polymers
Article
pH- and Metal Ion- Sensitive Hydrogels based on
N-[2-(dimethylaminoethyl)acrylamide]
Leena Nebhani 1, *, Veena Choudhary 1 , Hans-Jürgen P. Adler 2 and Dirk Kuckling 3, *
1
2
3
*
Centre for Polymer Science and Engineering, Indian Institute of Technology, Hauz Khas,
New Delhi 110016, India; [email protected]
Institute for Macromolecular Chemistry and Textile Chemistry, Dresden University of Technology,
D-01062 Dresden, Germany; [email protected]
Chemistry Department, University of Paderborn, Warburger Str. 100, D-33098 Paderborn, Germany
Correspondence: [email protected] (L.N.); [email protected] (D.K.);
Tel.: +91-11-2659-6691 (L.N.); +49-5251-602-171 (D.K.)
Academic Editors: André Laschewsky and Wei Min Huang
Received: 24 February 2016; Accepted: 6 June 2016; Published: 15 June 2016
Abstract: Smart hydrogels are promising materials for actuators and sensors, as they can respond
to small changes in their environment with a large property change. Hydrogels can respond to a
variety of stimuli, for example temperature, pH, metal ions, etc. In this article, the synthesis and
characterization of polyampholyte hydrogels based on open chain ligands showing pH and metal ion
sensitivity are described. Copolymer and terpolymer gels using different mixtures of monomers i.e.,
N-[2-(dimethylaminoethyl)acrylamide] (DMAEAAm), N,N-dimethylacrylamide (DMAAm), acrylic
acid (AA) and 2-acrylamido-2-methyl-1-propanesulphonic acid (AMPS), have been synthesized.
The effect of copolymer composition, i.e., the ratio and amount of ionic monomers and the degree of
crosslinking on the swelling characteristics, was evaluated as a function of pH. On this basis, metal
ion sensitivity measurements were performed at selected pH values. The metal ion sensitivity was
measured by varying the concentration of Cu2+ , Zn2+ and Ag+ ions under acidic pH conditions.
Keywords:
smart
hydrogels;
pH
sensitive;
N-[2-(dimethylaminoethyl)acrylamide]; photopolymerization
metal
ion
sensitive;
1. Introduction
Microsystems based on hydrogels are widely used as sensors and actuators [1–4].
pH-responsive hydrogels [5–9] can be used, for example, in micromechanical cantilevers [10],
microvalves [11] and microfluidic devices [12]. Hydrogels can undergo phase transitions due to various
stimuli, for example pH, temperature, metal ions, etc. [13–15]. Phase transitions due to temperature [16]
and pH [17,18] are widely reported; however, a limited number of studies have been carried out on
phase transition due to metal ions. The phase transition in hydrogels due to metal ions can make
hydrogels very important materials for various environmental and clinical applications. There is a
great need for sensors based on hydrogels that can detect metal ions in aqueous solutions [19,20].
In order to make hydrogels sensitive to metal ions, it is necessary to attach groups or ligands onto
the hydrogel network, which can selectively bind with metal ions. The approach, which had been
earlier used for the preparation of metal ion-sensitive hydrogels, incorporates crown ether [21] or
other cyclic ligands into the hydrogel network [22]. The crown ether selectively binds to the metal
ions. This binding of metal ions brings free charges into the gel network, which consequently causes
hydration and, thus, swelling. Sensors of this kind have been reported for the detection of Na+ [23],
Pb2+ [24,25], Ba2+ [25] and K+ [23,25]. However, for these cyclic ligands to be incorporated as a pendant
group into sensitive polymers, they have to be functionalized first. This functionalization of the cyclic
Polymers 2016, 8, 233; doi:10.3390/polym8060233
www.mdpi.com/journal/polymers
Polymers 2016, 8, 233
2 of 16
ligand is a multi-step process involving various steps of protection and deprotection. Another limiting
factor of cyclic ligands is their cost. These cyclic ligands are mostly studied with temperature-sensitive
polymers and, therefore, have a limited temperature range, in which the sensitivity toward the metal
ions can be controlled.
In this work, the synthesis and characterization of smart hydrogels based on N-[2(dimethylaminoethyl)acrylamide] (DMAEAAm) possessing pH and metal ion sensitivity is reported.
The approach used in this work makes use of open chain ligands in combination with a hydrophilic
monomer N,N-dimethylacrylamide (DMAAm) to maintain swellability over a wide range of pH.
The monomer selected for the study is N-[2-(dimethylaminoethyl)acrylamide] (DMAEAAm) in
which dimethylamino groups are the potential sites that are ionizable, as well as being able to
have interaction with metal ions. Other ionizable monomers, for example, acrylic acid (AA) and
2-acrylamido-2-methyl-1-propanesulphonic acid (AMPS), were also used to modulate the swelling
properties of the resulting hydrogels by competing ionic interactions. Depending on the monomer
combination used, three different systems were prepared.
System I A two-component system consisting of N-[2-(dimethylaminoethyl)acrylamide]
(DMAEAAm) and N,N-dimethylacrylamide (DMAAm).
System II A three-component system consisting of N-[2-(dimethylaminoethyl) acrylamide]
(DMAEAAm), N,N-dimethylacrylamide (DMAAm) and acrylic acid (AA).
System III A three-component system consisting of N-[2-(dimethylaminoethyl) acrylamide]
(DMAEAAm), N,N-dimethylacrylamide (DMAAm) and 2-acrylamido-2-methyl-1-propane sulfonic
acid (AMPS).
In all three systems used for the preparation of hydrogels, N,N’-methylenebis(acrylamide) (BIS)
and Irgacure-2959 (1-[4-(2-hydroxyethoxy)-phenyl]-2-hydroxy-2-methyl-1-propane-1-one) were used
as a crosslinking agent and a photo initiator, respectively.
2. Materials and Methods
2,6-Di-tert-butyl-4-methyl phenol, 2-acrylamido-2-methyl-1-propanesulphonic acid [AMPS]
(Aldrich), 2-hydroxy-1-[4-(2-hydroxyethoxy)phenyl]-2-methyl-1-propanone [Irgacure 2959] (Aldrich),
acryloyl chloride (Fluka, St. Louis, MO, USA), 0.2 N sodium hydroxide (Aldrich, St. Louis,
MO, USA), anhydrous sodium carbonate, anhydrous sodium sulfate, copper slfate anhydrous
(Merck, Darmstadt, Germany), N,N-dimethylethylenediamine (Fluka), zinc sulfate hepta hydrate,
silver nitrate, silica gel, ethyl acetate, methanol and triethylamine were used as received.
Phosphate-buffered saline was prepared by dissolving one tablet in 200 mL double-distilled water
providing a pH of 7.5. Dichloromethane was distilled over CaCl2 . Acrylic acid (AA) (Fluka)
and N,N-dimethylacrylamide (DMAAm) (Fluka) were distilled under vacuum and stored at a
low temperature. N-[2-(Dimethylaminoethyl)acrylamide] (DMAEAAm) monomer was synthesized
according to the procedure discussed below [26].
In a three-necked flask equipped with a condenser, a thermometer, an addition funnel and a stirrer
are placed dichloromethane (100 mL), N,N-dimethylethylenediamine (0.1 mol), anhydrous sodium
carbonate (0.1 mol) and 2,4-di-tert-butyl-4-methyl phenol (0.2% with respect to acryloyl chloride)
and then cooled to 0–5 ˝ C. Acryloyl chloride (0.1 mol) was slowly dropped to the mixture under
nitrogen. After the addition of acryloyl chloride, the reaction mixture was allowed to warm up to room
temperature and stirred for 4 h. The resulting solution was centrifuged to remove sodium carbonate,
dried with sodium sulfate and evaporated. The product was purified by column chromatography
eluting with ethyl acetate:methanol (3:1) (v/v) gradually increasing to 1:1 under the pressure of nitrogen
to give a light yellowish oil. TLC of the product was checked in methanol:triethylamine (20:1). The Rf
value of the product was found to be 0.58. The product was characterized by 1 H-NMR and 13 C-NMR.
The crude yield was 10.0 g (70%), and the yield after flash chromatography was 9.0 g (63%).
1 H NMR (CDCl ) δ (ppm) = 6.6 (broad singlet, NH), 5.5–6.2 (multiplet, 3H, CH =CH), 3.35 (quartet
3
2
like multiplet, 2H, NHCH2 ), 2.4 (triplet, 2H, CH2 N), 2.2 (singlet, 6H, N(CH3 )2 ).
Polymers 2016, 8, 233
3 of 16
Polymers 2016, 8, 233
13 C NMR (CDCl ) δ (ppm)
13C NMR (CDCl3)3 δ (ppm) =
Polymers
8, 233
44.84 (CH2016,
3 ), 36.56 (CH2 N).
= 165.45 (C=O), 130.74 (=CH), 125.73 (CH2 =), 57.51 (NHCH2 ),
165.45 (C=O), 130.74 (=CH), 125.73 (CH2=), 57.51
(NHCH2), 44.84
(CH3), 36.56 (CH2N).
The
reaction scheme for the synthesis of N-[2-(dimethylaminoethyl)acrylamide] (DMAEAAm) is
13C NMR (CDCl3) δ (ppm) = 165.45 (C=O), 130.74 (=CH), 125.73 (CH2=), 57.51 (NHCH2), 44.84
The
reaction scheme for the synthesis of N-[2-(dimethylaminoethyl)acrylamide] (DMAEAAm)
shown in Scheme 1.
(CH
3
),
36.56
(CH2N).
is shown in Scheme
1.
The reaction scheme for the synthesis of N-[2-(dimethylaminoethyl)acrylamide] (DMAEAAm)
is shown in Scheme 1.
Scheme 1. Synthesis of monomer N-[2-(dimethylaminoethyl)acrylamide].
Scheme 1. Synthesis of monomer N-[2-(dimethylaminoethyl)acrylamide].
2.1. Synthesis
of Hydrogels
Hydrogels
2.1.
Synthesis of
2.1.A
of Hydrogels
ASynthesis
set-up consisting
consisting
of aa UV
UV lamp
lamp (100
(100 W
W Hg
Hg lamp,
lamp, Osram,
Osram, Munich,
Munich, Germany)
Germany) equipped
equipped with
with
set-up
of
an
optical
lens,
a
mirror
and
connected
to
a
water
circulating
thermostat
(HAAKE)
operating
at aa
an optical
lens, consisting
a mirror and
to aW
water
circulating
(HAAKE)
operating
at
A set-up
of aconnected
UV lamp (100
Hg lamp,
Osram,thermostat
Munich, Germany)
equipped
with
˝
temperature
of 7.6
7.6a °C
wasand
used
for the
the photo
photo
polymerization
process. No
No(HAAKE)
special filters
filters
wereatused
used
temperature
of
C was
used
for
polymerization
special
were
an optical lens,
mirror
connected
to a water
circulating process.
thermostat
operating
a
during
photo
polymerization.
Glass
slides
separated
by
a
spacer
(thickness
of
500
µm)
were
used
as
during
photo polymerization.
Glass
slides
separated
by a spacer
(thickness
of 500
µm)
were
used
temperature
of 7.6 °C was used
for the
photo
polymerization
process.
No special
filters
were
used
theduring
reactor
for for
polymerization,
allowing
UVseparated
radiation
above
310 (thickness
nm
pass
through
The
UV
photo
polymerization.
Glass
slides
by
a spacer
500 through
µm)it.were
asUV
as
the
reactor
polymerization,
allowing
UV
radiation
above
310to
nm
toofpass
it.used
Thelamp
provides
theforradiation
in the
range
from
265–360
nm.
Hydrogels
by
photo
the reactor
polymerization,
UVfrom
radiation
above
310
nm to passwere
through
it. The UV
lamp
provides
the
radiation
inallowing
the
range
265–360
nm.
Hydrogels
wereprepared
prepared
bylamp
photo
polymerization
of
the specific
specific
composition
of 265–360
monomer
solutions
at room
room
temperature.
of the
the
provides the of
radiation
in the
range from
nm.
Hydrogels
weretemperature.
prepared byAll
photo
polymerization
the
composition
of
monomer
solutions
at
All
of
polymerization
of the specific
composition
monomer
solutions Three
at room
temperature.
All of the
solutions
were degassed
degassed
with argon
argon
prior to
toofthe
the
polymerization.
Three
different
copolymerization
solutions
were
with
prior
polymerization.
different
copolymerization
solutions
were
degassed
with
argon
prior
to
the
polymerization.
Three
different
copolymerization
systems
were
prepared
with
the
aim
to
investigate
systematically
the
effect
of
crosslinking
density
systems were prepared with the aim to investigate systematically the effect of crosslinking density
systems
were
prepared
with
the
aim
to
investigate
systematically
the
effect
of
crosslinking
density
and
the
concentration
of
ionic
monomers.
For
photo
patterning,
the
glass
reactor
was
filled
with
the
and the concentration of ionic monomers. For photo patterning, the glass reactor was filled with the
and
the
concentration
of
ionic
monomers.
For
photo
patterning,
the
glass
reactor
was
filled
with
the
argon purged
purged solution
solution of
of the
the monomers,
monomers, crosslinking
crosslinking agent,
agent, photo
photo initiator
initiator and
and water.
water. The
The reactor
reactor
argon
argon
purged
solution
ofplate
the monomers,
crosslinking
agent,
photo initiator
and water.
The reactor
was
covered
with
a
glass
followed
by
a
mask
having
a
pattern
of
a
circular
disc
(diameter
of 2
was covered with a glass plate followed by a mask having a pattern of a circular disc (diameter
was
covered
with
a
glass
plate
followed
by
a
mask
having
a
pattern
of
a
circular
disc
(diameter
of
mm).
The photo
polymerization
time time
required
to produce
a pattern
varies
fromfrom
20–50
s fors 2the
of
2 mm).
The photo
polymerization
required
to produce
a pattern
varies
20–50
for
mm).
The
photo
polymerization
time
required
to
produce
a
pattern
varies
from
20–50
s
for
the
different
systems.
After
irradiating
for
the
desired
time
intervals,
the
patterned
hydrogels
were
the different systems. After irradiating for the desired time intervals, the patterned hydrogels were
different systems. After irradiating for the desired time intervals, the patterned hydrogels were
maintained in
in distilled
distilled water
five days
days with
with aa change
change of
of water
water each
each day
day for
for the
the removal
removal of
of
maintained
water for
for five
maintained in distilled water for five days with a change of water each day for the removal of
unreacted starting
starting materials from
from the samples.
samples. Scheme
shows the
the different
different systems
systems of hydrogels
hydrogels
unreacted
Scheme 222 shows
shows
unreacted startingmaterials
materials fromthe
the samples. Scheme
the different
systems ofof
hydrogels
studied.
The
compositional
details
of
each
system
are
summarized
in
Table
1.
studied.
The
compositional
summarizedin
inTable
Table1.1.
studied.
The
compositionaldetails
detailsof
ofeach
each system
system are
are summarized
(a)
(a)
Scheme 2. Cont.
Scheme
2. Cont.
Scheme
2. Cont.
Polymers 2016, 8, 233
Polymers 2016, 8, 233
4 of 16
(b)
Scheme 2. (a) Copolymerization of DMAEAAm and DMAAm (System I), DMAEAAm, DMAAm and
Scheme 2. (a) Copolymerization of DMAEAAm and DMAAm (System I), DMAEAAm, DMAAm
AA (System II) and DMAEAAm, DMAAm and AMPS (System III); (b) shape of hydrogels after
and AA (System II) and DMAEAAm, DMAAm and AMPS (System III); (b) shape of hydrogels after
photo polymerization.
photo polymerization.
Table 1. Composition of hydrogels prepared for Systems I, II and III. D, N-[2Table
1. Composition of hydrogels prepared
for Systems I, II and III. D, N-[2-(dimethylaminoethyl)acrylamide];
(dimethylaminoethyl)acrylamide];
M, N,N-dimethylacrylamide;
B, N,N-methylenebisacrylamide; A,
M, acrylic
N,N-dimethylacrylamide;
B,
N,N-methylenebis
acrylamide;
A, acrylic2959,
acid,0.1
S, mmol;
2-acrylamido-2acid, S, 2-acrylamido-2-methyl-1-propanesulphonic
acid [(Irgacure
distilled
methyl-1-propanesulphonic
acid
[(Irgacure
2959,
0.1
mmol;
distilled
water,
3.5
mL).
The
superscript
water, 3.5 mL). The superscript a stands for the concentration of crosslinker in % (mmol/mmol)
with
a stands
themonomer
concentration
of crosslinker
% (mmol/mmol)
with of
respect
to the
monomer
respectfor
to the
concentration;
b and cin
stand
for the concentration
monomers
D and
A in
concentration;
b andby
c stand
thee concentration
of monomers of
D monomers
and A in mmol
mmol multiplied
four; dfor
and
stand for the concentration
D andmultiplied
S in mmolby
four;
d and e stand
for the concentration of monomers D and S in mmol multiplied by four.
multiplied
by four.
SystemII
System
Designation used DB a
Designation used
a 1
DBDB
1 2
DBDB
2 4
DBDB
4
DBDB
10
DB 10
Designation used
Designation
c
DbAused
Db Ac
D8A2
D8 A2
D6A4
D6 A
4
D55A5
D5 A
D4 A
D64A6
D2 A
D82A8
DMAEAAm (D) (mmol)
DMAAm (M) (mmol)
DMAEAAm (D)2.5(mmol)
2.5 2.5
2.5 2.5
2.5 2.5
2.5
DMAAm (M)2.5
(mmol)
System II
2.5 2.5
2.5 2.5
2.5 2.5
2.5
BIS (B) (mmol)
BIS (B) 0.05
(mmol)
0.1
0.05
0.1
0.2
0.2
0.5
0.5
System II
DMAEAAm (D) (mmol)
DMAEAAm (D) (mmol)
2.0
1.5
1.25
1.0
0.5
2.0
1.5
1.25
1.0
0.5
AA (A) (mmol)
AA (A) (mmol)
0.5
1.0
1.25
1.5
2.0
0.5
1.0
1.25
1.5
2.0
DMAAm (M) (mmol)
DMAAm (M) (mmol)
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
BIS (B) (mmol)
BIS (B) (mmol)
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
System
SystemIII
III
Designation used
used DdSe
DMAEAAm (D) (mmol)
AMPS (S) (mmol)
DMAAm (M) (mmol)
Designation
DMAEAAm (D) (mmol) AMPS (S) (mmol)
DMAAm (M) (mmol)
Dd SDe8S2
2.0
0.5
2.5
D8 S2
2.0
0.5
2.5
D6S4
1.5
1.0
2.5
D6 S4
1.5
1.0
2.5
5S5
D
1.25
1.25
2.5
D5 S5
1.25
1.25
2.5
D4 SD64S6
1.0 1.0
1.5 1.5
2.5 2.5
D2 SD82S8
0.5 0.5
2.0 2.0
2.5 2.5
BIS (B) (mmol)
BIS (B) (mmol)
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
Characterization
Hydrogels
2.2.2.2.
Characterization
of of
Hydrogels
diameter
thegels
gelswas
wasmeasured
measured by
by aa stereomicroscope
stereomicroscope (Hund,
TheThe
diameter
of ofthe
(Hund,Wetzlar,
Wetzlar,Germany)
Germany)
equipped with a digital camera (JVC) having a charge coupled device (CCD, which is an image
equipped with a digital camera (JVC) having a charge coupled device (CCD, which is an image
sensor, consisting of an integrated circuit containing an array of linked, or coupled, light-sensitive
sensor, consisting of an integrated circuit containing an array of linked, or coupled, light-sensitive
capacitors). The swelling ratio for a bulk gel was determined by taking the ratio of the diameter of
capacitors). The swelling ratio for a bulk gel was determined by taking the ratio of the diameter of the
the swollen hydrogel and the diameter of the gel in the reference state (e.g., as prepared). The degree
swollen hydrogel and the diameter of the gel in the reference state (e.g., as prepared). The degree of
of swelling is expressed as the ratio of the gel volume in equilibrium state (V) to the volume at
swelling is expressed as the ratio of the gel volume in equilibrium state (V) to the volume at preparation
preparation (V0), calculated by equation shown below:
(V 0 ), calculated by equation shown below:
V/V0 = (d/d0)3
(1)
3
pd{ddiameter
0q
d is the diameter of the swollen hydrogel,V{V
and 0d0“
is the
of the hydrogel in the reference state.(1)
d is the diameter of the swollen hydrogel, and d0 is the diameter of the hydrogel in the reference state.
Polymers 2016, 8, 233
Polymers 2016, 8, 233
5 of 16
For
pH
sensitivitymeasurements,
measurements,swollen
swollen hydrogels
hydrogels of
inin
aa
For
pH
sensitivity
of aa known
knowndiameter
diameterwere
wereimmersed
immersed
medium of known pH, and the diameter was determined by the microscope. For one measurement,
medium of known pH, and the diameter was determined by the microscope. For one measurement,
the average diameter of three dots was taken for the calculation of the volume degree of swelling.
the average diameter of three dots was taken for the calculation of the volume degree of swelling.
Before each measurement, the hydrogels were equilibrated for 2 h in that pH medium. Buffer
Before each measurement, the hydrogels were equilibrated for 2 h in that pH medium. Buffer solutions
solutions having pH ranging from 2–12 were prepared by dissolving Component A (composition in
having pH ranging from 2–12 were prepared by dissolving Component A (composition in 1 liter
1 liter double-distilled water): 6.008 g citric acid monohydrate (35%), 1.769 g boric acid (10.4%),
double-distilled water): 6.008 g citric acid monohydrate (35%), 1.769 g boric acid (10.4%), 3.893 g
3.893 g potassium hydrogen sulfate (23.0%), 5.266 g 5,5-diethylbarbituric acid (31.1%); Component B:
potassium hydrogen sulfate (23.0%), 5.266 g 5,5-diethylbarbituric acid (31.1%); Component B: 0.2 N
0.2 N sodium hydroxide solution. For the determination of metal ion sensitivity, 0.01 M solutions of
sodium
solution.
the
determination
of metal
ion were
sensitivity,
0.01 in
M 0.01
solutions
of CuSO
CuSO4hydroxide
, ZnSO4 and
AgNO3 For
were
prepared.
Hydrogel
samples
immersed
M acetic
acid, 4 ,
ZnSO
and
AgNO
were
prepared.
Hydrogel
samples
were
immersed
in
0.01
M
acetic
acid,
and
the
4
3
and the change in diameter of hydrogels after the addition of 10 µL of metal ion solution at
change
in
diameter
of
hydrogels
after
the
addition
of
10
µL
of
metal
ion
solution
at
equilibrium,
i.e.,
equilibrium, i.e., 2 h was determined.
2 h was determined.
3. Results and Discussion
3. Results and Discussion
3.1. pH Sensitivity
3.1. pH Sensitivity
3.1.1. Effect of Crosslinking
3.1.1. Effect of Crosslinking
In this study, System I is a two-component system having DMAEAAm and DMAAm. The effect
In this study, System I is a two-component system having DMAEAAm and DMAAm. The effect
of crosslinker concentration on the swelling behavior of hydrogels under different pH conditions is
of crosslinker concentration on the swelling behavior of hydrogels under different pH conditions is
shown in Figure 1.
shown in Figure 1.
(a)
Volume Degree of Swelling
4
DB
3
DB
DB
1
2
4
2
DB
10
1
2
4
6
8
10
12
pH
(b)
(c)
Figure 1. (a) Chemical composition of System I hydrogels in different pH states; (b) variation of the
Figure 1. (a) Chemical composition of System I hydrogels in different pH states; (b) variation of the
volume degree of swelling with pH for different compositions of hydrogels; (c) optical micrographs
volume degree of swelling with pH for4 different compositions of hydrogels; (c) optical micrographs
showing the change in diameter of DB hydrogels at pH 2.6 and 9.6.
showing the change in diameter of DB4 hydrogels at pH 2.6 and 9.6.
Polymers 2016, 8, 233
Polymers 2016, 8, 233
6 of 16
The system having the lowest amount of crosslinking (1 mol %) shows the highest swelling, and
the system having the highest amount of crosslinking (10 mol %) shows the lowest swelling. There is
an The
increase
in having
the volume
degreeamount
of swelling
with a change
pH
to a lower
value.swelling,
At higher
pH
system
the lowest
of crosslinking
(1 molof%)
shows
the highest
and
non-ionized
groups
the DMAEAAm
moietyThere
are less
thevalues,
systemthe
having
the highestpendant
amount dimethylamino
of crosslinking (10
mol %)ofshows
the lowest swelling.
is
hydrophilic.
As
a
consequence,
they
likely
associate
and
exclude
water
from
the
polymer
network
an increase in the volume degree of swelling with a change of pH to a lower value. At higher pH
(the collapsed
state). pendant
When the
solution pH groups
is decreased
to values below
theare
pKless
a of hydrophilic.
the ionizable
values,
the non-ionized
dimethylamino
of the DMAEAAm
moiety
protonation
occurs,
resulting
in the
formation
of positively-charged
pendant
Asdimethylamino
a consequence,group,
they likely
associate
and exclude
water
from
the polymer
network (the collapsed
groups
in
the
polymeric
backbone.
Protonation
of
pendant
dimethylamino
groups
gives
rise
to two
state). When the solution pH is decreased to values below the pKa of the ionizable dimethylamino
phenomena,
eachoccurs,
of which
contributes
to the swelling
behavior of the
hydrogel.
group,
protonation
resulting
in the formation
of positively-charged
pendant
groupsFirst,
in thethe
positively-charged
amine
groups
repel
one
another,
causing
the
polymer
chains
to
move
spatially.
polymeric backbone. Protonation of pendant dimethylamino groups gives rise to two phenomena,In
addition,
to contributes
maintain the
electro
neutrality
(Donnan
equilibrium)
within
the gel, solvated amine
counter
each
of which
to the
swelling
behavior
of the hydrogel.
First,
the positively-charged
ions are
drawn
the polymer
thus,
the positively-charged
groups become
caged
groups
repel
one into
another,
causingstructure;
the polymer
chains
to move spatially.amine
In addition,
to maintain
by
these
solvated
counter
ions
and
additional
water
molecules.
Both
of
these
phenomena
lead
the electro neutrality (Donnan equilibrium) within the gel, solvated counter ions are drawn into to
thethe
increased
sorption
of water
(degree of hydration)
the hydrogel,
causing
it to swell,
as counter
shown in
polymer
structure;
thus,
the positively-charged
amineinto
groups
become caged
by these
solvated
Figure
1.
ions
and additional
water molecules. Both of these phenomena lead to the increased sorption of water
(degree of hydration) into the hydrogel, causing it to swell, as shown in Figure 1.
3.1.2. Effect of Ionizable Monomer
3.1.2. Effect of Ionizable Monomer
In Systems II and III, the effect of ionizable monomer at different pH was investigated. In the
systems
that are
bothIII,
crosslinked,
well containing
acidic
(anionic)pH
and
basic
(cationic) pendant
In Systems
II and
the effect ofasionizable
monomer
at different
was
investigated.
In the
groups,that
swelling
andcrosslinked,
deswelling are
dependent
on solution
pH, as well
ionic
composition
of the
systems
are both
as well
containing
acidic (anionic)
andthe
basic
(cationic)
pendant
hydrogel.
In theand
case
of hydrogels
pendant
degree of swelling
groups,
swelling
deswelling
are containing
dependent acidic
on solution
pH,groups,
as well the
the volume
ionic composition
of the
increasesInasthe
thecase
pH of
of hydrogels
the solution
increases,acidic
whereas
a decrease
in the
the volume
pH enhances
hydrogel.
containing
pendant
groups,
degreethe
of swelling
swellingof
hydrogels
containing
basic
pendant
groups.whereas
In case ofa amphoteric
theenhances
volume degree
of swelling
increases
as the
pH of the
solution
increases,
decrease in gels,
the pH
the swelling
of
is also dependent
thependant
relative groups.
amountIn
ofcase
ionic
Therefore,
between
hydrogels
containingon
basic
ofgroups.
amphoteric
gels, thespecific
volumebonding
degree of
swellingthe
and cationic
groups
should
be considered.
The specific
bonding
between
cationic
and anionic
is anionic
also dependent
on the
relative
amount
of ionic groups.
Therefore,
specific
bonding
between
the
groups
can
act asgroups
a cross-linking
which
can result
in a decrease
in volume
anionic
and
cationic
should bestructure,
considered.
The specific
bonding
between cationic
and degree
anionic of
swelling.
groups
can act as a cross-linking structure, which can result in a decrease in volume degree of swelling.
System
three-component
system
having
DMAEAAm,
AA
and
DMAAm,
from
which
System
II II
is is
thethe
three-component
system
having
DMAEAAm,
AA
and
DMAAm,
from
which
DMAEAAm
thebasic
basiccomponent
componentand
andAA
AAisisthe
theacidic
acidiccomponent.
component. The composition was
DMAEAAm
is is
the
was chosen
chosen in
content of
of 50%
50%(with
(withrespect
respecttotonon-crosslinkable
non-crosslinkablemonomers)
monomers)was
was
insuch
such way
way that
that a DMAAm content
maintained.
The
hydrogels
synthesized
by varying
theofratio
of two ionizable
components,
maintained.
The
hydrogels
werewere
synthesized
by varying
the ratio
two ionizable
components,
which
in an state
ionized
state at different
pH conditions.
Therefore,
one extreme,
the system
has
arewhich
in anare
ionized
at different
pH conditions.
Therefore,
on oneonextreme,
the system
has an
an excess
of basic
groups,
and
onother
the other
extreme,
the system
hasexcess
an excess
of acidic
groups;
and
excess
of basic
groups,
and on
the
extreme,
the system
has an
of acidic
groups;
and in
in between
extreme
compositions
is the
system
having
equal
ratio
basic
and
acidic
groups.
between
thesethese
extreme
compositions
is the
system
having
an an
equal
ratio
of of
basic
and
acidic
groups.
Depending
state
of particular
the particular
co-monomer,
different
types
of interactions
are inside
present
Depending
on on
thethe
state
of the
co-monomer,
different
types of
interactions
are present
the hydrogel
The of
variation
of the
volume
degree of
swelling
respect
to pH for
theinside
hydrogel
network. network.
The variation
the volume
degree
of swelling
with
respectwith
to pH
for hydrogels
hydrogels incorporating
a weakly-ionizable
component
added
to the system
ofDMAAm
DMAEAAm
and
incorporating
a weakly-ionizable
component added
to the system
of DMAEAAm
and
having
DMAAm
having a fixed
(2 molin
%)Figure
of BIS2.is shown in Figure 2.
a fixed
concentration
(2 molconcentration
%) of BIS is shown
(a)
Figure 2. Cont.
Figure 2. Cont.
Polymers 2016, 8, 233
Polymers 2016, 8, 233
7 of 16
8
Volume Degree of Swelling
7
D8A2
6
D6A4
5
D5A5
4
D4A6
3
D2A8
2
1
2
4
6
8
10
12
pH
(b)
(c)
Figure 2.
2. (a)
(a) Chemical
Chemical composition
composition of
of System
System II
II hydrogels
hydrogels in
in different
different pH
pH states;
states; (b)
(b) variation
variation of
of the
the
Figure
volume degree
degree of
ofswelling
swelling for
fordifferent
differentcompositions
compositions of
ofhydrogels;
hydrogels;(c)
(c)optical
opticalmicrographs
micrographsshowing
showing
volume
the
change
in
diameter
of
D
5A5 hydrogels at pH 2.6, 5.7 and 9.6
the change in diameter of D5 A5 hydrogels at pH 2.6, 5.7 and 9.6.
The weakly-ionizable components in System II are both DMAEAAm and AA. The concentration
The weakly-ionizable components in System II are both DMAEAAm and AA. The concentration
of AA is varied from 10 to 40% with respect to the total monomer content. Figure 2 shows different
of AA is varied from 10 to 40% with respect to the total monomer content. Figure 2 shows different
compositions of hydrogels for System II under varying pH conditions. The hydrogels having the
compositions of hydrogels for System II under varying pH conditions. The hydrogels having the
composition of D8A2, i.e., having the lowest amount of AA and the highest amount of DMAEAAm,
composition of D8A2, i.e., having the lowest amount of AA and the highest amount of DMAEAAm,
shows no swelling at a pH ranging from 7–12, while swelling is stronger in the pH range of less than
shows no swelling at a pH ranging from 7–12, while swelling is stronger in the pH range of less than
five, which can be explained due to the protonation of the dimethylamino group of DMAEAAm. For
five, which can be explained due to the protonation of the dimethylamino group of DMAEAAm.
composition D6A4, swelling was observed in a pH range greater than nine and less than five. This
For composition D6A4, swelling was observed in a pH range greater than nine and less than five.
can be explained by the ionization of the carboxylic groups of AA at a higher pH range and the
This can be explained by the ionization of the carboxylic groups of AA at a higher pH range and the
protonation of the dimethylamino groups of DMAEAAm in the low pH range. In the intermediate
protonation of the dimethylamino groups of DMAEAAm in the low pH range. In the intermediate
pH range (5–9), where both carboxylic and dimethylamino groups are ionized, the volume degree of
pH range (5–9), where both carboxylic and dimethylamino groups are ionized, the volume degree of
swelling is lowest due to the ionic interactions between positive charges of the dimethylamino group
swelling is lowest due to the ionic interactions between positive charges of the dimethylamino group
and negative charges of the carboxylic groups. This intermediate pH range is generally referred to as
and negative charges of the carboxylic groups. This intermediate pH range is generally referred to
the isoelectric pH range (pI), where the electrostatic attraction due to opposite charges is highest.
as the isoelectric pH range (pI), where the electrostatic attraction due to opposite charges is highest.
Therefore, in the pI range, there are two types of crosslinks, one due to the BIS and the other due to
Therefore, in the pI range, there are two types of crosslinks, one due to the BIS and the other due to the
the creation of electrostatic junction points (ionic interactions).
creation of electrostatic junction points (ionic interactions).
For composition D5A5, swelling is observed in a pH range greater than 7.7 and less than 3.6, and
For composition D A , swelling is observed in a pH range greater than 7.7 and less than 3.6,
in between pH 3.6 and 57.7,5 there is very less swelling. For composition D4A6, higher swelling was
and in between pH 3.6 and 7.7, there is very less swelling. For composition D4 A6 , higher swelling
observed in the pH range greater than 3.6 and less than pH 3.6; at pH 3.6, there is a minimum amount
was observed in the pH range greater than 3.6 and less than pH 3.6; at pH 3.6, there is a minimum
of swelling. As the ratio of ionizable components is varied from 1:1, the isoelectric pH range decreases
amount of swelling. As the ratio of ionizable components is varied from 1:1, the isoelectric pH range
because of the imbalance of the ratio of positive and negative charges. For composition D2A8, a higher
decreases because of the imbalance of the ratio of positive and negative charges. For composition
amount of swelling was observed at pH greater than 3.6, and a relatively small amount of swelling is
observed at a pH lower than 3.6; this is because less protonated dimethylamino groups from
DMAEAAm are available. The variation of the volume degree of swelling depending on the
Polymers 2016, 8, 233
8 of 16
D2 A8 , a higher amount of swelling was observed at pH greater than 3.6, and a relatively small amount
of swelling is observed at a pH lower than 3.6; this is because less protonated dimethylamino groups
from DMAEAAm are available. The variation of the volume degree of swelling depending on the
composition of hydrogels and varying pH can be explained by the different states of ionization of
two ionizable co-monomers. At higher pH values, the pendant dimethylamino groups of DMAEAAm
present in the non-ionized state are less hydrophilic. However, carboxylic groups present in AA
are in the ionized state at higher pH values. This ionization is reversed when the pH is decreased;
dimethylamino groups are in the ionized state at low pH, while carboxylic groups are in the non-ionized
state in low pH medium. Therefore, for System II, hydrogels are in the swollen state at both high and
low pH.
System III is also a three-component system having DMAEAAm, AMPS and DMAAm, in which
DMAEAAm is the basic component and AMPS the acidic component. The hydrogels were synthesized
by varying the ratio of two ionizable components, from which AMPS is in the ionized state over the
whole pH range.
AMPS has a strongly ionizable sulfonate group; it remains in the dissociated state in the pH range
of 2–12, and therefore, hydrogels derived from AMPS exhibit a pH-independent swelling behavior.
The effect of the addition of a second ionizable component, which is completely ionized over the whole
pH range, is shown in Figure 3. The concentration of AMPS was varied from 10%–40% with respect to
total monomer content.
For composition D8 S2 , having the lowest amount of AMPS and the highest amount of DMAEAAm,
it showed higher swelling in a pH range higher than nine and a pH lower than six, which is due to
the protonation of the dimethylamino group of DMAEAAm in the lower pH region. At higher pH,
dimethylamino groups are deprotonated, and therefore, higher swelling as compared to hydrogels
having only DMAEAAm as the ionizable component is due to the sulfonate groups of AMPS, which
are ionized over the whole pH range. In the pH range of 6–9, there is a very small amount of
swelling, which is due to the formation of additional ionic interaction between the positive charges of
the protonated dimethylamino groups and the negative charge of the ionized sulfonic acid groups.
For compositions around the isoelectric range (D6 S4 , D5 S5 and D4 S6 ), swelling was observed at a
pH range > 7, and at a pH < 7, a very small amount of swelling was seen. This is because of the
much lesser amount of ionic content, as positive charges due to protonated dimethylamino groups of
DMAEAAm are electrostatically neutralized with negative charges due to the sulfonic acid groups of
AMPS. For composition D2 S8 , a high amount of swelling is observed over the whole pH range due to
the excess of sulfonate groups. The optical micrographs for composition D5 S5 in three different pH
conditions is shown in Figure 3.
System I is a weak basic polyelectrolyte gel with its classical swelling behavior. With the increase
in pH, more and more side groups are deprotonated, finally resulting in a drastic decrease in swelling.
For this system the critical pH value is around pH 5. The increase of the content of crosslinker screens
this effect. Hence, the amount of crosslinker should be kept as low as possible, but not effecting the
mechanical integrity. Systems II and III are polyampholyte gels with balanced and imbalanced charges.
In addition to the polybase part, System II has a pH-dependent anionic component, whereas System III
has an additional pH-independent component. Polyampholyte gels are of interest, since they show a
unique behavior, e.g., increased swelling with increased ionic strength [27] or enhanced mechanical
stability [28]. In order to minimize the effect of ionic strength, in this study, a particular buffer was
used maintaining almost the same ionic strength over the whole pH range. Polyampholyte gels are
obtained by copolymerizing a monomer with anionic functional groups and a monomer with cationic
functional groups forming anionic–cationic charges in different polymer repeat units or polymerizing a
zwitterionic monomer leading to the formation of anionic–cationic charges in the same polymer repeat
units. However, the swelling capacity is larger for the first case [27]. Changes in both charge density and
crosslink density are suggested to contribute to the swelling mechanism of polyampholytic hydrogels.
It has been shown that the swelling response of anionic offset polyampholytic and poly-zwitterionic
Polymers 2016, 8, 233
9 of 16
hydrogels can be regarded as a super-position of responses measured for charge balanced and pure
anionic hydrogels. This approximation was not valid for cationic offset hydrogels [27]. The charges
within polyampholyte hydrogels can act as reversible crosslinks that also result in the decrease of the
Polymers 2016, 8, 233
effective hydrogel charge density. The breakage of the physical crosslinks leads to the decrease of the
effective
crosslink
densitynetwork.
in the polymer
network.
For
chargeable
units within
thethe
polyampholyte
density
in the polymer
For chargeable
units
within
the polyampholyte
gels,
swelling
is associated
the occurrence
of an
isoelectricof
point
[29]. For gels
with
a significant
gels, behavior
the swelling
behaviorwith
is associated
with the
occurrence
an isoelectric
point
[29].
For gels with a
charge charge
imbalance,
this behavior
also can beItseen
System
III, the
significant
imbalance,
this vanishes.
behaviorItvanishes.
alsothat
caninbe
seen that
inanionic
Systemcomponent
III, the anionic
is
charged
over
the
whole
pH
range,
resulting
in
a
stronger
interaction
with
the
cationic
component
component is charged over the whole pH range, resulting in a stronger interaction with the cationic
and, hence,
a decreased
swelling. swelling.
component
and,inhence,
in a decreased
Volume Degree of Swelling
(a)
4
D8 S2
D 6S 4
3
D 5S 5
D 4S 6
D 2S 8
2
2
4
6
8
10
12
pH
(b)
(c)
Figure 3. (a) Chemical composition of System III hydrogels in different pH states; (b) variation of the
Figure 3. (a) Chemical composition of System III hydrogels in different pH states; (b) variation of the
volume degree of swelling for different compositions of hydrogels; (c) optical micrograph showing
volume degree of swelling for different compositions of hydrogels; (c) optical micrograph showing the
the change in the diameter of D5S5 hydrogels at pH 2.6, 5.7 and 9.6
change in the diameter of D5 S5 hydrogels at pH 2.6, 5.7 and 9.6.
3.2. Metal Ion Sensitivity
3.2. Metal Ion Sensitivity
3.2.1. Effect of Crosslinking
3.2.1. Effect of Crosslinking
In System I, the effect of crosslinking density towards metal ion sensitivity is evaluated. In
DMAEAAm,
tertiary
nitrogen
atom is a potential
sitetowards
for both proton
ion binding,
thus
In System I,thethe
effect
of crosslinking
density
metaland
ionmetal
sensitivity
is evaluated.
In DMAEAAm, the tertiary nitrogen atom is a potential site for both proton and metal ion binding,
Polymers 2016, 8, 233
Polymers 2016, 8, 233
10 of 16
conferring
on the
gel gel
both
pHpH
and
chains of
of
thus
conferring
on the
both
andmetal
metalion
ionsensitivity.
sensitivity. The
The covalently-bound
covalently-bound side chains
dimethylamino groups
groups have
have tertiary
tertiary nitrogen
nitrogen as
as the
the donor
donor atom
atom (Lewis
(Lewis base)
base) and
and can
can potentially
potentially
dimethylamino
bindwith
withtransition
transitionmetal
metalions
ions(Lewis
(Lewisacids).
acids).The
Theinteraction
interactionbetween
betweendimethylamino
dimethylamino side
sidegroups
groups
bind
and transition
transition metal
metal ions
ions offers
offers high
high selectivity
selectivity to
to its
its hydrogel
hydrogel towards
towards transition
transition metal
metal ions
ions over
over
and
non-transitionmetal
metalions.
ions.For
Forthe
themetal
metalion
ionsensitivity
sensitivitymeasurements,
measurements,gels
gelsare
arefirst
firstswollen
swollenin
in0.01
0.01M
M
non-transition
aceticacid,
acid,and
andthen
thenmetal
metalion
ion solution
solution was
was added
added successively.
successively.The
ThepH
pH of
of the
the solution
solution is
is around
around 4.0,
4.0,
acetic
andat
atthis
thispH,
pH,all
alldimethylamino
dimethylaminoligands
ligandsare
arein
inthe
theprotonated
protonatedstate.
state.The
Themeasurement
measurementof
ofmetal
metalion
ion
and
sensitivity
in
acetic
acid
will
indicate
the
ability
of
dimethylamino
ligands
present
in
the
hydrogel
sensitivity in acetic acid will indicate the ability of dimethylamino ligands present in the hydrogel
networkto
tobind
bindthe
themetal
metalions
ionsunder
undermore
morecompetitive
competitiveconditions.
conditions.The
Theweak
weakbasic
basicfunctional
functionalgroups
groups
network
ofthe
thedimethylamino
dimethylaminoligand
ligandshow
showhigh
highaffinities
affinitiestowards
towardshydrogen
hydrogenions
ionsas
asaaresult
resultmetal
metalion
ionbinding
binding
of
inthe
thegelgel
becoming
more
selective
to the formidable
competition
from acidic
H+ under
acidic
in
becoming
more
selective
due todue
the formidable
competition
from H+ under
conditions.
conditions.
addition
of 100
µLsolution
metal salt
solution corresponds
to equal
molarofamounts
of metal
The
additionThe
of 100
µL metal
salt
corresponds
to equal molar
amounts
metal ions
and
ions andsites.
binding sites.
binding
Figure44shows
showsthe
thevariation
variation
volume
degree
of swelling
respect
the addition
of
Figure
of of
thethe
volume
degree
of swelling
withwith
respect
to thetoaddition
of Cu2+
2+
Cuhydrogels
in hydrogels
containing
crosslinking
density.
With the
increase
in concentration,
the metal ion
in
containing
differentdifferent
crosslinking
density. With
the increase
in the
metal ion
concentration,
deswellingoccurs.
of hydrogels
occurs. This
behaviorasis in
observed,
as in
acetic acid
medium,
deswelling
of hydrogels
This behavior
is observed,
acetic acid
medium,
most
of the
most of the dimethylamino
are in thestate,
protonated
state,the
and
hence, the
are in more
dimethylamino
ligands are inligands
the protonated
and hence,
hydrogels
arehydrogels
in more hydrophilic
hydrophilic
state.
With the
addition
metal
ions, are
the being
protons
are being
by metal
Thus,
state.
With the
addition
of metal
ions,ofthe
protons
replaced
by replaced
metal ions.
Thus, ions.
hydrogels
hydrogels
are
in
a
deprotonated
state
after
the
addition
of
metal
ions,
which
makes
the
gels
less
are in a deprotonated state after the addition of metal ions, which makes the gels less hydrophilic [30].
hydrophilic
[30].
the of
successive
addition
of metal
ions, of
andimethylamino
increasing amount
of
Therefore,
with
theTherefore,
successive with
addition
metal ions,
an increasing
amount
ligands
dimethylamino
ligands
is
deprotonated,
and
thus,
there
is
deswelling
of
hydrogels.
Further,
the
metal
is deprotonated, and thus, there is deswelling of hydrogels. Further, the metal ions can interact with
ions can
withgroup,
more than
one amino
group,crosslinking
resulting inand,
additional
and,
thus,
in
more
thaninteract
one amino
resulting
in additional
thus, incrosslinking
a deswelling
of the
gels.
a deswelling
the gels. Theisinterchain
supported
by the fact
rapid decrease
in
The
interchainofcrosslinking
supportedcrosslinking
by the fact is
that
a rapid decrease
inthat
the avolume
degree of
the
volume
degree
of
swelling
can
be
observed
for
the
addition
of
metal
salt
of
50
µL
corresponding
swelling can be observed for the addition of metal salt of 50 µL corresponding to a ratio of functional
to a ratio
functional
to metal
ions of
the change is less pronounced.
groups
to of
metal
ions of groups
2:1. Later,
the change
is 2:1.
lessLater,
pronounced.
7
Volume Degree of Swelling
6
5
2
2+
4
2+
DB -Cu
DB -Cu
10
4
2+
DB -Cu
2
2+
2
+
DB -Zn
DB -Ag
3
2
1
0
50
100
150
200
Metal Ion Solution Added (μL)
Figure4.4.Variation
Variation
volume
degree
of swelling
with respect
to varying
CuSO4
Figure
of of
thethe
volume
degree
of swelling
with respect
to varying
amountsamounts
of CuSO4ofsolution
solution
(0.01
M) forcrosslinking
different crosslinking
of and
hydrogels
and
of the
volume
degree
(0.01
M) for
different
densities ofdensities
hydrogels
variation
ofvariation
the volume
degree
of swelling
2 hydrogels with respect to the addition of different metal ions for System I
2 hydrogels
ofDB
swelling
of DBwith
of
respect to the addition of different metal ions for System I.
In addition, Figure 4 shows the variation of the volume degree of swelling of DB2 hydrogels with
In addition, Figure 4 shows the variation of the volume degree of swelling of DB2 hydrogels
respect to the addition of Cu2+, Zn2+ and Ag+. The deswelling behavior was observed with the addition
with respect to the addition of Cu2+ , Zn2+ and Ag+ . The deswelling behavior was observed with the
of Cu2+ and Zn2+, while no change is observed with the addition of Ag+ ions. Because of the high
addition of Cu2+ and Zn2+ , while no change is observed with the addition of Ag+ ions. Because of the
affinity of weak basic functionalities towards H+ and also because of the lower binding constant or
high affinity of weak basic functionalities towards H+ and also because of the lower binding constant
formation constant for Ag+ ions, the protonation is preferred for these ligands. The acid dissociation
constants for the tridentate ligand, for example, diethylene triamine [31] are pKa1 = 4.25,
pKa2 = 8.98 and pKa3 = 9.70 and for the formation constant of the metal complex (log β) with Cu2+ and
Polymers 2016, 8, 233
11 of 16
or formation constant for Ag+ ions, the protonation is preferred for these ligands. The acid dissociation
constants
for 8,the
Polymers 2016,
233tridentate ligand, for example, diethylene triamine [31] are pKa1 = 4.25, pKa2 = 8.98
and pKa3 = 9.70 and for the formation constant of the metal complex (log β) with Cu2+ and Zn2+ 16.0
+ with N,N-tetramethylethylenediamine
2+
and
respectively.
The formation
constant
β) [32] of Ag
Zn8.9,
16.0
and 8.9,
respectively.
The (log
formation
constant
(log β) [32] of Ag+ with
isN,N-tetramethylethylenediamine
around 3.3–5.9. From these values,isitaround
can be inferred
forthese
aminevalues,
ligands,
constant
of
3.3–5.9. that
From
it the
canformation
be inferred
that for
2+
2+
amine
ligands,isthe
formation
constanttoofthe
metal
is higher
as compared
theZn
acid .dissociation
metal
complex
higher
as compared
acidcomplex
dissociation
constant
for Cu toand
Thus, there
2+ and Zn2+. Thus, there2+
2+ and Zn2+ with the+
for Cu
preferential
binding
of metal ions Cu
isconstant
preferential
binding
of metal ions Cu is and
Zn2+ with
the dimethylamino
ligand.
While for Ag
dimethylamino
ligand. While
for complex
Ag+ formation,
the as
constant
of metal
complex
is lower as compared
formation,
the constant
of metal
is lower
compared
to the
acid dissociation
constant;
+
to the acid
dissociation
constant;binding
therefore,
there
no preferential binding with Ag+ ions.
therefore,
there
is no preferential
with
Agis ions.
Theinteraction
interactionofofmetal
metalions
ionswith
withthe
theligand
ligand is
is based
based on
on ideas,
ideas, such as the hard and
The
and soft
soft acid
acid
and
base
(HSAB)
principle
of
Pearson
[33].
According
to
this
principle,
hard
bases
prefer
to
bind
with
and base (HSAB) principle of Pearson [33]. According to this
to bind with
hardacids,
acids,and
andsoft
softbases
basesprefer
prefertotobind
bindwith
withsoft
softacids
acidsand
and vice
vice versa.
versa. Based
Based on
on this
this principle,
hard
principle, the
the
functionalgroups
groupsthat
thatare
arepresent
presenton
onthe
themonomer
monomerand
andmetal
metalions
ions that
that are
are used
used in
in this
functional
this study
study can
can also
also
classifiedasashard
hardand
andsoft
softacids
acidsand
andbases.
bases. Thus,
Thus, in
in System
System I,
I, there
there are
are dimethylamino
dimethylamino groups,
bebeclassified
groups,
2+
2+
+
2+
2+
whichare
aretertiary
tertiaryamines
aminesand
andhard
hardbases.
bases.Cu
Cu and
and Zn
Zn are
which
are borderline
borderline acids,
acids, and
and Ag
Ag+isisaasoft
softacid.
acid.
2+ and Zn2+
2+ to dimethylamino
2+
Therefore,
from
the
HSAB
principle,
we
can
expect
higher
binding
of
Cu
Therefore, from the HSAB principle, we can expect higher binding of Cu and Zn to dimethylamino
ligandsbecause
becauseofofthe
thehard
hardacid-hard
acid-hardbase
baseinteraction
interaction as
as compared
compared to
to Ag
Ag++,, which
ligands
which is
is aa soft
softacid
acidand,
and,
hence,
has
lower
binding
ability
with
the
dimethylamino
group.
hence, has lower binding ability with the dimethylamino group.
3.2.2.Effect
Effectofofthe
theAddition
AdditionofofAcetic
AceticAcid
Acidon
onIonizable
IonizableMonomer
Monomer
3.2.2.
Duetoto
relative
high
ionic
strength
the buffer
used buffer
solutions,
theofeffect
acetic
acid
Due
thethe
relative
high
ionic
strength
of theofused
solutions,
the effect
aceticofacid
addition
low ionic
was investigated.
High ionic
often screens
effects in
ataddition
low ionicatstrength
wasstrength
investigated.
High ionic strength
oftenstrength
screens effects
in polyelectrolyte
polyelectrolyte
systems.
Figure
5
shows
the
variation
of
the
volume
degree
of
swelling
with the
systems. Figure 5 shows the variation of the volume degree of swelling with the successive addition
of
successive
addition
of
acetic
acid.
For
the
composition
having
an
excess
of
dimethylamino
groups
as
acetic acid. For the composition having an excess of dimethylamino groups as compared to carboxylic
compared
to carboxylic
samples D8A2 and D6A4, an increase in the volume degree of
groups,
i.e., samples
D8 A2 groups,
and D6 Ai.e.,
4 , an increase in the volume degree of swelling with respect to the
swelling
with
respect
to
the
addition
of acetic
was
observed. This
is due to the protonation
of
addition of acetic acid was observed. This
is dueacid
to the
protonation
of dimethylamino
groups, which
dimethylamino
groups,
which
in
turn
increases
the
hydrophilicity
and,
thus,
increases
swelling.
in turn increases the hydrophilicity and, thus, increases swelling. Samples having an equal amount of
Samples
an equal
basic rich
groups,
i.e., sample
D5A5i.e.,
, or D
samples
rich in
acidic
and having
basic groups,
i.e.,amount
sampleof
D5acidic
A5 , orand
samples
in acidic
compound
4 A6 and D2 A8 ,
acidic
compound
i.e.,
D
4A6 and D2A8, the swelling behavior showed no change upon the addition of
the swelling behavior showed no change upon the addition of acetic acid. These hydrogels have an
acetic acid. These hydrogels have an excess of weakly-ionizable carboxylic groups. The
excess
of weakly-ionizable carboxylic groups. The dimethylamino groups are almost in the protonated
dimethylamino groups are almost in the protonated state in double-distilled water, and the addition
state in double-distilled water, and the addition of increasing amounts of acetic acid does not affect the
of increasing amounts of acetic acid does not affect the volume degree of swelling.
volume degree of swelling.
7
Volume Degree of Swelling
6
D8A2
5
D6A4
D5A5
4
D4A6
D2A8
3
2
1
0
50
100
150
200
Acetic Acid Solution Added (μL)
Figure
II.
Figure5.5.Variation
Variationofofthe
thevolume
volumedegree
degreeof
ofswelling
swellingwith
withthe
theaddition
addition of
of acetic
acetic acid
acid for
for System
System II.
Figure 6 shows the variation of the volume degree of swelling with respect to the addition of
acetic acid for System III. For the composition having an excess of dimethylamino ligands, with the
addition of acetic acid, an increase in the volume degree of swelling is observed. For the composition
Polymers 2016, 8, 233
12 of 16
Polymers 2016, 8, 233
Figure 6 shows the variation of the volume degree of swelling with respect to the addition of acetic
acid for System III. For the composition having an excess of dimethylamino ligands, with the addition
having an equal ratio of dimethylamino ligands and sulfonic acid groups or less, there is no change
of acetic acid, an increase in the volume degree of swelling is observed. For the composition having an
in the volume degree of swelling. This can be explained by the fact that all of the dimethylamino
equal ratio of dimethylamino ligands and sulfonic acid groups or less, there is no change in the volume
ligands are already in a protonated state due to the ionization of sulfonic acid groups. For the
degree of swelling. This can be explained by the fact that all of the dimethylamino ligands are already
composition having a higher ratio of the sulfonic acid group, the volume degree of swelling is higher
in a protonated state due to the ionization of sulfonic acid groups. For the composition having a higher
as compared to the D5S5 composition, because of the excess of ionized sulfonic acid groups not
ratio of the sulfonic acid group, the volume degree of swelling is higher as compared to the D5 S5
involved in ionic crosslinking.
composition, because of the excess of ionized sulfonic acid groups not involved in ionic crosslinking.
6
Volume Degree of Swelling
5
D8S2
4
D6S4
D5S5
3
D4S6
2
1
0
50
100
150
200
Acetic Acid Solution Added (μL)
Figure
Figure 6.
6. Variation
Variationof
ofthe
thevolume
volumedegree
degreeswelling
swellingwith
withthe
theaddition
additionof
ofacetic
aceticacid
acidfor
forSystem
SystemIII.
III.
3.2.3.
3.2.3. Effect
Effectof
ofIonizable
IonizableMonomer
Monomeron
onMetal
MetalIon
IonSensitivity
Sensitivity
In
effect
ofof
ionizable
monomer
on on
metal
ion ion
sensitivity
is analyzed.
Metal
ion
InSystems
SystemsIIIIand
andIII,
III,the
the
effect
ionizable
monomer
metal
sensitivity
is analyzed.
Metal
measurement
in acetic
acidacid
shows
a decrease
in in
thethe
volume
degree
ion measurement
in acetic
shows
a decrease
volume
degreeofofswelling
swellingwith
withthe
theaddition
addition
2+
2+
2+
2+
of
Cu
,
Zn
,
as
shown
in
Figure
7.
In
the
acetic
acid
medium,
most
of
the
carboxylic
groups
of Cu
, as shown in
In
of the carboxylic groups are
are
protonated,
still
a competition
of carboxylic
groups
being
protonated
and bound
in an ionic
protonated,but
butthere
thereis is
still
a competition
of carboxylic
groups
being
protonated
and bound
in an
complex.
Metal Metal
ions can
bind
protonated
dimethylamino
ligandligand
by firstby
deprotonating
them,
ionic complex.
ions
canwith
bindawith
a protonated
dimethylamino
first deprotonating
then
binding
with
the
ligand.
As
discussed
in
System
I,
binding
of
metal
ions
with
dimethylamino
them, then binding with the ligand. As discussed in System I, binding of metal ions with
ligands
by the release
decreases
the hydrophilicity
of networks, of
and
thus, deswelling
dimethylamino
ligandsofbyprotons
the release
of protons
decreases the hydrophilicity
networks,
and thus,
isdeswelling
observed is
with
the successive
addition ofaddition
metal ions.
As the
carboxylic
groups have
nohave
role in
observed
with the successive
of metal
ions.
As the carboxylic
groups
no
this
case,
the
deswelling
behavior
is
governed
by
the
dimethylamino
group,
and
thus,
as
shown
in
role in this case, the deswelling behavior is governed by the dimethylamino group, and thus, as
the
plots,inthe
deswelling
with
the decrease
thedecrease
amount of
shown
thedegree
plots, ofthe
degree ofdecreased
deswelling
decreased
withinthe
in dimethylamino
the amount of
+ ions again shows
+
groups.
The
addition
of
Ag
no
significant
change
in
the
volume
degree
dimethylamino groups. The addition of Ag ions again shows no significant change in of
theswelling.
volume
The
reason
for the insignificant
in the volumedecrease
degree ofinswelling
afterdegree
the addition
of AgNO
degree
of swelling.
The reasondecrease
for the insignificant
the volume
of swelling
after
3
isthe
discussed
in System
I. With increased
AA
content,
binding
capacity
the gelsthe
decreased.
additionabove
of AgNO
3 is discussed
above in
System
I. the
With
increased
AA of
content,
binding
Gels
with of
nothe
excess
DMEAAmGels
hardly
respond
to metal
salts, because
the dimethylamino
groups
capacity
gelsofdecreased.
with
no excess
of DMEAAm
hardly
respond to metal
salts,
are
bound
indimethylamino
the ionic complex.
because
the
groups are bound in the ionic complex.
For System III, metal ion measurement was performed in a similar way as for Systems I and II.
In the case of System III, also, there is a decrease in the volume degree of swelling with the successive
addition of Cu2+ and Zn2+ , as shown in Figure 8. For the composition having a higher ratio of
dimethylamino ligand, i.e., D8 S2 and D6 S4 , with the addition of metal ions, there is a decrease in
the volume degree of swelling. The replacement of protons with metal ions causes a decrease in
Polymers 2016, 8, 233
13 of 16
hydrophilicity and, in turn, decreases the volume degree of swelling. For the hydrogels having
composition D5 S5 , i.e., having an equal ratio of dimethylamino and sulfonate groups, there is no
change in the volume degree of swelling at all. The possible explanation for this is that metal ions are
not able to bind dimethylamino ligands by first breaking ionic interactions. For hydrogel D4 S6 having
a higher amount of sulfonic acid groups with the addition of metal ions, there is deswelling observed;
the possible explanation for this is neutralization of the charges of sulfonic acid groups by metal ions.
The addition of Ag+ showed no change in the volume degree of swelling due to the reasons explained
Polymers
2016, 8,
233 II.
for
Systems
I and
7
Volume Degree of Swelling
6
2+
D8A2-Cu
5
2+
D6A4-Cu
2+
D5A5-Cu
4
2+
D4A6-Cu
2+
D2A8-Cu
3
D8A2-Zn
2+
+
2
D8A2-Ag
1
0
50
100
150
200
Metal Ion Solution Added (μL)
Figure 7.7.Variation
Variationofof
volume
degree
of swelling
with respect
to varying
CuSO4
Figure
thethe
volume
degree
of swelling
with respect
to varying
amountsamounts
of CuSO4ofsolution
solution
(0.01
M)
for
all
compositions
of
hydrogels
and
variation
of
the
volume
degree
of
swelling
(0.01 M) for all compositions of hydrogels and variation of the volume degree of swelling of D8 Aof
2
with respect
the addition
of different
ions
for System
II
D8A28,hydrogels
Polymers hydrogels
2016,
233 with respect
to the to
addition
of different
metal metal
ions for
System
II.
Volume Degree of Swelling
For System III, metal ion measurement was performed in a similar way as for Systems I and II.
In the case of System III, also, there is a decrease in the volume degree of swelling with the successive
addition of Cu2+ and5 Zn2+, as shown in Figure 8. For the composition having a higher ratio of
dimethylamino ligand, i.e., D8S2 and D6S4, with the addition of metal ions, there is a decrease in the
volume degree of swelling.
The replacement of protons with metal ions causes
a decrease in
4
2+
D8S2-Cu
hydrophilicity and, in turn, decreases the volume degree of swelling. For the hydrogels having
2+
D6S4-Cu
composition D5S5, i.e., having an equal ratio of dimethylamino and sulfonate
groups, there is no
2+
D5S5-Cu
change in the volume 3degree of swelling at all. The possible explanation for this
is that metal ions are
2+
D4S6-Cu
not able to bind dimethylamino ligands by first breaking ionic interactions. For
hydrogel D4S6 having
2+
S2-Zn
a higher amount of sulfonic
acid groups with the addition of metal ions, thereD8is
deswelling observed;
2
+
the possible explanation for this is neutralization of the charges of sulfonic acid
groups
by metal ions.
D8S2-Ag
+
The addition of Ag showed no change in the volume degree of swelling due to the reasons explained
for Systems I and II. 1
2+
Based on these results, it0 can be concluded
that the DMAEAAm
50
100
150
200 moiety shows sensitivity to Cu
2+
and Zn ions under acidic conditions.
If DMAEAAm moieties are present in excess in any system,
Metal Ion Solution Added (μL)
deswelling of hydrogels is observed with the successive addition of selective metal ions. The reasons
forFigure
deswelling
as discussed
above degree
are
theofdeprotonation
ofrespect
DMEAAm
moieties
by
metal
ions,4 as well
Figure
Variation
the volume
with
respect
to varying
amounts
of CuSO
solution
8. 8.
Variation
ofofthe
degree
ofswelling
swelling
with
to varying
amounts
of 4CuSO
(0.01ions
M)
for
allfor
compositions
of hydrogels
variation
ofresulting
the
degree
of swelling
of D
assolution
metal
interacting
with more
than
oneand
amino
in additional
crosslinking.
(0.01
M)
all compositions
of hydrogels
andgroup,
variation
of volume
the volume
degree
of
swelling
of8 S2In the
hydrogels
with
respect
to
the
addition
of
different
metal
ions
for
System
III.
case
of
hydrogels
containing
the
weakly-acidic
component
(AA)
in
addition
to
DMAEAAm,
D8S2 hydrogels with respect to the addition of different metal ions for System III
sensitivity to metal ions is mostly controlled by the binding of metal ions to the DMAEAAm moiety.
2+
4. Conclusions
Weakly
acidic
components
are
not
to bindthat
to metal
ions, as theymoiety
are in shows
the protonated
state.
For
Based
on these
results, it
can
beable
concluded
the DMAEAAm
sensitivity
to Cu
2+
systems
a acidic
component
that
isIfinDMAEAAm
an ionized
state
in allare
pHpresent
conditions
(AMPS)
in addition
and
ions
under
conditions.
moieties
in and
excess
in any
system,
InZn
thiscontaining
study,
pHand metal
ion-sensitive
hydrogels
were
synthesized,
their
swelling
to
DMAEAAm,
deswelling
is
observed
both
due
to
the
binding
of
metal
ions
to
dimethylamino,
behavior under different pH conditions and with different metal ions was investigated. The as
well as the of
sulfonate
component.
introduction
multi-sensitive
components into hydrogels can enhance the potential of such
materials
for
fabricating
sensors.
The
introduction
of
monomer
N-[2(dimethylaminoethyl)acrylamide] (DMAEAAm) confers both pH and metal ion sensitivity on the
hydrogels. Introduction of other ionizable monomers, like acrylic acid (AA, weakly ionizable) and 2-
Polymers 2016, 8, 233
14 of 16
deswelling of hydrogels is observed with the successive addition of selective metal ions. The reasons
for deswelling as discussed above are the deprotonation of DMEAAm moieties by metal ions, as
well as metal ions interacting with more than one amino group, resulting in additional crosslinking.
In the case of hydrogels containing the weakly-acidic component (AA) in addition to DMAEAAm,
sensitivity to metal ions is mostly controlled by the binding of metal ions to the DMAEAAm moiety.
Weakly acidic components are not able to bind to metal ions, as they are in the protonated state.
For systems containing a component that is in an ionized state in all pH conditions (AMPS) in addition
to DMAEAAm, deswelling is observed both due to the binding of metal ions to dimethylamino, as
well as the sulfonate component.
4. Conclusions
In this study, pH- and metal ion-sensitive hydrogels were synthesized, and their swelling behavior
under different pH conditions and with different metal ions was investigated. The introduction of
multi-sensitive components into hydrogels can enhance the potential of such materials for fabricating
sensors. The introduction of monomer N-[2-(dimethylaminoethyl)acrylamide] (DMAEAAm) confers
both pH and metal ion sensitivity on the hydrogels. Introduction of other ionizable monomers, like
acrylic acid (AA, weakly ionizable) and 2-acrylamido-2-methyl-1-propanesulphonic acid (AMPS,
highly ionizable), results in polyampholyte networks. Variation of the crosslinking density and the
ratio of the composition of ionizable monomers generated different responses of the volume degree of
swelling. Thus, the desired response can be obtained by fine-tuning the ratio of ionizable components
or by varying crosslinking density. The preliminary pH sensitivity measurement establishes the
different pH ranges in which hydrogels have different characteristics due to the presence of additional
interactions, which develop as the result of the presence of different species in the network structure.
Metal ion sensitivity measurements were done under acidic conditions to understand the sensitivity of
these hydrogels towards metal ions, like Cu2+ , Zn2+ and Ag+ , in a competitive environment. It was
observed that different responses were obtained under different conditions of measurement and
different pre-treatment conditions. The response of hydrogels towards the addition of metal ions
depends largely on the initial state of existence of the hydrogel network, which in-turn depends on
various factors, like the composition of hydrogels and the pH of the external solution. Thus, the desired
response can be obtained by adjusting the parameters, like the composition, pH and initial state of
the hydrogels. It can be concluded that this study provides detailed information on the synthesis and
characterization of the swelling behavior of pH- and metal ion-sensitive hydrogels under different pH
conditions, with different types of metal ions and varying concentrations of metal ions.
Acknowledgments: Leena Nebhani acknowledges funding from Deutscher Akademischer Austausch Dienst
(DAAD) in the form of the Indian Institute of Technology (IIT) model sandwich scholarship and seed grant from
the Indian Institute of Technology Delhi.
Author Contributions: Leena Nebhani performed the experiments, analyzed the data and contributed to the
manuscript writing and discussion of the manuscript. Veena Choudhary, Hans-Jürgen P. Adler and Dirk Kuckling
conceived of the main ideas of this research and provided financial support, reviewed this article and discussed
the results and data.
Conflicts of Interest: The authors declare no conflict of interest.
Abbreviations
The following abbreviations are used in this manuscript:
DMAEAAm
DMAAm
AA
AMPS
BIS
PBS
Irgacure 2959
N-[2-(dimethylaminoethyl)acrylamide]
N,N-dimethylacrylamide
Acrylic acid
2-acrylamido-2-methyl-1-propanesulphonic acid
N,N-Methylenebisacrylamide
Phosphate-buffered saline
2-Hydroxy-1-[4-(2-hydroxyethoxy) phenyl]-2-methyl-1-propanone
Polymers 2016, 8, 233
15 of 16
References
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
Beebe, D.J.; Moore, J.S.; Bauer, J.M.; Yu, Q.; Liu, R.H.; Devadoss, C.; Jo, B.H. Functional hydrogel structures
for autonomous flow control inside microfluidic channels. Nature 2000, 404, 588. [CrossRef] [PubMed]
Eddington, D.T.; Liu, R.H.; Moore, J.S.; Beebe, D.J. An organic self-regulating microfluidic system. Lab. Chip
2001, 1, 96. [CrossRef] [PubMed]
Ionov, L. Hydrogel-based actuators: possibilities and limitations. Mater. Today 2014, 17, 494. [CrossRef]
Döring, A.; Birnbaum, W.; Kuckling, D. Responsive hydrogels – structurally and dimensionally optimized
frameworks for application in catalysis, micro-system, technology and material science. Chem. Soc. Rev.
2013, 42, 7391. [CrossRef] [PubMed]
Katchalsky, A.; Michaeli, I. Polyelectrolyte gels in salt solutions. J. Polym. Sci. 1955, 15, 69. [CrossRef]
Brannon-Peppas, L.; Peppas, N.A. Equilibrium swelling behavior of pH-sensitive hydrogels. Chem. Eng. Sci.
1991, 46, 715. [CrossRef]
Oppermann, W. Polyelectrolyte gels. In Proceedings of the ACS Symposium Series No. 480, Washington,
DC, USA, August 1990; American Chemical Society: Washington, DC, USA, 1992; p. 159.
Siegel, R.A.; Firestone, B.A. pH-dependent equilibrium swelling properties of hydrophobic polyelectrolyte
copolymer gels. Macromolecules 1988, 21, 3254. [CrossRef]
Cornejo-Bravo, J.M.; Siegel, R.A. Water vapour sorption behaviour of copolymers of N,N-diethylaminoethyl
methacrylate and methy methacrylate. Biomaterials 1996, 17, 1187. [CrossRef]
Bashir, R.; Hilt, J.Z.; Elibol, O.; Gupta, A.; Peppas, N.A. Micromechanical cantilever as an ultrasensitive pH
microsensor. Appl. Phy. Lett. 2002, 81, 3091. [CrossRef]
Liu, R.H.; Yu, Q.; Beebe, D.J. Fabrication and characterization of hydrogel-based microvalves.
J. Microelectromech. Syst. 2002, 11, 45. [CrossRef]
Yajima, Y.; Yamada, M.; Yamada, E.; Iwase, M.; Seki, M. Facile fabrication processes for hydrogel-based
microfluidic devices made of natural biopolymers. Biomicrofluidics 2014, 8, 024115. [CrossRef] [PubMed]
Tanaka, T. Collapse of gels and the critical endpoint. Phys. Rev. Lett. 1978, 40, 820. [CrossRef]
Hirotsu, S.; Hirokawa, Y.; Tanaka, T. Volume phase transition of ionized N-isopropylacrylamide gels.
J. Chem. Phys. 1987, 87, 1392. [CrossRef]
Beltran, S.; Baker, J.P.; Hooper, H.H.; Blanch, H.W.; Prausnitz, J.M. Swelling equilibria for weakly ionizable,
temperature-sensitive hydrogels. Macromolecules 1991, 24, 549. [CrossRef]
Taylor, L.D.; Ceranknowski, L.D. Preparation of films exhibiting a balanced temperature dependence to
permeation by aqueous solution–A study of lower consolute behavior. J. Polym. Sci. Part A 1975, 13, 2551.
[CrossRef]
Prochazka, K.; Matin, T.J.; Webber, S.E.; Munk, P. Onion-type micelles in aqueous media. Macromolecules
1996, 29, 6525. [CrossRef]
Kuckling, D.; Adler, H.-J.P.; Arndt, K.F.; Ling, L.; Habicher, W.D. Temperature and pH dependent solubility
of novel poly(N-isopropylacrylamide)-copolymers. Macromol. Chem. Phys. 2000, 201, 273. [CrossRef]
Wang, X.; Ye, G.; Wang, X. Hydrogel diffraction gratings functionalized with crown ether for heavy metal
ion detection. Sens. Actuators B 2014, 193, 413. [CrossRef]
Pi, S.-W.; Ju, X.-J.; Wu, H.-G.; Xie, R.; Chu, L.-Y. Smart responsive microcapsules capable of recognizing
heavy metal ions. J. Colloid Interface Sci. 2010, 349, 512. [CrossRef] [PubMed]
Luo, Q.; Guan, Y.; Zhang, Y.; Siddiq, M. Lead-sensitive PNIPAM microgels modified with crown ether
groups. J. Polym. Sci. Part A 2010, 48, 4120. [CrossRef]
Kuckling, D.; Pareek, P. Synthesis of transition-metal-ion-selective poly(N-isopropylacrylamide) hydrogels
by the incorporation of an aza crown ether. J. Polym. Sci. 2003, 41, 1594. [CrossRef]
Mayes, A.G.; Blyth, J.; Millington, R.B.; Lowe, C.R. Metal ion-sensitive holographic sensors. Anal. Chem.
2002, 74, 3649. [CrossRef] [PubMed]
Holtz, J.H.; Hotlz, J.S.; Munro, C.H.; Asher, S.A. Intelligent polymerized crystalline colloidal arrays: novel
chemical sensor materials. Anal. Chem. 1998, 70, 780. [CrossRef]
Holtz, J.H.; Asher, S.A. Polymerized colloidal crystal hydrogel films as intelligent chemical sensing material.
Nature 1997, 389, 829. [CrossRef]
Polymers 2016, 8, 233
26.
27.
28.
29.
30.
31.
32.
33.
16 of 16
Bünemann, H.; Dattagupta, N.; Schuetz, H.J.; Müller, W. Synthesis and properties of acrylamide-substituted
base pair specific dyes for deoxyribonucleic acid template mediated synthesis of dye polymers. Biochemistry
1981, 20, 2864. [CrossRef] [PubMed]
Gao, M.; Gawel, K.; Stokke, B.T. Polyelectrolyte and antipolyelectrolyte effects in swelling of polyampholyte
and polyzwitterionic charge balanced and charge offset hydrogels. Eur. Polym. J. 2014, 53, 65. [CrossRef]
Ihsan, A.B.; Sun, T.L.; Kuroda, S.; Haque, M.A.; Kurokawa, T.; Nakajima, T.; Gong, J.P. A phase diagram of
neutral polyampholyte—From solution to tough hydrogel. J. Mater. Chem. B 2013, 1, 4555. [CrossRef]
Masaki, M.; Kokufuta, E. Polyampholyte gels of a cross-linked polyanion or polycation network into which
an oppositely charged polyion was immobilized. Colloid Polym. Sci. 2013, 291, 669. [CrossRef]
Cai, Q.Y.; Grimes, C.A. A remote query magnetoelastic pH sensor. Sens. Actuators B 2000, 71, 112. [CrossRef]
Yang, R.; Zompa, L.J. Metal complexes of cyclic triamines. 1. Complexes of 1,4,5-triazacyclononane ([9]aneN3)
with nickel (II), copper (II), and zinc (II). Inorg. Chem. 1976, 15, 1499. [CrossRef]
Hilliard, H.M.; Yoke, J.T. Silver(I) complexes of bicyclic tertiary amines. Inorg. Chem. 1966, 5, 57. [CrossRef]
Pearson, R.G. Hard and soft acids and bases. J. Am. Chem. Soc. 1963, 85, 3533. [CrossRef]
© 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access
article distributed under the terms and conditions of the Creative Commons Attribution
(CC-BY) license (http://creativecommons.org/licenses/by/4.0/).