Thiazolidine based fluorescent chemosensors for aluminum ions and their applications in biological imaging

Article abstract of DOI:10.1016/j.saa.2020.118431

Utilization of fluorescent techniques in detection of various metal ions actively pursued allow ultrasensitive and selective detections of metal ions and prevent the adverse effect of cations such as aluminum (III) ions. In this study, two novel fluoresce

Full text of DOI:10.1016/j.saa.2020.118431

Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 238 (2020) 118431
Contents lists available at ScienceDirect
Spectrochimica Acta Part A: Molecular and Biomolecular
Spectroscopy
journal homepage: www.elsevier.com/locate/saa
Thiazolidine based fluorescent chemosensors for aluminum ions and
their applications in biological imaging
a
c
a,
Duygu Aydin b, , Emel Karakilic , Serdar Karakurt , Arif Baran
⁎
⁎
a
Sakarya University, Department of Chemistry, Sakarya 54187, Turkey
Karamanoglu Mehmetbey University, Department of Chemistry, Karaman 70100, Turkey
Selcuk University, Department of Biochemistry, Konya 42031, Turkey
b
c
a r t i c l e i n f o
a b s t r a c t
Article history:
Utilization of fluorescent techniques in detection of various metal ions actively pursued allow ultrasensitive and
selective detections of metal ions and prevent the adverse effect of cations such as aluminum (III) ions. In this
study, two novel fluorescent chemosensors containing thiazole derivatives, ((E)-2-(4-hydroxy-3-(((2-
hydroxyphenyl)imino)methyl)phenyl)-3-phenyl thiazolidin-4-one) AM1 and (2,3-bis(4-hydroxy-3-((E)-((2-
hydroxyphenyl)imino) methyl) phenyl) thiazolidin-4-one) AM2, have been fabricated. The probes AM1 and
AM2 were prepared using the condensation reaction between 2-hydroxy-5-(4-oxo-3-phenyl thiazolidin-2-yl)
benzaldehyde and 2-aminophenol for the probe AM1 and 5,5′-(4-oxothiazolidine-2,3-diyl)bis(2-hydroxy benz-
aldehyde) and 2-aminophenol for the probe AM2. Afterwards, they were analyzed by various types of NMR and
FT-IR spectroscopy, ESI-MS spectra, and elemental anayzer. As a second step, each fabricated chemosensor was
able to use turn on fluorescence sensing for detecting of Al3+ ions in ACN/H2O (v/v = 50/50, 10.0 μM, pH =
7.0) solution. Clear complexes formed between the probe AM1 and Al3+ ions and also the probe AM2 and
Al3+ ions was determined by not only 1H NMR titration study but also calculated by using the Job's plot. The
limit of detection (LOD) value was found to be 0.11 μM (AM1) and 4.4 μM (AM2) for Al3+ ions. Likewise, cell im-
aging and in vitro cytotoxicity experiments of Al3+ ions in Human epithelium Lovo cells exhibited that prepared
chemosensors had low cytotoxicity and blue fluorescence when they treated with of Al3+ ions in the cellular
system.
Received 15 March 2020
Received in revised form 27 April 2020
Accepted 27 April 2020
Available online 03 May 2020
Keywords:
Thiazolidine
Fluorescence sensor
Aluminum
© 2020 Elsevier B.V. All rights reserved.
1. Introduction
trace amounts of aluminum ions in environmental monitoring and bio-
logical assays are highly demanded [[9–12]].
Al3+ ion is the maximum abundant d-block metal ions in the earth
behind iron and zinc and compounds of Al3+ have a vital role in water
purification, food additives, clinical drugs, the production of light alloys,
the paper industry, clinical therapy and so on. Aluminum (III) ions have
been widely utilized in daily life for example, in food, aluminum-based
pharmaceuticals, drinking water sources, environmental and biological
sources and kitchen utensils [1–3]. However, high concentration of alu-
minum is harmful to the environment systems and human health since
its toxicity may induce wide range of diseases, for example dialysis en-
cephalopathy, osteomalacia, Parkinson's and Alzheimer's disease breast
cancer and etc. [4–8]. The World Health Organization (WHO) has re-
ported that the maximum admissible level of weekly human intake of
Al3+ is about 3 mg/day of the body weight. Therefore, monitoring
Numerous analytical methods, atomic absorption/emission spec-
trometry and electrochemical assays and so on are generally utilized
for the detection of aluminum ions, but they address main challenges
such as high cost instrumentations, lack of selectivity, the requirement
of specific operating skills and extensive instrument [13–17]. In this
concept, recent decades have witnessed an increasing trend in the ap-
plication of fluorescent signaling for monitoring of Al (III) ions, since it
is a technique with highly sensitive and selective detection and shows
functional simplicity, high efficiency, sensitive detection, low cost,
non-destructive and so on [18,19].
Fluorescent probes based on the determination of the aluminum
ions are emerging as an area of keen interest [20]. Appropriate selection
of fluorescent probes allows sensitive and selective determination of
aluminum ions in the solutions. In this concept, anthracene, BODIPY,
fluorescein, rhodamine, resorufin, coumarin and cyanine based organic
molecules have been extensively used as fluorescent probes for the de-
termination of Al3+ in solutions [21,22]. Also, thiazolidines have been
employed in several research areas since they are associated with
⁎
Corresponding authors.
E-mail addresses: duyguaydin@kmu.edu.tr (D. Aydin), abaran@sakarya.edu.tr
(A. Baran).
https://doi.org/10.1016/j.saa.2020.118431
1386-1425/© 2020 Elsevier B.V. All rights reserved.

2
D. Aydin et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 238 (2020) 118431
several biological and antitumor activities, and utilized as antimicrobial,
anti-inflammatory and as antiviral agent. Thus, thioazolidones can be
used as a promising scaffold to develop drug analogs, or as antimicro-
bial, anti-inflammatory and antiviral agents [23–25].
(Waltham, MA, USA) and Agilent 6230 equipment (Agilent Technolo-
gies Inc., Wilmington, DE, USA), respectively.
2.2.
Synthesize
of
the
compound
2-(4-hydroxyphenyl)-3-
Herein, we report the production of two new fluorescent “turn on”
probes containing 4-thiazolidine derivative. The probes showed the ul-
trasensitive and highly selective determination of Al3+ in ACN/H2O (v/
v = 50/50, 10 μM, pH = 7.0) solution at 524 nm. Finally, the synthesized
fluorescent probes were used as a tool to identify Al3+ ions in living
cells.
phenylthiazolidin-4-one (1), 2-hydroxy-5-(4-oxo-3-phenylthiazolidin-2-
yl)benzaldehyde (1a) and 2,3-bis(4-hydroxy phenyl)thiazolidin-4-one (2)
Compounds 1 and 2 were prepared by slight modification according
to reported literature [26,27]. Procedures of compounds 1, 2, 1a and 2a
were given in the supporting information section.
2.3. Synthesis of the probe AM1
2. Experimental
2-aminophenol (0.2 g, 1.82 mmol) was added to an absolute ethanol
(10 mL) solution of 1a (0.5 g, 1.67 mmol) and the solution was refluxed
for 3 h. After this period, the mixture was cooled down. Obtained pre-
cipitate was washed with plenty of water then cold ethanol, dried in
vacuo, and then recrystallized from absolute ethanol to obtain orange
powder in % 61 yields; Mp 110–112 °C. 1H NMR (300 MHz, DMSO‑d6):
δ(ppm): 8.91 (s, 1H, -CH=N-), 7.64 (d, J = 2.1 Hz, 1H, H4″), 7.39–7.24
(m, 6H, Hx, Hx′, Hy, Hy′, Hk, H4′), 7.28 (m, 2H, Hx″′, Hy′), 6.92 (d,1H,
J = 8.0 Hz), 6.83 (dd, J = 15.8, 7.3 Hz, 1H, Hy″′, Hx″), 6.46 (bs, 1H),
3.94 (q, J = 15.8 Hz, 2H, H5). 13C NMR (75 MHz, DMSO‑d6): 196.22,
171.1, 162.0, 161.5, 151.9, 138.3, 135.0, 132.6, 131.7, 130.5, 129.5,
129.0, 127.3, 126.7, 120.3, 120.1, 119.7, 118.0, 117.2, 64.0, 33.5. FT-IR
(cm−1): 3620, 3062, 2934, 1623, 1492, 1150, 747, 693. Anal. Calc. for
2.1. General and reagents
In the study, Heidoph Laborota 4001 and Bibby rotary evaporator,
were used for removal solvent. Chemicals and solvents (Sigma-Aldrich
Co., USA) were purchased commercially suppliers. Thin layer chroma-
tography (TLC on Merck 0.2 mm silica gel 60 F254 analytical aluminum
plates) was used for proceeding reaction controls. 1H NMR, 13C NMR
and another NMR technique (COSY, HETCOR) were taken on 300 and
600 MHz for 1H NMR and 75 and 150 MHz for 13C NMR spectrometer.
IR spectra were realized on Perkin-Elmer 1600 FT-IR instrument (Perkin
Elmer, Waltham, MA, USA). Absorption and emission spectra were mea-
sured utilizing a Shimadzu (model 2600) UV spectrophotometer and
Agilent Technologies Cary Eclipse spectrophotometer, respectively. Ele-
mental (CHNS) and TOF-MS analysis were obtaied via an Perkin-Elmer
C
22H18N2O3S (390,46) (%): C, 67.68; H, 4.65; N, 7.17. Found (%): C,
67.72; H, 4.54; N, 7.25.
Scheme 1. Synthesis routes of the probe AM1 and AM2.

D. Aydin et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 238 (2020) 118431
3
Fig. 1. The fluorescence emission spectra of AM1 (a) and AM2 (b) (10 μM in ACN/H2O (v/v = 50/50) and after addition of 5.0 equiv. of different metal ions (Fe2+, Hg2+, K+, Co2+, Ni2+
Mg2+, Cd2+, Sr2+, Fe3+, Cu2+, Mn2+, Ca2+, Al3+, Zn2+, Ba2+ and Pb2+) (λex = 390 nm, slit: 5–10).
,
2.4. Synthesis of the probe AM2
utilized to prepare the stock solutions of AM1 and AM2 and then these
solutions were diluted with growth medium. The concentration of
DMSO was kept under %0.1. Lovo cells were treated with various con-
centrations of compounds ranging from 1 μM to 200 μM. The IC50 values
were determined from the reciprocal plot of normalized inhibition (%)
compound concentration (Log) by GraphPad Prism 5.0 software. For
showing the applicibility of the probes in living cells, the cells were
treated with the probe AM1 and AM2 (10.0 μM) and incubated for
30 min. To eliminate excess probes, the cells were washed with PBS
A solution of 4-oxothiazolidine 2a (0.2 g, 0,58 mmol) was solved in
absolute ethanol (20 mL) and added 2-aminophenol (0.12 g,
1.86 mmol) at rt. and the stirring was maintained in this temperature
for a while. Then the temperature was elevated to reflux and left to
stand in this temperature for 6 h. Afterwards, the precitated was filtered
off, washed with water and recrystallized from cold ethanol to give de-
sired product AM2 (0.23 g, 75%) as a tile colored solid. mp 110–112 °C.
1H NMR (600 MHz, DMSO‑d6) δ(ppm): 9.77 (s, 1H, OH), 9.75 (s, 1H,
OH), 8.91 (s, 1H, OH), 8.84 (s, 1H, OH), 7.66 (s, 1H, -CH=N), 7.56 (s,
1H, -CH=N), 7.33–7.30 (m, 4H), 7.09 (t, 2H, J = 8.0 Hz), 6.92 (d, 2H,
J = 8.0 Hz), 6.83 (d, 4H, J = 8.1 Hz), 6.35 (s, 1H, -CH=, H2), 4.02 (d,
1H, J = 16.00 Hz, -CH2-), 3.89 (d, 1H, J = 15.17 Hz, -CH2-). 13C NMR
(150 MHz, DMSO‑d6) 170.9, 161.7, 161.4, 160.9, 159.8, 151.6, 151.5,
134.92, 134.90, 132.5, 131.6, 130.4, 130.2, 129.0, 128.72, 128.66,
120.04 (3C), 119.91, 119.88, 119.74, 119.51, 117.74, 117.55, 117.0
(2C), 64.0, 33.12. FT-IR (cm−1): 3058, 2943, 2840, 2707, 1663, 1622,
1490, 1356, 1192, 1142, 745. Anal. Calc. for C29H23N3O5S (525.58) (%):
C, 66.27; H, 4.41; N, 8.00. Found (%): C, 66.17; H, 4.45; N, 7.98.
2.5. Measurement procedures
For fluorescence and UV–Vis measurements, the stock solution of
the probe AM1 and AM2 was prepared in DMSO (10 mM) and diluted
in ACN/H2O (v/v, 50/50) (10 μM). Perchlorate salts of metals (Fe2+
,
,
Hg2+, K+, Co2+, Ni2+, Mg2+, Cd2+, Sr2+, Fe3+, Cu2+, Mn2+, Al3+
Zn2+, Ba2+ and Pb2+) were utilized and solved in deionized water
(10 mM). 3 mL probe solution was added to a cuvette to assess the de-
termination of various metal ions. Corresponding volume of perchlorate
salts was added into solution of AM1 and AM2. Afterwards, the spectral
data of the solution was mesaured by UV–Vis and fluorescence spec-
troscopy after mixing for 10 min (λex = 390 nm, slit widths = 5 nm/
10 nm).
2.6. Cell culturing and cytotoxicity testing
Human epithelium Lovo cells were grown in ATCC-formulated F-
12K medium supplemented with 10% fetal bovine serum (FBS, Gibco)
at 37 °C containing 5% CO2. To explore the applicibility of sensors in
cell imaging, the cytotoxicity of the probe AM1 and AM2 on Lovo cells
was evaluated. Determination of cell viability and cytotoxicity were per-
formed with Alamar Blue assay as described previously [28]. DMSO was
Fig. 2. The fluorescence responds of (a) AM1 and (b) AM2 (10 μM) with different
concentrations of Al3+ (0.0–5.0 equiv) in ACN/H2O (v/v = 50/50, pH: 7) (λex = 390 nm).

4
D. Aydin et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 238 (2020) 118431
Fig. 3. Job's plots of (a) AM1-Al3+and (b) AM2-Al3+ complex in ACN/H2O (v/v = 50/50, pH 7).
(2 × 10 mM). Afterwards, they were treated with Al3+ (100 μM) and
reincubated for 30 min. Bio-Rad ZOE fluorescence microscope was
used to take images of the cells.
coupling constant of J3′4′ = 8.0 Hz. The Hy″′ and Hx′ protons were reso-
nated at 6.83 ppm as dublet of dublet with coupling constant, J = 15.8
and 7.3 Hz respectively (Fig. S9). Twenty-two carbon atoms observed
in 13C NMR are compatible with the synthesized structure (Fig. S10).
3. Results and discussion
In the IR spectrum, the band belongs to the group -OH at 3262 cm−1
Other striking bands belong to the group -C=O at 1664.13 cm−1
.
,
3.1. Fabrication and structural characteristics of the probes AM1 and AM2
1623.16 cm−1. The results of the analysis of theoretically calculated el-
ements, C, H, N are in agreement with the experimental results of the
same elements.
The synthetic routes of the probe AM1 and AM2 are shown in
Scheme 1. The compounds 1, 2, 1a, 2a, and the probe AM1 and AM2,
were synthesized and then the structures of prepared compounds
were analyzed by various spectroscopic methods (Figs. S1–S23).
For the characterization of the probe AM1, the resonance signals of
protons H2 and H5 in 1H NMR are shown as in compounds 1 and 2 in
supporting information. The H2 appears as singlet at 6.46 ppm and H5
appear as quartet at 3.95 ppm. At 8.91 ppm, the azide double band pro-
ton signal was resonated as singlet. The other prominent proton belongs
All hydroxyl group protons from the characterization of the struc-
ture of AM2 were resonated at 9.77 and 9.75 ppm. Then, schiff bases
protons were resonated as singlets at 8.91 and 8.84 ppm. Other promi-
nent protons of the molecule are the resonances of H2 and H5. The H2
proton was resonated as singlet at 6.35 ppm and the H5 proton was res-
onate as dublet at 4.02 ppm (J = 16.00 Hz) and at 3.89 ppm (J =
15.17 Hz) as dublet respectively (Fig. S22). 13C NMR exhibited a good in-
dication for one carbon of carbonyl group at 170.93 ppm and four hy-
droxyl bonded carbons at 161.72 ppm, 161.39 ppm, 151.57 ppm,
151.53 ppm. Also, double bond carbons, bounded to nitrogen appear
at 160.90 ppm, 159.78 ppm. Other aromatic carbons remaining reso-
nated at 136–115 ppm in the regions they deserve. The other most
to H4″ resonated at 7.64 ppm as dublet with coupling constant J4″4′
=
2.1 Hz. The Hx, Hx′, Hy, Hy′, Hk, H4′ protons were resonated as multiplet
between 7.39 and 7.24 ppm. Other protons Hx″′ and Hy′ resonate as mul-
tiplet at 7.28 ppm. The H3′ was resonated at 6.95 ppm as a dublet with
Fig. 4. Interference of other metal ions on the fluorescence intensity of Al3+ (5.0 equiv) (a) with AM1 (10.0 μM) and (b) AM2 (10.0 μM).

D. Aydin et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 238 (2020) 118431
5
Fig. 5. 1H NMR spectra of (a) AM1 and (b) AM2 in presence of various equiv. of Al3+
.
striking carbon resonance signals are that appear for the C2 and C5 car-
bons, where C2 resonance at 64.03 ppm and C5 at 33.12 ppm (Fig. S23).
In the analysis of FT-IR spectrum for probe AM2, the -OH group bands
appeared at 3058 and 2943 cm−1. The carbonyl group bands appeared
at 1663.93 cm−1 and 1621.67 cm−1. These NMR results are consistent
with the structure and the element analysis results correspond to the
structure.
constants (Ka) as determined by fluorescence titration method for
each sensors with Al3+ were calculated to be 7.7 × 103 M−1 for Al3+
AM1 and 3.1 × 1010 M−2 for Al3+/AM2 (Fig. S25a and b) [29].
/
To assign LOD of the probe AM1 and AM2, linear the emission inten-
sity plots for AM1 and AM2 with the Al3+ concentration in nanomolar
levels were determined. LOD values (LOD = 3 std./K) [30,31] of the
probe AM1 and AM2 are 0.11 μM and 4.4 μM, respectively and these
values are below the permitted limit values of 7.41 μM for aluminum
(III) ions in the World Water Organization's drinking water guidelines
(Fig. S26a and b) [4].
3.2. Fluorogenic sensing for Al3+ in ACN/H2O
Solutions of the both of the chemosensor AM1 and AM2 in ACN/H2O
(v/v = 50/50, 10 μM, pH = 7.0) solution were colorless at 524 nm and
gave negligible fluorescence emission after excitation at 390 nm due to
the PET (Photo-induced electron transfer) and C=N isomerisation
mechanisms from the imine nitrogen to the thiazolidine unit. However,
Furthermore, the UV–visible absorption bands of each sensor were
investigated in ACN/H2O (v/v = 50/50, 10 μM, pH = 7.0) solution.
The absorption bands of AM1 and AM2 (10.0 μM) were observed at
320 nm and 440 nm for AM1 and AM2 and it could easily said that
these bands associated with n–π* and π–π* transitions in sensors.
After the addition of the Al3+ ions (5.0 equiv.), the absorption bands
of AM1 and AM2 demonstrated the large spectral bathochromic shifted
showing deprotonation of the hydroxyl of the phenol unit to allow the
probes binding with Al3+. Upon cation recognition process, the λmax
of AM1 at 320 and 440 nm reduced and a novel band at 420 nm was ob-
served because the band at 440 bathochromically shifted. Also, the λmax
of AM2 shifted from 440 nm and 420 nm (Fig. S27a and b).
after the adding of various metal ions (Zn2+, K+, Hg2+, Al3+, Co2+
,
Mg2+, Sr2+, Ni2+, Cd2+, Ba2+, Mn2+, Fe2+, Cu2+, Ca2+, Fe3+ and
Pb2+) (5.0 equiv.) to AM1 and AM2 in ACN/H2O (v/v = 50/50, 10 μM,
pH = 7.0) solution, each sensing compound exhibited remarkable se-
lective and sensitive response to Al3+ ions in same apparent colors
while other metal cations cause almost no fluorescence increase (Fig. 1).
The -C=N- groups in the probe AM1 and AM2 act as electrondonors
and the formation of the stable chelation between each probe and Al3+
might be suppressed by the PET and C=N isomerisation process in the
probes and so lead strong fluorescence enhancement (Scheme 1). The
complex between AM1 and Al3+ has strong green emission with the
maximum emission wavelength (λem = 524 nm, λex = 390 nm), and
also the AM2-Al3+ showed an obvious “turn-on” response toward
Al3+ at λem = 524 nm. As a result of the additional thiazolidine and
amine substituents, the HOMO-LUMO band gaps of AM2 reduced and
also radiactive decay process was affected. These results suggested
that the complex formation between each probe (AM1 and AM2) and
Al3+ was accomplished and strong fluorescence turn on behavior at
524 nm against aluminum ions could be easily observed.
As a next step, the selectivity study of AM1 and AM2 toward Al3+ in
the presence of different metal ions was performed. The fluorescence
spectroscopy was utilized for selectivity studies and enabled us to
In order to assess the sensitivity of the fabricated probe AM1 and
AM2 against Al3+, the fluorescence intensity of the probe AM1 and
AM2 solutions were recorded in 2 min following in the presence of
Al3+ ions and the results were demonstrated in Fig. 2a and b. As a result
of the gradual addition of Al3+ (0.0–5.0 equiv) to the AM1 and AM2 so-
lutions (10.0 μM), the emission intensity for AM1 and AM2 at 524 nm
increased and remained constant after the adding of 1.0 and 2.0 equiv.
of Al3+ concentration for AM1 and AM2, respectively (Fig. 2a and b).
The Job plots demonstrated Al3+/AM1 and Al3+/AM2 to have 1:1
and 2:1 metal/ligand ratio, respectively (Fig. 3a and b). The association
Scheme 2. Proposed sensing mechanisms and binding modes of (a) AM1 and (b) AM2
with aluminum (III) ions.

6
D. Aydin et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 238 (2020) 118431
Fig. 6. The optimized configurations along with the HOMO and LUMO distributions of the probe AM1 and AM2 and the AM1-Al3+ and AM2-Al3+ complexes.
understand the possible interference from other competitive metal ions
in determination of Al3+. As shown in Fig. 4a and b, the other metal ions
induced either a negligible change or some quenching in the fluores-
cence intensity of probe AM1-Al3+ and AM2-Al3+, only addition of
Hg2+ and Cu2+ and Fe3+ induced a slightly decrease of fluorescence.
These results clearly displayed that the fabricated probes, AM1 and
AM2, have selectivity for the sensing of Al3+ ions in the presence of
even competing various cations.
In addition, pH range plays critical roles in sensors, so generally sen-
sors must function over a suitable physiological pH range to be usable
for their biological applications. The best results for the sensitivity of
AM1-Al3+ and AM2-Al3+ were obtained at pH = 7. The probe AM1
and AM2 displayed a remarkable turn on fluorescence signal at pH =
7 after adding of Al3+ ions. However, fluorescence intensities of AM1-
Al3+ and AM2-Al3+ decreased due to the competition of -OH ions
interacted with Al3+coordination at high pH values (Fig. S28).
Fig. 7. (a) Fluorescence images of Human epithelium Lovo cells: A for AM1 and D for AM2 represent bright field images of the cells treated with the probes (10.0 μM) for 30 min. Images (B
for AM1 and E for AM2) represent the fluorescence images of A for AM1 and D for AM2 in the presence of Al (III) ions for 30 min. C for AM1 and F for AM2 represent the merged images of
the bright-light field (A) and (D), and also fluorescence (B) and (E). (b) Cytotoxicity graphs of the probes AM1 and AM2. Scale bar = 100 μm, λBlue-channel-ex: 355/40 nm; λBlue-channel-em
:
433/36 nm.

D. Aydin et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 238 (2020) 118431
7
3.3. The proposed interaction mechanism for AM1-Al3+ and AM2-Al3+
CRediT authorship contribution statement
1H NMR titration was carried out to deeper understand the binding
mode of probe AM1- and AM2 with Al3+. In free AM1, imine proton sig-
nal in DMSO‑d6 was appeared at 8.91 ppm. Upon interaction with 1.0
equiv. of Al3+, two novel signals formed at 10.9 ppm and 9.8 ppm
which clearly indicated the deprotonation of hydroxyl proton by inter-
action with Al3+(Fig. 5a). In the probe AM2, hydroxyl protons of the
phenol units at 9.77 and 9.75 ppm, and also imine proton signals at
8.91 and 8.84 ppm were appeared. Both hydroxyl protons of the phenol
at 9.77 and 9.75 ppm and imine proton signals at 8.91 and 8.84 ppm
Duygu Aydin:Supervision, Investigation, Methodology, Conceptual-
ization, Formal analysis, Writing - original draft.Emel Karakilic:Investi-
gation.Serdar
Karakurt:Investigation.Arif
Baran:Supervision,
Methodology, Conceptualization, Formal analysis.
Declaration of competing interest
The authors declare that they have no known competing financial
interests or personal relationships that could have appeared to influ-
ence the work reported in this paper.
gradually decreased as a result of the increasing concentration of Al+3
,
indicating the complex formation between the oxygen, nitrogen atom
and Al3+ (Fig. 5a and b).
Acknowledgements
Based on the above results from 1H NMR titration and job's plot, the
possible complex structure of AM1-Al3+ and AM2-Al3+ has been shown
in Scheme 2.
The authors are indebted to the TÜBITAK (Scientific and Technolog-
ical Research Council of Turkey with grant number 217Z043) and the
KMU Scientific Research Project Center for their support with the pro-
ject 30-M-16 to provide the Gaussian 09W and Gauss view 5.0.8 pro-
grams. Also, authors thank Abdurrahman KARAGOZ for help with DFT
studies.
Additionally, density functional theory (DFT) was used to verify the
optimized configurations and HOMO and LUMO energy levels of the
probe AM1 and AM2 and the AM1-Al3+ and AM2-Al3+ complexes.
B3LYP and 3-21G/Lanl2dz basis set parametes were utilized to optimize
Gaussian 09 software. As shown in Fig. 6, it is clear that the HOMO and
LUMO are distributed different parts of AM1 and AM2 and the AM1-
Al3+ and AM2-Al3+. The energy gap between HOMO and LUMO orbitals
of AM1 and AM2 are 3.65 and 3.94, respectively while these gaps are
3.06 and 0.18 eV for the AM1-Al3+ and AM2-Al3+. From these calcula-
tion, it is easily said that the probe AM1 and AM2 form stable AM1-
Al3+ and AM2-Al3+ complexes as evident from the lower HOMO–
LUMO energy gaps of the complexes compared to the probe AM1 and
AM2 (Fig. 6).
Appendix A. Supplementary data
Supplementary data to this article can be found online at https://doi.
org/10.1016/j.saa.2020.118431.
References
[1] D. Maity, T. Govindaraju, Conformationally constrained (Coumarin-Triazolyl-
Bipyridyl) click fluoroionophore as a selective Al3+ sensor, Inorg. Chem. 49 (2010)
7229–7231, https://doi.org/10.1021/ic1009994.
[2] Y. Lu, S. Huang, Y. Liu, S. He, L. Zhao, X. Zeng, Highly selective and sensitive fluores-
cent turn-on chemosensor for AI3+ based on a novel photoinduced electron transfer
approach, Org. Lett. 13 (2011) 5274–5277, https://doi.org/10.1021/ol202054v.
[3] W.H. Ding, W. Cao, X.J. Zheng, D.C. Fang, W.T. Wong, L.P. Jin, A highly selective fluo-
rescent chemosensor for Al(III) ion and fluorescent species formed in the solution,
Inorg. Chem. 52 (2013) 7320–7322, https://doi.org/10.1021/ic401028u.
[4] Z. Li, C. Liu, J. Wang, S. Wang, L. Xiao, X. Jing, Spectrochimica Acta Part A: molecular
and biomolecular spectroscopy A selective diaminomaleonitrile-based dual channel
emissive probe for Al3+ and its application in living cell imaging, Spectrochim. Acta
A Mol. Biomol. Spectrosc. 212 (2019) 349–355, https://doi.org/10.1016/j.saa.2019.
01.031.
[5] J. Fu, K. Yao, Y. Chang, B. Li, L. Yang, K. Xu, Spectrochimica Acta Part A: Molecular and
Biomolecular Spectroscopy A novel colorimetric-fluorescent probe for Al3+ and the
resultant complex for F− and its applications in cell imaging, Spectrochim. Acta A
Mol. Biomol. Spectrosc. 222 (2019), 117234. https://doi.org/10.1016/j.saa.2019.
117234.
[6] J. Fu, B. Li, H. Mei, Y. Chang, K. Xu, Spectrochimica Acta Part A: Molecular and Biomo-
lecular Spectroscopy Fluorescent schiff base probes for sequential detection of Al3+
and F− and cell imaging applications, Spectrochim. Acta A Mol. Biomol. Spectrosc.
227 (2020), 117678. https://doi.org/10.1016/j.saa.2019.117678.
[7] Q. Huang, T. Wang, N. Xiao, Spectrochimica Acta Part A: Molecular and Biomolecular
Spectroscopy Selective monitoring ATP using a fluorogenic Al(III) probe complex in
aqueous medium, Spectrochim. Acta A Mol. Biomol. Spectrosc. 229 (2020) 117946,
https://doi.org/10.1016/j.saa.2019.117946.
[8] J. Tian, X. Yan, H. Yang, F. Tian, A novel turn-on Schiff-base fluorescent sensor for
aluminum(III) ions in living cells, RSC Adv. 5 (2015) 107012–107019, https://doi.
org/10.1039/c5ra17557g.
[9] K. Boonkitpatarakul, J. Wang, N. Niamnont, B. Liu, L. Mcdonald, Y. Pang, M.
Sukwattanasinitt, Novel turn-on fluorescent sensors with mega stokes shifts for
dual detection of Al3+ and Zn2+, ACS Sensors 1 (2016) 144–150, https://doi.org/
10.1021/acssensors.5b00136.
[10] B. Liu, P.F. Wang, J. Chai, X.Q. Hu, T. Gao, J. Bin Chao, T.G. Chen, B.S. Yang, Naphthol-
based fluorescent sensors for aluminium ion and application to bioimaging,
Spectrochimica Acta - Part A: Molecular and Biomolecular Spectroscopy 168
(2016) 98–103, https://doi.org/10.1016/j.saa.2016.06.002.
[11] L.Q. Yan, Y. Ma, M.F. Cui, Z.J. Qi, A novel coumarin-based fluorescence chemosensor
containing l-histidine for aluminium(III) ions in aqueous solution, Anal. Methods 7
(2015) 6133–6138, https://doi.org/10.1039/c5ay01466b.
3.4. Bio-imaging applications
As a model application, the Human epithelium Lovo cells were uti-
lized for fluorescence imaging of the AM1 and AM2 against Al3+ in
the live cells. Human epithelium Lovo cells were grown in ATCC-
formulated F-12K medium. The cells were incubated with AM1 and
AM2 and no fluorescence were obtained. After the addition of Al3+
ions to the AM1 and AM2 pretreated cell medium, it was found that
each sensor in the cell medium could achieve the Al3+ detection behav-
ior as in the solution medium (Fig. 7a). Moreover, the cell viability as-
says show that the probe AM1 and AM2 are partially toxic (Fig. 7b).
Suprisingly, it was evident that cells threated with AM2 led to lower
cell death than cells threated with AM1 (Fig. 7b). Overall, developing
AM1 and AM2 sensors could be utilized as probes to detect Al3+ in liv-
ing cells.
4. Conclusion
In summary, two novel thiazole–based fluorescent sensors (AM1
and AM2) were designed and fabricated and the sensors offer realistic
potential for the trace monitoring of Al3+ in the presence of various
metal cations in ACN/H2O (v/v = 50/50, 10.0 μM, pH = 7.0). Prepared
probes AM1 and AM2 are capable of the determination of Al3+ via
turn on fluorescence emission because of the prevention of PET. The
limits of detection were calculated as 0.11 μM for AM1 and 4.40 μM
for AM2 on the basis of 3σ/k and these values were below WHO guide-
line for drinking water. The binding mode of AM1/Al3+ and AM2/Al3+
was established by the Job method and found to be 1:1 and 1:2 ratio, re-
spectively. Also, both in vitro cytotoxicity and fluorescence microscopy
images in living cells point out the ability of these sensors for sensing
of Al3+. Overall, the thiazolidine based chemosensors for determining
of aluminum ions outlined here provides an attractive and tunable plat-
form for fluorescent detection of Al3+ in biological applications.
[12] X. Sun, Y.W. Wang, Y. Peng, A selective and ratiometric bifunctional fluorescent
probe for Al3+ ion and proton, Org. Lett. 14 (2012) 3420–3423, https://doi.org/10.
1021/ol301390g.
[13] X. Leng, W. Xu, C. Qiao, X. Jia, Y. Long, B. Yang, New rhodamine B-based chromo-
fluorogenic probes for highly selective detection of aluminium(III) ions and their
application in living cell imaging, RSC Adv. 9 (2019) 6027–6034, https://doi.org/
10.1039/c8ra09850f.

8
D. Aydin et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 238 (2020) 118431
[14] O. Alici, S. Erdemir, A cyanobiphenyl containing fluorescence “turn on” sensor for
Al3+ ion in CH3CN–water, Sensors Actuators B Chem. 208 (2015) 159–163,
https://doi.org/10.1016/j.snb.2014.11.033.
[15] S. Erdemir, M. Yuksekogul, S. Karakurt, O. Kocyigit, Dual-channel fluorescent probe
based on bisphenol A-rhodamine for Zn2+ and Hg2+ through different signaling
mechanisms and its bioimaging studies, Sensors Actuators B Chem. 241 (2017)
230–238, https://doi.org/10.1016/j.snb.2016.10.082.
and Medicinal Chemistry 20 (2012) 3378–3395, https://doi.org/10.1016/j.bmc.
2012.03.069.
[24] A.C. Tripathi, S.J. Gupta, G.N. Fatima, P.K. Sonar, A. Verma, S.K. Saraf, 4-
Thiazolidinones: the advances continue, Eur. J. Med. Chem. 72 (2014) 52–77,
https://doi.org/10.1016/j.ejmech.2013.11.017.
[25] H.M. Hosni, M.M. Abdulla, Anti-inflammatory and analgesic activities of some newly
synthesized pyridinedicarbonitrile and benzopyranopyridine derivatives, Acta
Pharma. 58 (2008) 175–186, https://doi.org/10.2478/v10007-008-0005-4.
[26] R.R. Harale, P.V. Shitre, B.R. Sathe, M.S. Shingare, Pd nanoparticles: an efficient cata-
lyst for the solvent-free synthesis of 2,3-disubstituted-4-thiazolidinones, Res. Chem.
Intermed. 42 (2016) 6695–6703, https://doi.org/10.1007/s11164-016-2490-2.
[27] M. Sala, A. Chimento, C. Saturnino, I.M. Gomez-Monterrey, S. Musella, A. Bertamino,
C. Milite, M.S. Sinicropi, A. Caruso, R. Sirianni, P. Tortorella, E. Novellino, P. Campiglia,
V. Pezzi, Synthesis and cytotoxic activity evaluation of 2,3-thiazolidin-4-one deriva-
tives on human breast cancer cell lines, Bioorganic and Medicinal Chemistry Letters
23 (2013) 4990–4995, https://doi.org/10.1016/j.bmcl.2013.06.051.
[28] S. Karakurt, Modulatory effects of rutin on the expression of cytochrome P450s and
antioxidant enzymes in human hepatoma cells, Acta Pharma. 66 (2016) 491–502,
https://doi.org/10.1515/acph-2016-0046.
[29] K. Aich, S. Goswami, S. Das, C. Das Mukhopadhyay, A new ICT and CHEF based visible
light excitable fluorescent probe easily detects in vivo Zn2+, RSC Adv. 5 (2015)
31189–31194, https://doi.org/10.1039/c5ra03353e.
[30] S. Nihan, K. Elmas, Z. Emine, A. Serol, A. Bostanci, I. Yilmaz, A novel fl uorescent
probe based on isocoumarin for Hg2+ and Fe3+ ions and its application in live-cell
imaging, Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy
224 (2020) 3–10, https://doi.org/10.1016/j.saa.2019.117402.
[31] S. Nihan, K. Elmas, I.B. Gunay, K. Koran, D. Aydin, F.N. Arslan, A.O. Gorgulu, An ultra-
sensitive and selective ‘turn off’ fluorescent sensor with simple operation for the de-
termination of trace copper(II) ions in water and various beverage samples,
Supramol. Chem. 31 (2019) 756–766, https://doi.org/10.1080/10610278.2019.
1702195.
[16] A. Sahana, A. Banerjee, S. Das, S. Lohar, D. Karak, B. Sarkar, S. Kanti Mukhopadhyay,
A.K. Mukherjee, D. Das, A naphthalene-based Al3+ selective fluorescent sensor for
living cell imaging, Org. Biomol. Chem. 9 (2011) 5523–5529, https://doi.org/10.
1039/c1ob05479a.
[17] S. Erdemir, Fluorometric dual sensing of Hg2+ and Al3+ by novel triphenylamine
appended rhodamine derivative in aqueous media, Sensors Actuators B Chem. 290
(2019) 558–564, https://doi.org/10.1016/j.snb.2019.04.037.
[18] S. Kim, J.Y. Noh, K.Y. Kim, J.H. Kim, H.K. Kang, S.W. Nam, S.H. Kim, S. Park, C. Kim, J.
Kim, Salicylimine-based fluorescent chemosensor for aluminum ions and applica-
tion to bioimaging, Inorg. Chem. 51 (2012) 3597–3602, https://doi.org/10.1021/
ic2024583.
[19] D. Aydin, A novel turn on fluorescent probe for the determination of Al3+ and Zn2+
ions and its cells applications, Talanta 210 (2020), 120615. https://doi.org/10.1016/
j.talanta.2019.120615.
[20] L. Bai, Y. Xu, G. Li, S. Tian, L. Li, F. Tao, A. Deng, S. Wang, L. Wang, A highly selective
turn-on and reversible fluorescent chemosensor for Al3+ detection based on novel
salicylidene schiff base-terminated PEG in pure aqueous solution, Polymers 11
(2019)https://doi.org/10.3390/polym11040573.
[21] M.K. Alici, Phentroimidazole based fluorescence “turn on” sensor for highly sensitive
detection of Zn2+ ions, J. Fluoresc. 30 (2020) 269–273, https://doi.org/10.1007/
s10895-020-02498-y.
[22] A. Gupta, N. Kumar, A review of mechanisms for fluorescent “turn-on” probes to de-
tect Al3+ ions, RSC Adv. 6 (2016) 106413–106434, https://doi.org/10.1039/
c6ra23682k.
[23] A.K. Jain, A. Vaidya, V. Ravichandran, S.K. Kashaw, R.K. Agrawal, Recent develop-
ments and biological activities of thiazolidinone derivatives: a review, Bioorganic