Uracil-bearing poly(2-isopropyl-2-oxazoline): Hg(II)-selective control of its thermoresponsiveness

Article abstract of DOI:10.1039/c7cc06728c

A poly(2-isopropyl-2-oxazoline)-containing mercury ion (Hg²⁺)-responsive uracil moiety (U-PiPOx-U) was synthesized and it exhibited thermoresponsiveness in its aqueous solution. The changes in the UV-Vis absorption and thermoresponsiveness of U-PiPOx-U upon the addition of Hg²⁺ were studied. Selective sensing of Hg²⁺ was also investigated.

Full text of DOI:10.1039/c7cc06728c

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Uracil-bearing Poly(2-isopropyl-2-oxazoline): Hg(II)-Selective
Control of its Thermoresponsiveness
Received 00th January 20xx,
Accepted 00th January 20xx
Jaehyuk Nam, Yongseok Jung, and Woo-Dong Jang*
DOI: 10.1039/x0xx00000x
www.rsc.org/
A
poly(2-isopropyl-2-oxazoline)-containing mercury ion (Hg2+)- blocks. Recently, several polymer-based materials have been
responsive uracil moiety (U-PiPOx-U) was synthesized and it investigated for the specific chemicals or metal ions
exhibited thermoresponsiveness in its aqueous solution. The detection.26-28 Photoluminescence or spectroscopic changes of
changes in the UV-Vis absorption and thermoresponsiveness of U- the polymeric materials have been used for the detection of
PiPOx-U upon addition of Hg2+ were studied. Selective sensing of specific chemicals or metal ions. To the best of our knowledge,
Hg2+ was also investigated.
chemoselective phase transition of thermoresponsive
polymers have not been reported yet. In this study, we
Polymers that change their properties under various external
stimuli such as the changes in temperature, pH, light, magnetic
field, electric field, and chemicals are known as stimuli-
responsive polymers and have been widely utilized in recent
years to design various functional materials.1-7 Among the
various stimuli-responsive polymers, thermoresponsive
polymers have several merits for applications as catalytic
supports, sensors, separation media, and biomedical device
prepared
a chemosensitive PiPOx by introducing uracil
moieties to both the initiation and termination ends, which
show a change in the thermal transition temperature in a
chemoselective manner to the mercuric ion (Hg2+).
O
O
O
O
CH2O
Et3N
NaN3
DMF
HN
HN
OH
HN
O
Cl
HN
N3
HCl 35%
H2O
O
N
H
O
N
H
N
H
O
N
H
fabrication
materials.8-11
Poly(2-isopropyl-2-oxazoline)s
U
U-OH
U-Cl
U-N3
(PiPOxs) are one of the representative thermoresponsive
O
N
polymers that show the hydrophilic-hydrophobic thermal
transition in aqueous media at their lower critical solution
temperature (LCST).12 Below the LCST, PiPOxs show high
solubility in aqueous solvents, but they become insoluble
above the LCST. Because the LCST of PiPOxs generally appears
NH
N
N
n
OTs
O
MeCN
Prop-PiPOx-Prop
near the human body temperature, PiPOx
extensively investigated for biomedical application.13-15 PiPOx
are obtained by living cationic ring opening polymerization of
s have been
O
O
s
HN
NH
HN
N3
N
N
N
17
2-isopropyl-2-oxazoline.16,
Owing to the characteristics of
N
O
N
O
O
N
H
N
n
O
HN
O
N
N
living polymerization, various functional groups can be easily
CuSO4, Na ascorbate, THF/H2
O
NH
n = ~35
introduced to both the initiation and termination ends of
19
Through the modification of end-group
PiPOxs.18,
U-PiPOx-U
Scheme 1 Synthesis of U-PiPOx-U.
functionalities, it is possible to design various types of
functional stimuli-responsive polymers.20-22 In our previous
research, we have prepared propargyl- or azide-bearing
PiPOxs to conjugate with various functional moieties. For
example, we have prepared several dual stimuli-responsive
PiPOxs by introducing pH-23 or photo-responsive24, 25 building
Synthesis of uracil-bearing PiPOx (U-PiPOx-U) is summarized
in Scheme 1. At first, formaldehyde was reacted with uracil to
obtain hydroxymethyluracil (U-OH), which was converted to
chloromethyluracil (U-Cl) by 35% HCl treatment. Subsequently,
NaN3 was added to U-Cl to obtain azidomethyluracil (U-N3).
α,ω-Propargyl-bearing PiPOx (Prop-PiPOx-Prop) was prepared
by the cationic ring opening polymerization of 2-isopropyl-2-
oxazoline using propargyl p-toluenesulfonate and N-
methylpropargyl amine as an initiator and the termination
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agent of polymerization, respectively. The ratio of initiator to absorption change was not observed when Hg2+ was added to
monomer was adjusted to 1:35. The number average PiPOx, i.e., without the uracil group. This indicated that the
molecular weight of the synthesized Prop-PiPOx-Prop was binding of Hg2+ takes place at the uracil moieties.
estimated to be 4.4 kDa on the basis of 1H NMR analysis.
Finally, the propargyl end groups of Prop-PiPOx-Prop were Hg2+ was titrated against an aqueous solution of uracil (100
reacted with U-N3 via Cu(I)-catalysed click reaction to obtain U- M) (Fig. 2b). It was found that the absorption of uracil
PiPOx-U
In order to confirm the binding of Hg2+ to the uracil moiety,
µ
.
showed a gradual bathochromic shift as the amount of Hg2+
increased, with a clear isosbestic point at 258.5 nm. From the
continuous variation method (Job’s plot), 1:1 binding of Hg2+ to
uracil was determined (Fig. 2c). Furthermore, the binding
constant of Hg2+ to uracil was estimated to be 1.42 × 104 M–1
by nonlinear curve fitting method, using commercially
available Hypspec software. The temperature dependent
transmittance change of U-PiPOx-U at 800 nm was recorded at
an increasing temperature rate of 2 °C min–1. Similar to typical
thermoresponsive polymers, the thermal transition
temperature was found to decrease as the concentration of U-
PiPOx-U increased.
Fig. 1 Characterization of Prop-PiPOx-Prop and U-PiPOx-U. a) 1H NMR spectra of Prop-
PiPOx-Prop (top), U-PiPOx-U (bottom) in CDCl3 and b) FT-IR spectra of U-N3 (black),
Prop-PiPOx-Prop (red), U-PiPOx-U (blue).
The synthesis of U-PiPOx-U from Prop-PiPOx-Prop was
confirmed by 1H, 13C NMR, and FT-IR measurements. The 1H
NMR spectrum of Prop-PiPOx-Prop showed a proton signal at
4.12 ppm corresponding to the methylene group at the
initiation end, which disappeared after click reaction with U-N3
After the click reaction, proton signals originating from uracil
and triazole groups could be observed (Fig. 1a). The 13C NMR
spectra also showed remarkable changes in the signals of the
end functional groups. Prop-PiPOx-Prop showed a peak at
73.66 ppm, which can be assigned to the acetylenic proton.
After the click reaction, U-PiPOx-U showed new peaks of the
uracil moiety at 164.03, 151.27, and 107.75 ppm (Fig. S5 and
.
S6). Figure 1b shows the FT-IR spectra of U-PiPOx-U, Prop-
PiPOx-Prop, and U-N3, respectively. The FT-IR spectrum of U-
PiPOx-U shows an intense carbonyl absorption at 1720 cm–1
owing to the existence of uracil moieties.
It is widely known that nucleobases have a strong binding
affinity to the mercuric ion (Hg2+).29 Therefore, we tested the
influence of various metal ions on U-PiPOx-U. First, we added
0.5 equivalents of various metal ions to 0.2 g L–1 of U-PiPOx-U
Fig. 2 a) UV-Vis absorption spectral changes of U-PiPOx-U aqueous solution (0.2 g L-1
upon addition of 0.5 eq. Hg2+ (red line) and Ag+, Al3+, Au+, Ba2+, Ca2+, Cd2+, Co2+, Cr3+
)
,
(Fig. 2a). It was found that U-PiPOx-U showed a change in its Cu2+, Fe2+, Fe3+, K+, Li+, Mg2+, Mn2+, Na+, Ni2+, Pb2+, Pt2+, Rh2+, Ru3+, Zn2+ (black lines), b)
absorption in a selective response to Hg2+ ions among the
UV-Vis absorption spectral changes of uracil aqueous solution (100 uM) upon addition
of 0.0 ~ 3.0 eq. Hg2+ (inset : binding isotherm monitored at 258 nm) and c) job’s plot of
different metal ions that were tested. On the other hand, the
uracil with Hg2+
.
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transmittance reaches 60% in the transmittance versus
temperature curves. At concentrations above 0.50 eq. of Hg2+,
no further changes in Tc were observed, indicating that the
additional Hg2+ did not influence the change in hydrophilicity
of the end groups (Fig. S10). Figure 4a shows the Hg2+
concentration-dependent changes in Tc. The Tc of U-PiPOx-U
without Hg2+ was 58.1 °C, which gradually decreased to 37.8 °C
as the concentration of Hg2+ increased. Based on this result, it
is possible to control the hydrophilicity and hydrophobicity
balance of U-PiPOx-U at a specific temperature using Hg2+. As
shown in Fig. 4b, the transparent solution of U-PiPOx-U at
50 °C became turbid upon addition of 0.5 eq. of Hg2+
Furthermore, a 100
M concentration of Hg2+ can be detected
.
µ
by turbidity measurements. As the Tc can be varied by the
molecular weight and concentration of PiPOx, it is possible to
tune the hydrophobic-hydrophilic balance of PiPOx for more
practical applications.
Fig. 3 Changes in the absorption and transmittance of U-PiPOx-U aqueous solution (0.8
g L–1) upon addition of Hg2+. (a) UV-Vis absorption spectral change upon addition of
Hg2+ (0.0–2.0 eq.) and (b) temperature dependent transmittance change upon addition
of Hg2+ (0.00–0.50 eq.).
Because clear thermal transition could be confirmed above
a concentration of 0.8 g L–1, we performed all experiments
with this concentration (Fig. S7). As mentioned before, the
absorption of U-PiPOx-U showed bathochromic shift upon the
addition of Hg2+ (Fig. 3a). Since it was possible to confirm the
selective binding of Hg2+ to the uracil moiety,
thermoresponsiveness of U-PiPOx-U was also tested in the
presence of Hg2+. Figure 3b shows the temperature dependent
transmittance changes of U-PiPOx-U at 800 nm with different
concentrations of Hg2+. Very interestingly, the thermal
transition temperature of U-PiPOx-U gradually decreased on
increasing the concentration of Hg2+. Generally, the thermal
transition temperature of thermoresponsive polymers
decreases with increasing hydrophobicity. Therefore, the
reduced thermal transition temperature of U-PiPOx-U
indicates that the binding of Hg2+ to U-PiPOx-U reduced the
hydrophilicity of the end functional uracil groups. Furthermore,
the addition of various metal ions to U-PiPOx-U and Hg2+ to
Fig. 4 a) Change of thermal transition temperature of U-PiPOx-U aqueous solution (0.8
g L–1) upon addition of 0.00–0.50 eq. of Hg2+ and b) Change in turbidity of the aqueous
solution of U-PiPOx-U (0.8 g L–1) at 50 °C by addition of 0.5 eq. of Hg2+
.
In conclusion, we have designed a dual mode stimuli-
responsive polymer which shows Hg2+-dependent thermal
transition changes. The thermal transition temperature of U-
PiPOx-U in its aqueous solution was gradually decreased by
the addition of Hg2+. Moreover, the binding of Hg2+ to the
terminal uracil moiety took place in a very selective and
sensitive manner. At a specific temperature, the transparent
another PiPOx (Me-PiPOx-N3) did not result in any changes in
thermoresponsiveness (Fig. S8, S9 and S11). We measured
Hg2+-dependent thermoresponsiveness of Me-PiPOx-U. The
change of thermal transition behavior of Me-PiPOx-U was
relatively smaller than that of U-PiPOx-U (Fig. S12).
U-PiPOx-U solution became turbid upon the addition of Hg2+
.
This unique property can be used for the detection of specific
ions in aqueous solutions.
This work was supported by the Mid-Career Researcher
Program (2014R1A2A1A10051083) funded by the National
Research Foundation (NRF) of Korea.
The cloud point temperature (Tc) decreased by about 20 °C
when the concentration of Hg2+ reached 0.50 eq. Here, Tc has
been considered as the temperature at which the
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Conflicts of interest
There are no conflicts to declare.
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