Two-step volume phase transition mechanism of poly(N-vinylcaprolactam) hydrogel online-tracked by two-dimensional correlation spectroscopy

Gehong Su , Tao Zhou *, Xifei Liu and Yulin Zhang
State Key Laboratory of Polymer Materials Engineering of China, Polymer Research Institute, Sichuan University, Chengdu 610065, China. E-mail: zhoutaopoly@scu.edu.cn; Fax: +86-28-85402465; Tel: +86-28-85402601

Received 7th July 2017 , Accepted 20th September 2017

First published on 21st September 2017


In this study, temperature-dependent FTIR spectroscopy in combination with the perturbation–correlation moving-window (PCMW2D) technique and generalized two-dimensional (2D) correlation analysis was applied to investigate the phase transition mechanism of poly(N-vinylcaprolactam) (PVCL) hydrogel upon heating. In the conventional 1D FTIR spectra, the gradual dehydration of C–H groups, as well as the gradual dissociation of hydrogen bonds between C[double bond, length as m-dash]O groups and water molecules, was observed during phase transition. Moreover, we found that the rate at which water molecules were expelled out of the gel network during phase transition was changed to a sigmoid mode, rather than increasing linearly with increasing temperature. PCMW2D FTIR spectra revealed that the phase transition of PVCL hydrogel can be divided into two steps (named as I and II) upon heating, and we further determined the temperature regions of steps I and II to be 29.0–35.7 °C and 35.7–47.5 °C, respectively. Step I is the formation of hydrophobic domains in the gel, and step II is the chain collapse of the gel. Finally, with the help of generalized 2D correlation analysis, it was confirmed that the transformation of hydrogen bonds was the driving force of the hydrophobic domain formation process, while the hydrophobic interaction of C–H groups was the driving force for the chain collapse process. Combined with the obtained sequential orders of step I and step II, an integrated two-step phase transition mechanism of PVCL hydrogel upon heating was proposed.


1. Introduction

Over the past few decades, environment-sensitive hydrogels, namely the so-called “smart” hydrogels, which are able to respond to external stimuli such as temperature,1,2 pressure,3 pH,4 and light,5 have attracted tremendous research attention due to their potential scientific and technological applications.6,7 Among various environment-sensitive hydrogels, lower critical solution temperature (LCST)-type temperature-sensitive hydrogels, which possess a LCST in aqueous solution, are especially focused on and are most investigated because of their wide applications in pharmaceutical and industrial fields, such as controlled drug delivery,8 biosensing,9 and tissue engineering,10 to name a few.

Up to the present, the most representative LCST-type temperature-sensitive hydrogel has been poly(N-isopropyl acrylamide) (PNIPAM) hydrogel, which undergoes a reversible, drastic and discontinuous volume phase transition at around its volume phase transition temperature (VPTT) of approximately 32 °C.11 This temperature is extremely close to the physiological one, making the PNIPAM hydrogel very suitable for biomedical applications. However, PNIPAM is known for its cytotoxicity, resulting in low cell viability, and thus its application in drug-delivery systems and also in any in vivo applications may be extremely restricted.12 For this reason, in recent years, poly(N-vinylcaprolactam) (PVCL) has been considered to be a valuable alternative to PNIPAM in biomedical applications, due to its better biocompatibility. Unlike PNIPAM, the hydrophilic carboxylic and amide groups of PVCL are directly connected to the hydrophobic carbon–carbon backbone chain so that PVCL does not produce extra toxic low molecular weight amines during hydrolysis,13 which has been proven by cytotoxicity evaluation.12 Additionally, in contrast to PNIPAM, the phase transition of PVCL is not as sharp and can occur in a wide temperature range from about 30 °C to 50 °C by tuning its molecular weight and concentration.14,15 Owing to their excellent biocompatibility and temperature sensitivity, PVCL-based materials such as copolymers,16 hydrogels,17 and microgels18 have been widely used in biomedical fields.

In the past few decades, the phase transition behavior of PVCL aqueous solution has been extensively investigated by a variety of methods, including dynamic light scattering,19 small-angle neutron scattering,20 fluorescence,21 infrared spectroscopy,22,23 and so on. It is widely accepted that the hydrophobic interaction is predominant in the phase transition of PVCL in aqueous solution, due to the absence of strong self-associated hydrogen bonds in the globular state.24,25 However, Sun and Wu revealed that hydrogen bonding transformation predominated at the first stage below LCST, while hydrophobic hydration dominated at the second stage above LCST.23 In contrast with the deeply studied PVCL aqueous solution, however, related research about the volume phase transition of PVCL hydrogel is very rare. Mikheeva et al. studied the volume phase transition behavior of PVCL hydrogel by using the high-sensitivity differential scanning calorimetry (HS-DSC) technique. They found that the PVCL hydrogel underwent two successive cooperative transitions between 25 and 50 °C.26 They considered that the low-temperature transition (about 31.5 °C) was connected with micro-segregation, resulting in formation of hydrophobic domains or micelles in the gel; while the high-temperature transition (about 37.6 °C) was associated with the volume collapse transition of the gel. Furthermore, they found that the VPTT of PVCL hydrogel was decreased in the presence of NaCl, and enhanced with a concentration increase of sodium dodecylsulfate (SDS). They thought this phenomenon suggested that both of these two discovered cooperative transitions of PVCL hydrogel were driven by the hydrophobic effect.26

In contrast, related studies of the volume phase transition of PVCL hydrogel are still relatively few, and the micro-dynamics mechanism of the volume phase transition of PVCL hydrogel at the molecular level has never been reported up to now. Moreover, PVCL hydrogel is widely used in both biomedical and industrial fields. Thus, a better understanding of the phase transition behavior of the PVCL hydrogel will be significant.

Generalized two-dimensional (2D) correlation infrared spectroscopy was originally proposed by Noda in 1993,27 and has received great attention in recent decades. By using this technique, the information which cannot readily be captured or is overlapped in conventional 1D FTIR spectra can be easily obtained due to the significantly enhanced spectral resolution.28 Besides, the sequential order of the spectral intensity change can also be easily obtained in combination with Noda's rule. Owing to these two inherent advantages, 2D correlation infrared spectroscopy has been widely used to investigate the complex physical or chemical transition processes of polymers.29–34 Perturbation correlation moving-window two-dimensional (PCMW2D) correlation spectroscopy is a newly-developed analytical tool, which was improved from the conventional moving-window two-dimensional (MW2D) correlation spectroscopy by Morita in 2006.35 In addition to its original ability in determining transition points as conventional MW2D does, PCMW2D can also monitor complicated spectral variations along the perturbation direction.

In this study, a thermal-sensitive PVCL hydrogel was synthesized by free-radical polymerization. After that, temperature-dependent FTIR spectroscopy in combination with the PCMW2D technique and generalized 2D correlation analysis were employed to study the volume phase transition mechanism of PVCL hydrogel upon heating. It was found that the phase transition of PVCL hydrogel can be divided into two steps during heating. The first step is the formation of hydrophobic domains in the gel, resulting predominantly from the weakening of hydrogen bonding between C[double bond, length as m-dash]O groups and water molecules. The second step is the chain collapse of the gel, driven by the hydrophobic interaction of C–H groups. Combining all the obtained information, a two-step phase transition mechanism of PVCL hydrogel was successfully revealed and elucidated.

2. Experimental

2.1. Materials

N-Vinylcaprolactam (VCL) was purchased from Sigma-Aldrich and purified by passing through a short alumina column before use. 2,2′-Azobis(isobutyronitrile) (AIBN) was obtained from Aladdin Reagent Co. and recrystallized from ethanol. N,N′-Methylenebisacrylamide (BIS) was purchased from J&K Scientific Ltd (Beijing, China) and used without further purification. Ethanol was kindly supplied by Chengdu Kelong Chemical Reagent Co. and used as received. Deuterated water (D2O, D-99.9%) was purchased from Cambridge Isotope Laboratories, Inc.

2.2. Synthesis of PVCL hydrogel

The PVCL hydrogel was synthesized via free-radical polymerization of VCL monomer in ethanol/water solution. BIS was used as the cross-linker, and AIBN was used as the initiator. The detailed synthesis procedure is shown in Scheme 1. To be specific, the VCL monomer (4 g) and the BIS cross-linker (0.2 g) were first dissolved in an ethanol (5 g)/water (5 g) co-solvent mixture in a beaker, and filtered to remove any possible precipitates. Then, the solution was transferred to a three-necked round-bottom flask equipped with a mechanical stirrer and reflux condenser, and stirred at 50 °C in a nitrogen atmosphere for at least 2 h to make sure the solution was evenly mixed, and at the same time oxygen was fully expelled from the solution. After natural cooling to room temperature, the solution was transferred into a cylinder vial, and 2 mL of an ethanolic solution containing 0.01 g AIBN was added to the solution to start the polymerization reaction. The reaction was carried out at 60 °C for 2 h. The reaction and chemical structure are shown in Fig. 1. The obtained hydrogel was dialyzed with deionized water for one week to remove the unreacted monomers and the solvent. Then, the purified hydrogel was freeze-dried to a dry gel before use.
image file: c7cp04571a-s1.tif
Scheme 1 Detailed synthesis procedure of PVCL hydrogel.

image file: c7cp04571a-f1.tif
Fig. 1 Free-radical polymerization of VCL to produce PVCL hydrogel.

2.3. Fourier transform infrared spectroscopy

Before the FTIR measurements, a small piece of purified and thoroughly freeze-dried PVCL hydrogel was immersed in D2O at 6 °C for at least three days to ensure that the hydrogel was sufficiently swollen. The well-swollen hydrogel was sealed between two small ZnSe windows and then placed into a liquid cell (programmable heating device). After that, the hydrogel was heated from 22 °C to 52 °C at a rate of 1 °C min−1, and the FTIR spectra in the region of 3800–1000 cm−1 were collected at the same time. A Nicolet iS50 Fourier transform spectrometer equipped with a deuterated triglycine sulfate detector was used for the FTIR measurements, and in total 71 FTIR spectra were obtained upon heating. All spectra were gathered using 20 scans with a resolution of 4 cm−1 to obtain an acceptable signal-to-noise ratio.

2.4. Two-dimensional correlation analysis

The theory and algorithms for PCMW2D and generalized 2D correlation techniques can be found in the literature.27,35 PCMW2D correlation FTIR spectra, as well as the generalized 2D correlation spectra, were all processed, calculated, and plotted by using 2DCS software, which was developed by one of the authors. To obtain a credible result, linear baseline corrections were performed in the regions of 3020–2835 cm−1, 2800–2110 cm−1, and 1645–1560 cm−1 before calculations and the analysis. To generate the high-quality 2D correlation spectra, the window size of PCMW2D spectra was chosen as 11 (2m + 1). In the 2D correlation FTIR spectra, the red areas were defined as positive correlation intensity, while the blue areas represent the negative correlation intensity.

3. Results and discussion

3.1. Temperature-dependent FTIR spectra upon heating

First, note that D2O (rather than H2O) is selected as the solvent here in order to eliminate the overlap of the broad ν(O–H) band of H2O around 3400 cm−1 with the C–H stretching vibration region, as well as the overlap of the δ(O–H) band of H2O around 1640 cm−1 with the amide I region of PVCL hydrogel. As has been reported, the transition temperature of PVCL in D2O is just a little lower than that in H2O,19 and therefore the deuterium isotope effect does not cause an obvious change in the magnitude of hysteresis. Thus, it is a good choice to use D2O as the solvent to investigate the phase transition behavior of PVCL hydrogel in our study.

The temperature-dependent FTIR spectra of PVCL hydrogel in D2O upon heating from 22 °C to 52 °C in the regions of 3020–2820 cm−1, 2800–2110 cm−1, and 1640–1570 cm−1 are illustrated in Fig. 2. For clarity, not all the spectra are displayed here, and the detailed assignments of the bands appearing in Fig. 2 are all summarized in Table 1. It is noted that the amount of the cross-linker (BIS) in the hydrogel is so little that the interaction between VCL repeat units and BIS units can be neglected, and no absorption peaks relating to BIS can be observed in Fig. 2. In addition, note that, in addition to the extensively studied C–H and amide I regions in PVCL-based systems, the stretching vibration of D2O (2800–2110 cm−1) is also investigated in this study. So far, this region has not received the attention of researchers when FTIR spectroscopy has been applied to investigate the phase transition behavior of temperature-sensitive polymer solutions or hydrogels. Moreover, to quantitatively describe the volume phase transition process of PVCL hydrogel upon heating, the temperature-dependent wavenumber shifts of νas(–CH2) and νs(–CH2), as well as the integral area changes of D2O and C[double bond, length as m-dash]O groups, were also determined, as presented in Fig. 3. For Fig. 3(b) and (c), before integration, baseline correction of the bands was needed. Specifically, the baseline corrections were first performed in the regions of 2800–2110 cm−1 and 1645–1560 cm−1, and the integration of these two bands was then carried out using Omnic 8.2 software. The bands after the baseline correction give a more accurate integral area. Here, the method of linear baseline correction was selected (rather than the spline or polynomial), and the peak shape and intensity distribution can be consistent with original spectra to the maximum extent. Only the baseline correction was performed before integration. We did not conduct any normalization and deconvolution.


image file: c7cp04571a-f2.tif
Fig. 2 Temperature-dependent FTIR spectra of PVCL hydrogel in D2O upon heating from 22 °C to 52 °C at a rate of 1 °C min−1. (a) 3020–2820 cm−1; (b) 2800–2110 cm−1; (c) 1645–1570 cm−1.
Table 1 Band assignments of PVCL hydrogel appearing in the temperature-dependent FTIR and PCMW2D spectra15,22,23,36–40
Wavenumber (cm−1) Assignment Wavenumber (cm−1) Assignment
2945 ν as(–CH2, hydrated) 2420 δ(O–D, D2O, overtone)
2910 ν as(–CH2, dehydrated) 1634 ν(C[double bond, length as m-dash]O, free)
2898 ν(–CH, backbone) 1620 ν(C[double bond, length as m-dash]O⋯D2O⋯O[double bond, length as m-dash]C)
2867 ν s(–CH2, hydrated) 1610 ν(C[double bond, length as m-dash]O⋯D2O)
2852 ν s(–CH2, dehydrated) 1590 ν(C[double bond, length as m-dash]O⋯2D2O)
2610 ν as(O–D, D2O)



image file: c7cp04571a-f3.tif
Fig. 3 (a) Temperature-dependent wavenumber shifts of νas(–CH2) around 2940 cm−1 and νs(–CH2) around 2860 cm−1; (b) integral area change in the region of 2800–2110 cm−1 (D2O); (c) integral area change in the region of 1640–1570 cm−1 (C[double bond, length as m-dash]O groups).

In Fig. 2(a), the region of 3020–2820 cm−1 corresponds to the stretching vibration of C–H groups. We find that all C–H stretching bands slightly shift to a lower wavenumber with increasing temperature, and this tendency can be easily observed in temperature-dependent wavenumber shifts of νas(–CH2) and νs(–CH2) in Fig. 3(a). This phenomenon can be explained by the hydrophobic interaction of C–H groups with neighboring water molecules. It has been reported that the bands of the hydrophobic alkyl groups shifted to a higher wavenumber when surrounded by water molecules, and more water molecules surrounding the alkyl groups give rise to the shift to a higher wavenumber.41 On the basis of this point, it can be deduced that the wavenumber changes of the C–H bands upon heating can be explained by a gradual dehydration of hydrophobic alkyl groups. Through carefully examining the wavenumber shifts of νas(–CH2) and νs(–CH2), a turning point located at 29 °C can be determined by the intersection of the tangent lines as shown in Fig. 3(a), indicating that the hydrophobic interaction of –CH2 groups starts from around 29 °C. Besides, it was found that both the wavenumber shifts of νas(–CH2) and νs(–CH2) show a sharp shift around VPTT and a gradual shift after VPTT (typical asymmetric sigmoid curve).

This wavenumber variation tendency of C–H groups is very much like that found in the LCST transition of linear PVCL aqueous solution.23 However, we found that the wavenumber changes of PVCL hydrogel are much more continuous than those of PVCL aqueous solution (the quantitative evidence is provided in Fig. S2 in the ESI), and the main reason is probably that the abrupt collapse of polymer chains around VPTT is restrained by the confined hydrogel network, resulting in the water molecules only being expelled gradually.

Fig. 2(c) shows the stretching vibration of amide I groups of PVCL hydrogel. In Fig. 2(c), a ternary spectral intensity change can be clearly observed. The intensity of the band at 1632 cm−1 increases, while that of 1610 cm−1 and 1590 cm−1 (the shoulder peak) gradually decreases. According to the literature,23,36–38 the band at 1632 cm−1 is assigned to the stretching vibration of “free” C[double bond, length as m-dash]O groups, and the bands at 1610 cm−1 and 1590 cm−1 are attributed to the C[double bond, length as m-dash]O stretching vibration in C[double bond, length as m-dash]O⋯D2O and C[double bond, length as m-dash]O⋯2D2O hydrogen bond structures, respectively.23,36–38 Thus, the spectral intensity changes within the amide I region upon heating can be roughly interpreted as a transformation from the hydrogen bonded C[double bond, length as m-dash]O (with water molecules) to the “free” ones. Fig. 3(c) shows the integral area change of C[double bond, length as m-dash]O groups during heating. From Fig. 3(c), a turning point at around 29 °C is also observed, and the integral area change of C[double bond, length as m-dash]O groups also exhibits a sharp change around VPTT and a gradual change above VPTT, just like the wavenumber shifts of νas(–CH2) and νs(–CH2) as shown in Fig. 3(a). In addition, we can see that the integral area shows a fastest decrease at around 32 °C.

It is noted that the wavenumber of C–H groups and the integral area of C[double bond, length as m-dash]O groups of PNIPAM hydrogel are both barely changed before and after the phase transition.42 However, for PVCL hydrogel, the wavenumber of C–H groups and the integral area of C[double bond, length as m-dash]O groups show a continuous decreasing tendency with increasing temperature after phase transition, indicating that PVCL hydrogel still has the capacity to expel water molecules continuously even after phase transition. Wu and Sun also studied this phenomenon using molecular simulations.23 Their results revealed that PVCL forms a “sponge-like” structure after phase transition due to the topological constraints of caprolactam rings and the absence of hydrogen bonds of the macromolecules themselves. In this “sponge-like” structure, there are still present water molecules with a distribution gradient, and therefore PVCL can further expel water molecules continuously with increasing temperature, even after phase transition. However, for PNIPAM hydrogel, a large number of hydrogen bonds are generated between PNIPAM macromolecules after phase transition, leading to the formation of a “cotton-ball-like” structure. In this “cotton-ball-like” structure of PNIPAM, there are no water molecules with a distribution gradient, so the behavior of PNIPAM after phase transition is completely different from that of PVCL hydrogel.

In Fig. 2(b), the broad band within 2800–2110 cm−1 is attributed to the stretching vibration of hydroxyl (O–D) groups in D2O.43 In Fig. 2(b), we can observe that the spectral intensity of the whole D2O region obviously decreases during heating, showing that D2O molecules are gradually expelled from the hydrogel network during phase transition upon heating. From Fig. 3(b), we can find that the integral area of D2O stretching vibration region also produces an approximately asymmetric sigmoid curve upon heating, revealing that the rate of water molecules being expelled out from the PVCL hydrogel network is changed in a sigmoid mode, rather than a linear increase with increasing temperature. This phenomenon was also observed during the phase transition process of the PNIPAM-based hydrogel in our previous work, and we think that this is closely related to the “regular” dehydration of C–H groups and the “regular” dissociation of D2O-related hydrogen bonds during phase transition.44 The meaning of “regular” here is to follow a specific law. In Fig. 3(b), a turning point at 29 °C can also be clearly observed, and the fastest speed of the integral area decrease is also located at around 32 °C, just like that in Fig. 3(c).

In summary, an initial analysis of the temperature-dependent FTIR spectra helps us in getting some useful information and reaching a preliminary conclusion about the volume phase transition behavior of PVCL hydrogel upon heating. However, on the one hand, it is hard to obtain an accurate VPTT from the asymmetric sigmoid curves from Fig. 3. On the other hand, the key information on the micro-dynamics mechanism in which we are most interested is still not clear. Thus, next, PCMW2D and generalized 2D correlation analysis were employed to address these key issues.

3.2. Perturbation–correlation moving window (PCMW2D) analysis

The PCMW2D technique was employed here to obtain an accurate VPTT and the transition temperature ranges of PVCL hydrogel during heating. PCMW2D spectra contain the synchronous and asynchronous spectra. In a PCMW2D spectrum, the horizontal axis is wavenumber, and the vertical axis is external perturbation (i.e., temperature). The synchronous PCMW2D spectrum is always used to determine the phase transition temperature of phase transition polymers, while the asynchronous one can be used to determine the transition temperature ranges according to the turning points in the contour map. The synchronous and asynchronous PCMW2D spectra of PVCL hydrogel in D2O upon heating from 22 °C to 52 °C are shown in Fig. 4. It is noted that in PNIPAM/D2O systems, the stretching vibration of O–D groups in D2O is highly overlapped with that of the N–D groups in PNIPAM in the region of 2800–2110 cm−1, which cannot be clearly distinguished even by the PCMW2D technique. Thus, when the PCMW2D technique was applied to determine the phase transition temperature of PNIPAM-based polymers, the analysis of D2O stretching vibration region was usually meaningless. However, there are no N–D groups existing in the PVCL/D2O system, since the N atom in the side chains of PVCL is directly linked to three carbon atoms. Therefore, PCMW2D analysis for the D2O stretching vibration region is feasible here. As far as we know, for the phase transition behavior of stimuli-sensitive polymers in D2O, this is the first time that the PCMW2D technique has been applied to investigate the D2O region. In the PCMW2D spectra of the stretching vibration region of D2O, two bands located at around 2610 cm−1 and 2410 cm−1 are determined. According to the literature, these two bands are assigned to the asymmetrical stretching vibration and the overtone of bending vibration of self-associated hydrogen bonded O–D groups in liquid D2O water, respectively.39,40
image file: c7cp04571a-f4.tif
Fig. 4 PCMW2D synchronous (top) and asynchronous (bottom) FTIR spectra of PVCL hydrogel upon heating from 22 °C to 52 °C. The pink areas represent positive correlation intensity, while blue areas represent negative correlation intensity.

It is known that, in PCMW2D synchronous spectra, positive correlation intensity represents an increase of spectral intensity in the temperature-dependent FTIR spectra, and negative correlation intensity shows a decrease of the spectral intensity at a given wavenumber. Besides, positive correlation intensity in the asynchronous spectra represents a convex spectral intensity variation in the temperature-dependent FTIR spectra, and negative correlation intensity can be observed for a concave variation.35 Thus, from the synchronous spectra in Fig. 4, it can be directly deduced that, with increasing temperature in temperature-dependent FTIR spectra, the spectral intensity of hydrated –CH2 groups, D2O, and hydrogen bonded C[double bond, length as m-dash]O groups gradually decreases, while that of dehydrated –CH2 and free C[double bond, length as m-dash]O groups gradually increases. At the same time, it is apparent that the spectral intensity change of many bands spreads over almost the whole temperature region, indicating that the volume phase transition of PVCL hydrogel is a relatively continuous process, which is consistent with the observations in Fig. 3.

For clarity, the obtained VPTTs and transition temperature ranges of different bands from Fig. 4 are summarized in Table 2. From Table 2, it is seen that some groups have two transition points during the heating process, such as 32.5 °C and 45.6 °C for 2945 cm−1, 31.7 °C and 42.0 °C for 2420 cm−1. These results clearly indicate that the phase transition behavior of PVCL hydrogel is very different from that of PVCL aqueous solution, which shows only one transition point upon heating.23 Meanwhile, it also reveals that the phase transition of PVCL hydrogel can be divided into two steps upon heating. According to the listed transition points of different bands in Table 2, the transition temperatures of these two steps can be roughly determined to be around 32 °C and 43 °C, respectively. Furthermore, on the basis of the PCMW2D spectra and the obtained transition regions, it is easy to judge that the transition temperature region of the first step (at lower temperature) is 29.0–35.7 °C. For the second step, the temperature at 47.5 °C is the highest temperature detected in the PCMW2D asynchronous spectra, which can be used as the end temperature for convenience. As discussed above, the phase transition behavior of PVCL hydrogel is a relatively continuous process, and therefore the end temperature of the first step can be employed as the onset temperature of the second step. So, the temperature range of the second step can be determined as 35.7–47.5 °C. Here, for convenience, these two steps are named as steps I and II, respectively. It is pointed out that the obtained transition temperature and the onset temperature of step I from PCMW2D spectra are completely in accordance with the observed temperature in Fig. 3, showing a powerful capacity of PCMW2D to investigate the complex transition of polymers.

Table 2 The VPTTs and transition regions of different bands determined from Fig. 4
Wavenumber (cm−1) Transition points (°C) Transition regions (°C)
2945 32.5; 45.6 30.2–34.3; 45.0–47.5
2910 29.8 29.0–32.1
2867 32.5 30.2–35.7
2852 30.8; 41.4 29.0–32.1; −47.5
2610 31.7 30.1–33.2
2420 31.7; 42.0 30.1–34.0; 40.3–43.0
1634 35.0; 44.5
1610 31.2 29.6–32.6


As mentioned in Section 1, Mikheeva's group also found that PVCL hydrogel underwent two successive cooperative transitions upon heating, which mainly occur at around 31.5 °C and 37.6 °C, respectively. The low-temperature transition around 31.5 °C was related to the formation of hydrophobic domains on a nanoscale (1–100 nm) in the gel, and the high-temperature transition about 37.6 °C was connected with the volume collapse transition of the gel.26 Comparing with their results, we found that the transition temperature of step I around 32 °C in our work is very close to that of the low-temperature transition in their work. Therefore, the essence of step I can be attributed to hydrophobic domain formation in the gel. The difference is that the transition temperature of step II around 43 °C here is 5.6 °C higher than that of the high-temperature transition in their work. From the DSC curve in their paper, however, the transition temperature range of the high-temperature transition was within 33–47 °C, which coincides with the transition region of step II. Furthermore, Sun investigated the phase transition of PVCL aqueous solution by temperature-dependent FTIR spectra, and they found the chain collapse of PVCL in D2O mainly occurred at 43.5 °C and between 40.5 °C and 45 °C,23 which are also close to the transition temperature and transition temperature ranges of step II determined by us. Therefore, step II should be assigned to the volume collapse of the gel. It is noticed that the transition temperatures displayed in PCMW2D spectra are possibly different from those observed in DSC experiments, since the movements of chemical groups may not exactly correlate with enthalpy changes. Besides, the temperatures measured by FTIR and DSC instruments also probably show some difference.

3.3. Generalized two-dimensional correlation analysis

On the basis of the temperature ranges of phase transitions determined from PCMW2D spectra, all the collected temperature-dependent FTIR spectra within step I (29.0–35.7 °C) and step II (35.7–47.5 °C) were used to performed the generalized 2D correlation analysis. Herein, we mainly focus on the C–H and C[double bond, length as m-dash]O stretching vibration regions, and in this way we are able to trace nearly all the group motions of PVCL hydrogel during the volume phase transition. Generalized 2D correlation FTIR spectra also contain synchronous and asynchronous spectra. The synchronous spectra are always symmetric with respect to the diagonal line. In the synchronous spectra, the peaks appearing along the diagonal line are called auto-peaks, and the signs of them are always positive since auto-peaks represent the degree of auto-correlation of perturbation-induced molecular movement. The off-diagonal peaks, called cross-peaks, can be positive or negative, and represent the simultaneous changes of spectral intensity variations measured at ν1 and ν2. Positive cross-peaks demonstrate that the intensity variations of the two peaks at ν1 and ν2 are taking place in the same direction (both increasing or decreasing) under external perturbation, while negative cross-peaks indicate that the intensities of the peaks at ν1 and ν2 change in opposite directions under external perturbation. The 2D asynchronous spectra are always asymmetric with respect to the diagonal line. Unlike synchronous spectra, only cross-peaks appear in the asynchronous spectra, and these peaks can also be positive or negative. The intensity of the asynchronous spectrum represents the successive changes of the spectral intensities at ν1 and ν2. Based on the signs of correlation peaks in the synchronous and asynchronous spectra, the sequential order of the spectral intensity changes can be easily judged. The judging rule can be outlined as Noda's rule45—that is, if the correlation intensity Φ(ν1, ν2) in the synchronous spectra has the same sign (positive or negative) as the correlation peak Ψ(ν1, ν2) in the asynchronous spectra, then the movement of band ν1 is prior to or earlier than that of band ν2, and vice versa. Additionally, if the correlation intensity in the synchronous spectra is not zero (or blank), but zero in the asynchronous spectra, then the movements of bands ν1 and ν2 are simultaneous. Furthermore, by spreading the original spectra along a second dimension, the bands which cannot be readily distinguished in the conventional 1D spectra can be easily obtained due to the significant enhancement of the spectral resolution.28
3.3.1. Step I. The generalized 2D correlation spectra calculated from the temperature-dependent FTIR spectra within step I (29.0–35.7 °C) are shown in Fig. 5. It is noted that an invisible band at 1620 cm−1 in 1D FTIR spectra is successfully observed in the asynchronous spectra due to the significantly enhanced spectral resolution. This invisible band can also be observed in the second derivative spectra (Fig. S1 in the ESI, slightly shifting to 1622 cm−1). However, as for the temperature-dependent FTIR spectra, the second derivative spectra have no capacity to determine the sequential order of groups’ motion during phase transition. The advantage of generalized 2D correlation spectra is not only the detection of bands that are invisible in the conventional 1D FTIR spectra, but also easily obtaining the sequential order of the groups’ motion. The detailed assignment of 1620 cm−1 band is listed in Table 1. According to Noda's rule, the sequential order between C–H and C[double bond, length as m-dash]O groups of PVCL hydrogel in D2O upon heating can be obtained. For brevity, the detailed calculation process is summarized in Table S1 in the ESI. The obtained sequential orders of step I are as follows: 1590 cm−1 → 1610 cm−1 → 1620 cm−1 → 2867 cm−1 → 2945 cm−1. The corresponding sequential order of the groups is ν(C[double bond, length as m-dash]O⋯2D2O) → ν(C[double bond, length as m-dash]O⋯D2O) → ν(C[double bond, length as m-dash]O⋯D2O⋯O[double bond, length as m-dash]C) → νs(–CH2, hydrated) → νas(–CH2, hydrated). Here, the symbol “ → ” represents “before”.
image file: c7cp04571a-f5.tif
Fig. 5 Generalized 2D correlation synchronous and asynchronous FTIR spectra of PVCL hydrogel calculated from all the spectra within step I (29.0–35.7 °C). Here, the pink areas are defined as positive correlation intensity, while blue the areas are negative correlation intensity.

For the bands related to the C[double bond, length as m-dash]O groups, the sequential order can be extracted as follows: 1590 cm−1 → 1610 cm−1 → 1620 cm−1. It is interesting that the wavenumber of C[double bond, length as m-dash]O related vibrations exhibits a gradual increase during heating. In general, the wavenumber of C[double bond, length as m-dash]O groups in FTIR spectra is really relevant to the hydrogen bond strength of C[double bond, length as m-dash]O groups. The stronger hydrogen bond of C[double bond, length as m-dash]O groups gives a lower wavenumber. Thus, this sequential order of C[double bond, length as m-dash]O-related groups indicates a gradual reduction of C[double bond, length as m-dash]O-related hydrogen bonds upon heating. More specifically, as the temperature increases, the C[double bond, length as m-dash]O⋯2D2O structure only releases one water molecule at first, and then the C[double bond, length as m-dash]O⋯D2O structure which has a higher wavenumber forms C[double bond, length as m-dash]O⋯D2O⋯O[double bond, length as m-dash]C structure with other C[double bond, length as m-dash]O groups. Finally, the C[double bond, length as m-dash]O⋯D2O···O[double bond, length as m-dash]C structure releases its last water molecule to form the “free” C[double bond, length as m-dash]O groups.

On the other hand, considering the movement of alkyl groups separately, the sequential order of νs(–CH2, hydrated) → νas(–CH2, hydrated) is determined. In this study, the –CH2 groups exist in both the side chain and the backbone of PVCL, and cannot be clearly distinguished in this circumstance. However, it can be inferred that the symmetric stretching vibration has an earlier response than the asymmetric stretching vibration upon heating. According to the literature, the direction of asymmetric stretching vibration is parallel to the polymer chain axis, while that of the symmetric stretching vibration is vertical to the polymer chain axis.46 Thus, we can conclude that the formation of local hydrophobic domains in PVCL hydrogel occurs and centres on the side chains upon heating. In other words, the hydrophobic domains are mainly formed around the caprolactam rings of side chains.

Overall, the whole sequential order of step I can be summarized as: C[double bond, length as m-dash]O → C–H. Obviously, this result reveals that the hydrogen-bonding transformation of C[double bond, length as m-dash]O groups is the driving force of the formation of hydrophobic domains in PVCL hydrogel, which is in contrast with Mikheeva's inference.26

3.3.2. Step II. The generalized 2D correlation spectra of step II (35.7–47.5 °C) are shown in Fig. 6. The essence of step II is the volume collapse of the hydrogel. It is noted that a new band at around 2898 cm−1 was observed in the asynchronous spectra of C–H stretching vibration region in step II, which was not observed in the asynchronous spectra of step I. It has been reported that the band at 2898 cm−1 is assigned to the stretching vibration of methyne (–CH) groups in the backbone.23 Thus, the non-response of the 2898 cm−1 band during step I also possibly indicates that the formation of local hydrophobic domains in PVCL hydrogel mainly occurs in the side chains.
image file: c7cp04571a-f6.tif
Fig. 6 Generalized 2D correlation synchronous and asynchronous FTIR spectra of PVCL hydrogel calculated from all the spectra within step II (35.7–47.5 °C).

Similar to step I, the sequential order of step II can be deduced as: 2898 cm−1 → 2867 cm−1 → 1620 cm−1 → 1610 cm−1 → 2945 cm−1 → 1590 cm−1. The corresponding sequential order of the groups is νs(–CH, backbone) → νs(–CH2, hydrated) → ν(C[double bond, length as m-dash]O⋯D2O⋯O[double bond, length as m-dash]C) → ν(C[double bond, length as m-dash]O⋯D2O) → ν(C[double bond, length as m-dash]O⋯2D2O) → νas(–CH2, hydrated). The detailed procedure can be found in Table S2 in the ESI.

Considering C–H related vibrations separately, the sequential order can be extracted as follows: 2898 cm−1 → 2867 cm−1 → 2945 cm−1. Furthermore, regardless of the difference in stretching modes, this sequence can be described as –CH → –CH2. Therefore, it is clear that the chain collapse of PVCL hydrogel during volume phase transition is along the backbone, which is identical to that of PNIPAM hydrogel.42

As for the bands related to C[double bond, length as m-dash]O groups, the sequential order can be summarized as 1620 cm−1 → 1610 cm−1 → 1590 cm−1. Obviously, this sequential order is completely opposite to that of step I, and it may indicate that the hydrogen bonds between C[double bond, length as m-dash]O groups and water molecules are gradually broken according to the order from the weak to the strong successively. This is because, on the one hand, the temperature of step II is much higher than that of step I, and, on the other hand, the movement of molecular chains in step II is more dramatic than that of step I due to chain collapse. Thus, the hydrogen bonds between C[double bond, length as m-dash]O groups and water molecules are directly dissociated into “free” C[double bond, length as m-dash]O groups and water molecules according to the order from the weak to the strong, other than a gradually weakened process just like step I.

In summary, the sequential order of step II can be described as: C–H → C[double bond, length as m-dash]O. This result clearly indicates that the hydrophobic interaction of C–H groups is the driving force for the chain collapse of PVCL hydrogel upon heating.

Based on the above analysis and discussions, we are able to propose an integrated two-step volume phase transition mechanism of PVCL hydrogel upon heating, as shown in Scheme 2. The volume phase transition of PVCL hydrogel can be divided into two steps. The first step is the formation of local hydrophobic domains in the gel, and its temperature region is mainly within 29.0–35.7 °C. The second step is the chain collapse of the gel, and its temperature range is mainly around 35.7–47.5 °C. At temperatures below the VPTT, the C[double bond, length as m-dash]O groups in side chains are all hydrogen-bonded with water molecules, and all the alkyl groups are fully hydrated. When the temperature increases above the VPTT, the hydrogen bonds between C[double bond, length as m-dash]O groups and water molecules gradually weaken at first, initiating the formation of local hydrophobic domains in the gel. Then, the hydrated –CH2 groups of caprolactam rings in side chains start to dehydrate, leading to the gradual formation of local hydrophobic domains in PVCL hydrogel. Meanwhile, some of the water molecules are expelled out of the gel network. With temperature continuing to increase, the molecular chains gradually collapse along the backbone, which is driven by the hydrophobic interaction of C–H groups. After that, all three types of hydrogen bonds between C[double bond, length as m-dash]O groups and water molecules are directly dissociated into “free” C[double bond, length as m-dash]O groups and water molecules. During the chain collapse, a lot of water molecules are expelled out from the hydrogel network, and the volume of PVCL hydrogel is significantly decreased.


image file: c7cp04571a-s2.tif
Scheme 2 Schematic illustration of the two-step phase transition mechanism of PVCL hydrogel in D2O during heating. D2O molecules are represented by the small blue globules, while the hydrophobic domains are represented by the elliptical areas of the red dotted lines. The red arrows are the direction of motion of water molecules.

It is noted that the driving force of the hydrophobic domain formation process (step I) discovered in our work is totally different from Mikheeva's deduction.26 However, the mechanism proposed by us can also explain the experimental observations in Mikheeva's work. According to the literature, the dissociation of hydrogen bonds is accelerated in the presence of salts (such as NaCl),47 which leads to a decrease of the dissociation temperature of hydrogen bonds between C[double bond, length as m-dash]O groups and water molecules. Therefore, the dissociation of hydrogen bonds between C[double bond, length as m-dash]O groups and water molecules, as well as the dehydration of C–H groups, appeared at a lower temperature when NaCl was added into the aqueous solution. That is the reason why the VPTT of PVCL hydrogel is decreased in the presence of NaCl. For SDS, the dodecylsulfate ions (DS) can be easily bonded to gel networks via hydrophobic interaction when SDS is added into PVCL hydrogel, thereby inducing ionic repulsion and an increase of gel osmotic pressure. Probably, these two effects significantly retarded the dissociation of hydrogen bonds, which led to an enhancement of the chain collapse temperature of PVCL hydrogel.

4. Conclusions

In this study, temperature-dependent FTIR spectroscopy in combination with PCMW2D and generalized 2D correlation analysis was employed to investigate the microdynamics mechanism of the volume phase transition of PVCL hydrogel in D2O upon heating.

In the temperature-dependent FTIR spectra, the gradual dehydration of C–H groups and the gradual dissociation of hydrogen bonds between C[double bond, length as m-dash]O groups and water molecules were observed during the phase transition of PVCL hydrogel upon heating. Furthermore, the D2O stretching vibration region, which has been less studied so far, was especially focused on. The gradual decrease of the spectral intensity of the D2O stretching vibration region indicated that water molecules were gradually expelled out of the gel network during phase transition. Furthermore, we found that the rate at which water molecules were expelled out of the gel network during phase transition was changed in a sigmoid mode, rather than increasing linearly with increasing temperature.

PCMW2D FTIR spectra revealed that the phase transition behavior of PVCL hydrogel was very different from that of PVCL aqueous solution, and it can be divided into two steps (denoted I and II). PCMW2D spectra further determined the phase transition temperature regions of steps I and II to be 29.0–35.7 °C and 35.7–47.5 °C, respectively. The essence of step I is the formation of hydrophobic domains in the gel, and step II represents the chain collapse of the hydrogel.

Generalized 2D correlation FTIR spectra were obtained to explore the sequential order of functional group motion during steps I and II. According to the obtained sequential order of step I, we found that the transformation of C[double bond, length as m-dash]O-related hydrogen bonding was the driving force of the hydrophobic domain formation process (step I), while the hydrophobic interaction of C–H groups was the driving force and was predominant in the chain collapse process (step II). Furthermore, we found that the hydrophobic domains were mainly formed around the caprolactam rings of side chains, and the chain collapse of PVCL hydrogel was along the backbone. In addition, according to the different sequential order of C[double bond, length as m-dash]O-related bands in step I and step II, a different dissociation mode of hydrogen bonds between C[double bond, length as m-dash]O groups and water molecules in steps I and II was revealed. Overall, combined with the obtained sequential orders of these two steps, an integrated two-step phase transition mechanism of PVCL hydrogel upon heating was proposed. We believe the proposed micro-dynamics mechanism will help improve understanding of the volume phase transition behavior of PVCL-based hydrogels, and that it will also provide a stimulus to research on the release kinetics of drugs or bio-enzymes in PVCL-based hydrogels.

Conflicts of interest

There are no conflicts to declare.

Acknowledgements

This work was supported by the National Natural Science Foundation of China (grant no. 51473104, 51773126), Outstanding Youth Foundation of Sichuan Province (2017JQ0006), and State Key Laboratory of Polymer Materials Engineering (grant no. sklpme2014-3-06, sklpme2016-3-10).

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Footnote

Electronic supplementary information (ESI) available. See DOI: 10.1039/c7cp04571a

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