Azathia crown ether possessing a dansyl fluorophore moiety functionalized silica nanoparticles as hybrid material for mercury detection in aqueous medium

Article abstract of DOI:10.1016/j.tet.2013.04.072

A novel fluorescent hybrid material for Hg²⁺detection using a derivative of dansyl fluorophore with azathia crown ether moiety grafted on silica nanoparticles (SiNPs) was prepared and characterized. The designed nanosensor exhibited pronounced Hg²⁺ selective ON-OFF type fluorescence switching upon binding. The presence of other metal ions has no observable effect on the sensitivity and selectivity of the prepared nanosensor toward the Hg²⁺ anions. The new nanosensor provided highly selective sensing to Hg²⁺) in EtOH/water solvent mixtures (pH=7) with a detection limit of 10^-7 M.

Full text of DOI:10.1016/j.tet.2013.04.072

Tetrahedron 69 (2013) 4866e4874
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Azathia crown ether possessing a dansyl fluorophore moiety
functionalized silica nanoparticles as hybrid material for mercury
detection in aqueous medium
,
b
,
a,b
Jalal Isaad a , Ahmida El Achari
*
a University Lille Nord de France, F-5900 Lille, France
b ENSAIT, GEMTEX, F-59056 Roubaix, France
a r t i c l e i n f o
a b s t r a c t
A novel fluorescent hybrid material for Hg2þdetection using a derivative of dansyl fluorophore with
azathia crown ether moiety grafted on silica nanoparticles (SiNPs) was prepared and characterized. The
designed nanosensor exhibited pronounced Hg2þ selective ONeOFF type fluorescence switching upon
binding. The presence of other metal ions has no observable effect on the sensitivity and selectivity of the
prepared nanosensor toward the Hg2þ anions. The new nanosensor provided highly selective sensing to
Hg2þ) in EtOH/water solvent mixtures (pH¼7) with a detection limit of 10ꢀ7 M.
Article history:
Received 7 March 2013
Received in revised form 7 April 2013
Accepted 12 April 2013
Available online 19 April 2013
Keywords:
Magnetite
Silica
Ó 2013 Elsevier Ltd. All rights reserved.
Nanoparticle
Mercury
Water
Hybrid material
1. Introduction
drawbacks in term of synthetic difficulty, high cost of starting
materials or lack of selectivity and act generally in organic solvent,
Mercury is one of the most highly poisonous and hazardous
pollutants with recognized accumulative and persistent characters
in the environment and biota.1e3 Inorganic mercury (Hg2þ) can be
converted into methyl mercury by bacteria in the marine system
and can easily enter the food chain and accumulate in the upper
level, especially in large edible fish.1e3 Mercury can cause serious
human health problems including DNA damage, mitosis impair-
ment, and permanent damage to the central nervous system.4,5 To
allow mercury detection with rapid, convenient, and inexpensive
methods, a fluorescent sensor can be useful. A number of macro-
molecules have been proposed and prepared as new fluorescent
sensors due to their high selectivity and sensitivity for the detection
of metal cations, including mercury.6e12 Recently many fluorescent
mercury ionophores have been designed for Hg2þ-sensing such as
calixarene,13 hydroxyquinolines,14,15 azines,16 cyclams,17e19 dia-
zacrown ethers,20 dioxocyclams,21 diazatetrathia crown ethers,22
and most of these studies have shown that nitrogen, oxygen, and
sulfur atoms present in the ionophores can promote the co-
which limits their use in the real environmental mediums.
Usually the colorimetric and fluorescent chemosensors for the
analytes detection contain generally binding sites and a signaling
subunit that has the ability to display selective changes in absorp-
tion or fluorescence spectra upon guest binding. In this sense, it is
reported that azathia macrocycle is generally thought to be a good
receptor due to its strong ability to coordinate with heavy and
23e25
transition metal ions such as Cu2þ and Hg2þ
and dansyl
chloride is a classical fluorophore widely used in the development of
fluorescent sensors due to its solvatochromism and high emission
quantum yields.26e28 Additionally, intramolecular charge transfer
(ICT) is an effective signaling mechanism employed in the design of
fluorescent sensors.29e32 All these may be useful to develop new
fluorescent sensors for Hg2þ in the environmental mediums.
On the other hand, hybrid organic/inorganic materials are
widely used for many applications such as catalysis,33 organic
synthesis,34 environment,35 and electronics.36 The anchoring of
organic fractions on the surface of a silica material represents the
key step for the development of new materials and can be mostly
achieved using two approaches.37 The first method consists in one-
pot synthesis involving co-condensation reactions between an
organo-tri-alkoxysilane and tetra-alkoxysilane (TEOS or TMOS) in
the presence or absence of a molecular structure-directing agent
ordination of Hg2þ 16e22
However, some of these sensors have
.
* Corresponding author. Tel.: þ33 (0)320258687; fax: þ33 (0)320272597; e-mail
addresses: jalal.isaad@ensait.fr, jisaadjalal@gmail.com (J. Isaad).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.04.072

J. Isaad, A. El Achari / Tetrahedron 69 (2013) 4866e4874
4867
like a ionic or non-ionic surfactant. The second option consists of
2. Results and discussions
a functionalization of silanol groups on the surface of the material
also called ‘post-synthetic’ functionalization method.
2.1. Synthesis of the fluorophore 2f
In particular, there are several advantages to using functional-
ized organiceinorganic hybrid nanomaterials as chemosensors in
the environment. First, functionalized nanomaterials can rapidly
and easily detect the metal ions.38 Second, these nanomaterials
would be useful as highly selective and efficient adsorbents for
specific guest molecules in environmental pollutants due to the
competition complex reaction. Third, the nanomaterials can be
easily controlled to interact with target guest molecules for de-
tection among various guest molecules in real analytical samples.
In this study, we selected a dansyl derivative as fluorophore with
azathia crown ether moiety; the final fluorescent probe was sup-
ported on silica nanoparticles (SiNPs) as sophisticated hosts, for
binding Hg2þ. The silica nanoparticles are particularly attractive as
they are easy to synthesize, are aqueous solution friendly, and can
be easily engineered to various sizes and shapes.
Fluorescence signaling, which translates molecular recognition
into tangible fluorescence signals, is one of the first choices due to its
high detection sensitivity and simplicity. On the other hand, as well
known, the sulfur and nitrogen can provide the soft binding unit for
Hg2þ according to the hardesoft acidebase theory. The Hg2þ binding
may affect intramolecular charge transfer (ICT) and consequently
induce spectral change. The foregoing may be also applicable to the
sensing of Hg2þ. With these in mind, an ICT fluorescent sensor 2f
based on azathia crown ether consisting of sulfur and nitrogen was
designed and synthesized, which can selectively coordinate with
Hg2þ. Scheme 1 reports the synthesis of the fluorophore 2f and the
azathia crown ether moiety 1d.
In order to synthesize the fluorophore 2f, the azathia crown
ether 1d was firstly synthesized from 1a through three steps. As
shown in Scheme 1A, bis (chloroethyl) amine 1a was reacted with
2-mercaptoethanol under a basic condition using Na2CO3 as an
inorganic base to afford the diol 1b. Then, 1c was prepared by the
nucleophilic substitution of the diols groups of 1b to their corre-
sponding dichloro derivatives in the presence of SOCl2. Finally, the
azathia crown ether 1d was obtained by the condensation of 1c
with 1,2-ethanedithiol under reflux and a basic condition. The
prepared azathia crown ether 1d was directly reacted with the
The methodology is showed in Scheme 1. First, the SiNPs were
prepared by condensation of TEOS in the presence of DIW/EtOH
and 30% aq ammonia solution. After the synthesis of the SiNPs, we
were able to specifically modify the external surface of the SiNTs by
using an adequate spacer such as aminopropyl-trimethoxysilane.
By this process, the fluorophore-coupled azathia crown ether re-
ceptor 2f was attached onto the surface of SiNPs as a chromogenic
receptor for Hg2þ
.
Scheme 1. Synthesis of the fluorophore 2f. Reagent and conditions: (a) Na2CO3, THF/H2O, 12h, 80 ꢁC; (b) SOCl2, DCM; (c) LiOH, THF, reflux, 3 days; (d) EtOH, rt, ultrasound (40 kHz),
30 min; (e) NEt3, MeCN, reflux, 18 h; (f) NaOH, MeCN, rt, ultrasound (40 kHz), 20 min; (g) cyanuric chloride, acetone, 18-crown-6, reflux, 20 h; (h) NEt3, DSM, 12 h, rt.

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J. Isaad, A. El Achari / Tetrahedron 69 (2013) 4866e4874
derivative 2b in the presence of NEt3 and under reflux for several
hours to give 2c. The esterification of the chlorosulfonate group
of compound 2a was carried out in EtOH and under ultrasound
irradiation in order to favor the nucleophilic substitution reaction
of the azathia crown ether 1d with the chloro group in the para-
position of the naphthalene moiety of 2a. The fluorophore 2f was
obtained by the coupling of the aminopropyl-trimethoxysilane
and compound 2e, which prepared by the saponification and sub-
sequently treated with cyanuric chloride. The structure of all de-
rivatives was confirmed by MS, NMR, and elemental analysis.
2.2. Synthesis and characterization of the functionalized
SiNPs
The study described here is based on design and development of
a fluorescent optical sensor containing SiNPs functionalized with
a metal ion chelating group. First, the SiNPs were prepared starting
from TEOS in the presence of the absolute EtOH, DIW, and 30% aq
ammonia solution. After, the surface of the prepared silica nano-
particles was modified by the fluorophore 2f containing the orga-
nosilane moiety as shown in Fig.1. The structural information of the
Fig. 1. General process for the synthesis of the functionalized silica nanoparticles (F-SiNPs). Reagents and conditions: (a) absolute EtOH, DIW/TEOS; sonicated for 2 h at 45 ꢁC and
30% aq NH3 solution was added and sonicated for 8 h at 45 ꢁC; (b) anhyd toluene,
for 8 h.
D

J. Isaad, A. El Achari / Tetrahedron 69 (2013) 4866e4874
4869
fluorophore on the surface of silica nanoparticles was studied by
solid-state characterization techniques: TEM imaging, TGA, and
FTIR.
intense band centered at 1104 cmꢀ1 is assigned to the structural
SieOeSi vibrations. The bands around 982 cmꢀ1 resulted from SieO
vibrations. However, in the case of the functionalized SiNPs, in the
FTIR spectrum (Fig. 4B), the silanol band disappears, whereas the
eNH vibration band appears at 3264 cmꢀ1. The weak bands at
2694 cmꢀ1 corresponding to the carbon chain (CH) of the pendant
group attached to the inorganic matrix. Also, the band at 1531 cmꢀ1
is attributed to the C]C aromatic stretch. The region between 1343
and 1489 cmꢀ1 corresponds to the aliphatic CeH stretching and the
S]O bands. These results showed that the fluorophore 2f had been
grafted onto the surface of the SiNPs after chemical modification.
Thermal stability of the SiNPs and the functionalized SiNPs has
been determined by thermogravimetric analysis. The results are
shown in Fig. 2. The TGA weight loss curves for modified and un-
modified SiNPs showed in Fig. 2 provide a qualitative comparison
of the changes induced after modification. The unmodified SiNPs
exhibit a weight loss at about 72 ꢁC corresponding to the loss of
physically adsorbed water, suggesting the surface to be hydrophilic
in nature.39 With increase in temperature the weight loss remains
constant, indicating no appreciable condensation of silanol groups
on the surface. There is a significant change in the weight loss curve
with modification of SiNPs. As reported in the literature, the
resulting pattern in the weight loss curve depends on the nature of
the ligand, and the step transition shows the decomposition of the
bonded organosilane with the height being roughly proportional to
the carbon content. In Fig. 2, a major weight loss region is seen
between 262 and 575 ꢁC, indicative of decomposition of the organic
ligand covalently bonded to the SiNPs surface.
Fig. 2. TGA weight loss curves of unmodified SiNPs and modified SiNPs.
The amount of organic compounds bound on the surface of the
nanoparticles is estimated from the percentage of weight loss from
the TGA curve. TGA of the in F-SiNPs indicated that the fluorophore
2f content was about 35%. Fluorophore 2f started to decompose at
about 262 ꢁC and was completely burned out at about 575 ꢁC.
The TEM images of the prepared SiNPs and the functionalized
SiNPs used in this study are shown in Fig. 3. The SiNPs present a
spherical shape with an average particle diameter of about 30 nm.
When the SiNPs were functionalized with the fluorophore 2f, the
two undergo copolymerization, giving an aggregation of SiNPs in
the range of 200 nm size particles, which comprises a network of
irregular shaped SiNPs as shown in Fig. 3.
Fig. 4. FTIR spectra of unmodified SiNPs (A) and modified SiNPs (B).
2.3. Sensitivity studies of the functionalized SiNPS
The effects of water ratio on the fluorescence emission of the
functionalized nanoparticles F-SiNPs in the absence and presence
of metal ions were systematically investigated in ethanol solutions
in order to optimize the conditions for practical applications in
environmental and biological samples. Fig. 5 reports the effect of
water ratio on the fluorescence behavior of F-SiNPs in ethanol
solutions.
Fig. 3. TEM images of the unmodified and the functionalized SiNPs.
The modified SiNPs were also confirmed by FTIR analysis. The
FTIR spectra of the modified and unmodified SiNPs are shown in
Fig. 4. As reported in the spectrum A, the broad band at 3468 cmꢀ1
represents the surface silanols of the unmodified SiNPs. The band
at 1621 cmꢀ1 represents the bending mode of eOH vibrations. The
Fig. 5. The fluorescence intensity variations of the F-SiNPs (0.5 mM) as a function of
the water ratio in ethanol solution at 525 nm in the absence and the presence of Hg2þ
(5 equiv), lex 340 nm.

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J. Isaad, A. El Achari / Tetrahedron 69 (2013) 4866e4874
The fluorescence emission of F-SiNPs was found to be strongly
dependent on the presence of water in the aq ethanol solution. This
result illustrated that when the water ratio increased, the fluores-
cence emission intensity of F-SiNPs decreased progressively. In the
low water ratio range, a similar decrease in the response of F-SiNPs
in the presence of 5 equiv of Hg2þ was observed, but with much
larger changes compared to the high water ratio region. Following
these results, we focused on the fluorescence behaviors of F-SiNPs
in response to the different metal ions in 30:70 ethanol/water
solution.
2.4. Selectivity study
As reported in the literature, the transition metal ions are well
known as fluorescence quenchers and function by means of nu-
merous mechanisms, such as fluorescence resonance energy
transfer, electronic energy transfer, charge-transfer phenomena,
heavy atom effects, magnetic perturbations, ground-state com-
plexation, and collisional conversion of electronic to kinetic en-
ergy.40 For an excellent chemosensor, high selectivity is a matter of
necessity. For this purpose, the selectivity studies of F-SiNPs were
performed in 30:70 ethanol/water solutions by recording the fluo-
rescence spectra of the solutions of F-SiNPs after the addition of
each representative metal ions. Fig. 6 shows the dependence of the
fluorescence intensity of F-SiNPs as a function of cation concen-
trations for Hg2þ, transition metal, heavy metal, alkali earth, and
Fig. 7. Fluorescence emission spectra (lex 340 nm) of F-SINPs (10ꢀ5 M) in 30:70 EtOH/
H2O as function of [Hg2þ] from 0.01 to 100
M.
m
mercury concentration was increased. When the added mercury
attained a concentration approximately more than three times
higher than that of F-SiNPs, about 95% quenching of initial fluo-
rescence of F-SiNPs was observed and the fluorescence response
reached a minimum point. The result provided a proof for the
formation of a new complex between Hg2þ and the fluorophore
grafted on the F-SiNPs.
The Job’s method for the emission was employed to investigate
the binding stoichiometry of the F-SiNPs and Hg2þ ions. The total
concentration of F-SiNPs and Hg2þ was maintained constant at
alkali ions including Kþ, Naþ, Agþ, Ba2þ, Mg2þ, Ca2þ, Cd2þ, Co2þ
,
10ꢀ5 M, with a continuous variation of the molar fraction of Hg2þ
.
Cu2þ, Fe2þ, Fe3þ, Mn2þ, Ni2þ, Pb2þ, and Zn2þ. The selectivity studies
clearly demonstrated the high selectivity of F-SiNPs to Hg2þ in
comparisonwith the other cations. Only the addition of Hg2þ caused
a dramatic decrease in the fluorescence spectra, while the other
metal ions did not cause obvious changes under identical condi-
tions. Furthermore, after addition of 5 equiv of Hg2þ to a solution of
F-SiNPs in EtOH/H2O: 30:70 mixture, avery noticeable decrease and
also a blue shift fluorescence change were caused when excited by
the radiation of 340 nm, which demonstrated F-SiNPs could selec-
tively recognize Hg2þ by simple fluorescence chemosensing.
Fig. 8 shows the fluorescence intensity variation at 525 nm as
a function of the ratio of F-SiNPs/Hg2þconcentration. Fig. 8 shows
that the complex of F-SiNPs/Hg2þ exhibited a maximum fluores-
cence emission at 525 nm when the molecular fraction of Hg2þ was
0.5. This indicated that a 1:1 stoichiometry is most possible for the
binding mode of F-SiNPs and Hg2þ
.
Fig. 8. Job’s plot of F-SiNPs/Hg2þ system in 30:70 EtOH/H2O. [F-SiNPs]þ[Hg2þ]¼
10ꢀ5 M.
Fig. 6. Fluorescence spectra of F-SiNPs (1.0ꢀ5 M) in the presence of 5 equiv of different
2.5. pH effect on sensor
metal ions (Hg2þ, Kþ, Naþ, Agþ, Ba2þ, Mg2þ, Ca2þ, Cd2þ, Co2þ, Cu2þ, Fe2þ, Fe3þ, Mn2þ
,
Ni2þ, Pb2þ, and Zn2þ) in EtOH/H2O: 30:70 mixture (lex 340 nm).
The performance characteristic of the sensor system was mon-
itored for its sensitivity toward different pH conditions. It is es-
sential for the sensor to perform satisfactorily at physiological pH
for its application toward biological sensing. In this sense, the flu-
orophore grafted on the F-SiNPs presents nitrogen with lone pair
electrons, the photophysical property of F-SiNPs and the sensing of
To evaluate the quantitative binding affinity of F-SiNPs, the
fluorescence titrations of F-SiNPs with increasing among of Hg2þ
ions were carried out in 30:70 ethanol/water (Fig. 7).
Following Fig. 7, the F-SiNPs showed the maximum emission
wavelength of 525 nm when excited by the radiation of 340 nm and
Hg2þ might be influenced by the pH of the solution. Therefore, the
2þ
has a high fluorescence quantum yield (
f
¼0.39). The fluorescence
response of the F-SiNPs toward Hg
at different pH values is re-
intensity of F-SiNPs was gradually decreased with increasing Hg2þ
concentration. In the absence of Hg2þ ions, the fluorescence re-
sponse was at a maximum and the response decreased as the
ported in Fig. 9. A 10ꢀ5 M stock solution of F-SiNPs containing 1
mM
Hg2þ solution was used for the experiment and different pH solu-
tions were prepared As reported in Fig. 9, in the absence of the Hg2þ

J. Isaad, A. El Achari / Tetrahedron 69 (2013) 4866e4874
4871
Fig. 9. Fluorescence emission response of F-SiNPs (10ꢀ5 M) at different pH (2e10), in
the absence (a) and in the presence (b) of Hg2þ cations (1.0
M) (lex 340 nm).
m
ions, at pH<3.0, the fluorescence intensity decreased with de-
creasing pH value, which was caused by the protonation of the
nitrogens of F-SiNPs.
Then, the fluorescence intensity of F-SiNPs almost did not vary
with pH in the range from 3.0 to 10.0 in the mixed solution. Upon
addition of Hg2þ, the fluorescence quenching almost did not cause
changes in the range from 2.0 to 8.0 in mixed solution. When the
pH was higher than 8.0, the fluorescence quenching was weakened
because too high a pH would lead to formation of the precipitation
Fig. 11. BenesieHildebrand plot of the chemosensor F-SiNPs/Hg2þ complexes in EtOH/
water: 30:70.
emission intensity was observed in case of HgCl2 and HgBr2, and
the minimum emission intensity was observed in case of HgCN2.
Overall, the effect of different counterions on the sensor system, as
compared with the chloride counterion used this work, is not more
than 5%.
of HgO, which in turn, would reduce its complexation with Hg2þ
.
The pH study shows that the F-SiNPs could be used as chemosensor
for Hg2þ under pH ranged from 2 to 8, which covered the physio-
logical pH condition.
The detection limit41 of the F-SiNPs as a fluorescent sensor for
the analysis of Hg2þ was determined from the plot of fluorescence
intensity as a function of the Hg2þ concentration as reported in
Fig. 10. The detection limit DL of chemosensor F-SiNPs was de-
termined from the following equation:
Fig. 12. Bar graph of ratio of fluorescence emission intensity, of F-SiNPs (10ꢀ5 M) with
different mercury ions at 1 mM of concentration.
3. Conclusions
A novel fluorometric sensor has been developed using func-
tionalized silica nanoparticles for sensitive and selective detection
of Hg2þ in aqueous suspension. A derivative of dansyl with azathia
crown ether moiety was used as fluorophore and metal ions che-
lator to functionalize the silica nanoparticles. The results of fluo-
rescence experiments exhibited a pronounced Hg2þ selective
ONeOFF type fluorescence switching upon binding. The detection
limit of 10ꢀ7 M Hg2þ in EtOH/H2O at neutral pH is observed. The
presence of other metal ions does not affect the selectivity of the
sensor, even in the presence of high concentrations 5.10ꢀ5 M of
Fig. 10. Calibration curve of F-SiNPS/Hg2þ in EtOH/water: 30:70. The excitation
wavelength was 340 nm.
DL ¼ K ꢂ Sb1=S
where: K¼3; Sb1 is the standard deviation of the blank solution and
S is the slope of the calibration curve.
It was found that the F-SiNPs have a detection limit of 10ꢀ7
M
Hg2þ, Kþ, Naþ, Agþ, Ba2þ, Mg2þ, Ca2þ, Cd2þ, Co2þ, Cu2þ, Fe2þ, Fe3þ
,
(see Supplementary data), which is allowed for the detection of
micromolar concentration range of Hg2þ
The association constant Ka was evaluated graphically by the
plotting 1/
F against 1/[Hg2þ] (Fig. 11).42 The data were linearly fit
Mn2þ, Ni2þ, Pb2þ, and Zn2þ. This sensor shows selective detection
of Hg2þ and can be used for Hg2þ chemosensing in physiological
environment and water quality monitoring.
.
D
according to the BenesieHilderbrand equation. The Ka value, ob-
tained from the slope and intercept of the line, was found to be
4. Experimental section
2.9.103 Mꢀ1
.
The effect of the different counterions on the sensor perfor-
mance was also evaluated using different mercury salts such as
4.1. Materials and instrumentation
NOꢀ3 , SO24ꢀ, CH3COOꢀ, CNꢀ, ClO24ꢀ, Clꢀ, Brꢀ, and Fꢀ at 1
mM as
All chemicals were reagent grade (Aldrich Chemical Co.) and
were used as purchased without further purification. Thin layer
chromatography (TLC) analysis was performed using Fluka
concentration. Fig. 12 shows the bar graph of the ratio of emission
intensity of F-SiNPs with the different mercury salts. The maximum

4872
J. Isaad, A. El Achari / Tetrahedron 69 (2013) 4866e4874
aluminum foils coated with 25 mm particle size silica gel matrix
F254. TLC development involved either UV (254 and 366 nm) or
visible light inspection, followed by either treatment with an acid
solution of p-anisaldehyde or a basic solution of KMnO4 and heat-
ing. Flash column chromatography was performed on Merck silica
gel 60 (particle size 0.040e0.063 nm, 230e400 mesh ASTM)
according to the procedure of Still. UVevis spectra were recorded
on a Cary-4000 Varian spectrophotometer, using either 0.1 or 1 cm
quartz cuvettes. Infrared spectra were recorded in a KBr disk on
a Perkin Elmer-Spectrum BX FTIR system. Absorptions are quoted in
wavenumbers (cmꢀ1). 1H and 13C NMR spectra were recorded at
200 MHz (for the 1H) and 50.0 MHz (for the 13C) on a Varian Gemini
4.4. 5-(1,4,7,10-Tetrathia-13-aza-cyclopentadec-13-yl)-naph-
thalene-1-sulfonyl chloride (2e)
To a solution of compound 2c (0.5 g, 0.97 mmol) in MeCN
(15 mL), 2 mL of NaOH solution 1 N was added and the mixture was
irradiated at rt in the water bath of an ultrasonic cleaner for 20 min.
Then the solvent was removed under reduced pressure and the
crude was washed with DCM, and the residue was dried under
pressure to afford the corresponding sodium sulfonate derivative
2d. After, this hydrolysis of compound 2c, the derivative 2d was
dissolved in 20 mL of acetone and 5 mL of cyanuric chloride was
added with a catalytic quantity of 18-crown-6 ether and the
resulting mixture was heated under reflux for 20 h. After cooling to
rt the solution was filtered through a Celite. Solvent was removed
(rotary evaporator) and the sulfonyl chloride was purified by FCC
using EtOAc/PE (5:2) as eluent to yield compound 2e in 75% as
spectrometer. Spin resonances are reported as chemical shifts (d) in
parts per million (ppm) and referenced to the residual peak as an
internal standard of the solvent employed, as follow: CDCl3
7.27 ppm (1H NMR), 77 ppm (13C NMR, central band), DMSO-d6
2.50 ppm (1H NMR, central band), 39.5 ppm (13C NMR, central
band). Spin multiplicity is showed by s¼singlet, d¼doublet,
t¼triplet, q¼quartet, m¼multiplet, br¼broad. Coupling constants J
are reported in hertz (Hz). Mass spectra were recorded on a Ther-
moScientific LCQ-Fleet mass spectrometer under electrospray
ionization (ESI, þc or ꢀc technique). High-resolution mass spectra
(HRMS) were recorded on a LTPOrbitrap mass spectrometer from
Thermo Electron Corporation under ESI (þc) technique. Mass
spectrometric analysis is quoted in the m/z form. Elemental anal-
yses were recorded on a Perkin Elmer 240 C Elemental Analyzer.
The fluorescence spectra were measured by Hitachi F-4500 fluo-
rescence spectrophotometer with a 1 cm quartz cell. Doubly dis-
tilled deionized water (DIW) was used for all experiments.
yield. H NMR (DMSO-d6, 200 MHz):
d
¼8.11e7.54 (m, 3H, ArH),
7.31e6.68 (m, 3H, ArH), 3.76 (t, 4H, J¼8.5 Hz, NCH2), 2.91e2.87 (m,
12H, CH2), 2.65 (t, 4H, J¼8.4 Hz, NCH2CH2) ppm. 13C NMR (DMSO-d6,
50 MHz):
d
¼152.1, 144.2, 134.3, 131.3, 130.4, 126.8, 125.9, 124.6,
123.4, 114.7, 58.2, 34.6, 34.3, 31.5 ppm. MS (ESI): m/z¼507.03
[Mþ1]þ. C20H26ClNO2S5 (508.31): C, 47.27; H, 5.16; N, 2.76. Found:
C, 47.35; H, 5.28; N, 2.86.
4.5. Synthesis of the compound 2f
In an ice bath, a solution of 2e (0.5 g, 0.98 mmol) in 15 mL of
DCM was added slowly to
a
mixture of aminopropyl-
trimethoxysilane and triethylamine in DCM (30 ml) and then was
stirred for 0.5 h. The reaction mixture was kept stirring for 12 h at
rt, and the progress of the reaction was monitored by thin layer
chromatography (TLC). After dilution with DCM, the mixture was
washed with saturated brine. The organic phase was dried over
anhydrous MgSO4, filtered, and evaporated under reduced pres-
sure. Purification of 2f was performed by using column chroma-
tography on silica gel using MeOH/DCM: 1:10 as eluent afford 2f in
4.2. Synthesis of 5-chloro-naphthalene-1-sulfonic acid ethyl
ester (2b)
A solution of 2a (1.00g, 3.84 mmol) was dissolved in EtOH
(7 mL), and the mixture was irradiated at rt in the water bath of an
ultrasonic cleaner for 30 min. Then, the solvent was removed under
reduce pressure, the crude was washed with water and DCM. The
resulting residue was dried under reduced pressure to afford 2b in
68% as yield. H NMR (DMSO-d6, 200 MHz):
d
¼8.03e7.56 (m, 3H,
ArH), 7.21e6.63 (m, 3H, ArH), 3.89 (m, 6H, SiOCH2), 3.71 (t, 4H,
J¼8.1 Hz, NCH2), 3.11 (t, 2H, J¼6.9 Hz, CH2N), 2.93e2.87 (m, 12H,
CH2), 2.65 (t, 4H, J¼7.6 Hz, NCH2CH2), 1.56e1.23 (m, 11H), 0.63 (t,
quantitative yield. H NMR (DMSO-d6, 200 MHz):
d
¼8.49e8.16 (m,
2H, ArH), 7.51e7.22 (m, 4H, ArH), 3.77 (q, 2H, J¼8.4 Hz, CH2), 1.38 (t,
2H, J¼6.4 Hz, SiCH2) ppm. 13C NMR (DMSO-d6, 50 MHz):
¼152.8,
d
3H, J¼8.4 Hz, CH3) ppm. 13C NMR (d6- DMSO, 50 MHz):
¼141.2,
d
139.3, 132.6, 130.6, 128.5, 126.6, 125.5, 124.1, 123.2, 114.5, 58.6, 51.1,
43.3, 35.1, 34.2, 31.4, 17.1, 15.6, 9.1 ppm. MS (ESI): m/z¼693.36
[Mþ1]þ. C29H48N2O5S5Si (692.19): C, 50.25; H, 6.98; N, 4.04. Found:
C, 50.35; H, 7.11; N, 4.16.
132.5, 131.8, 130.4, 128.3, 127.3, 126.7, 126.1, 125.5, 124.9, 52.3,
13.3 ppm. MS (ESI): m/z¼271.36 [Mþ1]þ. C12H11ClO3S (270.01): C,
53.24; H, 4.10. Found: C, 53.33; H, 4.21.
4.3. 5-(1,4,7,10-Tetrathia-13-aza-cyclopentadec-13-yl)-naph-
thalene-1-sulfonic acid ethyl ester (2c)
4.6. Synthesis of 2-{2-[2-(2-hydroxy-ethylsulfanyl)-ethyl-
amino]-ethylsulfanyl}-ethanol (1b)
MeCN solution (15 mL) was added to a 100-mL round bottom
flask containing the azatha crown ether 1d (0.5 g, 1.76 mmol),
compound 2b (0.48 g, 1.76 mmol), and NEt3 (0.74 g, 5.28 mmol), the
mixture was stirred under reflux for 18 h under a nitrogen atmo-
sphere. After completion of the reaction (which was monitored by
TLC), MeCN was removed from the mixture under reduced pres-
sure. The resulting crude product was purified by silica gel column
chromatography using EtOAc/PE (5:2) to yield compound 2c in 35%
To a 50 mL reactor were added sodium carbonate (1.0 g,
8.98 mmol), tetrahydrofuran (15 mL), water (2 mL), and compound
1a (1.0 g, 6.95 mmol). The reaction mixture was flushed with ni-
trogen for 20 min, and then 2-mercaptoethanol (0.99 mL,
13.9 mmol) was added in one portion. The reaction mixture was
stirred for 12 h at 80 ꢁC under nitrogen atmosphere. The reaction
mixture was diluted with water (20 mL) and extracted with
dichloromethane (5ꢂ50 mL). The combined organic phase was
dried over MgSO4. After filtration, the filtrate was condensed to
dryness. The residue was purified by column chromatography
(EtOAc/PE, 4:1, v/v) to afford 1b in 32.0% as yield. H NMR (DMSO-d6,
as yield. H NMR (DMSO-d6, 200 MHz):
d
¼8.12e7.56 (m, 3H, ArH),
7.21e6.66 (m, 3H, ArH), 3.77 (t, 4H, J¼8.1 Hz, NCH2), 3.51 (q, 2H,
J¼7.8 Hz, CH2), 2.91e2.88 (m, 12H, CH2), 2.63 (t, 4H, J¼8.1 Hz,
NCH2CH2), 1.36 (t, 3H, J¼7.8 Hz, CH3) ppm. 13C NMR (DMSO-d6,
200 MHz):
d
¼3.88 (t, 4H, J¼7.7 Hz, OCH2), 2.91 (t, 4H, J¼6.7 Hz,
50 MHz):
d¼152.5, 141.5, 131.9, 130.3, 128.2, 127.4, 125.3, 124.4,
NCH2), 2.63e2.58 (m, 8H) ppm. 13C NMR (DMSO-d6, 50 MHz):
122.3, 115.2, 58.3, 54.1, 34.7, 34.2, 31.2, 13.3 ppm. MS (ESI): m/
z¼518.29 [Mþ1]þ. C22H31NO3S5 (517.08): C, 51.03; H, 6.03; N, 2.70.
Found: C, 51.18; H, 6.21; N, 2.84.
d
¼66.7, 50.6, 35.1, 34.8 ppm. MS (ESI): m/z¼226.32 [Mþ1]þ.
C8H19NO2S2 (225.09): C, 42.63; H, 8.50; N, 6.21. Found: C, 42.72; H,
8.64; N, 6.32.

J. Isaad, A. El Achari / Tetrahedron 69 (2013) 4866e4874
4873
4.7. Synthesis of bis-[2-(2-chloro-ethylsulfanyl)-ethyl]-amine
(1c)
collected and titrated against standardized 0.05 M aq HCl (A ml)
using 0.1% phenolphthalein as indicator. The above procedure was
repeated with blank solution. The amount of HCl solution con-
sumed for neutralization was designated as B mL. The reading for A
and B were collected from the average of three titration experi-
ments. The amount of total hydroxyl groups (X mmol gꢀ1) per unit
gram of the silica was estimated (X¼1.82 mmol g) according to the
following Eq. 1.
To a solution of compound 1b (1 g, 4.44 mmol) in 15 mL of DCM,
a solution of thionyl chloride (049 g, 4.44 mmol) was added
dropwise to the above solution and stirred at ꢀ4 to 6 ꢁC for 1 h.
After the reaction mixture was placed at rt to react for 4 h and was
heated to 60 ꢁC to react for 5 h. The reactant was then washed with
chloroform and purified by FCC (MeOH/DCM: 6:1) to afford 1c (81%,
ðB ꢀ AÞ ꢂ 0:005 ꢂ 5
Rf¼0.65). H NMR (DMSO-d6, 200 MHz): ¼3.77 (t, 4H, J¼7.2 Hz,
d
X ¼
(1)
ClCH2), 2.91 (t, 4H, J¼6.3 Hz, NCH2), 2.69e2.57 (m, 8H) ppm. 13C
W
NMR (d6- DMSO, 50 MHz):
d
¼50.3, 48.2, 35.4, 34.3 ppm. MS (ESI):
4.12. Surface functionalization of SiNPs with the fluorophore
2f
m/z¼263.28 [Mþ1]þ. C8H17Cl2NS2 (261.02): C, 36.64; H, 6.53; N,
5.34. Found: C, 36.72; H, 6.63; N, 5.43.
In a round bottom flask, 250.0 mg (0.44 mmol) of SiNPs was
suspended in a solution of 25.0 mL of anhydrous toluene and
0.08 mL DIW, and sonicated for 30 min at rt. The silane 2f (0.47 g;
0.68 mmol) was hydrolyzed in 25.0 mL of anhydrous toluene and
0.12 mL DIW for 15 min at rt then added to SiNPs suspension and
sonicated again for 30 min. The reaction mixture was refluxed for
24 h without magnetic stirring. The functionalized SiNPs were
separated and washed twice with 90% toluene/DIW and 80% EtOH/
DIW using centrifugation (11,200 g for 10 min) technique. Finally,
the functionalized SiNPs were dried under vacuum at 110 ꢁC for
24 h before use.
4.8. Synthesis of 1,4,7,10-tetrathia-13-aza-cyclopentadecane
(1d)
To a solution of 1c (1 g, 3.81 mmol), ethane-1,2-dithiol (0.56 g,
3.81 mmol) and lithium hydroxide (94 mg, 3.81 mmol) in 15 mL of
absolute tetrahydrofuran and the resulting mixture was refluxed
under a nitrogen atmosphere for 3 days. The reaction mixture was
filtered and then concentrated at reduced pressure. The residue
was extracted three times with chloroform and the extract was
washed with water. The solvent was removed after drying over
anhydrous sodium sulfate. The crude product was purified by FCC
(MeOH/DCM: 1:12, Rf¼0.57) to give 1d in 53% as yield. H NMR
Supplementary data
(DMSO-d6, 200 MHz):
d
¼2.93e2.88 (m, 16H), 2.55 (t, 4H, J¼6.7 Hz,
NCH2) ppm. 13C NMR (DMSO-d6, 50 MHz):
d
¼50.8, 35.5, 34.8,
34.2 ppm. MS (ESI): m/z¼284.32 [Mþ1]þ. C10H21NS4 (283.06): C,
Supplementary data associated with this article can be found in
the online version, at http://dx.doi.org/10.1016/j.tet.2013.04.072.
42.36; H, 7.47; N, 4.94. Found: C, 42.44; H, 7.53; N, 5.12.
4.9. Fluorescence studies for metal ion detection
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