Solvent dependent colorimetric, ratiometric dual sensor for copper and fluoride ions: Real sample analysis, cytotoxicity and computational studies

Article abstract of DOI:10.1016/j.ica.2016.04.022

A novel colorimetric chemosensor based on terephthalic acid and pyridine aldehyde moiety was designed to detect Cu²⁺/F^- ions in aqueous and DMSO solutions at physiological pH conditions with the detection limit of 0.25 μM and 3 μM for Cu²⁺/F^- ions respectively. The probe was found to be highly selective to sense F^- ion rather than CH₃COO^- and H₂PO₄^- ions. Interestingly, the probe behaved as a promising receptor by detecting F^- ions even in ordinary tap water through distinct colour change. Moreover, the chemosensor showed lower cytotoxicity against AGS cancer cells and thus found to be biologically friendly. The reversibility of probe-F^- binding was investigated using HCl in UV-vis experiment. The binding mechanism of chemosensor to Cu²⁺/F^- ions was elucidated based on the UV-vis spectroscopy, NMR, ESI-Mass spectroscopy and cyclic voltammogram techniques. Furthermore, theoretical investigation was carried out using Gaussian 09 program.

Full text of DOI:10.1016/j.ica.2016.04.022

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Accepted Manuscript
Solvent dependent Colorimetric, Ratiometric dual sensor for copper and fluoride
ions: Real sample analysis, Cytotoxicity and Computational Studies
Arumugam Senthil Murugan, Enose Rajan Abel Noelson, Jamespandi Annaraj
PII:
S0020-1693(16)30188-8
http://dx.doi.org/10.1016/j.ica.2016.04.022
ICA 17006
DOI:
Reference:
Inorganica Chimica Acta
To appear in:
Received Date:
Revised Date:
Accepted Date:
29 February 2016
11 April 2016
12 April 2016
Please cite this article as: A.S. Murugan, E.R.A. Noelson, J. Annaraj, Solvent dependent Colorimetric, Ratiometric
dual sensor for copper and fluoride ions: Real sample analysis, Cytotoxicity and Computational Studies, Inorganica
Chimica Acta (2016), doi: http://dx.doi.org/10.1016/j.ica.2016.04.022
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Solvent dependent Colorimetric, Ratiometric dual sensor for copper and fluoride ions:
Real sample analysis, Cytotoxicity and Computational Studies.
Arumugam Senthil Murugan, Enose Rajan Abel Noelson and Jamespandi Annaraj*
Department of Materials Science, School of Chemistry, Madurai Kamaraj University,
Madurai-21, India.
E-mail: annaraj.chem@mkuniversity.org
Abstract
A novel colorimetric chemosensor based on terephthalic acid and pyridine aldehyde moiety
was designed to detect Cu2+/ F- ions in aqueous and DMSO solutions at physiological pH
conditions with the detection limit of 0.25 µM and 3 µM for Cu2+ / F- ions respectively. The
-
probe was found to be highly selective to sense F- ion rather than CH3COO- and H2PO4 ions.
Interestingly, the probe behaved as a promising receptor by detecting F- ions even in ordinary
tap water through distinct colour change. Moreover, the chemosensor showed lower
cytotoxicity against AGS cancer cells and thus found to be biologically friendly. The
reversibility of probe-F- binding was investigated using HCl in UV-vis experiment. The
binding mechanism of chemosensor to Cu2+/ F- ions was elucidated based on the UV-vis
spectroscopy, NMR, ESI-Mass spectroscopy and cyclic voltammogram techniques.
Furthermore, theoretical investigation was carried out using Gaussian 09 program.
Keywords: Ratiometric, Colorimetric, Dual sensor, Real sample Analysis, cytotoxicity and
Theoretical studies.
Introduction
For the past few decades researchers were mainly interested on design and synthesis of
fluorescence probes to recognize diverse of single guest species such as anions,
cations and neutral molecules [1-3]. Recently, bifunctional probes, which refer to
those based on a single host that can independently recognize two guest species with
distinct spectral responses is becoming a novel research focus [4]. Among them,
anions and cations sensing probes hold the utmost importance due to their biological
and environmental significance. As per our knowledge, only very few reports are
available on simultaneous recognition of cations and anions. Among them, a very few
accounts for probes which can detect F-/Cu2+ ions through ratiometric and colorimetric

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techniques [5]. Generally, the interaction of anions/cations with the host molecules can
be analysed by fluorometric [6-9] (or) visible colorimetric techniques [10-14]. Among
the above mentioned analytical methods, the latter is commendable in view of its
application [15]. Anions are omnipresent and play a vital role in the biological system
such as co-factors and enzyme substrates [16-19]. Among all other biologically
functional anions, F- ion is the smallest and highly electro negative atom and it can
form strong hydrogen bond with various donor atoms [20]. F- ions plays a vital role in
medicinal department such as dental health and has the potential for the treatment of
osteoporosis [21-23] also, it’s recognition and detection is allied with nerve gases,
drinking water analysis, and the refinement of uranium used in nuclear weapons
manufacture [24]. In general, F- ions are identified by Lewis acid-base interaction [25]
-
or hydrogen bonding [26]. As anions such as CH3COO- and H2PO4 have same
basicity as that of F-, they can interfere with the detection of F- ions. Hence only a very
few probes which are free from cross sensitivities towards these ions are reported in
the literature. [27-30].
Besides, transition metal ions are very paramount for the living organisms [31].
Copper is the third most essential trace element after FeIII and ZnII in biological system
[32] and it plays an important role in various biological processes such as electron
transfer, catalytic activities, neurotransmitter biosynthesis and denaturation, as well as
the functioning and maintenance of the structural stability of proteins. However
overdose of copper ion can be highly toxic [33-35], as it causes serious cellular or
organ damage and neuro degenerative diseases like Wilson disease and Alzheimer’s
disease [36-39]. Therefore, it is highly desirable to design and synthesize novel
sensors for its measurement and detection. Consequently, we have designed and
synthesized a probe based on terephthlic acid, which can colorimetrically and
ratiometrically detect F-/Cu2+ ions in DMSO and water: DMSO mixture (9:1) system.
Materials and Methods
Terephthalic acid, methanol, dimethylsulfoxide (DMSO), potassium bromide (KBr)
(for IR spectroscopy) and all metal salts such as Cd, Zn, Hg, Cu, Ni, Co, Mn (as
perchlorate salts), Fe, Al, Ba, Ca, Mg, Pb, K, Na (as chloride salt) and Ag, Cr (as
nitrate) were purchased from Merck. Hydrazine monohydrate (CDH), pyridine
aldehyde (Alfa Acer) and double distilled water were purchased and used without
further purification. All anions as tetra-n-butyl ammonium salts were purchased from
1 13
the Sigma-Aldrich. H NMR and C NMR spectra were recorded using Bruker 300

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MHz spectrometer. The chemical shifts were shown in parts per million (ppm)
downfield from tetramethylsilane (reference chemical shift is zero ppm) using residual
DMSO (internal standard). Multiplicities were reported as follows: s (singlet), d
(doublet), t (triplet), m (multiplet) and br (broadened). UV-vis absorbance spectrum
measurements were recorded using UV-8453 Agilent spectrometer in the range of
190-1100 nm at room temperature. ESI-Mass spectrum was performed in the positive
ion mode on liquid chromatography-ion trap mass spectrometer at room temperature
(LCQ Fleet, Thermo Fisher instruments limited, USA). FT-IR spectrum was recorded
in Shimadzu instrument in solid state at room temperature by embedding them in KBr
discs. The broad and sharp bands are represented as ‘br’ and‘s’ respectively.
Synthesis of the probe (BPTH)
The synthetic procedure of the probe is illustrated in the Scheme 1. Methanolic
solution (10 ml) of terephthalic acid in the presence of con.H2SO4 (10:1) was refluxed
for 6h. The reaction mixture was cooled to room temperature and evaporated under
pressure, provided a dirty white colour solid. The solid formed was extracted with
DCM for at least 3 times in order to completely remove the impurities and dried using
MgSO4. The solution was then filtered and evaporated to give milky white solid (1
mmol). Subsequently, it was re-dissolved in methanol followed by slow addition of
hydrazine monohydrate (2mmol) and allowed to reflux for 3 h. The obtained white
solid (bis-hydrazine derivative) was filtered, washed with water and dried under
vacuum. A hot-aqueous solution of bis-hydrazine derivative (1 mmol) was mixed
°
dropwise with pyridine-2-aldehyde (2 mmol) and again refluxed at 80 C for 2 h. The
probe (BPTH) was obtained as a white puffy solid which was filtered and dried in
1
vacuum. H NMR (300 MHz, DMSO-d6) δ 12.2 (s, 1H), 8.6 (d,
J
= 4.5 Hz, 1H), 8.5
(s, 1H), 8.1 (s, 1H), 8.0 (d,
J = 8.0 Hz, 1H), 7.9 (t, J = 7.1 Hz, 1H), 7.5 – 7.4 (m, 1H)
(ESI Fig. S1). 13C NMR (75 MHz, DMSO-d6) δ 163.15, 153.62, 150.00, 149.07,
137.35, 136.50, 128.37, 124.94, 120.50. (ESI Fig. S2). Mass: 373.10(M+1),
395.11(M+Na). (ESI Fig. S3). IR-Spectrum 3412, 3202, 3053, 2926, 2555, 1647,
1562, 1470, 1435, 1360, 1284, 1148, 1068, 1018, 955, 918, 868, 779, 714, 673, 621,
522, 465 cm-1 (Fig. S4).
UV-vis titration of probe with Cu2+ ions
The probe was dissolved in minimum amount of DMSO and diluted to make 10-3 M
solution using buffer (the ratio of DMSO and buffer is 1:9). 40 µL of this solution was