flood AH, Botros YY, Stoddart JF. High
hopes: Can molecular electronics realise its potential? Chem Soc Rev 2012;41:4827–59.
[36] Coskun A, Banaszak M, Astumian RD, Stoddart JF, Grzybowski BA. Great expectations:
can artificial molecular machines deliver on their promise? Chem Soc Rev 2012;41:19−30.
[37] Hong Y, Lam JWY, Tang BZ. Aggregation-induced emission. Chem Soc Rev
2
011;40:5361−88.
[38] Lee H, Noh TH, Jung O-S. Halogen effects on photoluminescence and catalytic properties:
a series of spatially arranged trimetallic zinc(II) complexes. Dalton Trans 2014;43:3842–49.
[39] Liu J, Xu Y, Li X, Tian H. Synthesis and characteristics of a novel pseudorotaxane with the
diarylethene as the functional stopper. Dyes Pigm 2008;76:294−8.
[
40] Luo J, Xie Z, Lam JWY, Cheng L, Qiu C, Kwok HS, Zhan X, Liu D, Zhu D, Tang BZ.
Aggregation-induced emission of 1-Methyl-1,2,3,4,5-Pentaphenylsilole. Chem Commun
001;18:1740−1.
2
2
7

ACCEPTED MANUSCRIPT
[41] Liang G, Lam JWY, Qin W, Li J, Tang BZ. Molecular luminogens based on restriction of
intramolecular motions through host–guest inclusion for cell imaging. Chem Commun
014;50:1725−27.
2
[42] Zhao Z, Deng C, Chen S, Lam JWY, Qin W, Lu P, Wang Z, Kwok HS, Ma Y, Qiu H, Tang
BZ. Full emission color tuning in luminogens constructed from tetraphenylethene, benzo-2,1,3-
thiadiazole and thiophene building blocks. Chem Commun 2011;47:8847–49.
[43] Upamali KAN, Estrada LA, Neckers DC. Selective detection of Cr(VI) in aqueous media
by carbazole-based fluorescent organic microcrystals. Anal Methods 2011;3:2469–71.
[44] Wei T, Zhang P, Shi B, Chen P, Lin Q, Liu J, Zhang Y. A highly selective chemosensor for
3
+
2+
colorimetric detection of Fe and fluorescence turn-on response of Zn . Dyes Pigm
013;97:297−02.
2
[
45] Zhang X, Chi Z, Li H, Xu B, Li X, Zhou W, Liu S, Zhang Y, Xu J. Piezofluorochromism of
an aggregation-induced emission compound derived from tetraphenylethylene. Chem Asian J
011;6:808–11.
2
[46] Wang J, Mei J, Yuan WZ, Lu P, Qin A, Sun J, Ma Y, Tang BZ. Hyperbranched
polytriazoles with high molecular compressibility: Aggregation-induced emission and
superamplified explosive detection. J Mater Chem 2011;21:4056–59.
[47] Zhou J, He B, Chen B, Lu P, Sung HHY, Williams ID, Qin A, Qiu H, Zhao Z, Tang BZ.
Deep blue fluorescent 2,5-bis(phenylsilyl)-substituted 3,4- diphenylsiloles: Synthesis, structure
and aggregation-induced emission. Dyes Pigm 2013;99:520–5.
2
8

ACCEPTED MANUSCRIPT
[48] Lin WL, Cao LZ, Feng J. A cell-permeable fluorescent prochelator responds to hydrogen
peroxide and metal ions by decreasing fluorescence. Anal Chim Acta 2009;634:262–6.
[49] Raju MVR, Lin H-C. A novel diketopyrrolopyrrole (DPP)-based [2]rotaxane for highly
selective optical sensing of fluoride. Org Lett 2013;15:1274–77.
[50] Dwivedi AK, Saikia G, Iyer PK. Aqueous polyfluorene probe for the detection and
3
+
estimation of Fe and inorganic phosphate in blood serum. J Mater Chem 2011;21:2502–07.
[51] Satapathy R, Wu Y-H, Lin H-C. Novel thieno-imidazole based probe for colorimetric
2
+
2+
detection of Hg and fluorescence turn-on response of Zn . Org Lett 2012;14:2564–67.
[52] Raju MVR, Lin H-C. Self-assembly of tetraphenylethene-based [2]catenane driven by
acid−base-controllable molecular switching and its enabled aggregation-induced emission. Org
Lett 2014;16:5564−67.
[53] Zhang X, Sato M, Sasahara M, Migita CT, Yoshida T. Unique features of recombinant
heme oxygenase of Drosophila melanogaster compared with those of other heme oxygenases
studied. Eur J Biochem 2004;271:1713–1724.
2
9