Dual Temperature and Metal Salts-Responsive Interpenetrating Polymer Networks Composed of Poly (N-isopropylacrylamide) and Polyethylene Glycol

Novel interpenetrating polymer networks (IPNs) composed of poly(N-isopropylacrylamide) (poly-NIPAM) and polyethers—namely, polyethylene glycol (PEG) and poly(tetramethylene oxide)—were synthesized in the absence and presence of polysiloxane containing a silanol residue. Gelation was accomplished using end-capped polyethers with trimethoxysilyl moieties and proceeded through simultaneous radical gelation of NIPAM and condensation of the silyl groups to form siloxane linkages. Thus, a novel one-step method constructing an IPN structure was provided. The obtained IPNs showed a gentle temperature-responsive volume change in water owing to the constructed poly-NIPAM gel component. In addition, a specific color-change response to chemical stimuli, such as CuCl2 and AgNO3 in water, was observed only when both components of poly-NIPAM and PEG existed in a gel form. For example, a single network gel composed of poly-NIPAM or PEG was isolated as a pale blue hydrogel, whereas IPNs composed of poly-NIPAM and PEG components turned yellow after swelling in an aqueous CuCl2 solution (0.1 M, pale blue). Dual-responsive functionalities of the synthesized hydrogels to temperature and metal salts, along with volume and color changes, were demonstrated.


Introduction
Hydrogels are hydrophilic polymer networks that hold large amounts of aqueous media. They have been frequently applied in biomedical fields, drug delivery, separation, self-healing technologies, etc.; thus, development of hydrogels is an area with a high potential. For example, chitosan hydrogels for ocular application and use as a 3D printing material were recently reported [1][2][3]. A hydrogel that changes (typically in volume) when exposed to external stimuli, such as temperature, pH, chemicals, and electricity, is called an intelligent or smart hydrogel [4][5][6]. A typical smart hydrogel is the poly(Nisopropylacrylamide) (poly-NIPAM) gel, which undergoes a volume phase transition at a low critical solution temperature of approximately 32 • C. Poly-NIPAM can be combined with other polymers, such as poly(acrylic acid) and polyethylene glycol (PEG), which contribute biocompatibility, permeability, metal complex formation ability, and hydrophilicity to form a gel with superior properties and functions. For instance, NIPAM is often combined with telechelic-type PEG macromonomers bearing vinyl groups and macroinitiators, forming gels with block and branched copolymer structures [7][8][9][10].
Interpenetrating polymer network (IPN) gels, consisting of two or more networks that are physically entangled but not covalently bonded, are attractive new materials because they synergistically affect the properties of the network and improve the gel strength. Various applications, including recent developments such as a nano-filtration membrane, have been made [11][12][13]. Therefore, the IPN is a valuable option for smart hydrogels [14][15][16]; Scheme 1. IPN synthesis with disilylated polyethers and NIPAM in the presence of polysiloxanecontaining silanol groups.

Preparation of Disilylated Polyethers
The disilylated polyethers DS-PEG and DS-PTMO were generated in situ by reacting their corresponding polyethers with IPTMS in the presence of DBTDL (molar ratio 1:2:0.01) in THF (35 wt.%) for 2 h at 50 °C, then for 1 h at room temperature under a N2 atmosphere. The prepared THF solutions were used without isolation.
A solution of DS-PEG or DS-PTMO in THF (1.5 mL) was introduced to a perfluoroalkoxyl (PFA) resin test tube and was left standing still for 20 h at 60 °C to allow the gel formation [29]. The obtained product was dried overnight under reduced pressure at 80 °C. Scheme 1. IPN synthesis with disilylated polyethers and NIPAM in the presence of polysiloxanecontaining silanol groups.

Preparation of Disilylated Polyethers
The disilylated polyethers DS-PEG and DS-PTMO were generated in situ by reacting their corresponding polyethers with IPTMS in the presence of DBTDL (molar ratio 1:2:0.01) in THF (35 wt.%) for 2 h at 50 • C, then for 1 h at room temperature under a N 2 atmosphere. The prepared THF solutions were used without isolation.
A solution of DS-PEG or DS-PTMO in THF (1.5 mL) was introduced to a perfluoroalkoxyl (PFA) resin test tube and was left standing still for 20 h at 60 • C to allow the gel formation [29]. The obtained product was dried overnight under reduced pressure at 80 • C. The homogeneous gels prepared from DS-PEG and DS-PTMO, called G PEG and G PTMO , respectively, were isolated with almost quantitative yields of 0.480 and 0.517 g, respectively. Figure 1 presents the FT-IR spectra of the obtained gels and the starting material (PEG). The characteristic absorptions of the C=O (1712 cm −1 ) and N-H (1529 cm −1 ) bonds in the urethane linkages and silyl groups, such as Si-C (1250 cm −1 ) and Si-O-Si (1110 cm −1 ), along with those of the polyether unit, were clearly observed. These results indicated that the polyether gels were effectively produced by the condensation reaction of the end-capped silyl groups of the polyethers. The homogeneous gels prepared from DS-PEG and DS-PTMO, called GPEG and GPTMO, respectively, were isolated with almost quantitative yields of 0.480 and 0.517 g, respectively. Figure 1 presents the FT-IR spectra of the obtained gels and the starting material (PEG). The characteristic absorptions of the C=O (1712 cm −1 ) and N-H (1529 cm −1 ) bonds in the urethane linkages and silyl groups, such as Si-C (1250 cm −1 ) and Si-O-Si (1110 cm −1 ), along with those of the polyether unit, were clearly observed. These results indicated that the polyether gels were effectively produced by the condensation reaction of the endcapped silyl groups of the polyethers.

IPN Synthesis
A THF solution of poly-SOLPh was prepared from poly-SOL (2.0 mL, 1.6 M, theoretical) with PhTMS (0.2 equivalent to the used silica). This solution was used without isolation, as previously reported [27]. NIPAM (0.90 g, 8.0 mmol), BIS, and AIBN ([NIPAM]/[BIS]/[AIBN] = 100/4/1) were introduced to the poly-SOLPh (2 mL) solution in a PFA test tube. In the reaction without poly-SOLPh, the polysiloxane solution was replaced with THF (2 mL). After adding the DS-PEG or DS-PTMO solution (1.5 mL), the mixture was gelated for 24 h at 60 °C under a N2 atmosphere. The obtained gel was immersed first in THF for 2 days, then in distilled water for 2 days. Finally, it was dried overnight under reduced pressure at 80 °C.
The swelling degrees of the obtained gels were evaluated by the conventional gravimetric method [23]. The gels were immersed in an excess amount of distilled water or an aqueous metal-salt solution for 24 h at an appropriate temperature. When swollen, the gels were removed from the medium and weighed. The degree of swelling (Q) was calculated as where md and mw are the weights of the dried and wet samples, respectively.

IPN Synthesis
A THF solution of poly-SOL Ph was prepared from poly-SOL (2.0 mL, 1.6 M, theoretical) with PhTMS (0.2 equivalent to the used silica). This solution was used without isolation, as previously reported [27]. NIPAM (0.90 g, 8.0 mmol), BIS, and AIBN ([NIPAM]/[BIS]/[AIBN] = 100/4/1) were introduced to the poly-SOL Ph (2 mL) solution in a PFA test tube. In the reaction without poly-SOL Ph , the polysiloxane solution was replaced with THF (2 mL). After adding the DS-PEG or DS-PTMO solution (1.5 mL), the mixture was gelated for 24 h at 60 • C under a N 2 atmosphere. The obtained gel was immersed first in THF for 2 days, then in distilled water for 2 days. Finally, it was dried overnight under reduced pressure at 80 • C.
The swelling degrees of the obtained gels were evaluated by the conventional gravimetric method [23]. The gels were immersed in an excess amount of distilled water or an aqueous metal-salt solution for 24 h at an appropriate temperature. When swollen, the gels were removed from the medium and weighed. The degree of swelling (Q) was calculated as where m d and m w are the weights of the dried and wet samples, respectively. Table 1 lists the yields and swelling degrees of the IPNs synthesized from the endcapped polyethers, NIPAM, and BIS in the presence and absence of the reactive polysiloxane, poly-SOL Ph . A single NIPAM network, G NIPAM , was prepared under the same conditions (NIPAM = 0.  The gelation was effective and afforded opaque white hydrogels after washing in excess water; in contrast, the G NIPAM hydrogel was clear, as shown in Figure 2. After drying, hard gels were isolated in good yield. For example, gelation with DS-PEG and no poly-SOL Ph produced 1.12 g of a THF-and water-insoluble product, IPN PEG (run 1). Although the poly-SOL Ph addition slightly reduced the yield of the gel product (runs 2 and 4), the method easily introduced a functional group into the PEG network. In this instance, a phenyl moiety was attached to the gel as described later. gelation was effective and afforded opaque white hydrogels after washing in excess water; in contrast, the GNIPAM hydrogel was clear, as shown in Figure 2. After drying, hard gels were isolated in good yield. For example, gelation with DS-PEG and no poly-SOLPh produced 1.12 g of a THF-and water-insoluble product, IPNPEG (run 1). Although the poly-SOLPh addition slightly reduced the yield of the gel product (runs 2 and 4), the method easily introduced a functional group into the PEG network. In this instance, a phenyl moiety was attached to the gel as described later.    (Table 1, runs 1-4) and GNIPAM. The spectra display the characteristic absorptions of the C=O bond (1700 cm −1 ) in the urethane linkages and the C-O-C group (1100 cm −1 ) of the polyether unit, along with the absorptions of poly-NIPAM (C=O, 1640 cm −1 ; N-H, 1540 cm −1 ; C-(CH3)2, 1386 and 1367 cm −1 ). The spectra of the IPNSOL + PEG and IPNSOL + PTMO gels additionally exhibited the characteristic bending-vibration band of the aromatic group around 690 cm −1 , indicating that these gels contained the poly-SOLPh component. These results indicated that the IPN structure was successfully constructed during gelation.  . The spectra of the IPN SOL + PEG and IPN SOL + PTMO gels additionally exhibited the characteristic bending-vibration band of the aromatic group around 690 cm −1 , indicating that these gels contained the poly-SOL Ph component. These results indicated that the IPN structure was successfully constructed during gelation.

Synthesis of IPNs
The IPN system can improve the poor mechanical properties of the poly-NIPAM gel [14][15][16]. The strengths of the G NIPAM , IPN PTMO (Table 1, run 3), and IPN SOL + PTMO (run 4) hydrogels were simply estimated using a rheometer equipped with a 5 mm φ cylindrical plunger, which was depressed to a depth of 4 or 5 mm into the sample. The maximum test force was then detected. Here the hydrogel samples were cut so that their height almost equaled the stroke displacement. The strengths of the G NIPAM , IPN PTMO , and IPN SOL + PTMO hydrogels were 0.035, 0.29, and 0.32 MPa, respectively. Note that the strength was nearly ten times higher in the IPN gels than in the poly-NIPAM gel, again supporting the IPN-type structure of the constructed gels.  The IPN system can improve the poor mechanical properties of the poly-NIPAM g [14][15][16]. The strengths of the GNIPAM, IPNPTMO (Table 1, run 3), and IPNSOL + PTMO (run hydrogels were simply estimated using a rheometer equipped with a 5 mm ϕ cylindric plunger, which was depressed to a depth of 4 or 5 mm into the sample. The maximum te force was then detected. Here the hydrogel samples were cut so that their height almo equaled the stroke displacement. The strengths of the GNIPAM, IPNPTMO, and IPNSOL + PTM hydrogels were 0.035, 0.29, and 0.32 MPa, respectively. Note that the strength was near ten times higher in the IPN gels than in the poly-NIPAM gel, again supporting the IPN type structure of the constructed gels. Figure 4 shows SEM images of the IPNPEG and IPNSOL + PEG cryogels isolated by freez drying from water. Images of GNIPAM are shown for comparison. The gels exhibited a h mogeneous sponge-like porous structure, but the morphologies greatly differed betwee GNIPAM and the IPNs containing the PEG network. In addition, the pore size was muc smaller in the IPNSOL + PEG containing the polysiloxane component than in the IPNPEG ge According to these observations, the polymer components forming the IPN structures sig nificantly affected the gel morphology.  (Table 1, run 1), and (c) IPNSOL + PEG (run 2) (magnification, × 1000; scale bar, 10 μm). Th gels were prepared by freeze-drying from water.

Swelling Properties of the Obtained IPNs in Water
The swelling degrees Q of the IPNs were measured at 3 °C in water and are listed Table 1. The Q value of the GNIPAM hydrogel (13.8 at 3 °C) was much higher than those the IPNs. The IPNPEG and IPNSOL + PEG gels containing a PEG chain tended to exhibit high  Figure 4 shows SEM images of the IPN PEG and IPN SOL + PEG cryogels isolated by freeze-drying from water. Images of G NIPAM are shown for comparison. The gels exhibited a homogeneous sponge-like porous structure, but the morphologies greatly differed between G NIPAM and the IPNs containing the PEG network. In addition, the pore size was much smaller in the IPN SOL + PEG containing the polysiloxane component than in the IPN PEG gel. According to these observations, the polymer components forming the IPN structures significantly affected the gel morphology. The IPN system can improve the poor mechanical properties of the poly-NIPAM gel [14][15][16]. The strengths of the GNIPAM, IPNPTMO (Table 1, run 3), and IPNSOL + PTMO (run 4) hydrogels were simply estimated using a rheometer equipped with a 5 mm ϕ cylindrical plunger, which was depressed to a depth of 4 or 5 mm into the sample. The maximum test force was then detected. Here the hydrogel samples were cut so that their height almost equaled the stroke displacement. The strengths of the GNIPAM, IPNPTMO, and IPNSOL + PTMO hydrogels were 0.035, 0.29, and 0.32 MPa, respectively. Note that the strength was nearly ten times higher in the IPN gels than in the poly-NIPAM gel, again supporting the IPNtype structure of the constructed gels. Figure 4 shows SEM images of the IPNPEG and IPNSOL + PEG cryogels isolated by freezedrying from water. Images of GNIPAM are shown for comparison. The gels exhibited a homogeneous sponge-like porous structure, but the morphologies greatly differed between GNIPAM and the IPNs containing the PEG network. In addition, the pore size was much smaller in the IPNSOL + PEG containing the polysiloxane component than in the IPNPEG gel. According to these observations, the polymer components forming the IPN structures significantly affected the gel morphology.  (Table 1, run 1), and (c) IPNSOL + PEG (run 2) (magnification, × 1000; scale bar, 10 μm). The gels were prepared by freeze-drying from water.

Swelling Properties of the Obtained IPNs in Water
The swelling degrees Q of the IPNs were measured at 3 °C in water and are listed in Table 1. The Q value of the GNIPAM hydrogel (13.8 at 3 °C) was much higher than those of the IPNs. The IPNPEG and IPNSOL + PEG gels containing a PEG chain tended to exhibit higher Qs than the IPNPTMO and IPNSOL + PTMO gels with a PTMO chain. Therefore, the hydrophilicity of the polyether chain influences the swelling properties of the synthesized IPNs.  (Table 1, run 1), and (c) IPN SOL + PEG (run 2) (magnification, × 1000; scale bar, 10 µm). The gels were prepared by freeze-drying from water.

Swelling Properties of the Obtained IPNs in Water
The swelling degrees Q of the IPNs were measured at 3 • C in water and are listed in Table 1. The Q value of the G NIPAM hydrogel (13.8 at 3 • C) was much higher than those of the IPNs. The IPN PEG and IPN SOL + PEG gels containing a PEG chain tended to exhibit higher Qs than the IPN PTMO and IPN SOL + PTMO gels with a PTMO chain. Therefore, the hydrophilicity of the polyether chain influences the swelling properties of the synthesized IPNs.
The temperature dependences of the swelling behaviors are depicted in Figure 5. The Q of the G NIPAM hydrogel sharply decreased with temperature. The synthesized IPNs also responded to temperature with a volume change, but their Q values decreased more gently with increasing temperature. At temperatures above the volume phase transition temperature (VPTT) of the poly-NIPAM gel, the IPNs containing a PTMO chain demonstrated low Q values similar to that of G NIPAM , whereas the IPN PEG and IPN SOL + PEG gels The temperature dependences of the swelling behaviors are depicted in Figure 5. The Q of the GNIPAM hydrogel sharply decreased with temperature. The synthesized IPNs also responded to temperature with a volume change, but their Q values decreased more gently with increasing temperature. At temperatures above the volume phase transition temperature (VPTT) of the poly-NIPAM gel, the IPNs containing a PTMO chain demonstrated low Q values similar to that of GNIPAM, whereas the IPNPEG and IPNSOL + PEG gels demonstrated higher swelling behavior than GNIPAM. These results again suggested that the hydrophilic property of the polyether chain significantly affected the swelling behavior of the IPNs.

Responses of the Obtained Hydrogels to Metal-Salt Stimuli in Water
The swelling responses of the gels in the presence of various metal salts (0.1 M) were tested in water at 24 °C. The observed behaviors were evaluated by their relative swelling ratios QX/Qnone, where QX and Qnone are the swelling degrees in the presence and absence of a metal salt (X), respectively. The IPN hydrogels were stable under the conditions of swelling experiments, and selected results are shown in Figure 6. The IPNSOL gel, composed of poly-NIPAM and poly-SOLPh with no polyether component, was prepared as previously reported [24] for comparison.

Responses of the Obtained Hydrogels to Metal-Salt Stimuli in Water
The swelling responses of the gels in the presence of various metal salts (0.1 M) were tested in water at 24 • C. The observed behaviors were evaluated by their relative swelling ratios Q X /Q none , where Q X and Q none are the swelling degrees in the presence and absence of a metal salt (X), respectively. The IPN hydrogels were stable under the conditions of swelling experiments, and selected results are shown in Figure 6. The IPN SOL gel, composed of poly-NIPAM and poly-SOL Ph with no polyether component, was prepared as previously reported [24] for comparison.
The relative swelling ratio of the poly-NIPAM gel was less than 1.0, indicating that it shrunk during exposure to aqueous solutions of various metal salts (LiCl, MgCl 2 , CuCl 2 , and AgNO 3 ). The estimated Q X /Q none values of the IPN SOL hydrogel were much lower than those of G NIPAM , indicating significant shrinkage in the presence of metal salts. This volume response was probably elicited by the hydrophobic property of the polysiloxane component. In contrast, when the IPN hydrogels containing polyether components (PEG and PTMO) were chemically stimulated by MgCl 2 , their Q X /Q none values notably increased. This behavior might be attributed to the coordinately incorporated magnesium ions in the polyether comonents, which improved the swelling ability. Aqueous media containing typical metal salts (NaCl, CH 3 CO 2 K, (CH 3 CO 2 ) 2 Ca, BaCl 2 , and LiCl), scarcely changed the volume of the IPNs. Therefore, the synthesized IPNs selectively responsed with a positive volume change to magnesium ions as an external stimulus in water. No response other than a volume change was observed in the MgCl 2 experiment. The relative swelling ratio of the poly-NIPAM gel was less than 1.0, indicating that shrunk during exposure to aqueous solutions of various metal salts (LiCl, MgCl2, CuCl and AgNO3). The estimated QX/Qnone values of the IPNSOL hydrogel were much lower tha those of GNIPAM, indicating significant shrinkage in the presence of metal salts. This volum response was probably elicited by the hydrophobic property of the polysiloxane compo nent. In contrast, when the IPN hydrogels containing polyether components (PEG an PTMO) were chemically stimulated by MgCl2, their QX/Qnone values notably increased This behavior might be attributed to the coordinately incorporated magnesium ions in th polyether comonents, which improved the swelling ability. Aqueous media containin typical metal salts (NaCl, CH3CO2K, (CH3CO2)2Ca, BaCl2, and LiCl), scarcely changed th volume of the IPNs. Therefore, the synthesized IPNs selectively responsed with a positiv volume change to magnesium ions as an external stimulus in water. No response othe than a volume change was observed in the MgCl2 experiment.
During the swelling experiments in aqueous solutions of transition metal salts (CuC and AgNO3), the IPN hydrogels containing a PEG component underwent a unique colo change response to the metal salts as external stimuli (Figure 7), although a volum change was hardly observed. During the swelling experiments in aqueous solutions of transition metal salts (CuCl 2 and AgNO 3 ), the IPN hydrogels containing a PEG component underwent a unique colorchange response to the metal salts as external stimuli (Figure 7), although a volume change was hardly observed. For example, the GNIPAM and GPEG gels composed of poly-NIPAM and PEG networks, respectively, were isolated as pale blue hydrogels after swelling in aqueous CuCl2 solution (panels a and b in Figure 7). In marked contrast, the IPNPEG and IPNSOL + PEG IPNs, composed of poly-NIPAM and PEG components, respectively, turned yellow when immersed in aqueous CuCl2 solution (Figure 7c,d), whereas IPNSOL+PTMO containing PTMO chains did For example, the G NIPAM and G PEG gels composed of poly-NIPAM and PEG networks, respectively, were isolated as pale blue hydrogels after swelling in aqueous CuCl 2 solution (panels a and b in Figure 7). In marked contrast, the IPN PEG and IPN SOL + PEG IPNs, composed of poly-NIPAM and PEG components, respectively, turned yellow when immersed in aqueous CuCl 2 solution (Figure 7c,d), whereas IPN SOL+PTMO containing PTMO chains did not change color (Figure 7e). Accordingly, a color-change response to an aqueous CuCl 2 occurred only in the gels containing poly-NIPAM and PEG. These observations suggested that a CuCl 2 complex coordinated by both the NIPAM and the ethylene glycol units selectively formed in the interior space of the hydrogels [31][32][33][34]. Furthermore, the IPNs containing a PEG chain presented no color change when swelled in an aqueous CuSO 4 solution.
The synthesized IPNs with a PEG component also changed color in response to AgNO 3 as an external stimulus. When swollen in a solution of AgNO 3 , these hydrogels turned dark brown (Figure 7c',d'), whereas the other gels (G NIPAM , G PEG , and IPN SOL + PTMO ) scarcely changed color or afforded a pale pink hydrogel. In summary, the IPN PEG and IPN SOL + PEG gels showed remarkable and selective color changes in response to external stimuli of aqueous metal salts (CuCl 2 and AgNO 3 ).
We recently developed a novel multi-responsive IPN composed of poly-NIPAM and polysiloxane networks containing a chromogenic receptor for anion species. This system attained characteristic color and volume changes responding to chemical stimuli, such as acetate and/or fluoride ions, in the organic solvent N,N-dimethylformamide, as well as a typical temperature-responsive volume change in water [23]. The IPNs synthesized in this study, such as IPN PEG and IPN SOL + PEG , provide another multi-responsive system to temperature and chemical stimuli of metal salts; in addition, these responsive behaviors occur in aqueous media.

Conclusions
Novel IPNs composed of poly-NIPAM and polyether (PEG or PTMO) were easily synthesized by a one-step method, where simultaneous reactions of radical gelation and condensation of alkoxysilanes attached on the polyether ends proceeded. The IPNs were formed in the presence or absence of polysiloxane-containing silanols. The obtained IPN hydrogels showed an improved mechanical property (gel strength) in comparison with a single network poly-NIPAM gel. In addition, the IPN hydrogels with a PEG chain demonstrated a synergistic effect of both networks on responsive behavior to chemical stimuli of metal salts, such as CuCl 2 and AgNO 3 , as well as a volume change in response to temperature. The external chemical stimulus was characterized by a remarkable color change. Therefore, the IPNs having dual-responsive functionalities, reacting to temperature (depending on the VPTT of poly-NIPAM gel in water) and metal salts, were successfully developed. The simultaneous gelation system established here could contribute to facile preparation of IPN with novel structure and function, and the constructed hydrogels may be applicable to sensing materials showing a characteristic responsive behavior.

Data Availability Statement:
The data presented in this study are available on request from the corresponding author.