Visible and near-infrared sensing of fluoride by indole conjugated urea/thiourea ligands

Article abstract of DOI:10.1039/b919128c

Two thiourea and urea based indole conjugated ligands show selective color changes with fluoride along with an absorbance band at 936 nm and 904 nm respectively. The Royal Society of Chemistry 2010.

Full text of DOI:10.1039/b919128c

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Visible and near-infrared sensing of fluoride by indole conjugated
urea/thiourea ligandsw
Purnandhu Bose and Pradyut Ghosh*
Received (in Cambridge, UK) 15th September 2009, Accepted 12th February 2010
First published as an Advance Article on the web 5th March 2010
DOI: 10.1039/b919128c
Two thiourea and urea based indole conjugated ligands show
selective color changes with fluoride along with an absorbance
band at 936 nm and 904 nm respectively.
Development of chemosensors for fluoride is important due to
their roles in the health, medical, and environmental sciences.1
In the past few years, many synthetic receptors have been
Chart 1 Structures of the chemosensors.
reported for sensing of fluoride ion along with the reports
which show selective visible colour changes in presence of this
ion.2 Color changes, as a signalling event detected by the
by condensation of corresponding indole aldehydes and
1,3-diaminothiourea/1,3-diaminourea in refluxed ethanol–water
(1: 1) mixture.5 All compounds are characterized by 1H-NMR,
13C-NMR, ESI-MS and elemental analysis. Compounds 1a
and 1b are further characterized by a single crystal X-ray
study.z Receptors 1a and 1b have a set of three types of acidic
protons, (CQS/O)NH, –CHQN and indole –NH that can
bind anion and based on the basicity and equivalence of the
anion, multiple acidic protons could also be deprotonated.
The UV-Vis-NIR absorption spectra suggest that ligands 1a
and 1b can selectively detect fluoride ion colorimetrically
(Fig. 1) with a NIR signature (Fig. 2), whereas their
indole –NH alkylated analogues 1c and 1d neither show a
visible colour change (Fig. S21, ESIw) nor a NIR signature
(Fig. S22, ESIw) with the fluoride ion. Also, in the case of
monothiocarbonohydrazone 1e, no visible colour change and
NIR signal are observed with fluoride (Fig. S21 and S22, ESIw).
In the case of 1a and 1b, Fꢀ shows selective colour changes
from colourless to pink even in the presenꢀce of other anions
like Clꢀ, Brꢀ, Iꢀ, AcOꢀ, NO3ꢀ, H2PO4 (Fig. 1). Fig. 2
presents the observed changes in the UV-Vis spectrum of
receptor 1a in the binary solvent system, acetonitrile : dimethyl
formamide 9.6 : 0.4 (v/v) upon the addition of tetrabutyl-
ammonium salts of halides, acetate, nitrate, hydrogen phosphate.
In the absence of anion, an absorption maxima is seen at
342 nm. This is mainly due to the Ar–CHQN–NH conjugation.
Upon addition of excess (50 equivalents) of Fꢀ, the UV-Vis
absorption of 1a at 342 nm vanishes, whilst new peaks at 522,
572, and 936 nm appear. Similar absorption is observed in the
presence of a mixture of anions (Fꢀ, Clꢀ, Brꢀ, Iꢀ, AcOꢀ,
NO3ꢀ and H2PO4ꢀ) indicative of selective sensing of Fꢀ by 1a.
Zhao et al. have nicely demonstrated bisthiocarbono-
hydrazones as chemosensors for fluoride with maximum
240 nm red-shift with an absorption at 605 nm.5 In the
case of 1a, the maximum peak shift is observed at 936 nm
(594 nm red-shift) along with two peaks in the visible region at
522 and 572 nm. Such a peak at the NIR region would be
useful for sensing of fluoride in the system where interference
from endogenous chromophores is possible in the visible
region. Such a huge shift of 1a could be attributed to the high
naked eye, are widely accepted due to the low cost and easy
detection without the help of instruments. On the other hand,
a chemosensor with a near-infrared (NIR) optical response
could avoid interference from endogenous chromophores and
would be more useful in biological systems.3 Moreover, they
can in principle be operated with inexpensive and compact
NIR diodes, lasers or light-emitting diodes.3b Colorimetric
anion chemosensors are generally based on a receptor–
chromophore format, where urea or thiourea units, among
others (amides, pyrroles etc.), are usually used as the binding
sites. For this kind of sensor, hydrogen-bond-induced
p-electron delocalization, or NH deprotonation, are believed
to be responsible for signalling the binding event.2,4 On the
other hand, bisthiocarbonohydrazones have recently been
found to be a class of colorimetric sensors for anions.5 The
indole and related heterocycles which have relatively acidic
hydrogen atoms and have also shown as components of neutral
anion-receptor systems.6 Herein, we report two simple indole
conjugated
bisthiocarbonohydrazone/biscarbonohydrazone
systems as efficient colorimetric anion sensors that can
selectively detect fluoride by naked eye with a characteristic
absorbance bands at 936 nm and 904 nm, respectively, in
acetonitrile–dimethyl formamide 9.6 : 0.4 (v/v). To the best of
our knowledge this represents the first example of a sensor with
a huge red-shifted (B600 nm) NIR signal at more than 900 nm
in presence of fluoride.
Indole conjugated urea/thio-urea ligands 1a and 1b, and
N-alkylated analogues 1c and 1d, bisthiocarbonohydrazones/
biscarbonohydrazones (Chart 1) are synthesized in good yield
Department of Inorganic Chemistry, Indian Association for the
Cultivation of Science, 2A&2B Raja S. C. Mullick Road,
Kolkata 700 032, India. E-mail: icpg@iacs.res.in;
Fax: (+91) 33-2473-2805
w Electronic supplementary information (ESI) available: Synthesis
and characterization of 1a–e, along with crystallographic data for 1a
and 1b, 1H-NMR titration of 1a with Fꢀ, UV-Vis spectra and titration
details of 1a–e with fluoride and acetate anion. CCDC 746353 and
746354. For ESI and crystallographic data in CIF or other electronic
format see DOI: 10.1039/b919128c
ꢁc
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2962 | Chem. Commun., 2010, 46, 2962–2964

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indole –NH in this class of fluoride chemosensor, compounds
1c and 1d are synthesized where the indole –NH is replaced
by –NCH2Ph. Astonishingly, both the thiourea and urea
derivatives 1c and 1d failed to show a NIR peak (Fig. S22,
ESIw). However, the tailing absorption at visible wavelengths
are observed in both the cases, along with a decrease in
the ligand absorption peak. This suggests an inefficient
deprotonation as well as ineffective conjugation upon binding
of fluoride to the receptor. Interestingly, the absorption study
in the presence of a mixture of different anions with 1c and 1d
do not show selectivity towards fluoride. At this juncture, we
are curious to see whether indole functionalized monothio
carbonohydrazone, 1e, could sense fluoride ion with a NIR
signature. Monosubstituted asymmetric thiourea 1e shows an
absorption maximum at 324 nm and shows only a minor red
shift (34 nm) upon addition of fluoride (Fig. 22, ESIw). We
have performed UV-Vis titration of 1e with fluoride and the
calculated binding constant is 2.77, which is smaller than that
of 1a, indicative of cooperative interaction in the case of 1a.
Further, mixtures of anions show the different absorption
spectra indicative of non-selectivity of 1e towards fluoride.
This also suggests bis-indole substituted thiocabonohydrazone
is essential for selective sensing of fluoride with a NIR
signature.
Fig. 1 Colour changes observed with the addition of anions to
acetonitrile/dimethyl formamide 9.6 : 0.4 (v/v) solution of 1a and 1b.
Fig. 2 Changes in the UV-Vis-NIR absorption spectrum of 1a and 1b
(1.0 ꢂ 10ꢀ4 M) in MeCN–DMF (9.6 : 0.4 v/v) solution upon addition
of 50 equiv. of anions.
conjugation and planarity of 1a (Fig. 3) which favours maximum
distribution of the negative charge of the deprotonated receptor
in the presence of fluoride.
To understand the binding and deprotonation phenomenon
of 1a and fluoride we performed UV-Vis titration experiments
(Fig. 4). With gradual addition of standard fluoride solution to
the solution of 1a, the UV-Vis absorption at 342 nm decreases
and a new peak at 442 nm appears up to the addition of four
equivalents of fluoride. After four equivalents of fluoride, the
peak at 342 nm diminishes completely, whereas the peak at
442 nm reaches its maximum. This change could be due to the
hydrogen-bonded fluoride complex formation with 1a and
the 442 nm peak corresponds to the fluoride–1a complex. As
the amount of fluoride increases, the peak at 442 nm gradually
decreases while four new peaks at 522, 572, and 936 nm along
with a small peak at 358 nm grow simultaneously. This process
starts when the fluoride concentration is more than four
equivalents and it reaches its saturation after the addition
of Btwelve equivalents of fluoride. With the increase of
fluoride concentration, 1a starts to deprotonate and forms
the conjugate base. The simultaneous generation of four new
peaks indicates simultaneous formation of multiple deprotonated
species in the system. The apparent binding constant of
fluoride binding to 1a is calculated using the increasing
absorption data at 442 nm and considering a 1 : 1 binding
isotherm (Fig. S24, ESIw); a value of log Kapp = 3.80
(error r 10%) is determined. In the case of receptor 1b,
the apparent binding constant is calculated with a value,
log Kapp = 2.31 (error r 10%) (Fig. S26, Table S2, ESIw).
In the cases of 1c and 1d where 1 : 1 binding of fluoride with
the receptor is the only process, the apparent binding
constants are higher than the cases observed in 1a and 1b
(Fig. S27, S28 and Table S2, ESIw).
Fig. 3 shows a representative structure of this class of
ligand. The structure of bisthiocarbonohydrazone 1a clearly
shows that all atoms associated in this receptor are almost in
one plane. Deprotonation does not effect the planarity of the
system which supports the maximum delocalization of the
negative charge upon deprotonation. Similar to 1a, the structure
of biscarbonohydrazone 1b is also found to be almost planar
(Fig. S31, ESIw). Receptor 1b shows a similar NIR signature at
a relatively lower wavelength of 904 nm, along with a visible
colour change in the presence of fluoride (Fig. 2). Since the
amide proton of the urea moiety is less acidic, compound 1b is
expected to show relatively weaker binding with Fꢀ compared
to 1a which is reflected in its UV-Vis spectrum in the presence
of fluoride. Upon addition of strong bases, like tetrabutyl salts
of CNꢀ and OHꢀ, to receptors 1a and 1b, the NIR band at
928 nm along with visible colour change is observed only in the
case of 1a with OHꢀ (Fig. S23, ESIw). This indicates that
1b can selectively detect fluoride among halides, acetate,
dihydrogenphosphate, nitrate, cyanide and hydroxide in the
binary solvent system acetonitrile : dimethyl formamide
9.6 : 0.4 (v/v). 1a also shows slight yellow coloration in the
presence of acetate which is due to hydrogen bonded adduct
formation (Fig. S20, ESIw), and the calculated acetate binding
constant (Fig. S25, ESIw) is 2.79. To see the importance of the
The 1H NMR titration of sensor 1a with TBA-F shows that
upon gradual addition of standard Fꢀ solution there is no
appreciable change in the chemical shift of the aryl/imine –CH
protons, whereas disappearance of –NH protons of both
the urea and indole moieties are observed (Fig. 5).
Fig. 3 Single crystal X-ray structure of sensor 1a (gray: C; white: H;
blue: N; yellow: S and red-plane of the molecule).
ꢁc
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Chem. Commun., 2010, 46, 2962–2964 | 2963

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can selectively sense fluoride ion over other anions by a visible
colour change along with a NIR signal at more than 900 nm.
PG gratefully acknowledges the Department of Science and
Technology (DST), New Delhi, India for financial support; PB
would like to acknowledge CSIR, New Delhi, India for SRF.
X-Ray crystallography was performed at the DST-funded
National Single Crystal X-Ray Diffraction Facility at the
Department of Inorganic Chemistry, IACS.
Notes and references
z Crystal data for 1a: C19H16N6S, Mr = 360.44, orthorhombic, space
group Pbca, a = 15.3835(16), b = 11.4337(12), c = 19.997(2) A,
a = 90, b = 90, g = 901, V = 3517.3(6) A3, Z = 8, rc = 1.361 g cmꢀ3
,
m = 0.200 mmꢀ1, T = 120(2) K, 30864 reflections, 3099 independent
(Rint = 0.058), and 2647 observed reflections [I 4 2s(I)], 235 refined
parameters, R1 = 0.0361, wR2 = 0.1029, GOF = 1.037. 1b:
C19H17N6O1.5, Mr = 353.39, Monoclinic, space group C2/c, a =
32.450(3), b = 5.330(5), c = 19.800(16) A, a = 90, b = 94.84(4), g =
Fig. 4 UV-Vis absorption titration of 1a (1.0 ꢂ 10ꢀ5 M) in
MeCN–DMF (9.6 : 0.4 v/v) solution upon addition of fluoride ions.
Inset showing separated spectra from the titration plot.
901, V = 3412.0(5) A3, Z = 8, rc = 1.376 g cmꢀ3, m = 0.093 mmꢀ1
,
The disappearance of the –NH protons is observed even after
the addition of 0.3 equivalents of Fꢀ ion. This may be due
to the binding induced broadening of the –NH signals rather
than deprotonation, which is supported by the absence of a
characteristic HF2ꢀ peak at B16.0 ppm.5 After the addition of
four equivalents of Fꢀ, appreciable upfield shifts of the Hb
(imine proton) and Hh (indole –CH proton) signal are
observed, indicative of a structural change of 1a that could
influence both the imine as well as indole protons. On the
other hand, the appearance of broad HF2ꢀ signals at 16.1 ppm
(Fig. S30, ESIw) suggests deprotnation of the –NH of indole
and/or thiourea protons. The negative charge of deprotonated
1a is delocalized over the molecule due to the overall conjugation
and could be responsible for the NIR signal at greater than
900 nm along with a visible colour change in the presence of
fluoride.
T = 296(2) K, 15446 reflections, 3018 independent (Rint = 0.1776),
and 1245 observed reflections [I 4 2s(I)], 241 refined parameters,
R1 = 0.0701, wR2 = 0.1290, GOF = 1.046. Data collected on several
crystals of complex 1a, did not show diffraction beyond theta(max) =
20.15. Attempts to obtain bigger and better quality crystals were not
fruitful. CCDC 746353 and CCDC 746354 contain the supplementary
crystallographic data for 1a and 1b respectively.
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Fig. 5 1H NMR (300 MHz) spectra in DMSO-d6 of sensor 1a
(29 mM) (a); 1a in presence of Fꢀ: 0.3 equiv. (b); 0.6 equiv. (c);
0.9 equiv. (d); 1.2 equiv. (e); 1.5 equiv. (f); 2.2 equiv. (g); 3.4 equiv. (h);
4.0 equiv. (i).
In conclusion, we have synthesized two indole conjugated
bisthiocarbonohydrazones and biscarbonohydrazones which
ꢁc
This journal is The Royal Society of Chemistry 2010
2964 | Chem. Commun., 2010, 46, 2962–2964