Full Paper
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To probe whether the drug molecules are being internal-
ized, we carried out cell imaging studies using 3-PyNAP on the
same cell line because of the fact that the naphthyl moiety of
NAP can easily been seen under laser scanning confocal
microscope (LSCM) and indeed, the drug NAP was internalized
H NMR (400 MHz, DMSO) δ 10.44 (s, 1H), 9.10 (d, J=1.6 Hz, 1H),
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.76 (dd, J=4.8, 1.4 Hz, 1H), 8.29 (d, J=7.9 Hz, 1H), 7.77 (d, J=
.8 Hz, 2H), 7.57 (dd, J=7.8, 4.9 Hz, 1H), 7.37 (t, J=7.9 Hz, 2H), 7.14
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(d, J=7.4 Hz, 1H); C NMR (100 MHz, DMSO) δ 164.09 (s), 152.07 (s),
148.62 (s), 138.78 (s), 135.44 (s), 130.62 (s), 128.69 (s), 124.03 (s),
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23.51 (s), 120.44 (s); HRMS-(MeOH): calculated for [M+H] is
(Figure S24).
199.08, found 199.0045.
Synthesis of N-phenylisonicotinamide (4-Py):
Conclusions
4-Py was synthesized following the same procedure to obtain 3-Py,
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except that in this case, isonicotinoyl chloride hydrochloride was
used instead of nicotinoyl chloride hydrochloride and dry THF
solvent was used instead of dry DCM (yield 57%).
A crystal engineering approach led us to designing a new series
of Zn(II)-coordination complexes from various NSAIDs and two
monopyridyl
monoamide
co-ligands
as
potential
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H NMR (400 MHz, DMSO) δ 10.49 (s, 1H), 8.78 (d, J=5.5 Hz, 2H),
supramolecular gelators. Out of the eight crystallographically
characterized complexes, four (50%) were able to form aqueous
metallogels. The overall 1D hydrogen boned network, including
an amide…amide synthon, appeared to have played a crucial
role in gelation. One of the gelator complexes, namely 3-
PyMEC, was found to have anticancer property against a human
breast cancer cell line (MDA-MB-231) as revealed by both MTT
and cell migration assay. Leaching experiments carried on a gel
bed of 3-PyMEC showed steady release of the drug molecule
into the bulk solvent (PBS). Cell imaging studies performed in
the same cancer cells using 3-PyNAP confirmed internalization
of the drug molecules. The results presented herein demon-
strated the merit of the crystal engineering approach in
designing metallogels for plausible biomedical applications.
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.85 (d, J=5.5 Hz, 2H), 7.76 (d, J=8.0 Hz, 2H), 7.38 (s, 2H), 7.15 (d,
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J=7.4 Hz, 1H); C NMR (100 MHz, DMSO) δ 164.10 (s), 150.28 (s),
142.04 (s), 138.56 (s), 128.77 (s), 124.33 (s), 121.61 (s), 120.62 (s).
+
HRMS-(MeOH): calculated for [M+Na] is 221.07, found 220.9224.
Synthesis of Coordination Complexes:
Co-ligand (3-Py/4-Py; 0.1 mmol) and Ligand (NSAID; 0.1 mmol)
were dissolved in 2 mL of water. Aqueous solution (2 mL) of Zn
(
NO ) (0.05 mmol) was added dropwise that resulted in white
3 2
colloidal suspension which as subjected to stirring for 30 min at rt.
Acetonitrile was added to the stirred colloidal suspension until it
produced clear a solution which was kept undisturbed at rt. for
slow evaporation. After 7–8 days, colorless, needle shaped crystals
were obtained.
Single Crystal X-ray Crystallography:
Experimental Section
After isolating a suitable single crystal, SXRD data were collected by
using Mo kα (λ=0.7107 Å) radiation on a BRUKER APEX II
diffractometer equipped with CCD area detector. Data collection
and data reduction were carried out using APEX II package
software. The structures were solved by using direct methods and
refined in routine manner. Data of 3-PyNAP and 4-PyFLU were
collected in Bruker D8VENTURE Micro focus diffractometer
equipped with PHOTON II detector (Mo kα λ=0.7107 Å). Data
collection and data reduction were carried out by using APEX3
software package. Final refinement and CIF finalization were
performed by using OLEX2 version 1.2.9. In all cases, the non-
hydrogen atoms were treated anisotropically whereas most of the
hydrogen atoms were geometrically fixed; wherever possible, the
hydrogen atoms associated with guest solvent were located and
refined. CIF files have been deposited with The Cambridge
Crystallographic Data Centre (CCDC). CCDC 1921937, 1921938,
1921939, 1921940, 1921941, 1921943, 1921944 and 1921945
contain the supplementary crystallographic data for this paper.
These data can be obtained free of charge from CCDC.
Materials and Methods
All reagents and chemicals are purchased from commercial sources
and used without further purification. FT-IR spectra were performed
on a FT-IR instrument (Perkin Elmer, FT-IR Spectrometer, Spectrom-
eter Two). X-ray powder diffraction patterns were recorded on a
Bruker AXS D8 Advance Powder (CuKa1 radiation, λ=1.5406 Å) X-
ray diffractometer. UV/Vis spectroscopic measurements were
recorded on a HewlettÀ Packard 8453 diode array spectrophotom-
eter equipped with a Peltier temperature controller. TEM photo-
graphs were taken using a JEOL instrument with 300 mesh copper
TEM grid. NMR spectra were performed using 400/500 MHz
spectrometer (Bruker Ultrasheild Plus- 400). Rheological experi-
ments were performed on MCR102 Anton Paar Modular compact
rheometer.
Synthesis of N-phenylnicotinamide (3-Py):
Nicotinoyl Chloride hydrochloride (1 g, 0.0056 mol) was dissolved in
dry DCM (100 ml) by adding dry tri-ethyl amine (1.5 ml) in a round
bottom flask (250 ml). Then aniline (0.5865 mL, 0.0056 mol) solution
in dry DCM were added drop wise under nitrogen atmosphere and
the reaction mixture were stirred for 12 h at reflux temperature
followed by evaporation to dryness. An aqueous solution (50 mL) of
sodium bicarbonate (5% in water) was added to make the
pyridinium moiety of the co-ligand 3-Py free from protonation. The
reaction product was then extracted to organic layer by washing
the aqueous layer by diethyl ether (3x30 mL) using a separating
funnel. Complete evaporation of the organic layer finally resulted in
the co-ligand 3-Py as a white solid (yield ~63%).
Powder X-ray Diffraction:
A thin film made on a glass slide by the bulk powdered sample (~
15 mg) was used to collect PXRD data. PXRD data were recorded
using Bruker AXS D8 Advanced powder diffractometer (Cukα1
radiation, λ=1.5406 Å) equipped with super speed LYNXEXE
detector with a scan speed 0.3 sec/step for scan range of 2θ (5°–
35°).
Chem Asian J. 2020, 15, 1–11
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© 2020 Wiley-VCH GmbH
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