RSC Advances
Paper
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1
60 C was measured, however, the compound polymerised
L
) of the host and each guest were mixed in different ratios
immediately upon melting.
and a plot of Dd against the molar fraction of monomer
multiplied by the CIS (X ꢁ Dd) was constructed.
i
Synthesis of glibenclamide tetrabutylammonium salt
Preparation of imprinted polymers
The tetrabutylammonium salt of GLIB (GLIB-TBA) was prepared
by mixing of equimolar amounts of GLIB and TBAOH in
methanol, followed by evaporation of the solvent under reduced
Stoichiometrically imprinted and corresponding non-imprinted
polymers, PGLIB, PGLIBTBA and NP respectively, were prepared by
photochemically initiated free radical polymerisation. The
compositions of all prepared polymers are presented in Table 2.
Briey, the template and the selected functional monomer were
transferred into to a glass vial and mixed with the porogen.
Upon complete dissolution, the cross-linker was added followed
by the initiator. The resulting pre-polymerisation solutions were
degassed by ultra-sonication for 5 min, purged with argon and
then hermetically sealed. The vials were then placed in the
chamber of a UVP CX-2000 UV curing reactor (UVP, Jena, Ger-
many) and irradiated at 360 nm for 3 hours at room tempera-
ture. The resulting rigid monoliths were coarsely ground and
washed with methanol in a Soxhlet apparatus for 24 h, in order
to remove the template and any unreacted monomers. The
coarse polymer particles were further ground using a mortar
and pestle, wet-sieved with acetone, and the 25–50 mm fraction
was collected, dried and stored at room temperature. The cor-
responding non-imprinted polymers were prepared in a similar
fashion, omitting addition of the template to the pre-
polymerisation mixture.
pressure to yield GLIB-TBA as a white solid in quantitative yield.
1
H NMR (600 MHz, DMSO-d ) d 8.23 (s, br, 1H), 7.69 (dd, J ¼ 2.8,
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1
.8 Hz, 1H), 7.67–7.63 (m, 2H), 7.50 (dd, J ¼ 8.9, 2.8 Hz, 1H), 7.21
(
d, J ¼ 8.3 Hz, 2H), 7.15 (d, J ¼ 8.9 Hz, 1H), 5.54 (s, 1H), 3.80 (s,
3
2
1
1
5
2
H), 3.51 (t, J ¼ 7.2 Hz, 2H), 3.20–3.12 (m, 8H), 2.83 (t, J ¼ 7.2 Hz,
H), 1.63–1.52 (m, 8H), 1.36–1.25 (m, 8H), 0.94 (t, J ¼ 7.4 Hz,
1
3
6
2H); C NMR (151 MHz, DMSO-d ) d 163.89, 156.24, 146.79,
40.53, 131.99, 130.05, 128.08, 126.99, 125.16, 124.78, 114.64,
8.00, 56.75, 49.00, 41.07, 40.54, 35.10, 33.95, 25.96, 25.28,
3.54, 19.68, 13.96.
Synthesis of 4-vinylbenzyltrimethylammonium bis(triuoro-
methylsulfonyl) imide
4-vinylbenzyltrimethylammonium bis(triuoromethylsulfonyl)
imide (VBTANTf ) was prepared by addition of two-fold excess
2
of LiNTf2 to an aqueous solution of 4-vinylbenzyltrimethyl
ammonium chloride (VBTAC), followed by solvent extraction of
the aqueous phase with chloroform, drying of the organic layer
with MgSO
4
, and solvent evaporation under reduced pressure,
P
GLIBTBA(NTf2) was prepared from PGLIBTBA by exchange of
1
to nally yield a white solid. H NMR (600 MHz, CDCl
3
) d 7.44
dd, J ¼ 41.3, 8.2 Hz, 4H), 6.71 (dd, J ¼ 17.6, 10.9 Hz, 1H), 5.83
chloride counter anions with bis-triimide. Briey, 0.5 g of
PGLIBTBA were suspended in 10 mL of distilled water containing
.5 g of LiNTf . The suspension was stirred at room temperature
overnight and then polymer particles were ltered, washed with
(
(d, J ¼ 17.6 Hz, 1H), 5.38 (d, J ¼ 11.1 Hz, 1H), 4.41 (s, 2H), 3.08 (s,
0
2
1
3
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H); C NMR (151 MHz, CDCl ) d 139.44 (s), 134.38 (s), 131.90
3
(
5
s), 126.09 (s), 124.67 (s), 121.98–115.60 (q), 115.64 (s), 68.84 (s),
distilled water and dried under reduced pressure prior to use.
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1.78–51.50 (t); F NMR (565 MHz, CDCl
3
) d ꢀ78.94 (s).
Polymers PGLIBTBA2 and NP
previous publication. An additional control polymer,
2
were prepared as described in our
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1
P
GLIBTBA(XL), was prepared in a similar fashion to PGLIBTBA, but
H NMR titration experiments
without the addition of a functional monomer.
The solution interactions of GLIB and GLIB-TBA with VBTMA,
VBTAC and VBTANTf , as well as the complexation of GLIB with
2
Rebinding experiments
1
TBACl, were studied by H NMR titrations in DMSO-d . Thus, to
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1
Polymer affinity and capacity for each analyte were measured
using equilibrium rebinding experiments performed in aceto-
nitrile. Thus, 10 mg of each polymer were transferred in 2 mL
glass vials and incubated with 1.5 mL of analyte solution of
a 1.0 mmol L
solution of the host (GLIB or GLIB-TBA),
increasing amounts of each guest were added, until at least
a 10-fold excess was reached. The complexation-induced shi
(CIS) of several protons was followed and titration isotherms
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increasing concentrations (0.0–3.0 mmol L ) for 24 hours. The
supernatants were then analysed by HPLC using the method
described above. The amount of analyte bound to the polymer
was calculated by subtracting the amount determined aer the
rebinding experiment from the starting amount of the drug.
The results were plotted as concentration of free analyte in
were constructed. The stoichiometry of the selected monomer–
template complexes was conrmed using Job's method of
continuous variation. Hence, equimolar solutions (10.0 mmol
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1
a
Table 1 Apparent association constants (K , M ) measured by H
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NMR titration experiments in DMSO-d
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solution (mol L ) vs. the amount of analyte bound on the
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1
polymers (mmol g ) to produce binding isotherms that were
tted using the appropriate binding model.
Host
Guest
GLIB
GLIB-TBA
Solid phase extractions
0 mg of imprinted or non-imprinted polymer particles (25–50
mm) were dry packed in 3 mL SPE cartridges using 20 mm porous
5
VBTMA
VBTAC
VBTANTf
TBACl
>10
53 ꢃ 6
5
34 ꢃ 5
No binding
2
No binding
22 ꢃ 3
3452 ꢃ 230
No binding polyethylene frits. Blood serum samples were prepared by
14214 | RSC Adv., 2018, 8, 14212–14220
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