Recognition of Al3+ through the off-on mechanism as a proficient driving force for the hydrolysis of BODIPY conjugated Schiff base and its application in bio-imaging

Article abstract of DOI:10.1016/j.ica.2019.119157

Two new BODIPY azine bearing quinoline and pyrazine attached Schiff base chemosensors (R1 and R2) have been synthesized and applied for the detection of Al³⁺ in CH₃CN/H₂O medium. Intramolecular hydrogen bonding makes both the sensors rigid and helps to encapsulate Al³⁺ in the cavity. The pink colour of R1 and R2 has been changed to green fluorescent upon excess addition of Al³⁺ which is only because of the hydrolysis of imine bond to regenerate compound 8. Another nitrogen atom present in quinoline and in pyrazine moiety made R1 and R2 more efficient in sensing of Al³⁺ ion compare to R1D, R2B and R2D. Cell viability and fluorescence microscopic experiments showed that the chemosensors are cytocompatible and can be used as an effective fluorescent probe for detecting Al³⁺ ion in the living cell.

Full text of DOI:10.1016/j.ica.2019.119157

InorganicaChimicaActa498(2019)119157
Contents lists available at ScienceDirect
Inorganica Chimica Acta
journal homepage: www.elsevier.com/locate/ica
Recognition of Al3+ through the off-on mechanism as a proficient driving
force for the hydrolysis of BODIPY conjugated Schiff base and its application
in bio-imaging
Kumari Somlata Kashyapa, Ashish Kumara, Sumit Kumar Hirab, Swapan Deya,⁎
a Department of Chemistry, Indian Institute of Technology (ISM), Dhanbad 826004, Jharkhand, India
b Department of Zoology, The University of Burdwan, Burdwan, West Bengal 713104, India
A R T I C L E I N F O
A B S T R A C T
Keywords:
Chemosensor
ICT
Two new BODIPY azine bearing quinoline and pyrazine attached Schiff base chemosensors (R1 and R2) have
been synthesized and applied for the detection of Al3+ in CH3CN/H2O medium. Intramolecular hydrogen
bonding makes both the sensors rigid and helps to encapsulate Al3+ in the cavity. The pink colour of R1 and R2
has been changed to green fluorescent upon excess addition of Al3+ which is only because of the hydrolysis of
imine bond to regenerate compound 8. Another nitrogen atom present in quinoline and in pyrazine moiety made
R1 and R2 more efficient in sensing of Al3+ ion compare to R1D, R2B and R2D. Cell viability and fluorescence
microscopic experiments showed that the chemosensors are cytocompatible and can be used as an effective
fluorescent probe for detecting Al3+ ion in the living cell.
Al3+
Schiff base hydrolysis
BODIPY
1. Introduction
have been reported where naphthyridine [10], rhodamine [11],
BODIPY [12], coumarin [13], and pyrene [14] were used as fluor-
Aluminium is one of the extensively used materials in our daily life.
This lightweight metal is soft, malleable and used in a huge variety of
products for preparing cans, foils, kitchen utensils, window frames, beer
kegs and aeroplane parts etc. Aluminium (III) is also applicable in the
paper, colour, deodorants industries [1], not only that, a huge germane
in the field of biochemical reactions such as bio-technological trans-
formation [2] and enzyme-catalyzed reactions [3] have also been in-
itiated by Al3+ ion. According to the guideline of WHO, the average
human intake of aluminium is around 3.0–10.0 mg/day and weekly
dietary intake is 7.0 mg kg−1 body weight [4]. It has already been
proved that large amounts of aluminium is harmful to human health
and can help in creating many diseases like bone and joint pain, neu-
ronal disorders leading to dementia, myopathy, Alzheimer's and Par-
kinson's disease [5]. Diverse instrumental facilities to identify and
quantify metal ion have been used for a long time. Among them, gra-
phite furnace atomic absorption spectrometry and inductively coupled
plasma atomic emission spectrometry are the most important [6,7].
While the instrumental techniques are time-consuming and most ex-
pansive, in a parallel way, the synthetic fluorescent probes are now
considered as an effective technique over other methods due to its low
cost, high sensitivity and selectivity, quick response and easy sample
preparation [8,9]. Now-a-days, few novel fluorescence chemosensors
ophore for the detection of metal ions. Among these, BODIPY attached
chromophores are well suitable in sensing of ions due to their high
molar absorption coefficients, strong absorption and emission in the
visible region, high quantum yield, and photochemical stability [15].
Due to the attractive properties of BODIPY as stated earlier, we de-
signed two BODIPY bearing chemosensors (R1 and R2) and other three
(R1D, R2B and R2D) are supportive for comparative studies. The
sensors showed high selectivity toward Al3+ ion with high LOD values
and produced strong green fluorescent. The structures of all the che-
mosensors were confirmed by 1H NMR, 13C NMR, ESI-MS and FT-IR
analysis (Scheme 1 and Scheme 2).
Reagent and conditions: (i) K2CO3, TBAB (tetra butyl ammonium
bromde), dry acetone, reflux, 24 hr. (ii) Hydrazine hydrate, ethanol,
reflux, 24 hr; (iii) Dry DCM, oxalyl chloride, one drop dry DMF, 2 hr;
and (iv) Hydrazine hydrate, ethanol, reflux, 24 hr.
Reagent and conditions: (i) Dry methanol, reflux, 24 hr.
2. Experimental
2.1. Reagents and instruments
All the chemicals and reagents were purchased from Sigma Aldrich
⁎ Corresponding author.
E-mail address: swapan@iitism.ac.in (S. Dey).
https://doi.org/10.1016/j.ica.2019.119157
Received 29 June 2019; Received in revised form 6 September 2019; Accepted 10 September 2019
Availableonline11September2019
0020-1693/©2019ElsevierB.V.Allrightsreserved.

K.S. Kashyap, et al.
InorganicaChimicaActa498(2019)119157
Scheme 1. Synthesis of compound 1, 2, 3, 4, 5, 6 and 7.
Scheme 2. Synthetic procedure of R1, R1D, R2, R2B and R2D.
Experimental OD570
Control OD570
and solvents were collected from TCI and Merck and were used without
further purification. 1H NMR spectra were recorded at 400 MHz, and
500 MHz and accordingly 13C NMR spectra were obtained in125 MHz
using CDCl3 with TMS as an internal standard. The fluorescence spectra
were recorded by using a Perkin Elmer LS55 and UV–Visible spectra
were recorded by using Perkin Elmer Lambda 365. The FT-IR spectra
were recorded on a Perkin Elmer RXI FTIR spectrometer.
⎡
⎣
⎤
⎦
% Cell Viability =
× 100
2.4. Fluorescence imaging
Firstly, stock solutions of chemosensors (R1 and R2) were prepared
(9/1, v/v) in H2O/Ethanol solution. MCF-7 Cells were plated in a 48
well cell-culture plate and allowed to adhere for 48 h. Experiment to
assess the Al3+ uptake was performed in phosphate-buffered saline
(PBS) in presence of Al(NO3)3. The cells were treated with 10 µM Al
(NO3)3, dissolved in sterile PBS (pH = 7.4) and incubated at 37 °C for
60 min. The treated cells were washed with PBS to remove the re-
maining metal ions. Culture medium (0.2 mL) was added to the cell
culture, which was then treated with a 10 µM solution of chemosensor
R1 and R2 in case of Al(NO3)3. The samples were incubated at 37 °C for
30 min. The culture medium was removed, and the treated cells were
washed with PBS before observation. Fluorescent images of the cells
were obtained using EVOS® FL Cell Imaging System [17]. Similar pro-
cedures were adopted for the competitive metal ion sensing experi-
ments.
2.2. Cell culture
MCF7 (ATCC® HTB-22™) cells were grown in DMEM supplemented
with 5% CO2 and10 % FBS at 37 °C. Cells were plated in a 48 or 96 well
culture plate and allowed to adhere for 48 h before experimentation.
2.3. Cell viability assay
To determining the cytotoxicity of receptors (R1 and R2) in MCF-7
cells the methyl thiazolyltetrazolium (MTT) assay [16] was used. MCF-
7 cells were seeded in a 96-well cell-culture plate. Numerous con-
centrations (0, 5, 10, 25, 50 & 100 µM) of receptors were added to the
cells. The cells were incubated under 5% CO2 at 37 °C for 24 h. MTT
(5 mg mL−1, 10 µL) was added to each well and incubated at 37 °C
under 5% CO2 for 4 h. After then MTT solution was removed and yellow
precipitates (formazan) observed in plates which were dissolved in
200 µL of acidic isopropanol. The absorbance at 570 nm for each well
was measured by Biotek SynergyHT microplate reader. The viability of
cells was calculated according to the following equation:
2.5. Synthesis of compound 3 and compound 4
To a stirred solution of 8-hydroxyquinoline (500 mg, 3.44 mmol) in
dry acetone, potassium carbonate (1.0 g) and TBAB (1.0 g) were added.
After sometime, ethylchloroacetate (0.757 mL, 6.88 mmol) was added.
The reaction mixture was continued to reflux for 24hr. Then, it was
cooled down and concentrated under reduced pressure. After extracting
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K.S. Kashyap, et al.
InorganicaChimicaActa498(2019)119157
with ethylacetate, the organic layer was evaporating to get compound
1, which was used for the next step. Hydrazine hydrate was added to
the ethanolic solution (20 mL) of compound 1 and it was refluxed for 24
hr. Completion of the reaction was checked by TLC and then solvent
was removed under vacuum. It was extracted with ethyl acetate and
then organic part was reducing to get solid compound 3. (Yield 50%).
[18]
was kept to cool down, filter and wash with methanol until to get pure
red R1 (yield 59%).1H -NMR (500 MHz, CDCl3): δ 11.82 (s, 1H), 8.98
(d, J = 4.1 Hz, 1H), 8.79 (s, 1H), 8.44 (s, 1H), 8.28 (dd, J = 8.3, 1.4 Hz,
1H), 7.58 (dd, J = 5.8, 6.2 Hz, 3H), 6.17 (s, 1H), 5.00 (s, 2H), 2.76 (s,
3H), 2.73 (s, 3H), 2.69 (s, 3H), 2.57 (s, 3H), 2.47 (s, 3H). 13C NMR
(125 MHz, CDCl3): δ 177.55, 168.46, 165.03, 155.21, 154.13, 148.99,
143.51, 137.31, 135.84, 126.93, 122.64, 121.99, 119.99, 21.65, 20.46,
17.25, 16.82, 14.30, 14.13.LC-Ms (m/z,%): ForC26H26BF2N5O2, calcu-
lated 489.218, found: 490.0[M + H+].
Following same procedure, compound 4 has been synthesized and
taking 1-naphthol as a starting material.
1H NMR (400 MHz, CDCl3) of compound 3: δ 10.09 (s, 1H), 8.85
(dd, J = 4.2, 1.6 Hz, 1H), 8.15 (dd, J = 8.3, 1.6 Hz, 1H), 7.49 – 7.41 (m,
3H), 7.09 (dd, J = 6.3, 2.5 Hz, 1H), 4.78 (s, 2H), 3.67 (s, 2H). 13C NMR
(101 MHz, DMSO) of compound 3: δ 170.60 (s), 154.08, 149.64,
139.50, 136.94, 129.63, 127.12, 122.69, 120.76, 110.87, 66.14.
1H NMR (400 MHz, DMSO) of compound 4: δ 8.29 (s, 1H), 7.84 (s,
2H), 7.50 (s, 2H), 7.36 (d, J = 8.0 Hz, 2H), 6.89 (d, J = 7.6 Hz, 1H),
4.67 (s, 2H), 3.45 (s, 2H). 13C NMR (100 MHz, DMSO): δ 166.85,
153.85, 134.45, 127.89, 127.16, 126.49, 125.76, 125.31, 122.62,
121.01, 106.32, 67.31.
2.9. Synthesis of R2
Compound 8 (100.0 mg, 0.34 mmol) and 5 (46.96 mg, 0.34 mmol)
were taken in dry methanol (20.0 mL) and maintaining same reaction
condition as reported earlier of R1, pure R2 (yield: 56%) was obtained.
1H NMR (500 MHz, CDCl3): δ 10.54 (s, 1H), 9.53 (s, 1H), 8.84 (s, 1H),
8.59 (s, 1H), 8.46 (s, 1H), 6.18 (s, 1H), 2.79 (s, 3H), 2.76 (s, 3H), 2.72
(s, 3H), 2.58 (s, 3H), 2.48 (s, 3H).13C NMR (125 MHz, CDCl3): δ
184.97, 168.96, 145.27, 144.09, 143.89, 143.35, 124.11, 123.04,
73.11, 73.07, 72.44, 68.94, 60.32, 31.38, 31.22, 29.89, 29.08, 28.79.
2.6. Synthesis of compound 5, 6 and 7
LC-Ms (m/z,%): for C20H21BF2N6O2, calculated 410.1838, found:
411.1916 [M + H].
Pyrazine-2-carboxylic acid (100.0 mg, 0.80 mmol) was dissolved in
dry DCM (50.0 mL) in a round bottom flask under the inert atmosphere.
Then, oxalyl chloride (0.10 mL) and one drop dry DMF were added to
the reaction mixture. The stirring was prolonged for 4 hr at room
temperature (∼25 °C). After completion of reaction, the solvent was
removed by vacuum to get solid compound. The solid compound was
dissolved in 20 mL ethanol and excess amount (0.5 mL) of hydrazine
hydrate was added. After refluxing for 24 hr, it was cooled down to
room temperature and the solvent was removed. The combined residue
was workup with ethyl acetate and water, the organic part was con-
centrated under reduced pressure to get compound 5. Following same
procedure, Compound 6 and Compound 7 were synthesized following
the same procedure taking pyridine-2carboxylic acid and benzoyl
chloride as a starting material.
2.10. Synthesis of R1D, R2 B and R2D
The same procedure of R1 has been followed to synthesis R1D, R2B
and R2D and the characteristic spectral data have been presented ac-
cordingly.
1H NMR of R1D (500 MHz, CDCl3): δ9.32 (s, 1H), 8.28(s, 1H), 7.87
(d, J = 2.31H), 7.58 (s, 1H), 6.93 (s, 1H), 6.18 (s, 1H), 5.28 (s, 1H),
2.84 (s, 3H), 2.73 (s, 3H), 2.68 (s, 3H), 2.58 (s, 3H), 2.55 (s, 3H), 2.479
(s, 3H). 13C NMR (100 MHz, d6-DMSO): δ 168.86, 156.01, 154.03,
144.12, 139.41, 134.49, 127.95, 126.64, 123.054, 122.22, 120.71,
105.79, 65.70, 17.63, 17.22, 15.31, 14.71, 14.54.
1H -NMR of R2B (400 MHz, d6-DMSO): δ 11.57 (s, 1H), 8.55 (s,
1H), 7.89 (d, J = 7.4 Hz, 2H), 7.50 (s, 2H), 6.32 (s, 1H), 2.68 (s, 3H),
2.65 (s, 3H), 2.62 (s, 3H), 2.48 (s, 3H), 2.44 (s, 3H). 13C NMR
(100 MHz, d6-DMSO) : δ 163.25 (s), 156.14, 152.72, 144.11, 143.48,
138.62, 133.99, 133.16, 132.05, 128.89, 127.91, 123.27, 123.00,
79.68, 79.35, 79.02, 17.58, 17.15, 14.69, 13.83.
1H NMR (400 MHz, d6-DMSO) of compound 5:
δ 9.09 (d,
J = 1.5 Hz, 1H), 8.91 (s, 1H), 8.79 (d, J = 2.5 Hz, 1H), 8.66 (m, 1H),
4.61 (s, 2H). 13C NMR (100 MHz, d6-DMSO) of compound 5: δ
169.29, 162.01, 147.70, 143.92, 143.65.
1H NMR (400 MHz, d6-DMSO) of compound 6: δ 9.89 (s, 1H),
8.55 (ddd, J = 4.7, 1.6, 1.0 Hz, 1H), 7.94 (m, 2H), 7.51 (ddd, J = 7.4,
4.8, 1.5 Hz, 1H), 4.62 (s, 2H). 13C NMR (100 MHz, d6-DMSO) of
compound 6: δ 163.17, 150.32, 148.62, 138.00, 126.93, 122.50.
1H NMR (400 MHz, CDCl3) of compound 7: δ 8.29 (s, 1H), 7.77 –
7.71 (m, 2H), 7.46 (t, J = 6.8 Hz, 1H), 7.37 (t, J = 7.5 Hz, 2H), 4.07 (s,
2H). 13C NMR (100 MHz, CDCl3) of compound 7: δ 168.71, 132.77,
131.83, 128.63 (s), 126.96 (s).
1H -NMR of R2D (500 MHz, CDCl3): δ 10.41(s, 1H), 8.64 (s, 1H),
8.40, 8.31, 8.22 (m, 2H), 7.92 (s, 1H), 7.50 (s, 1H), 6.14 (s, 1H), 2.79 (s,
3H), 2.74 (s, 3H), 2.69 (s, 3H), 2.57 (s, 3H), 2.46 (s, 3H). 13C NMR
(100 MHz, d6-DMSO): δ 160.23, 155.86, 152.38, 150.11, 149.01,
144.98 (s), 144.07, 138.88, 133.05, 131.47, 127.41, 123.39, 122.99,
31.26, 17.58, 17.15, 14.63, 13.84.
LC-MS (m/z,%): calculated for C20H21BF2N6O2 [409.1838], found:
410.47[ M + H].
2.7. Synthesis of compound 8
3. Result and discussion
A mixture of DMF (1.50 mL) and POCl3 (1.50 mL) were stirred in
0–5 °C under nitrogen atmosphere for 10 min to form a semi so-
lidcompound and then stirring it for another 30 min at room
temperature.The solution of BODIPY (300 mg, 1.14 mmol) in 1,2 di-
chloroethane (30 mL) was addeddrop wise and heated at 50 °C for 3 hr.
The reaction mixture was cooled down and neutralised by aqueous
solution of sodium bicarbonate under ice condition. After usual
workup, compound 8 was purified by column chromatography with
20% ethyl acetate in pet ether.
3.1. Photo-physical properties
All the reported compounds were readily prepared according to the
reported procedure and the structure was assigned and confirmed un-
ambiguously by NMR and ESI-MS. With these two chemosensors (R1
and R2), the photo physical properties were examined in CH3CN/H2O
adding different metal ions such as Cs+, Ba2+, Al3+, V3+, Cr3+, Mn2+
,
Fe3+, Co2+, Ni2+, Cu2+ and Zn2+. Both the sensors complexed with
Al3+ and up to 1:1 proportion ratio accordingly, the nominal shifting of
λmax was recorded. Addition of excess Al3+ developed a strong green
colouration of compound 8 and the change of colour from pink to
yellowish green was observed under visible light (Figs. 1a, 2a). The
solution became strong green with high fluorescence under long range
UV light, upon employing of Al3+ (Figs. 1b and 2b).
2.8. Synthesis of R1
Compound 8 (100.0 mg, 0.34 mmol) and 3 (74.0 mg, 0.34 mmol)
were taken together in dry methanol (20.0 mL) under nitrogen atmo-
sphere. Then, it was refluxed for 24 hr to get precipitate. The system
The colour change properties of R1 and R2 were also monitored by
3

K.S. Kashyap, et al.
InorganicaChimicaActa498(2019)119157
Fig. 1. Colour change of R1 and upon addition of different metal ions in CH3CN/H2O (a) under visible and (b) long wavelength UV-light.
the absorption spectra in UV–Vis in CH3CN/H2O (Fig. 3a and b). Only
Al3+ ion caused the change in absorption by shifting its λmax, while
other metal ions did not show any spectral alteration (Fig. S34a and b).
In the UV–Vis spectra, both R1 (3.0 × 10−5 M) and R2 (8.0 × 10−5
M) exhibited absorption band at λmax517 nm which was due to the
presence of BODIPY moiety. Addition of Al3+ made the peak shifted to
hydrazone moiety, both the sensors exhibited weak fluorescence [20].
An emission peak of R1 was observed at λmax556 nm while it was
shifted to λmax552 nm in the presence of Al3+ with increasing intensity
(Fig. 4a). Like R1, R2 also exhibited peak maxima at λmax556 nm and
shifted to λmax552 nm upon complexation (Fig. 4b). The same experi-
ment was carried out with R1D, R2B and R2D, where no change in
photophysical properties has been recorded.
λ
max508 nm and the absorbance value was regularly decreased and got
constant at 1:1 [G/H]. Then, the absorbance was slowly increased with
continuous blue shifting of maxima upon addition of more Al3+. The
peak was stable at λmax 497 nm which is responsive for the compound
8. Accordingly, the colour of R1 and R2 were changed from pink to
yellowish green and it was observed through the naked eye (Figs. 1a
and 2a) [19]. Initially the sensor made complexed with Al3+ (λmax508)
and fit to the template of the sensor created. Upon excess guest addi-
tion, ion induced hydrolysis of imine bond was occurred and compound
8 was resulted as a yellowish green fluorescent (Fig. 3a and b).
Due to intramolecular charge transfer between BODIPY and
The limit of detection (LOD) of R1 and R2 were calculated by using
fluorescence titration spectra and obtained higher capability
[86.6 × 10−8 M and 13.7 × 10−8 M] to perceive Al3+, respectively
[21]. The binding constant (Ka) of R1 and R2 with Al3+ were obtained
5.5 × 104 M−1 and 6.6 × 104 M−1 correspondingly by linear regres-
sion analysis method (Fig. S33) [22].
3.2. Possible mode of binding
The possible binding mode of R1:Al3+ and R2:Al3+ complexes
Fig. 2. Colour change of R2 and upon addition of different metal ions in CH3CN/H2O (a) under visible and (b) long wavelength UV-light.
4

K.S. Kashyap, et al.
InorganicaChimicaActa498(2019)119157
Fig. 3. Absorption spectra of (a) R1 in CH3CN/H2O (9:1, v/v) upon addition of Al3+ and (b) R2 in CH3CN/H2O (9:1, v/v) upon addition of Al3+
.
Fig. 4. Fluorescent spectra of (a) R1 (3.0 × 10−6 M) and (b) (8.0 × 10−6 M) R2 in CH3CN/H2O (9:1, V/V) with the addition of Al3+
.
Fig. 5. Proposed mechanism for sensing of Al3+(> 1.0 equiv.).
have been clarified with the help of different spectroscopic analysis
(Fig. 5). The supporting sensors R1D, R2B and R2D were reported
herewith required to explain the actual mode of complexation as the
single co-crystals of both the sensors were unable to grown up. From 1H
NMR of R1, the imine (-HC = N-) and amide (-CO-NH) protons were
appeared at δ 8.98 ppm, and δ 11.82 ppm, respectively (Fig. S2). δ The
N atom of quinoline and ‘O’ atom of carbonyl in R1 were actively taken
part in complexation. In presence of excess Al3+ ion, the imine bond of
R1 molecule was hydrolysed and compounds 8 and 3 were regenerated.
The peak at δ 10.10 ppm was assigned for compound 8 (-CHO), whereas
δ 8.78 ppm (-CO-NH) and δ5.37 ppm (-NH2) were appeared for com-
pound 3 (Fig. S26). Nothing has been happened when we omitted the
N-atom of quinoline ring (R1D). This increased nucleophilicity of imine
functionality and created a driving force for the hydrolysis of imine
5

K.S. Kashyap, et al.
InorganicaChimicaActa498(2019)119157
only and does not produce any fluorescence signals. However, after
treatment with Al3+, a bright green fluorescence was observed in the
MCF-7 cells (Fig. 7B). Cells were exposed to Al3+ ion and after addition
of R2 a weak green fluorescent signals images were obtained (Fig. 7E)
and localized in the intracellular areas of cells. Overlaying of fluores-
cence and bright-field images (Fig. 7C, F) showed that the fluorescence
signals were localized in the intracellular areas, indicating subcellular
distribution of Al3+ besides efficient cell-membrane permeability for
R1 & R2. Specificity of R1 and R2 towards Al3+ was demonstrated by
performing similar experiments using competing ions in absence of
selective ions.
4. Conclusion
Hence, we represented a new chemistry as Al3+ induced imine bond
hydrolysis of two BODIPY attached quinoline and pyrazine chemo-
sensors (R1 and R2) in a competitive way with other metal ions and on
the spot naked eye detection of Al3+ was also reported. Both the sen-
sors are efficient to detect aluminium ion at very low concentrations.
Due to extra nitrogen atom present in quinoline as well as in pyrazine
moiety and intramolecular hydrogen bonding made R1 and R2 more
efficient in sensing of Al3+ ion. In addition to that, bio-imaging studies
of chemosensors R1 and R2 were capable of selective identification of
Al3+ ions in living cells, which exhibited a turn-on response both in vitro
and in the live cell. These chemosensors (R1 and R2) were cyto-com-
patible and can be used as a fluorescent marker for further ions sensing.
Three supporting sensors (R1D R2B and R2D) used to assign the most
appropriate mode of complexation and to propose photo physical
properties.
Fig. 6. MTT assay of MCF-7 cells treated in the presence of chemosensor’s
(0–100 µM) incubated at 37 °C for 24 h.
bond. In a similar manner, R2 was hydrolysed and produced compound
8 with an aldehydic proton’s peak at δ10.08 ppm (Fig. S27) upon excess
guest molecule. However, taking benzene ring (R2D) instead pyrazine
(R2) no more complexation and bond breaking was recorded. One extra
‘N’atom in pyrazine ring (R2) also enhanced nucleophilic attack to the
system and exhibited hydrolysis of the imine bond. It also noted that the
absence of N atom either in quinoline (R1D) or pyrazine ring (R2D) and
benzene ring (R2B) did not responsible for any photo physical changes
or chemodosimeter approaches. The formation of compound 8 of both
cases was confirmed by the mass spectra (Fig. S28 and S29).
3.3. Bio-imaging studies
Acknowledgements
The potential of BODIPY hydrazone bearing quinoline (R1) and
pyrazine (R2) attached chemosensors for sensing of Al3+ in living cells
was investigated to determine the cyto-compatibility in MTT assay for
MCF-7 (breast adenocarcinoma) cells (Fig. 6). The cell viability was
greater than 80%, at following treatment (0–100 µM) with the com-
pound (R1 and R2) for 24 h. This resulted R1 and R2 were safe and
induced low cytotoxicity even at higher concentration.
KSK is thankful to IIT (ISM), Dhanbad for providing research fel-
lowship. SD acknowledges SERB-DST, (project no. EMR/2016/002183)
and DST- FIST (project no. SR/FST/CSI-256/2013) Govt. of India, for
financial assistance.
Appendix A. Supplementary data
By using EVOS® FL Cell Imaging System Bio-imaging analysis were
performed for representing bio-distribution of the metal ion Al3+ in
living cells. MCF-7cells was incubated with chemosensors (R1 and R2)
Supplementary data to this article can be found online at https://
doi.org/10.1016/j.ica.2019.119157.
Fig. 7. Fluorescence images of MCF-7 cells treated with chemosensors (R1 and R2) and Al3+ (A-C). (Top) Bright field image; (middle) fluorescence image and
(bottom) merged image.
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K.S. Kashyap, et al.
InorganicaChimicaActa498(2019)119157
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