Next Article in Journal
Biomedical Grade Stainless Steel Coating of Polycaffeic Acid via Combined Oxidative and Ultraviolet Light-Assisted Polymerization Process for Bioactive Implant Application
Previous Article in Journal
Dispersion of Boron Nitride Nanotubes by Pluronic Triblock Copolymer in Aqueous Solution
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Polymers
Volume 11
Issue 4
10.3390/polym11040583
polymers-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles thumb_up
...
Endorse textsms
...
Comment
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

Synthesis and Properties of Side-Chain Functionalized Polytetrahydrofuran Derivatives via the Blue-Light Photocatalytic Thiol-Ene Reaction

by
Xiuzhong Zhu
1,
Ting Bai
1,
Zichao Wang
1,
Jie Liu
1,
Xin Min
1,
Tong Wang
1,
Wanbin Zhang
2 and
Xiaodong Fan
1,*
1
The Key Laboratory of Space Applied Physics and Chemistry, Ministry of Education and Shaanxi Key Laboratory of Macromolecular Science and Technology, School of Science, Northwestern Polytechnical University, Xi’an 710072, China
2
Shaanxi Collaborative Innovation Center of Industrial Auxiliary Chemistry and Technology, Shaanxi University of Science and Technology, Xi’an 710021, China
*
Author to whom correspondence should be addressed.
Polymers 2019, 11(4), 583; https://doi.org/10.3390/polym11040583
Submission received: 23 February 2019 / Revised: 26 March 2019 / Accepted: 26 March 2019 / Published: 1 April 2019
Browse Figures
Versions Notes

Abstract

:
A series of side-chain functionalized polytetrahydrofuran (PTHF) derivatives were synthesized via the blue-light photocatalytic thiol-ene “click” reaction. Firstly, unsaturated polytetrahydrofuran (UPTHF) as a new unsaturated polyether was synthesized via condensation polymerization of cis-2-butene-1,4-diol and trans-1,4-dibromo-2-butene using potassium hydroxide (KOH) as a catalyst. Then, double bonds in the backbone of UPTHF were modified into different pendant functionality side groups by blue-light photocatalytic thiol-ene “click” reaction using Ru(bpy)3Cl2 as a photoredox catalyst, obtaining different side-chain functionalized PTHF derivatives. The structure and the morphology of the side-chain functionalized PTHF derivatives was characterized via Fourier-transform infrared spectra (FTIR), nuclear magnetic resonance (NMR), size exclusion chromatography/multi-angle laser light scattering (SEC/MALLS), and differential scanning calorimeter (DSC). The results showed that the blue-light photocatalytic thiol-ene reaction exhibited high efficiency, and all the unsaturated bonds were modified. Different branch units bestowed different performance of PTHF derivatives; we systematically investigated the thermal properties, pH-triggered and temperature-triggered, self-assembly behaviors of different PTHF derivatives.

Graphical Abstract

1. Introduction

Polytetrahydrofuran (PTHF) is an extremely versatile polyether used as adhesives and biomedical and elastomeric materials [1,2,3,4,5]. As a commodity telechelic polymer, ~200,000 tons of PTHF are produced annually [6]. For the foreseeable future, the PTHF derivatives should also prove to be useful in a wide range of applications. However, a fundamental challenge with all PTHF-based systems is the lack of functional handles along the polymer backbone, which limits the modification and tunability of this valuable material’s platform, so that the preparation of the PTHF derivatives just are a,ω-telechelic poly(THF)s [7,8]. Therefore, the synthesis of the side-chain functionalized PTHF derivatives with a precisely defined molecular weight, composition, and architecture can still pose a significant challenge, and have not been reported in the literature yet.
As is known, post-polymerization modification is a very effective strategy for synthesis of functionalized polymers [9,10,11,12]. For instance, functionalized polyethylene has been obtained through functionalization reactions of polybutadiene (PB) [13]. This is because the internal bond of PB can be reacted with a range of functional molecules. This method successfully solved the limitation that the common industrial techniques had no way to synthesize functionalized polyethylene. Inspired by this, we designed a new polyether named unsaturated polytetrahydrofuran (UPTHF), and then through post-modification of UPTHF got a chance to obtain side-chain functionalized PTHFs [14,15]. Among the various ways about the post-modification of unsaturated polymers, the most widely used is the thiol-ene “click” reaction.
Recently, the thiol-ene “click” reaction has been widely applied in organic and polymer syntheses as well as the preparation of gels, thermosets, and the post-modification of polymers [16,17,18,19,20]. In general, thermal or UV light is required to induce thiol-ene “click” reaction by using corresponding radical initiators; among the several available methods, the technique employing the UV light was the most widely used [21,22,23]. For instance, Schlaad and co-workers successfully prepared polyolefin derivatives via the thiol-ene “click” reaction by ultraviolet (UV) irradiation and adopting polybutadiene with a high content of 1,2-units as a polymer precursor; they also investigated the photoinitiation polymerization mechanism in detail [24]. As one of the available living polymerization methods, the ring-opening metathesis polymerization (ROMP) is a versatile and an efficient synthetic strategy for the polymerization of cyclic olefins by using metal alkylidene initiators, which create a series of polyolefin polymers. Simultaneously, UV light photocatalytic thiol-ene reaction is also widely used to modify those polyolefin polymers [25,26]. Hence, we initially intended to synthesize side-chain functionalized PTHFs via the UV light photocatalytic thiol-ene reaction, but unfortunately, the double bonds in the UPTHF backbone could not be fully transformed; indeed, only a part of double bonds was involved in the reaction, when the reaction time was set limited to 24 h. The underlying cause creating this issue was likely that in-chain double bonds of UPTHF exhibited a low-activity, which was in agreement with the experimental observation that in-chain double bonds of polybutadiene were 10 times less reactive than vinyl double bonds [27]. Moreover, the use of the UV light implies the development of harsh and expensive conditions for the functionalization of polymers. Recently, it was reported that thiol-ene reaction could be initiated at room temperature by visible light using novel visible-light-absorbing transition metal photocatalysts, becoming widely available for the synthesis of small molecular compounds [28,29,30,31]. As for polymers, Boyer and Zhang reported the thiol-ene modification of polybutadiene using visible light, showing that all double bonds were converted in a short time [32,33].
Based on the above considerations and inspired by previous research outcomes, we reported a simple strategy to synthesize UPTHF via condensation polymerization and then post-polymerization modification of UPTHF to obtain side-chain functionalized PTHFs via the blue-light photocatalytic thiol-ene reaction. UPTHF was synthesized via the condensation polymerization using cis-2-butene-1,4-diol and trans-1,4-dibromo-2-butene as monomers. Then, blue light was used to induce the thiol-ene reaction between UPTHF and a range of thiol-containing compounds, such as mercaptoethanol, n-butyl mercaptan, mercaptopropionic acid, as well as methoxy- polyethylene glycol-thiol (mPEG-SH) (Mn = 750 g mol−1), to obtain different PTHFs named PTHFOH, PTHFbut, PTHFacid, and PTHFmPEG, respectively Figure 1). Afterward, we characterized the structure and the morphology of the polymers via FTIR, 1H NMR, 13C NMR, size exclusion chromatography/multi-angle laser light scattering (SEC/MALLS), and differential scanning calorimeter (DSC). The pH-triggered self-assemble behaviors of PTHFacid and temperature-triggered self-assemble behaviors of PTHFmPEG were investigated via various methods, including dynamic light scattering DLS, and UV-Vis spectroscopy. The biocompatibility of PTHFacid and PTHFmPEG was also studied via the in vitro cytotoxicity assay [34,35]. The overall experimental procedure is illustrated in Figure 1.

2. Experimental Section

2.1. Materials

Cis-2-butene-1,4-diol (97%, Macklin, Shanghai, China), trans-1,4-dibromo-2-butene (98%, Alfa Aesar, Heysham, UK), tris(acetonitrile)cyclopentadienylruthenium(II) hexafluorophosphate ([CpRu(CH3CN)3]PF6, 98%, Acros, BE), Quinaldic acid (98%, Aladdin, Shanghai, China), Ru(bpy)3Cl2 (98%, Adamas, Basel, Switzerland), and p-toluidine (98%, Adamas, Basel, Switzerland) were used as received, and 2-mercaptoethanol, n-butyl mercaptan and 3-mercaptopropionic acid were purchased from Macklin. mPEG16-SH was bought from Shanghai ToYong Bio Company. Terahydrofuran (THF, 99.9%, Alfa Aesar, Heysham, UK), dichloromethane (DCM, 99.5%, Sinopharm Chemical Reagent Co., Ltd., Tianjin, China), diethyl ether (99.5%, Alfa Aesar, Heysham, UK), and acetone (9.5%, Sinopharm Chemical Reagent Co., Ltd., Tianjin, China) were refluxed over sodium wire (Na, 98.0%, Sinopharm Chemical Reagent Co., Ltd., Tianjin, China) in the presence of benzophenone until a blue color presence, and was distilled before use. Methanol, N-methyl-2-pyrrolidone (NMP), and other organic solvents were all purchased from Sinopharm Chemical Reagent Co., Ltd. (SCRC, Tianjin, China) and used without any purification.

2.2. Synthesis of Unsaturated Polytetrahydrofuran (UPTHF)

A 50 mL flask loaded with a stir bar, cis-2-butene-1,4-diol (880 mg, 10 mmol), trans-1,4-dibromo-2-butene (2139 mg, 10 mmol) and potassium hydroxide (KOH, 1685 mg, 30 mol) were dissolved in solution of acetone (15 mL). The solution was stirred with a reflux condenser at 65 °C for 72 h, and then 2 mL purified water was added into the flask, keeping reaction for 24 h at 40 °C. The polymer was extracted using DCM, and then was precipitated into an excess of cold n-hexane. The obtained brown viscous liquid was redissolved with 2 mL of THF and precipitated again with methanol. The polymer was washed three times with methanol and dissolved in 5 mL dichloromethane. Finally, the polymer was obtained by rotary evaporation removal of DCM. The final yield of UPTHF was 81% (1280 mg). Mn,SEC = 4300 g mol−1, Mw/Mn = 1.48. 1H NMR (DMSO-d6, δ): 5.74 (–CH=CH–, trans-1,4), 5.62 (–CH=CH–, cis-1,4), 4.7 (–CH2–OH), 3.99 (–CH2–CH2–, cis-1,4), 3.92 (–CH2–CH2–, trans-1,4).

2.3. Synthesis of Side-Chain Functionalized PTHFs

2.3.1. Synthesis of PTHFs with a Hydroxy Branching Unit (PTHFOH)

PTHF derivative with a hydroxy branching unit (PTHFOH) was synthesized by blue-light photocatalytic thiol-ene reaction between UPTHF and mercaptoethanol. UPTHF (260 mg, –C=C–, 3.7 mmol), mercaptoethanol (3.16 mL, 45 mmol), Ru(bpy)3Cl2 (4.5 mg, 7 × 10−3 mmol), and p-toluidine (30 mg, 0.28 mmol) were dissolved in NMP and irradiated by a household blue LED lights bulb (7 W) for 5 h at room temperature. After reaction, unreacted mercaptoethanol and NMR were isolated by dialyzed (molecular weight cut off: 300) against distilled water for 48 h, and the final product was obtained by freeze drying. 1H NMR (DMSO-d6, δ): 4.75 (–OH), 3.87–3.18 (–CH2–O–), 2.90 (–(CH2)2–CH–S), 2.62 (–CH2–S–), 1.92–1.55 (–CH2–CH2–).

2.3.2. Synthesis of PTHFs with a Carboxyl Branching Unit (PTHFbut)

PTHF derivative with a butyl branching unit (PTHFbut) was synthesized by blue-light photocatalytic thiol-ene reaction between UPTHF and n-butyl mercaptan. UPTHF (260 mg, –C=C–, 3.7 mmol), n-butyl mercaptan (4.83 mL, 45 mmol), Ru(bpy)3Cl2 (4.5 mg, 7 × 10−3 mmol) and p-toluidine (30 mg, 0.28 mmol) were dissolved in NMP and irradiated by a household blue LED lights bulb (7 W) for 5 h at room temperature. After reaction, unreacted n-butyl mercaptan and NMR were isolated by dialyzed (molecular weight cut off: 300) against mix solution of methyl alcohol and distilled water for 48 h, and the final product was obtained by rotary evaporation removal of methyl alcohol and then freeze dried. 1H NMR (DMSO-d6, δ): 3.67–3.17 (–CH2–O–), 2.98–2.37 (–CH2–S–CH–), 2.01–1.25 (CH3–CH2–CH2–, –CH2–O–), 0.87 (CH3–CH2–).

2.3.3. Synthesis of PTHF Derivative with a Carboxyl Branching Unit (PTHFacid)

PTHF derivative with a carboxyl branching unit (PTHFacid) was synthesized by blue-light photocatalytic thiol-ene reaction between UPTHF and 3-mercaptopropionic acid. UPTHF (260 mg, –C=C–, 3.7 mmol), 3-mercaptopropionic acid (3.95 mL, 45 mmol), Ru(bpy)3Cl2 (4.5 mg, 7 × 10−3 mmol) and p-toluidine (30 mg, 0.28 mmol) were dissolved in NMP and irradiated by a household blue LED lights bulb (7 W) for 5 h at room temperature. After reaction, unreacted 3-mercaptopropionic and NMR were isolated by dialyzed (molecular weight cut off: 300) against distilled water for 48 h, and the final product was obtained by freeze drying. 1H NMR (DMSO-d6, δ): 12.20 (–COOH), 2.49 (–CH2–COOH), 2.66 (–CH2–S–), 1.50 (saturation protons in –CH2–).

2.3.4. Synthesis of PTHF Derivative with a mPEG Branching Unit (PTHFmPEG)

A series of PTHFmPEG with different degrees of functionalization were synthesized by blue-light photocatalytic thiol-ene reaction between UPTHF and mPEG-SH. UPTHF (33 mg, 0.01 mmol), mPEG-SH (75 mg, 10 mmol; 150 mg, 20mmol, 750 mg, 100mmol), Ru(bpy)3Cl2 (2.25 mg, 3.5 × 10−3 mmol) and p-toluidine (15 mg, 0.14 mmol) were dissolved in NMP and irradiated by a household blue LED lights bulb (7 W) for a certain time at room temperature. After reaction, unreacted mPEG-SH and NMR were isolated by dialyzed (molecular weight cut off: 1000) against distilled water for 48 h, and the final product was obtained by freeze drying. 1H NMR (DMSO-d6, δ): 3.64 (–CH2–CH2–S–), 3.52 (–CH2–CH2–OH), 3.43 (–CH2–O–), 2.90 (–CH2–S–), 2.69 (–CH–S–), 2.01 (–CH2–CH2–O–).

2.4. Measurements

Fourier-transform infrared spectra (FTIR) were obtained on a Nicolet iS10 FT-IR instrument (Nicolet Instrument Corporation, Madison, WI, USA) in the region from 4000 to 500 cm−1. The 1H NMR and 13C NMR spectra were carried out on a Bruker 400 MHz NMR spectrometer (Bruker Corporation, Karlsruhe, Germany) using deuterated chloroform (CDCl3) or deuterated dimethylsulfoxide (DMSO-d6) as solvents, and tetramethylsilane (TMS) as the internal standard. The molecular weights and polydispersity indexes of the polymers were determined on a Wyatt DAWN EOS SEC-MALLS, THF was used as the eluent with a flow rate of 0.5 mL min−1 at 25 °C.
The glass transition and melting behaviors of polymers were investigated via DSC using a DSC200PC thermal analysis system (Netzsch Instruments, Selb, Germany). Samples weighing approximately 8 mg were scanned at a rate of 10 °C min−1 from −90 to 100 °C. To remove thermal history, all the samples were first heated to 125 °C and, subsequently, cooled down to −90 °C; the samples were held at this temperature for 5 min before the scan.
The optical transmittance of polymer solutions at varying pH or temperature values were measured by UV-Vis spectroscopy (Shimadzu UV-2550, Kyoto, Japan) at a wavelength of 500 nm.
The hydrodynamic diameter, diameter distribution, as well as zeta potentials of the aggregates were determined by dynamic light scattering (DLS, Malvern Instruments, Malvern, UK) at different pH or temperature values. The scattered light of a He-Ne laser at 633 nm was measured at an angle of 173°. All the samples were measured directly without any filtration.
The in vitro cytotoxicity of the PTHFmPEG2 and the viability of A549 cells were evaluated by using the cell counting kit (CCK-8) assay. The A549 cells in dulbecco’s modified eagle medium (DMEM) supplemented with 10% fetal bovine serum (FBS) were seeded into 96-well plates at a density of 1 × 104 cells per well and cultured for 24 h at 37 °C under CO2/air (5/95, v/v). Then, the cells were cultured with a medium containing various concentrations of PTHFmPEG2 from 50 to 750 μg mL−1. After the cells were incubated for 24 h, 10 μL of CCK-8 solution was added to each well and the cells were incubated for another 2 h at 37 °C. Cell viability was determined by using a microplate reader of absorbance at 450 nm.

3. Results and Discussion

3.1. Synthesis of UPTHF

In order to obtain a high molecular weight of UPTHF, polycondensations of UPTHF were performed using cis-2-butene-1,4-diol and trans-1,4-dibromo-2-butene as a monomer at different process conditions, resulting in a series of polymers with number-average molecular weight (Mn) ranging from 279 to 4300 g mol−1 and a dispersity index of ~1.5 (Table 1). As shown in Table 1, the Mn of UPTHF was only 279 g mol−1, if potassium carbonate (K2CO3) was used as a catalyst. Meanwhile, the Mn of the UPTHF was 423 g mol−1 using sodium hydride (NaH) as a catalyst (Table 1, Sample 1). Experimental results have shown: By using KOH as a catalyst, the Mn of UPTHF was 4306 g mol−1 reaction for 72 h (Table 1, Sample 2). Therefore, KOH is an appropriate catalyst for the synthesis of UPTHF. The 1H NMR spectrum for UPTHF (Mn = 4300 g mol−1) is provided in Figure 2a. The integral ratio of the peaks at δ = 5.74 and 5.63 ppm, which are attributable to the double bone protons resonance in trans-2-butenyl ether and cis-2-butenyl ether, is 1.00:0.95, which is very close to 1:1, indicating that UPTHF has been successfully synthesized (Figure 2a and Figure S1).

3.2. Synthesis of the Side-Chain Functionalized PTHFs

The preparation of the side-chain functionalized PTHFs, such as PTHFOH, PTHFbut, and PTHFacid was performed in similar process conditions. Blue-light (7 W) photocatalytic thiol-ene reaction of UPTHF (260 mg, Mn = 4300 g mol−1, 0.079 mmol, –C=C–, 3.7 mmol) and mercaptoethanol, n-butyl mercaptan, or mercaptopropionic acid (45 mmol) in the presence of Ru(bpy)3Cl2 (2.25 mg, 3.5 × 10−3 mmol) and p-toluidine (5.0 mg, 0.05 mmol) in N-methyl pyrrolidone (NMP, 3 mL) led to the formation of PTHFOH, PTHFbut, and PTHFacid, respectively. The 1H NMR spectra of PTHFOH, PTHFbut, and PTHFacid are displayed in Figure 2b–d, respectively. It can be seen that the peaks at δ = 5.74 and 5.63 ppm (associated to the double bond protons resonance in UPTHF, shown in Figure 2a) have all disappeared, whereas three new peaks appear: The peak at δ = 4.75 corresponds to the hydroxy protons resonance of the branching unit in PTHFOH (Figure 2b), the one at δ = 0.87 ppm can be attributed to the methyl group protons resonance of the branching unit in PTHFbut (Figure 2c), and the one at δ = 2.48 ppm can be associated to the methylene protons resonance of the branching unit in PTHFacid (Figure 2d) appear respectively, suggesting all the double bonds in UPTHF modified via thiol-ene reaction. Moreover, Figure 3 shows the FTIR spectra of UPTHF, PTHF, and the following PTHF derivatives: PTHFOH, PTHFbut, and PTHFacid. The appearance of a stretching vibration peak at 3340 cm−1 (characteristic absorption peaks of the hydroxyl group in PTHFOH), a spike vibration peak at 1458 cm−1 (characteristic absorption peaks of the methyl group in PTHFbut), and a stretching vibration peak at 1705 cm−1 (characteristic absorption peaks of carboxyl group in PTHFacid) also confirms the complete consumption of the double bonds and successful introduction of branch units. Furthermore, the SEC traces of PTHFOH, PTHFbut, and PTHFacid are monomodal, and all the elution parks were located at the higher molecular weight side, similarly to the SEC traces of UPTHF (Figure 4). The Mn,SEC values of the PTHFOH, PTHFbut, and PTHFacid were 6500, 7900 and 9300 g mol−1. Besides, the Mw/Mn of PTHFOH, PTHFbut, and PTHFacid were 1.46, 1.48, and 1.36, respectively. Therefore, based on the above spectral analyses and SEC measurements, we infer that a set of branch units can be efficiently grafted to the backbone of UPTHF via the blue-light photocatalytic thiol-ene reaction.
Although the side-chain functionalized PTHFs have a backbone structure similar with PTHF, the presence of different side-groups in the PTHFs can lead to chemical physical properties which are different to those exhibited by PTHF. Different performance and further application of the side-chain functionalized PTHFs were systematically studied as follows.

3.3. Thermal Properties of PTHFOH and PTHFbut

It is well established that PTHF can be used to synthesize polyurethane materials. However, due to its crystallization, the application of PTHF has been limited to low temperatures. Theoretically, the addition of an alcohol group and butyl branching units could drastically change the thermal properties. [36] To assess the thermal properties and glass transition temperature, the melting and crystallization behaviors of PTHF (Mn = 3000 g mol−1, having a molecular weight similar to the main chains of the PTHF derivatives), PTHFOH, and PTHFbut were investigated via DSC. As it can be seen from Figure 5, PTHF is crystalline and exhibits a fine single peak during the crystallization (Tc = −0.2 °C) and melting (Tm = 29.4 °C) processes. As we expected, compared with PTHF, the PTHFOH and PTHFbut were completely amorphous, with glass transition temperatures at −36.5 and −51.3 °C, respectively. Meanwhile, various brunching units could lead to applications in different fields. The PTHFOH abundance of active hydroxyl-side groups can be used as a hydrogel material, whereas PTHFbut being completely amorphous at low temperatures, can be applied as polyurethanes and polyetheresters in very cold areas.

3.4. pH-Responsive Behavior of PTHFacid

Recently, the interest for pH-responsive polymers has remarkably increased. PTHFacid composed with a hydrophobic PTHF backbone and hydrophilic carboxyl side groups is a promising pH-responsive polymer, which can self-assemble into aggregates in aqueous solution at appropriate conditions. In general, pH-responsive polymers that dissolve in aqueous solution can show dissolution-assembly-aggregation peculiarity with the decrease of pH. This transformation process can be observed macroscopically via UV-Vis spectroscopy. As shown in Figure 6a, the color of the polymer solution changes from completely transparent to pale blue opalescent and then, to fully opalescent, when the pH decreased from 9.0 to 5.0 to 3.0. The UV transmittance of the polymer solution gradually moved from 100% to 20% and finally to 0%, following a pH decreasing from 11 to 3, thus proving the transformation process of pH-responsive polymers (shown in Figure 6a). Moreover, the size and distribution of the PTHF acid aggregates in aqueous solution with pH 6.0, 5.0, and 4.0 were estimated via DLS. The Z-averaged diameters (Dz) of the PTHFacid aggregates were 125, 274, and 447 nm, when the pH values were 6.0, 5.0, and 4.0, respectively (Figure 6b); the size distributions presented a narrow polydispersity at 0.26, 0.18, and 0.11, respectively, further indicating that the transformation process of PTHFacid in aqueous solution follows the dissolution-assembly-aggregation transition behavior as pH decreases. The mechanism of the abovementioned pH-triggered dissolution-assembly-aggregation transition behavior is depicted in Figure 6c. Two types of the carboxyl group can be identified in different conditions: The ionized and non-ionized carboxyl ones. In an alkaline environment, carboxyl groups are all ionized, and PTHFacid dissolves in aqueous solution as monomers (dissolution). In mild acidic conditions, ionized and non-ionized carboxyl groups coexist, and PTHFacid exists as an amphiphilic homopolymer forming solid spherical micelles (assembly). With the decrease of the pH, the amount of non-ionized carboxyl groups increases, and PTHFacid is more hydrophobic, enabling the micelles to aggregate and to form larger micelles (aggregation). As shown in Figure 7, the ζ-potential absolute value decreases sharply as pH value decreases, confirming the validity of the mechanism of the pH-triggered dissolution-assembly-aggregation transition behavior.

3.5. Backbone-Thermoresponsive Behavior of PTHFmPEG

In the past decades, the backbone-thermoresponsive polymers have been extensively studied because of their various promising applications, especially in the synthesis of hyperbranched polymers, which are indeed prepared by combining both hydrophobic and hydrophilic components into the polymer backbone to form a hydrophobic-hydrophilic balance system [37,38,39]. However, up to now, the brush polyether with a backbone-thermoresponsive has not yet been synthesized. Here, we employed the same thiol-ene reaction between UPTHF and mPEG-SH to synthesize PTHFmPEG. When all the double bonds of UPTHF have reacted with mPEG-SH, the obtained polymer (i.e., PTHFmPEG1) can only self-assemble into micelles without exhibiting any thermoresponsive properties in aqueous solution (as determined by the analysis of the 1H NMR spectrum of PTHFmPEG1 in Figure S4a). The possible reason is that the content of mPEG is too rich in hydrophilic components. Fortunately, by regulating the number of hydrophilic branched chains of mPEG to form a hydrophobic-hydrophilic balance system with the backbone of PTHF having ~5.3 branch units of mPEG, we could successfully prepare the backbone-thermoresponsive brush polyether (i.e., PTHFmPEG2). The 1H NMR spectrum of PTHFmPEG2 is displayed in Figure S4b. UV-Vis spectroscopy was used to determine lower critical solution temperature (LCST) of the backbone-thermoresponsive brush polyether. The LCST of PTHFmPEG2 was determined to be 35.2 °C (Figure 8a). Meanwhile, the sizes and distribution of the PTHFmPEG2 aggregates in aqueous solution at 25, 37 and 52 °C were assessed via DLS. When the temperature had been set at 25 °C (i.e., below LCST), the Dz and the size distributions of the PTHFmPEG2 were 91 nm and 0.26, respectively. In contrast, when the temperatures had set at 37 and 52 °C (i.e., above LCST), the Dz of the PTHFmPEG2 gradually increased to 116 and 451 nm, respectively, whereas the size distributions gradually decreased to 0.16 at 37 °C and 0.14 at 52 °C (Figure 8b). The simple mechanisms of the thermoresponsive aggregation of the PTHFmPEG2 are shown in Figure 8c. The PTHFmPEG2 self-assembles into the stabilized nano-micelles below the LCST. When the temperature is above LCST, the hydrophilic-hydrophobic balance breaks and the micelles gradually aggregate into the larger micelles.

3.6. In Vitro Cytotoxicity of PTHFacid and PTHFmPEG

pH-responsive and thermo-responsive polymers are widely used in biomaterials, especially in drug delivery. Therefore, the biocompatibility is of great importance. We, thus, evaluated the in vitro cytotoxicity of micelles of PTHFacid and PTHFmPEG in A549 cells by performing the CCK-8 assay to ensure the potential application for biomaterials. As shown in Figure 9a,b, the cell viabilities of A549 cells after incubation for 24 h were both more than 85%, even at a high concentration of 750 μg mL−1. Furthermore, the optical microscopy observation (Figure 9c,d) of A549 cells treated with PTHFacid and PTHFmPEG of different concentrations show almost no dead cells, implying good biocompatibility with living cells.

4. Conclusions

Herein, we reported the synthesis of side-chain functionalized PTHFs. The blue-light photocatalytic thiol-ene “click” reaction was employed to prepare a series of side-chain functionalized PTHFs containing hydroxyl, butyl, and carboxylate groups, as well as PEG branch units linking in the PTHF backbone. Distinct branch units in the PTHF derivatives led to different performances. For instance, PTHFOH and PTHFbut were all completely amorphous; PTHFacid and PTHFmPEG were pH-responsive and thermo-responsive polymers, respectively, both exhibiting good biocompatibility with living cells. Therefore, the blue-light photocatalytic thiol-ene “click” reaction represents a versatile strategy to synthesize multiple side-chain functionalized PTHFs with designed properties.

Supplementary Materials

The following are available online at https://www.mdpi.com/2073-4360/11/4/583/s1, Figure S1: 1H NMR spectrum of UPTHF (Mn = 4300 g mol−1) in CDCl3; Figure S2: 13C NMR spectrum of UPTHF (Mn = 4300 g mol−1) in CDCl3; Figure S3: 1H NMR spectrum of PTHFacid in DMSO-d6; Figure S4: 1H NMR spectra of PTHFmPEG1 (a) and PTHFmPEG2 (b) in DMSO-d6.

Author Contributions

Conceptualization, X.F. and W.Z.; Methodology, X.Z. and X.M.; Validation, X.Z. and Z.W.; Formal Analysis, X.Z. and T.B; Investigation, T.W.; Resources, X.F.; Data Curation, X.Z. and W.Z.; Writing-Original Draft Preparation, X.Z.; Writing-Review & Editing, X.Z.; Visualization, Z.W.; Supervision, X.F. and J.L.; Project Administration, X.F.; Funding Acquisition, X.F. and W.Z.

Funding

This research was funded by [the scientific research project of Ministry of Industry and Information Technology of P. R. China] grant number [no. JSJL2016140B004], [the National Science Foundation for Young Scientists of China] grant number [no. 51803111] and [the key laboratory project of the department of science and technology of Shannxi province of China] grant number [no. 2013SZS17-Z02].

Conflicts of Interest

The authors declare no conflicts of interest.

References

  1. Jiang, T.; Kai, D.; Liu, J.; Huang, Y.; Heng, J.; Zhao, M.; Chen, B.Q.Y.; Loh, X.J.; Zhu, Y.; Mao, C.; et al. Mechan-ically cartilage-mimicking poly(PCL-PTHF urethane)/collagennanofibers induce chondrogenesis by blocking NFe-kappa B signaling pathway. Biomaterials 2018, 178, 281–292. [Google Scholar] [CrossRef]
  2. Bai, Y.; Xie, F.Y.; Tian, W. Controlled Self-assembly of Thermo-responsive Amphiphilic H-shaped Polymer for Adjustable Drug Release. Chin. J. Polym. Sci. 2018, 36, 406–416. [Google Scholar] [CrossRef]
  3. Zhang, H.; Chen, Y.; Lin, Y.; Fang, X.; Xu, Y.; Ruan, Y.; Weng, W. Spiropyran as a Mechanochromic Probe in Dual Cross-Linked Elastomers. Macromolecules 2014, 47, 6783–6790. [Google Scholar] [CrossRef]
  4. Balko, J.; Fernandez-d’Arlas, B.; Poselt, E.; Dabbous, R.; Muller, A.J.; Thurn-Albrecht, T. Clarifying the Origin of Multiple Melting of Segmented Thermoplastic Polyurethanes by Fast Scanning Calorimetry. Macromolecules 2017, 50, 7672–7680. [Google Scholar] [CrossRef]
  5. Sagara, Y.; Karman, M.; Verde-Sesto, E.; Matsuo, E.; Kim, Y.; Tamaoki, N.; Weder, C. Rotaxanes as Mechanochromic Fluorescent Force Transducers in Polymers. J. Am. Chem. Soc. 2018, 140, 1584–1587. [Google Scholar] [CrossRef] [Green Version]
  6. Zeitsch, K.J. The Chemistry and Technology of Furfural and its Many By-products; Elsevier: Amsterdam, The Netherlands, 2000. [Google Scholar]
  7. Malkappa, K.; Jana, T. Hydrophobic, Water-Dispersible Polyurethane: Role of Polybutadiene Diol Structure. Ind. Eng. Chem. Res. 2015, 54, 7423–7435. [Google Scholar] [CrossRef]
  8. Dubreuil, M.F.; Farcy, N.C.; Goethals, E.J. Influence of the alkyl group of triflate esters on their initiation ability for the cationic ring-opening polymerization of tetrahydrofuran. Macromol. Rapid Commun. 1999, 20, 383–386. [Google Scholar] [CrossRef]
  9. Konig, N.F.; Ouahabi, A.A.; Poyer, S.; Charles, L.; Lutz, J.F. A Simple Post-Polymerization Modification Method for Controlling Side-Chain Information in Digital Polymers. Angew. Chem. Int. Ed. 2017, 56, 7297–7301. [Google Scholar] [CrossRef] [PubMed]
  10. Oakdale, J.S.; Kwisnek, L.; Fokin, V.V. Selective and Orthogonal Post-Polymerization Modifi cation using Sulfur(VI) Fluoride Exchange (SuFEx) and Copper-Catalyzed Azide-Alkyne Cycloaddition (CuAAC) Reactions. Macromolecules 2016, 49, 4473–4479. [Google Scholar] [CrossRef]
  11. Kubo, T.; Swartz, J.L.; Scheutz, G.M.; Sumerlin, B.S. Synthesis of Multifunctional Homopolymers through Using Thiazolidine Chemistry and Post-Polymerization Modification. Macromol. Rapid Commun. 2018, 1800590. [Google Scholar] [CrossRef] [PubMed]
  12. Hyvl, J.; Autenrieth, B.; Schrock, R.R. Proof of Tacticity of Stereoregular ROMP Polymers through Post Polymerization Modification. Macromolecules 2015, 48, 3148–3152. [Google Scholar] [CrossRef]
  13. Xiao, Z.; Bennett, C.W.; Connal, L.A. Facile and Versatile Platform for the Preparation of Functional Polyethylenes via Thiol-Ene Chemistry. J. Polym. Sci. Part A: Polym. Chem. 2015, 53, 1957–1960. [Google Scholar] [CrossRef]
  14. Yokozawa, T.; Suzuki, Y.; Hiraoka, S. Aromatic Polyethers with Low Polydispersities from Chain-Growth Polycondensation. J. Am. Chem. Soc. 2001, 123, 9902–9903. [Google Scholar] [CrossRef] [PubMed]
  15. Yokozawa, T.; Yokoyama, A. Chain-Growth Condensation Polymerization for the Synthesis of Well-Defined Condensation Polymers and π-Conjugated Polymers. Chem. Rev. 2009, 109, 5595–5619. [Google Scholar] [CrossRef] [PubMed]
  16. Li, J.; Li, L.; Du, X.; Feng, W.; Welle, A.; Trapp, O.; Grunze, M.; Hirtz, M.; Levkin, P.A. Reactive Superhydrophobic Surface and Its Photoinduced Disulfideene and Thiol-ene (Bio) functionalization. Nano Lett. 2015, 15, 675–681. [Google Scholar] [CrossRef]
  17. Tucker-Schwartz, A.K.; Farrell, R.A.; Garrell, R.L. Thiol-ene Click Reaction as a General Route to Functional Trialkoxysilanes for Surface Coating Applications. J. Am. Chem. Soc. 2011, 133, 11026–11029. [Google Scholar] [CrossRef]
  18. Li, L.; Li, S.; Cui, D. Highly Cis-1,4-Selective Living Polymerization of 3-Methylenehepta-1,6-diene and Its Subsequent Thiol-Ene Reaction: An Efficient Approach to Functionalized Diene-Based Elastomer. Macromolecules 2016, 49, 1242–1251. [Google Scholar] [CrossRef]
  19. Kwon, J.S.; Park, H.W.; Kim, D.H.; Kwark, Y. Solvent-Free Processable and Photo-Patternable Hybrid Gate Dielectric for Flexible Top-Gate Organic Field-Effect Transistors. ACS Appl. Mater. Interfaces. 2017, 9, 5366–5374. [Google Scholar] [CrossRef]
  20. Zuo, Y.; Gou, Z.; Zhang, J.; Feng, S. Color-Transformable Silicone Elastomers Prepared by Thiol-Ene Reaction with Potential Application in UV-LEDs. Macromol. Rapid Commun. 2016, 37, 597–604. [Google Scholar] [CrossRef]
  21. Zuo, Y.; Gou, Z.; Zhang, C.; Feng, S. Polysiloxane-Based Autonomic Self-Healing Elastomers Obtained through Dynamic Boronic Ester Bonds Prepared by Thiol-Ene “Click” Chemistry. Macromol. Rapid Commun. 2016, 37, 1052–1059. [Google Scholar] [CrossRef]
  22. Bai, J.; Li, H.; Shi, Z.; Yin, J. An Eco-Friendly Scheme for the Cross-Linked Polybutadiene Elastomer via Thiol-Ene and Diels-Alder Click Chemistry. Macromolecules 2015, 48, 3539–3546. [Google Scholar] [CrossRef]
  23. Berthold, A.; Sagar, K.; Ndoni, S. Patterned Hydrophilization of Nanoporous 1,2-PB by Thiol-ene Photochemistry. Macromol. Rapid Commun. 2011, 32, 1259–1263. [Google Scholar] [CrossRef] [PubMed]
  24. Brummelhuis, N.; Diehl, C.; Schlaad, H. Thiol-Ene Modification of 1,2-Polybutadiene Using UV Light or Sunlight. Macromolecules 2008, 41, 9946–9947. [Google Scholar] [CrossRef]
  25. Wolfberger, A.; Rupp, B.; Kern, W.; Griesser, T.; Slugovc, C. Ring Opening Metathesis Polymerization Derived Polymers as Photoresists: Making Use of Thiol-ene Chemistry. Macromol. Rapid Commun. 2011, 32, 518–522. [Google Scholar] [CrossRef]
  26. Gauthier, M.A.; Gibson, M.I.; Klok, H.A. Synthesis of Functional Polymers by Post-Polymerization Modification. Angew. Chem. Int. Ed. 2009, 48, 48–58. [Google Scholar] [CrossRef]
  27. Silverstein, J.S.; Casey, B.J.; Natoli, M.E.; Dair, B.J.; Kofinas, P. Rapid Modular Synthesis and Processing of Thiol-Ene Functionalized Styrene-Butadiene Block Copolymers. Macromolecules 2012, 45, 3161–3167. [Google Scholar] [CrossRef]
  28. Tyson, E.L.; Niemeyer, L.Z.; Yoon, T.P. Redox Mediators in Visible Light Photocatalysis: Photocatalytic Radical Thiol-Ene Additions. J. Org. Chem. 2014, 79, 1427–1436. [Google Scholar] [CrossRef]
  29. Tyson, E.L.; Ament, M.S.; Yoon, T.P. Transition Metal Photoredox Catalysis of Radical Thiol-Ene Reac-tions. J. Org. Chem. 2013, 78, 2046–2050. [Google Scholar] [CrossRef] [PubMed]
  30. Liu, H.; Chung, H. Thiol-Ene Reaction on Natural Lignin. ACS Sustainable Chem. Eng. 2017, 5, 9160–9168. [Google Scholar] [CrossRef]
  31. Santandrea, J.; Kairouz, V.; Collins, S.K. Flow Science in an Undergraduate Teaching Laboratory: Photocatalytic Thiol-Ene Reaction Using Visible Light. J. Chem. Educ. 2018, 95, 1073–1077. [Google Scholar] [CrossRef]
  32. Xu, J.; Boyer, C. Visible Light Photocatalytic Thiol-Ene Reaction: An Elegant Approach for Fast Polymer Postfunctionalization and Step-Growth Polymerization. Macromolecules 2015, 48, 520–529. [Google Scholar] [CrossRef]
  33. Zhang, W.; Zhang, G.; Du, L.; Zhang, C.; Li, L.; Zhu, J.; Pei, J. Synthesis of hydroxyl-terminated polybutadiene bearing pendant carboxyl groups by combination of anionic polymerization and blue light photocatalytic thiol-ene reaction and its pH-triggered self-assemble behavior. React. Funct. Polym. 2018, 127, 161–167. [Google Scholar] [CrossRef]
  34. Zhang, S.; Xu, J.; Chen, H.; Song, Z.; Wu, Y.; Dai, X.; Kong, J. Acid-Cleavable Unimolecular Micelles from Amphiphilic Star Co-polymers for Triggered Release of Anticancer Drugs. Macromol. Biosci. 2017, 17, 1600258. [Google Scholar] [CrossRef]
  35. Bai, T.; Du, J.; Chen, J.; Duan, X.; Zhuang, Q.; Chen, H.; Kong, J. Reduction-responsive dithiomaleimide-based polymeric micelles for controlled anti-cancer drug delivery and bioimaging. Polym. Chem. 2017, 8, 7160–7168. [Google Scholar] [CrossRef]
  36. Ilg, A.D.; Price, C.J.; Miller, S.A. Linear Low-Density Polyoxymethylene versus Linear Low-Density Polyethylene. Macromolecules 2007, 40, 7739–7741. [Google Scholar] [CrossRef]
  37. Jia, Z.; Chen, H.; Zhu, X.; Yan, D. Backbone-Thermoresponsive Hyperbranched Polyethers. J. Am. Chem. Soc. 2006, 128, 8144–8145. [Google Scholar] [CrossRef]
  38. Fan, W.; Fan, X.; Tian, W.; Zhang, X.; Wang, G.; Zhang, W.; Bai, Y.; Zhu, X. Phase transition dynamics and mechanism for backbone-thermoresponsive hyperbranched polyethers. Polym. Chem. 2014, 5, 4022–4031. [Google Scholar] [CrossRef]
  39. Cao, G.; Li, G.; Yang, Q.; Liu, Z.; Liu, Z.; Jiang, J. LCST-Type Hyperbranched Poly(oligo(ethylene glycol) with Thermo- and CO2-Responsive Backbone. Macromol. Rapid Commun. 2018, 39, 1700684. [Google Scholar] [CrossRef] [PubMed]
Polymers 11 00583 g001 550
Figure 1. The synthesis routes of unsaturated polytetrahydrofuran (UPTHF) and side-chain functional polytetrahydrofuran (PTHF) derivatives.
Figure 1. The synthesis routes of unsaturated polytetrahydrofuran (UPTHF) and side-chain functional polytetrahydrofuran (PTHF) derivatives.
Polymers 11 00583 g001
Polymers 11 00583 g002 550
Figure 2. 1H NMR spectra of UPTHF ((a), Sample 2 in Table 1), PTHFOH (b), PTHFbut (c) and PTHFacid (d) in DMSO-d6.
Figure 2. 1H NMR spectra of UPTHF ((a), Sample 2 in Table 1), PTHFOH (b), PTHFbut (c) and PTHFacid (d) in DMSO-d6.
Polymers 11 00583 g002
Polymers 11 00583 g003 550
Figure 3. FTIR spectra of UPTHF, PTHF, PTHFOH, PTHFbut and PTHFacid.
Figure 3. FTIR spectra of UPTHF, PTHF, PTHFOH, PTHFbut and PTHFacid.
Polymers 11 00583 g003
Polymers 11 00583 g004 550
Figure 4. Size exclusion chromatography (SEC) elution curves of UPTHF ((a), sample 2 in Table 1), PTHFOH (b), PTHFbut (c) and PTHFacid (d). Terahydrofuran (THF) was used as the eluent.
Figure 4. Size exclusion chromatography (SEC) elution curves of UPTHF ((a), sample 2 in Table 1), PTHFOH (b), PTHFbut (c) and PTHFacid (d). Terahydrofuran (THF) was used as the eluent.
Polymers 11 00583 g004
Polymers 11 00583 g005 550
Figure 5. Differential scanning calorimeter (DSC) cooling scans (a) and heating scans (b) at 5 °C min−1 after melting at 90 °C for the indicated polymers.
Figure 5. Differential scanning calorimeter (DSC) cooling scans (a) and heating scans (b) at 5 °C min−1 after melting at 90 °C for the indicated polymers.
Polymers 11 00583 g005
Polymers 11 00583 g006 550
Figure 6. Transmittances of PTHFacid solutions with different pH values (a). Dynamic light scattering (DLS) traces of aggregates formed by the self-assembly of PTHFacid in aqueous solution at pH 6, 5, and 4 (b), [Polymer] = 0.5 mg mL−1. Schematic illustration of the mechanism for the pH-triggered dissolution- assembly-disassembly transition behavior (c).
Figure 6. Transmittances of PTHFacid solutions with different pH values (a). Dynamic light scattering (DLS) traces of aggregates formed by the self-assembly of PTHFacid in aqueous solution at pH 6, 5, and 4 (b), [Polymer] = 0.5 mg mL−1. Schematic illustration of the mechanism for the pH-triggered dissolution- assembly-disassembly transition behavior (c).
Polymers 11 00583 g006
Polymers 11 00583 g007 550
Figure 7. Zeta potential of PTHFacid solution at varying pH.
Figure 7. Zeta potential of PTHFacid solution at varying pH.
Polymers 11 00583 g007
Polymers 11 00583 g008 550
Figure 8. Transmittances of PTHFmPEG solution in different temperature (a). DLS traces of aggregates formed by the self-assembly PTHFmPEG in aqueous solution at temperature 25, 37 and 52 °C (b), [Polymer] = 0.5 mg mL−1. Schematic illustration of the mechanism for the temperature-triggered self-assembly behavior (c).
Figure 8. Transmittances of PTHFmPEG solution in different temperature (a). DLS traces of aggregates formed by the self-assembly PTHFmPEG in aqueous solution at temperature 25, 37 and 52 °C (b), [Polymer] = 0.5 mg mL−1. Schematic illustration of the mechanism for the temperature-triggered self-assembly behavior (c).
Polymers 11 00583 g008
Polymers 11 00583 g009 550
Figure 9. The cell viability of A549 cells after incubation with PTHFacid and PTHFmPEG for 24 h (PTHFacid for (a) and PTHFmPEG for (b), optical microscopy images of A549 cells after incubation with different concentrations of PTHFacid and PTHFmPEG for 24 h (PTHFacid for (c) and PTHFmPEG for (d)).
Figure 9. The cell viability of A549 cells after incubation with PTHFacid and PTHFmPEG for 24 h (PTHFacid for (a) and PTHFmPEG for (b), optical microscopy images of A549 cells after incubation with different concentrations of PTHFacid and PTHFmPEG for 24 h (PTHFacid for (c) and PTHFmPEG for (d)).
Polymers 11 00583 g009
Table
Table 1. Synthesis of UPTHF with different polymerization technology.
Table 1. Synthesis of UPTHF with different polymerization technology.
SampleSolventTemperature (°C)CatalystReaction Time (h)Mn (g mol−1)Mw/Mn
1acetonerefluxNaH484231.31
2acetonerefluxKOH7243061.48
3acetonerefluxKOH4818061.72
4acetonerefluxK2CO3722791.18

Share and Cite

MDPI and ACS Style

Zhu, X.; Bai, T.; Wang, Z.; Liu, J.; Min, X.; Wang, T.; Zhang, W.; Fan, X. Synthesis and Properties of Side-Chain Functionalized Polytetrahydrofuran Derivatives via the Blue-Light Photocatalytic Thiol-Ene Reaction. Polymers 2019, 11, 583. https://doi.org/10.3390/polym11040583

AMA Style

Zhu X, Bai T, Wang Z, Liu J, Min X, Wang T, Zhang W, Fan X. Synthesis and Properties of Side-Chain Functionalized Polytetrahydrofuran Derivatives via the Blue-Light Photocatalytic Thiol-Ene Reaction. Polymers. 2019; 11(4):583. https://doi.org/10.3390/polym11040583

Chicago/Turabian Style

Zhu, Xiuzhong, Ting Bai, Zichao Wang, Jie Liu, Xin Min, Tong Wang, Wanbin Zhang, and Xiaodong Fan. 2019. "Synthesis and Properties of Side-Chain Functionalized Polytetrahydrofuran Derivatives via the Blue-Light Photocatalytic Thiol-Ene Reaction" Polymers 11, no. 4: 583. https://doi.org/10.3390/polym11040583

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop