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Original article
12 (
6
); 800-815
doi:
10.1016/j.arabjc.2017.05.018

Synthesis of ferrocene boronic acid-based block copolymers via RAFT polymerization and their micellization, redox responsive and glucose sensing properties

, , ,
 State Key Laboratory of Chemical Engineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, China

⁎Corresponding authors. Fax: +86 571 8795 1612. opl_wl@dial.zju.edu.cn (Li Wang), hjyu@zju.edu.cn (Haojie Yu)

Received: , Accepted: ,
© The Author(s) 2017
Disclaimer:
This article was originally published by Elsevier and was migrated to Scientific Scholar after the change of Publisher.

Peer review under responsibility of King Saud University.

Abstract

Abstract

Current study is focused on the synthesis of three novel diblock copolymers poly(2-methacryloyloxy)ethyl ferrocene carboxylate-b-polymethyl vinyl amido phenyl boronic acid, poly(2-methacryloyloxy)ethyl ferrocene carboxylate-b-poly vinylamido phenyl boronic acid and poly(2-methacryloyloxy)ethyl ferrocene carboxylate-b-polystyrene boronic acid using S-methoxycarbonylphenylmethyl dithiobenzoate as reversible addition–fragmentation chain transfer polymerization agent. The synthesized block copolymers were characterized by gel permeation chromatography, fourier transform infrared spectroscopy, 1H nuclear magnetic resonance spectroscopy, dynamic light scattering, scanning electron microscopy and transmission electron microscopy. Detailed micellization behaviour of poly(2-methacryloyloxy)ethyl ferrocene carboxylate-b-polymethyl vinyl amido phenyl boronic acid (in binary organic solvents mixture and aqueous solution) was studied. Comparative studies of micellization showed that the larger aggregates were obtained in binary organic solvents system than during dialysis in aqueous medium. The redox responsive behaviour of poly(2-methacryloyloxy)ethyl ferrocene carboxylate-b-polymethyl vinyl amido phenyl boronic acid was investigated by water soluble oxidizing (Ammonium cerium nitrate) and reducing (Sodium hydrogen sulphite) agents. Glucose binding/sensing properties of poly(2-methacryloyloxy)ethyl ferrocene carboxylate-b-polymethyl vinyl amido phenyl boronic acid were also explored by micellization. It was found that the increase in polarity and swelling of poly(2-methacryloyloxy)ethyl ferrocene carboxylate-b-polymethyl vinyl amidophenyl boronic acid micelles was due to the redox behaviour of ferrocene, while binding of glucose with boronic acids hydroxyls appears as unimers or small aggregates.

Keywords

Ferrocene boronic acid
Block copolymer
Micellization
Redox responsive
1

1 Introduction

The synthesis of block copolymers is a versatile approach to combine characteristics of different polymers (Behbahani et al., 2014; Buonerba et al., 2013; Hadjichristidis et al., 2006; Lazzari and López-Quintela, 2003). Currently, considerable efforts have been done to combine the distinctive characteristics of different organic polymers with the diverse advantages of metal-containing structures (Behbahani et al., 2016; Hosseini et al., 2014; Kulbaba and Manners, 2001; Majonis et al., 2010). Metallocene-containing polymers have great potential in magnetic, optical, catalytic and biological applications due to their great physicochemical properties and unique geometries (Braunecker and Matyjaszewski, 2008; Hawker et al., 2001; Kamigaito et al., 2001; Moad et al., 2005). Different methods are employed in glucose detection such as Glucose oxidase (GOx), and Lectin and phenylboronic acid (PBA) method. Among these methods GOx based biosensors and Lectin based biosensors have some disadvantages, such as the poor stability of the enzyme and consumption of the substrate during the detection process, which limit their biosensing applications. As an alternative to enzymatic detection methods (i.e. GOx and Lectin), phenyl boronic acid functionalized compounds and materials have been widely used as recognition medium for biosensing of biological analytes for example dopamine, saccharides, and glycoproteins (M. Li et al., 2015; Saleem et al., 2015). It is well-known that supramolecular assemblies such as micelles are formed on dissolving block copolymer in a selective solvent (Marinos Pitsikalis and Hadjichristidis, 2000). In the past few decades, micellization of amphiphilic block copolymers in selective solvent systems has been widely studied (Chen et al., 2014; Pitsikalis et al., 2004; Wang et al., 2014). A typical polymeric micelle consists of a stretched shell and a compact core formed by soluble and insoluble blocks, respectively. The core of hydrophobic micelle forms a microenvironment for the incorporation of different substances, while its hydrophilic shell inhibits the interactions of hydrophobic segments and aggregation (Riess, 2003). The size and shape of the micelle are greatly dependent on the block copolymer composition, which makes it crucial to control the blocks length with narrow polydispersity index (PDI).

Controlled radical polymerization (CRP) including atom transfer radical polymerization (ATRP), nitroxide-mediated polymerization (NMP) and reversible addition–fragmentation chain transfer polymerization (RAFT) are most commonly studied polymerization techniques for the development of well-defined polymers and block copolymers (Gallei, 2014; Harrisson et al., 2014; Liu et al., 2015). Among CRP, RAFT is considered as one of the best polymerization techniques and can be conducted under relatively mild conditions for polymerization of variety of functional monomers (Roy and Sumerlin, 2012; Shi et al., 2007). Many studies have been reported in the literature concerning the micelles properties of copolymers consisting of polystyrene (PS) and polymethacrylate (PMA) blocks (Gao et al., 2011; Liu et al., 1996; Qin et al., 1994; Siqueira et al., 1994). Most of these studies are referred to polystyrene-b-poly(methyl methacrylate) (PS-b-PMMA) (Duval and Picot, 1987; Edwards et al., 1986; Gao et al., 2011; Kotaka et al., 1978; Liu et al., 1996; Qin et al., 1994; Siqueira et al., 1994; Utiyama et al., 1974). Copolymers either in single solvent (e.g., p-xylene or acetone) or in solvent combinations (e.g., toluene/p-cumene and toluene/furfuryl alcohol). More recently, Choi et al. reported micellization of poly(styrene-b-ethylene-alt-propylene) diblock copolymer micelles in binary solvents mixtures and determined the overall effect of corona on size and shape of the micelles (Choi et al., 2016). In general, along with high degree of aggregation, the micelles obtained were mainly star and spherical shaped. To produce aggregate structures of the copolymers, the copolymer is usually dissolved in a common solvent, which is capable to dissolve all blocks of the copolymer. However, a solvent having same solubility for all the blocks of a copolymer is rare. Hence, it is extremely important to synthesize block copolymer, which can form micelles in a common solvent. Stimuli-responsive polymers have been in the focus of intensive research for the last decade. The vast majority of the reports deal with temperature, light or pH changes as external triggers. In recent years, the redox stimulus has gained significant attention for switching polymer conformation or the polarity of surfaces. The introduction of ferrocene moiety into polymers has been extensively used for the construction of redox stimuli-responsive polymers owing to reversible oxidation and reduction in ferrocene units by electrochemical and chemical means (Morsbach et al., 2013; Schmidt et al., 2014). Ferrocene-containing block copolymers self-assembly may induce change in the polarity of ferrocene-bearing blocks due to reversible redox reactions. Thereby, it forms micelles with redox-triggered activity, which is particularly useful for potential applications of redox-regulated release of encapsulants (Du et al., 2011; P. Li et al., 2015; Liu et al., 2015b). Polymers with boronic acid (BA) groups are versatile, especially for saccharide sensing applications. BA recognizes cis-diol configuration of saccharides by forming reversible covalent complexes in aqueous solution and thus represents an ideal synthetic molecular receptor and can be utilized for sensing biologically related molecules including proteins, peptides, drugs and enzymes (Li et al., 2012). In addition, change in redox behaviour could trigger an electrochemical stimulus on binding of diols with BA. The covalent attachment of BA with biomolecules can provide the opportunity to develop novel materials with the integrated properties of both systems (redox responsive ferrocene and BA for binding diols) for several applications such as biotechnology, nanotechnology, medicine and especially for saccharide sensing. Furthermore, self-assembly of the biomolecule and block copolymer may also form redox-responsive micelles, which can exhibit redox-triggered response by the change in their shape or size. Therefore, synthesis and binding of glucose with BA, both can demonstrate an example of saccharide sensing, which can be utilized to construct redox responsive saccharide detection methods. Among metallocene based polymers, ferrocene-containing acrylates and methacrylates are well-known due to their ease of synthesis, stability and more importantly, reversible redox behaviour of ferrocene. The oxidation states of ferrocene (+2 and +3) can be varied and may be used to alter electronic properties of the polymers backbone. Keeping aforementioned crucial findings for the facile synthesis of ferrocene boronic acid-based block copolymers, we have chosen acrylates and methacrylates derivatives of ferrocene and BA. This method of synthesis provides facile synthetic procedure to prepare dual responsive block copolymer (redox active ferrocene and saccharide sensing boronic acid moiety), which can self-assemble. In continuation of our interest in ferrocene-boron chemistry (Saleem et al., 2016), we synthesized ferrocene boronic acid-based block copolymers (PMAEFc-b-PMVAPBA, PMAEFc-b-PVAPBA and PMAEFc-b-PSBA) using MCPDB as RAFT agent. Detailed micellization behaviour, glucose sensing and redox responsive nature of the reported dual responsive block copolymer through micellization was studied.

2

2 Experimental

2.1

2.1 Materials

Ferrocenemonocarboxylic acid and ferrocenedicarboxylic acid were purchased from Energy Chemicals Shanghai, China and used without further purification. Oxalyl chloride was purchased from Sinopharm Chemical Reagent Co., Ltd. Shanghai, China and used without further purification. Triethyl amine (TEA), pyridine, ethyl acetate, acetonitrile (MeCN), dimethylformamide (DMF), and methanol anhydrous were purchased from Sinopharm Chemical Reagent Co., Ltd. Shanghai, China and used after drying using 4Å-type molecular sieves. Vinylamidophenyl, methyl vinylamido phenyl and 2-(methacryloyloxy)ethyl ferrocene carboxylate (MAEFc) were synthesized according to previously reported methods (Perrier et al., 2004; Roy et al., 2009a). Methyl-2-bromo-2-phenylacetate was purchased from Tokyo chemical industry (TCI) Co., Ltd. Tokyo, Japan. S-methoxycarbonylphenylmethyl dithiobenzoate (MCPDB) as RAFT chain transfer agent was synthesized according to the reported literature (Perrier et al., 2004). 2,2-Azobis(isobutyronitrile) (AIBN), 4-vinylphenyl boronic acid, and bromo benzene and magnesium (Mg) turnings were purchased from J & K scientific Ltd. Beijing, China. AIBN was recrystallized thrice from methanol.

2.2

2.2 Synthesis of PMAEFc-b-PVAPBA, PMAEFc-b-PMVAPBA and PMAEFc-b-PSBA

Three diblock copolymers (PMAEFc-b-PVAPBA, PMAEFc-b-PMVAPBA and PMAEFc-b-PSBA) were synthesized using PMAEFc as ferrocene-based macroinitiator and using VAPBA, MVAPBA and SBA as boronic acid-based monomers, respectively. The detailed synthetic procedure is as follows.

2.2.1

2.2.1 Ferrocenemonocarbonyl chloride

Ferrocenecarbonyl chloride (FcCOCl) was synthesized using oxalyl chloride (as a chlorinating agent) and ferrocenecarboxylic acid (FcCOOH) in CH2Cl2 employing pyridine as a catalyst. In a typical procedure, FcCOOH (20.714 g 83.92 mmol) was dissolved in freshly distilled CH2Cl2 (150 mL) and then the solution mixture was stirred under Ar atmosphere. Pyridine (14.50 mL) and oxalyl chloride (15.50 mL, 180.72 mmol) were added to the above solution. The resulting solution was then stirred for 30 min at room temperature and allowed to reflux for 5 h. The reaction mixture was evaporated under reduced pressure using liquid nitrogen and residue was extracted with petroleum ether (150 mL) using in situ filtration.

2.2.2

2.2.2 2-(Methacryloyloxy)ethyl ferrocencarboxylate

2-(Methacryloyloxy)ethyl ferrocencarboxylate (MAEFc) was synthesized with slight modification in the reported method (Zhang et al., 2012b). FcCOCl (12.61 g, 50.7 mmol), 2-hydroxyethyl methacrylate (6.15 mL, 50.7 mmol) and pyridine (10 mL) were dissolved in freshly distilled THF (100 mL) and then the resulting solution was refluxed for 4 h. The reaction mixture was filtered, and then filtrate was dried on rotary evaporator. The product was precipitated in cold water and then washed thrice with distilled water to obtained pure brownish solid. 1H NMR (600 MHz, CDCl3) δ ppm: 6.22 (1H, vinyl CH), 5.61(1H, Vinyl CH), 4.80 (2H, Cp), 4.45 (4H, OCH2CH2O), 4.40 (2H, Cp), 4.21 (5H, Cp) and 2.00 (3H, CH3).

2.2.3

2.2.3 S-methoxycarbonylphenylmethyl dithiobenzoate

S-methoxycarbonylphenylmethyl dithiobenzoate (MCPDB) was prepared with little modification in the reported method (Perrier et al., 2004). Typically, bromobenzene (4.2 mL, 39.9 mmol) was mixed with Mg turnings (1 g, 41.1 mmol) in 30 mL of dried THF. The solution of phenyl magnesium bromide was heated to 40 °C and then CS2 (2.25 mL, 26.0 mmol) was added dropwise to the previous solution in approximately 10 min to obtain a dark brown solution. Methyl α-bromophenylacetate (6.84 mL, 43.6 mmol) was injected into the above solution. The reaction mixture was refluxed for 20 h. Ice cold water was then added to the obtained solution and organic layer was extracted with diethyl ether (50 mL). Furthermore, the combined organic extracts were rinsed with water and dried over anhydrous magnesium sulphate (MgSO4). In the final step, column chromatography was undertaken (dichloromethane: n-hexane (1:1)) to obtain pure product as orange red oil. 1H NMR (600 MHz, CDCl3) δ ppm: 7.90 (2H, ArH), 7.58–7.20 (8H, ArH), 4.20 (1H, CH) and 2.70 (3H, CH3).

2.2.4

2.2.4 Vinylamidophenylboronic acid monomers

Vinylamidophenylboronic acid (VAPBA) and methyl vinylamidophenylboronic acid (MVAPBA) were synthesized according to previously published report (Roy et al., 2009c). For the synthesis of VAPBA, APBA (1.50 g, 0.010 mol) was dissolved in solvent mixture of THF and water (20 mL each) in 1:1 volume-by-volume ratio. Sodium hydrogen carbonate (NaHCO3) (1.85 g, 0.022 mol) and acryloyl chloride (2.00 g, 0.022 mol) were added to the flask at 0–5 °C. The solution was then stirred for 4 h and solvent was evaporated under reduced pressure. A solid crude product was obtained, which was further stirred in ethyl acetate (50 mL) for 2 h. The solution was filtered and ethyl acetate layer was washed four times, first time with water, second time with saturated sodium bicarbonate (NaHCO3) solution, third time again with water and fourth time with brine (saturated solution of NaCl) (40 mL of each solution was used). The ethyl acetate layer was concentrated on rotary evaporator providing white solid. The VAPBA was purified by recrystallization in hot water (thrice).

For the synthesis of MVAPBA, APBA (1.50 g, 0.010 mol) was dissolved in solvent mixture of THF and water (20 mL each) in 1:1 volume-by-volume ratio. Sodium hydrogen carbonate (NaHCO3) (1.85 g, 0.022 mol) and methyl acryloyl chloride (2.29 g, 0.022 mol) were added to the flask at 0–5 °C. The solution was then stirred for 4 h and solvent was evaporated under reduced pressure. A solid crude product was obtained, which was further stirred in ethyl acetate (50 mL) for 2 h. The solution was filtered and ethyl acetate layer was washed four times: first with water, second time with saturated sodium bicarbonate (NaHCO3) solution, third time again with water and fourth time with brine (saturated solution of NaCl) (40 mL of each solution was used). The ethyl acetate layer was concentrated on rotary evaporator providing white solid. The MVAPBA was purified by recrystallization in hot water (thrice). 1H NMR data of VAPBA (600 MHz, DMSO) δ ppm: 10.15 (1H, NH), 8.20 (2H, B(OH)2), 7.86–7.20 (4H, ArH), 6.50 (1H, vinyl CH), 6.25 and 5.75 (1H each, vinyl CH2). 1H NMR data of MVAPBA (600 MHz, DMSO) δ ppm: 9.70 (1H, NH), 8.05 (2H, B(OH)2), 7.90–7.29 (4H, ArH), 5.85 and 5.50 (1H each, vinyl CH2) and 2.00 (3H, CH3).

2.2.5

2.2.5 Poly(methacryloyloxy)ethyl ferrocenecarboxylate

The synthesis of poly(methacryloyloxy)ethyl ferrocenecarboxylate) (PMAEFc) was performed with slight modification to the reported literature (Zhang et al., 2012b). In a typical procedure, MAEFc (5.00 g, 14.60 mmol), MCPDB (66.99 mg, 0.22 mmol) and AIBN (11.80 mg, 0.07 mmol) were dissolved in 8 mL of acetonitrile in a 20 mL reaction tube and then reaction mixture was degassed with three cycles of freeze-pump–thaw. The reaction mixture was refluxed for 7 h and reaction was quenched at a conversion of 85%. The reaction mixture was precipitated in methanol (250 mL) and then centrifuged for 10 min. Afterwards the resulting mixture was dried in vacuum oven to obtain a yellowish solid. 1H NMR data of PMAEFc (600 MHz, DMSO) δ ppm: 4.80 (2H, Cp), 4.50 (4H, OCH2CH2O), 4.40 (2H, Cp), 4.30 (5H, Cp), 1.90 (2H, CH2C) and 0.95–1.05 (3H, CH3).

2.2.6

2.2.6 Kinetic study of polymerization for 2-(methacryloyloxy)ethyl ferrocencarboxylate

Kinetic study of (2-methacryloyloxy)ethyl ferrocencarboxylate) MAEFc was done using similar procedure as reported in the literature (Zhang et al., 2012b). MAEFc (400.30 mg, 1.17 mmol), MCPDB (5.36 mg, 0.015 mmol) and AIBN (0.96 mg, 0.0058 mmol) were dissolved in 1.2 mL of DMF and then the reaction mixture was inserted into a 20 mL reaction tube. Before polymerization, the reaction tube was degassed (with three cycles of freeze-pumpthaw). The reaction mixture was heated at 90 °C for 8 h. Samples were taken out carefully at different time intervals under the protection of Ar gas and polymerization was quenched using liquid nitrogen. 1H NMR and GPC were used to monitor monomer conversion.

2.2.7

2.2.7 Synthesis of diblock copolymers

Three diblock copolymers (PMAEFc-b-PVAPBA, PMAEFc-b-PMVAPBA and PMAEFc-b-PSBA) were synthesized using PMAEFc as ferrocene-based macroinitiator and VAPBA, MVAPBA and SBA as boronic acid-based monomers. For the synthesis of PMAEFc-b-PVAPBA, VAPBA (754.41 mg, 4 mmol), PMAEFc (300 mg, 0.02 mmol) and AIBN (0.70 mg, 0.004 mmol) were dissolved in 1.2 mL of DMF in a 20 mL reaction tube and then contents of reaction tube were purged with Ar gas for 20 min. For the synthesis of PMAEFc-b-PMVAPBA, MVAPBA (809.80 mg, 4 mmol), PMAEFc (300 mg, 0.02 mmol) and AIBN (0.70 mg, 0.004 mmol) were dissolved in 1.2 mL of DMF in a 20 mL reaction tube and then contents of reaction tube were purged with Ar gas for 20 min. For the synthesis of PMAEFc-b-PSBA, SBA (584 mg, 4 mmol), PMAEFc (300 mg, 0.02 mmol) and AIBN (0.70 mg, 0.004 mmol) were also dissolved in 1.2 mL of DMF in a 20 mL reaction tube and then contents of reaction tube were purged with Ar gas for 20 min. All the reaction tubes were sealed before polymerization. VAPBA and SBA were polymerized at 90 °C, while MVAPBA was polymerized at 70 °C for 7 h to obtain PMAEFc-b-PVAPBA, PMAEFc-b-PSBA and PMAEFc-b-PMVAPBA block copolymers, respectively. Finally, all the synthesized diblock copolymers were precipitated in methanol (250 mL of methanol was used for each diblock copolymer). Afterwards, all three diblock copolymers were filtered and dried in vacuum oven to obtain yellow brownish solid. 1H NMR (600 MHz, DMSO) δ ppm: For PMAEFc-b-PVAPBA: 9.50 (1H, NH), 8.05 (2H, (B(OH)2), 7.10–7.80 (4H, ArH), 4.80–4.47 (4H, OCH2CH2O), 4.30–4.20 (Cp from Cp2Fc), 1.10 (4H, CH2C) and 0.95–1.05 (2H, CH3), For PMAEFc-b-PMVAPBA: 9.70 (1H, NH) 8.00 (2H, (B(OH)2), 7.10–7.850 (4H, ArH), 4.75–4.50 (4H, OCH2CH2O), 4.30–4.20 (Cp from Cp2Fc), and 1.90 (4H, CH2C) and 1.25 (6H, CH3). For PMAEFc-b-PSBA: 7.90 (2H, (B(OH)2), 7.70 (2H, ArH), 7.40 (2H, ArH), 4.75–4.45 (4H, OCH2CH2O), 4.41–4.22 (Cp from Cp2Fc), 2.40–1.45 (4H, CH2C), 0.80–0.60 (2H, CH2CH) and 0.55 (3H, CH3).

2.2.8

2.2.8 Micellization in selective binary organic solvents mixtures

The procedure of micelles formation in selective binary organic solvents systems (DMF:CHCl3, DMF:CH3CN and DMSO:CHCl3 with volume-to-volume ratio (1:2) was as follows: Two solvents (1 mL and 2 mL) were mixed and sonicated for 3 min to decrease the overall polarity of the solvents. PMAEFc-b-PMVAPBA (3 mg) was dissolved in binary solvent system with vigorous stirring. The solution was miniemulsified by sonicating for further 30 min at room temperature. The resulting colloidal solution was collected and characterized. The substantial difference in the solubility of hydrophobic part (ferrocene) led to form the core and hydrophilic part (boronic acid) as corona of PMAEFc-b-PMVAPBA micelles.

2.3

2.3 Micellization in aqueous medium

The procedure of micelles formation in water is as follows: PMAEFc-b-PMVAPBA (2.5 mg) was dissolved in 1 mL of THF and followed by dropwise addition in 15 mL of deionized water with vigorous stirring. The solution was sonicated at room temperature for 30 min. The resulting colloidal solution was dialyzed using a semipermeable membrane (MWCO = 3500) against distilled water for 2 d at 15 °C to remove THF. The substantial removal of THF decreased the solubility of hydrophobic part (ferrocene) to form the core and hydrophilic part (boronic acid) as corona of PMAEFc-b-PMVAPBA micelles. The water (in which dialysis bags were putted) was replaced at appropriate intervals.

2.3.1

2.3.1 Glucose binding of PMAEFc-b-PMVAPBA micelles

The procedure for glucose binding of PMAEFc-b-PMVAPBA micelles is same as PMAEFc-b-PMVAPBA micelles formation in aqueous medium. In a typical procedure, 1 mg of glucose powder and 2.5 mg of PMAEFc-b-PMVAPBA block copolymer were dissolved in THF (1 mL) and then this solution was added dropwise in deionized water (10 mL) over 30 min under stirring. THF was removed by dialysis using a semi permeable membrane (MWCO = 3500) against deionized water for 2 d at 15 °C and fresh water was exchanged after every 5 h to ensure full removal of excess glucose (which failed to bind with BA).

2.3.2

2.3.2 Redox reactions of PMAEFc-b-PMAVPBA micelles in aqueous solution

The well dispersed micelles solution was treated with slight excess amount of (NH4)2Ce(NO3)6 compared to total ferrocene units present in PMAEFc-b-PMAVPBA and slowly stirred until the yellow colour of the micelles changed to green. Subsequently, NaHSO3 was introduced to the dispersion of oxidized micelles and stirred until the colour was recovered back to yellow. All the samples were subjected to dialysis prior to SEM measurements.

2.3.3

2.3.3 Characterization

1H NMR and 11B NMR spectra were measured using a 600 MHz AVANCE NMR spectrometer. The chemical shifts were referenced to tetramethylsilane (TMS) at δ = 0 ppm. Molecular weight of the synthesized polymers was determined by GPC (Waters Company, Model 2515-2414) with laser refractive index detector with Ultrastyral gel column (pore size: 103–105 Å). The mobile phase was 0.5 M solution of NaNO3 in dimethyl formamide (DMF) at 30 °C. Molecular weights were determined versus narrow distributed PMMA standards at a flow rate of 1.0 mL/min. The samples were prepared by dissolving 2 mg of corresponding polymer in 1 mL of DMF. Thermogravimetric (TG) and differential thermogravimetric (DTG) analysis were performed on a Perkin-Elmer Pyris 1 thermogravimetric instrument at a heating rate of 20 °C/min under N2 atmosphere in range of 50–800 °C, while Tg of ferrocene boronic acid-based derivatives was determined by diffraction scanning calorimetry (DSC) (Model TAQ 200) with heating rate of 20 °C/min under N2 atmosphere. The diameter of micelles was determined by Nano Measurer 1.2.5 software. Twenty well defined micelles have been taken into account for measurements and results were averaged. Scanning electron microscope (SEM) images were taken from scanning emission microscope (SEM, JEOL-6700F) operated at 10 kV. Transmission electron microscope (TEM) images were obtained from JEOL model 1200EX microscope operated at 160 kV.

3

3 Results and discussion

3.1

3.1 Synthesis of diblock copolymers (PMAEFc-b-PVAPBA, PMAEFc-b-PMVAPBA and PMAEFc-b-PSBA)

Three diblock copolymers (PMAEFc-b-PVAPBA, PMAEFc-b-PMVAPBA and PMAEFc-b-PSBA) were synthesized using PMAEFc as ferrocene-based macroinitiator with VAPBA, MVAPBA and SBA as boronic acid-based monomers, respectively. MAEFc was synthesized by followed protocol of the reported work (Zhang et al., 2012b), which involves an esterification reaction between 2-hydroxyethyl methacrylate and ferrocene acyl chloride in the presence of TEA.

Vinyl amidophenylboronic acid monomers were synthesized according to previously published report (Scheme S1) (Roy and Sumerlin, 2012). In 1H NMR spectra of vinylamidophenyl boronic acid (VAPBA) and metylamidophenylboronic acid (MVAPBA), signals at 10.15 and 9.75 ppm correspond to NH protons, while signals at 8.20 and 8.05 ppm related to boronic acid hydroxyls. Signals at 5.70–6.46 ppm correspond to vinyl protons. Furthermore, signals at 7.20–7.86 ppm related to benzene ring protons of both VAPBA and MVAPBA. A distinguish peak at 1.95 ppm only presents in MVAPBA 1H NMR spectrum corresponds to methyl group. All these findings from 1H NMR spectra confirmed successful synthesis of VAPBA and MVAPBA (Fig. S1). MCPDB was prepared with little modification to the method reported by Perrier et al. (2004). Synthesis of MCPDB was achieved by a Grignard reaction, through the addition of methyl-α-bromophenylacetate to a solution of phenylmagnesium bromide and carbon disulfide in THF (Scheme S2). In 1H NMR spectrum of MCPDB, signals at 8.10–7.20 ppm correspond to aromatic ring. The signal at 5.75 ppm related to methylene proton, while signal at 2.70 ppm corresponds to methyl protons. All these finds confirm the synthesis of MCPDB (Fig. S2 A). MAEFc was synthesized by followed protocol of the reported work (Zhang et al., 2012b).

In 1H NMR spectrum of MAEFc, monomer signals at 6.22 and 5.65 ppm agreed to vinyl protons of methacrylate double bonds (Fig. S2 B). The signals at 4.20, 4.40, and 4.75 ppm were related to the cyclopentadiene (Cp) rings of the ferrocene unit. The ethylene protons of MAEFc showed signal at 4.49 ppm. RAFT polymerization was employed to prepare ferrocene-containing homopolymer PMAEFc from MAEFc. The polymerization was carried out at 90 °C using MCPDB as a chain transfer agent. In 1H NMR spectrum of PMAEFc, the disappearance of the vinyl protons from the methacrylate and appearance of new peaks at 0.90–1.05 and 1.75–2.10 ppm confirmed the successful polymerization (Fig. S2 C). The complete reaction scheme for MAEFc and synthesized block copolymers (PMAEFc-b-PVAPBA, PMAEFc-b-PMVAPBA and PMAEFc-b-PSBA) was shown in Scheme 1.

Synthesis of ferrocene-based homopolymer and diblock copolymers via RAFT.
Scheme 1
Synthesis of ferrocene-based homopolymer and diblock copolymers via RAFT.

Ferrocene boronic acid-based block polymers (PMAEFc-b-PVAPBA, PMAEFc-b-PMVAPBA and PMAEFc-b-PSBA) were also characterized by FTIR spectroscopy (Fig. S3 and Table S1). All the synthesized polymers showed characteristics amide peaks around 1680 and 1710 cm−1 asymmetric C⚌O stretching vibrations (Zhang et al., 2014). N—H stretching vibrations (3100–3120 cm−1) also supported amide presence in derivatives. Hydroxyl (−OH) absorption band of boronic acids was appeared at 3600–3490 and 3390 cm−1, while significant absorption peaks for B—O bond stretching were observed at 1375 and 1343 cm−1 (Zhang et al., 2014). Vibrational bands of ferrocenyl rings at 1023–1045, 805–823 and 500–503 cm−1 were observed (Zain ul et al., 2016).

Kinetic study was performed to monitor RAFT polymerization of MAEFc. The conversion rate was monitored by comparing peak area of vinyl proton at 5.70 ppm with peaks area of Cp rings at 4.20–4.40 ppm. The plot (Fig. 1) showed a linear relationship between reaction time and conversion rate indicating that the RAFT polymerization followed a controlled living character. After 8 h, 85% conversion of monomer was achieved. GPC data are shown in Table S2, which is also in agreement with 1H NMR results that polymerization followed a controlled character.

A plot of MAEFc conducted via RAFT polymerization.
Figure 1
A plot of MAEFc conducted via RAFT polymerization.

Ferrocene-containing diblock copolymers were synthesized using PMAEFc as a macroinitiator. Boronic acid-based monomers (MVAPBA, VAPBA and SBA) were used to prepare novel diblock polymers. All polymerizations were carried out in DMF with mole ratio [PMAEFc]:[AIBN]:[monomer] = 1:0.2:200. All the block copolymers: poly(2-methacryloyloxy)ethyl ferrocene carboxylate-b-polymethyl vinyl amido phenyl boronic acid (PMAEFc-b-PMVAPBA), poly(2-methacryloyloxy)ethyl ferrocene carboxylate-b-polymethyl vinylamido phenyl boronic acid (PMAEFc-b-PVAPBA), and poly(2-methacryloyloxy)ethyl ferrocene carboxylate-b-polystyrene boronic acid (PMAEFc-b-PSBA) were successfully synthesized by RAFT polymerization.

In 1H NMR spectra of (Fig. 2), the vanishing of vinyl protons at 5.60 and 6.20 ppm and appearance of new peaks at 0.9–1.10 and 1.80–2.0 ppm indicated successful polymerization of MVAPBA, VAPBA and SBA. GPC results (Table S3) confirmed the chain extension of block copolymers (PMAEFc-b-PVAPBA, PMAEFc-b-PMVAPBA and PMAEFc-b-PSBA).

1H NMR spectra of: (A) PMAEFc-b-PVAPBA, (B) PMAEFc-b-PMVAPBA and (C) PMAEFc-b-PSBA.
Figure 2
1H NMR spectra of: (A) PMAEFc-b-PVAPBA, (B) PMAEFc-b-PMVAPBA and (C) PMAEFc-b-PSBA.

3.2

3.2 Micellization of PMAEFc-b-PMVAPBA

The block copolymer micellization in selective solvent system is a typical feature of its colloidal properties. When the block copolymer is dissolved in a solvent, which is thermodynamically good for one block and a precipitant for the other, and then copolymer chains may assemble reversibly to form micellar aggregates. The micelle consists of a more or less swollen core of the insoluble blocks, which is surrounded by a flexible fringe of soluble blocks. Such micelles are usually spherical with narrow size distribution and may change in their size distribution and shape under certain conditions. In this study, we investigated micellization of the block copolymer by two different methods. In a typical procedure, binary mixture of suitable solvents with different volume ratios was mixed and appropriate amount of PMAEFc-b-PMVAPBA was dissolved to form micelles (Zhang et al., 2012a). In second method, block copolymer (PMAEFc-b-PMVAPBA) was dissolved in THF and dialyzed it in water for 2 d at 15 °C.

3.2.1

3.2.1 Micellization in binary organic solvents systems

The synthesis of block copolymers provides access to various well-defined micelle morphologies (Jain and Bates, 2003; Villacampa et al., 1995; Won et al., 2002). In this regard, addition of selective solvents provides a facile approach to tune the state of self-assembly. Difference between the core block solvent and corona block–solvent interactions can be adjusted by choice of the solvent, blends of solvents and temperature (Abbas et al., 2007; Bang et al., 2006, 2004; Cambre et al., 2012; Castro et al., 2008; Cheng et al., 2012; Choi et al., 2009; Duval and Picot, 1987; Eloi et al., 2011; Gilroy et al., 2011; Hanley et al., 2000; Hardy et al., 2011; Hussain et al., 2009; LaRue et al., 2006; Lodge et al., 2005; Lund et al., 2009, 2004; Quintana et al., 1995; Schuewer and Klok, 2011; Wei et al., 2011; Xing et al., 2011; Zhang and Eisenberg, 1999). However, a solvent having the exact same solubility to all the blocks of a copolymer is rare. Hence, the effect of solvent selectivity on the micelle structure is an extremely important factor. The choice of binary solvents system (based on polarity) plays a critical role in the construction of self-assembled nanostructures, which can directly affect the stretching degree of the different blocks of the nanostructures to form the micelles. Therefore, for our prepared block copolymer, three different binary organic solvents systems (DMF:CH3CN), (DMF:CHCl3) and (DMSO:CHCl3) were chosen to inspect the self-assembly behaviour of the ferrocene-boron containing diblock copolymer (PMAEFc-b-PMVAPBA). The significant difference in solubility of PMAEFc and MVAPBA blocks motivated us to study self-assembly of PMAEFc-b-PMVAPBA. The self-assembly was performed in the mixture of DMF/MeCN, DMF/CHCl3 and DMSO/CHCl3 with volume-by-volume ratio 1:2. Spherical micelles with prominent core and corona were observed in combination with DMF/MeCN in which both blocks of PMAEFc-b-PMVAPBA showed good solubility in DMF, while selective solubility in acetonitrile. SEM and TEM images of PMAEFc-b-PMVAPBA showed spherical shaped micelles (diameter in the range of 187 ± 42.87 nm) in tested solvents mixtures (Fig. 3).

(A) SEM image (B) TEM image and (C) histogram of PMAEFc-b-PMVAPBA in DMF: CH3CN (1:2).
Figure 3
(A) SEM image (B) TEM image and (C) histogram of PMAEFc-b-PMVAPBA in DMF: CH3CN (1:2).

On the other hand, combination with DMF/CHCl3 in which both blocks of PMAEFc-b-PMVAPBA showed good solubility in DMF, while selective in chloroform showed oval shaped morphology with more or less micelles aggregation. SEM and TEM images of PMAEFc-b-PMVAPBA showed spherical shaped micelles (diameter in the range of 264 ± 56.59 nm) in tested solvents mixtures (Fig. 4). These micelles obtained from DMF/CHCl3, have comparatively larger diameter than the micelles obtained by the combination of DMF/CH3CN. Possible reason might be core chain stretching of the block with DMF/CHCl3 mixture. Micelles obtained with combination of DMSO/CHCl3 were more or less spherical in shape with almost same micelles radii and diameter as obtained by the combination of DMF/CH3CN. SEM and TEM images of PMAEFc-b-PMVAPBA showed spherical shaped micelles (diameter was in the range of 180 ± 49.37 nm) in tested solvents mixtures (Fig. 5). Depending on the combination of binary organic solvents employed, more or less elongated oval shaped micelles to perfect sphere-like micelles were obtained. Moreover, micelles tend to aggregate in combination with DMF: CHCl3 (Rh = 263 ± 56.59 nm) and DMSO:CHCl3 (Rh = 180 ± 49.37 nm) due to comparative less solubility difference than DMF:CH3CN (Rh = 187 ± 42.87 nm). The combination of DMF:CH3CN (1:2) was found to be the best binary organic solvent system for PMAEFc-b-PMVAPBA, as micelles with distinguished core and corona were obtained in this solvent system. The reason might be greater accumulative solvent polarity as compared to other solvents system used (Table S4).

(A) SEM image (B) TEM image and (C) histogram of PMAEFc-b-PMVAPBA in DMF: CHCl3 (1:2).
Figure 4
(A) SEM image (B) TEM image and (C) histogram of PMAEFc-b-PMVAPBA in DMF: CHCl3 (1:2).
(A) SEM image, (B) TEM image and (C) histogram of PMAEFc-b-PMVAPBA in DMSO: CHCl3 (1:2).
Figure 5
(A) SEM image, (B) TEM image and (C) histogram of PMAEFc-b-PMVAPBA in DMSO: CHCl3 (1:2).

The core chain stretching, corona repulsion and interfacial tension are believed to be main factors, which involved in overall micelles morphology (Marinos Pitsikalis and Hadjichristidis, 2000; Shen and Eisenberg, 2000; Zhang et al., 2005). In the case of block copolymer (PMAEFc-b-PMVAPBA) studied here, it seems that amount of hydrophobic groups mainly control the micelles morphology. In addition to these factors, due to low molecular weight of PMAEFc-b-PMVAPBA, another possibility is that hydrophobic benzene side chains of MCPDB in main chain of PMAEFc-b-PMVAPBA might be partly responsible for (core and corona) morphology of the micelles reported here.

3.2.2

3.2.2 Micellization in aqueous medium

The significant solubility difference of the two blocks of block copolymers tends to self-assemble into a variety of nanostructures with wide varieties of structures including spheres, cylindrical, lamellae and large compound micelles. Micelles are widely used in industrial and biological fields for their ability to dissolve and move nonpolar substances through an aqueous medium or to carry drugs which are often scarcely soluble in water. Owing to aforementioned importance of micelles in aqueous solution, we also reported micellization in aqueous medium (Fig. 6).

(A) SEM image and (B) TEM image of the micelles 0.07 mgL−1 PMAEFc-b-PMVAPBA (Rh = 283 nm) dissolved in THF and dialyzed in H2O.
Figure 6
(A) SEM image and (B) TEM image of the micelles 0.07 mgL−1 PMAEFc-b-PMVAPBA (Rh = 283 nm) dissolved in THF and dialyzed in H2O.

The carrying ability of micelles can be altered by changing the parameters determining their size and shape. PMAEFc-b-PMVAPBA diblock copolymer with its inherent significant amphiphilic nature was expected to self-assemble in aqueous medium. The micellization was triggered by adding water into a solution of PMAEFc-b-PMVAPBA prepared in THF. Substantial removal of THF during dialysis decreased solubility of hydrophobic part (ferrocene) to form the core and hydrophilic part (boronic acid) as corona of PMAEFc-b-PMVAPBA micelles.

3.3

3.3 Glucose binding of PMAEFc-b-PMVAPBA micelles

Micellization of redox-based integrated chemical systems involving boronic acid and ferrocene has received considerable attention in recent years and it has proved invaluable to the advancement of biosensor. An assimilated chemical system of micellization can be viewed as the controlled assembly of several chemical components resulting in a system which functions efficiently and effectively as specified by the designer to attain qualitative determination of a biological component. These type of design for particular application, such as glucose biding, has increased the applicability of incorporated chemical systems to biosensor technology. The integrated chemical system of micellization described here involves the formation of a block copolymer PMAEFc-b-PMVAPBA structure by dialysis, consisting of redox polymer and its investigation of glucose binding with PMAEFc-b-PMVAPBA.

In order to investigate the glucose binding of ferrocene boron-containing block copolymer, PMAEFc-b-PMVAPBA and glucose were mixed together in equimolar ratio (number of boronic acid blocks and glucose molecules) and employed to bind. The solution was further dialyzed to form micelles and to remove unbound glucose molecules. The binding of glucose at physiological pH ∼ 7.4 with boronic acid was confirmed by SEM, TEM and DLS studies (Fig. 7), which showed that due to binding of glucose with boronic acid hydroxyls, micelles disintegrate (disturbed the ratio of hydrophobic and hydrophilic part, which led to core and corona undistinguishable) into separate blocks, which resulted in abrupt reduction in size or low aggregation (Rh = 106 nm), as compared to unbound micelles of PMAEFc-b-PMVAPBA (Rh = 283 nm) as observed by DLS.

(A) SEM image and (B) TEM image of PMAEFc-b-PMVAPBA + Glucose (Rh = 106 nm) micelles 0.07 mg L−1 dissolved in THF and dialyzed in H2O.
Figure 7
(A) SEM image and (B) TEM image of PMAEFc-b-PMVAPBA + Glucose (Rh = 106 nm) micelles 0.07 mg L−1 dissolved in THF and dialyzed in H2O.

This phenomenon can be explained as transition of the block copolymer from amphiphilic (where itself assembles to form micelles) to completely hydrophilic (where it would exist as unimers) after binding of the glucose to the boronic acid units. Essentially, esterification of the boronic acid moieties with the glucose led to the boronic acid block becoming more hydrophilic. These results are in agreement with the reported literature, except the size of unimers was little bigger, which could be due to significant aggregation caused by oxidation of ferrocene to ferrocenium within the system. In addition to the DLS results, disconnection was also obvious by visual examination, as the slightly turbid and yellowish aggregate solution of PMAEFc-b-PMVAPBA instantly became transparent on addition of glucose.

This phenomenon was ascribed to transformation of the mostly neutral/hydrophobic boronic acid groups in the aggregate, which were converted to anionic/hydrophilic cyclic boronates upon binding to glucose, thus disturbed hydrophilicity of boronic acid and disintegrate into smaller parts (Roy et al., 2009b; Roy and Sumerlin, 2012).

3.4

3.4 Redox reactions of PMAEFc-b-PMAVPBA micelles

The ability to control the formation and disassembly of micellar aggregates has attracted deep recent attention and is of particular interest for drug delivery applications when the disassembly of the micelles (and associated drug release) needs to be triggered under special conditions. In this regard redox-triggered self-assembly of block copolymers in solution is much less explored as compared to other several strategies such as pH and temperature based self-assembly. In this section use of redox reactions (electron transfer reactions) as a means to govern the self-assembly of block copolymer with an electroactive ferrocene moiety was reported. Specifically, the redox-triggered self-assembly of (PMAEFc-b-PMVAPBA) diblock copolymer is described, which involves bond reorganization redox processes to disassemble micelles was reported. In addition to being glucose-responsive, PMAEFc-b-PMVAPBA was also expected to respond to change in oxidation state of ferrocene by introduction of oxidizing agent. The possible mechanism taking place for redox responsive in micelles is shown in Fig. 8.

Possible mechanism taking place upon oxidation and reduction of PMAEFc-b-PMVAPBA.
Figure 8
Possible mechanism taking place upon oxidation and reduction of PMAEFc-b-PMVAPBA.

The spherical micelles were consisted of ferrocene PMAEFc blocks as core and soluble boronic acid blocks as corona. Different micelles properties such as size of the micelles could be triggered via redox stimuli, i.e., changing the redox state of ferrocene by redox reaction. The reversible redox reactions of PMAEFc-b-PMAVPBA micelles were conducted using (NH4)2Ce(NO3)6 and NaHSO3, as oxidizing and reducing agents, respectively. However, ferrocene containing block copolymer (PMAEFc-b-PMAVPBA) showed change in their sizes due to the redox reactions, as evidenced by the measurements of SEM (Fig. 9). Oxidation of micelles by (NH4)2Ce(NO3)6 increased size of the micelles (Rh was changed from 63 to 89 nm). Such variation in size was attributed to the conversion of ferrocene (neutral) moiety to ferrocenium (positively charged) after oxidation reaction in the core.

SEM images and hydrodynamic distribution of PMAEFc-b-PMVAPBA micelles 0.03 mg L−1 (A) before oxidation, (B) after oxidation and (C) after reduction, while D, E and F are graphical representations, respectively.
Figure 9
SEM images and hydrodynamic distribution of PMAEFc-b-PMVAPBA micelles 0.03 mg L−1 (A) before oxidation, (B) after oxidation and (C) after reduction, while D, E and F are graphical representations, respectively.

The electrostatic repulsion between the positively charged ferrocene blocks resulted in an incompact core and thus larger apparent size of micelles was obtained. The micelles recovered to almost their original size upon reduction in NaHSO3, as change of ferrocenium to ferrocene. These findings showed that PMAEFc-b-PMAVPBA micelles experienced a reversible redox- triggered change in their size.

3.5

3.5 Saccharide sensing of PMAEFc-b-PVAPBA

The binding interaction (i.e. BA-diol) of the block copolymers with saccharide (fructose) was investigated by 1H NMR and 11B NMR spectroscopy. The characteristic vanishing and shifting of specific peaks can be visualized in 1H NMR and 11B NMR spectra, respectively.

3.5.1

3.5.1 1H NMR study of PMAEFc-b-PVAPBA for saccharide sensing

The binding interaction of PMAEFc-b-PVAPBA with fructose was investigated by 1H NMR spectroscopy (Fig. S4). The calculated data were internally referenced to a residual DMSO signal at 2.5 ppm. The vanishing of the boronic acid hydroxyl signal around 8.00 ppm in 1H NMR spectra after binding with fructose, is important finding as direct significance of the fructose interactions with PMAEFc-b-PVAPBA (Lacina et al., 2014; Saleem et al., 2016).

3.5.2

3.5.2 11B NMR study of PMAEFc-b-PVAPBA for saccharide sensing

11B NMR spectroscopy has been used in a number of recent studies for elucidating the configuration of boron atom in solution. Boron (B) present in boronic acids possesses different geometries (i.e. trigonal, tetrahedral, diol adducts, etc.) and have unique chemical shift upon binding with saccharides.

In this study, binding of saccharide with ferrocene boronic acid-based block copolymers was further confirmed by 11B NMR spectroscopy. The down field chemical shift of the signal from 25.7 to 29.2 ppm in 11B NMR spectrum of PMAEFc-b-PVAPBA is significant verdict for the BA-glucose interaction. This 11B NMR spectrum results are in agreement with the electrochemical properties PMAEFc-b-PMVPABA, PMAEFc-b-PVPABA and PMAEFc-b-PSBA.

The electrochemical studies of ferrocene boronic acid-based methacrylate homopolymer and diblock copolymers were performed in DMSO using tetra-n-butylammonium hexafluorophosphate as a supporting electrolyte. The homopolymer (PMAEFc) showed reversible redox process with reduction (0.15 V) and oxidation potential (0.29 V) due to the reversible electrochemistry of the ferrocene moiety. For diblock copolymers, (PMAEFc-b-PMVPABA, PMAEFc-b-PVPABA and PMAEFc-b-PSBA) reversible peaks were observed (Fig. 10 and Table S5). The reason for not significant peak might be due to greater distance of ferrocene moiety with boronic acid groups, which may led to weak electronic signal translation of ferrocene electrons on boronic acid binding with diols.

CV curves of 1 mM (A) PMAEFc, (B) PMAEFc-b-PMVAPBA, (C) PMAEFc-b-PVAPBA and (D) PMAEFc-b-PSBA.
Figure 10
CV curves of 1 mM (A) PMAEFc, (B) PMAEFc-b-PMVAPBA, (C) PMAEFc-b-PVAPBA and (D) PMAEFc-b-PSBA.

Electrochemical studies of ferrocene-containing block polymers and their saccharide sensing were carried out using freshly prepared samples in dried solvent purged with Ar gas for 30 min. Freshly prepared solutions (all polymers used in this study) in DMSO were clear and yellow in colour. After 2 d, the solutions turned turbid and brown, probably due to the oxidation of ferrocene (Fig. S6). The colour of polymer solution was changed from yellow to brown possibly due to precipitation and generating ferrocenium moiety. These phenomena might be induced due to the cross-linking of the polymer. The produced ferrocenium was further oxidized to [Fc—O—O—Fc]+, probably due to the decomposition into cyclopentdiene or 4-cyclopenten-1,3-dione along with the formation of Fe2O3 (Lorans et al., 1997; Zotti et al., 1998). Detailed electrochemical data related to change in peak current and peak potential (cathodic and anodic shift) are presented in Table S5.

3.6

3.6 Thermal properties of PMAEFc-b-PVAPBA, PMAEFc-b-PMVAPBA and PMAEFc-b-PSBA

Differential scanning calorimetry (DSC) and thermal gravimetric analysis (TGA) were performed to investigate the thermal properties of ferrocene-based homopolymers and blocked copolymers. The glass transition temperature (Tg) of homopolymer (PMAEFc) was 50 °C, while block copolymers exhibited comparatively higher Tg (78–91 °C) with no melting endotherms until 150 °C. The difference in Tg of block copolymers was mainly due to the nature of incorporation of second block. In comparison, PMAEFc-b-PVAPBA showed high Tg (91 °C) due to better polymer chain packing, while pendant methyl group in PMAEFc-b-PMVAPBA increased the free volume of polymer chains by reducing polymer chain packing and decreased the block copolymer Tg to 78 °C (Fig. S7).

PMAEFc-b-PSBA demonstrated Tg of 88 °C, which is slightly lower than Tg of PMAEFc-b-PVAPBA. Such decrease can be attributed to the presence of amide groups in PMAEFc-b-PVAPBA, which can play an important role in intermolecular hydrogen bonding and increase in the intermolecular polymer chain interactions. The temperature of 5% weight loss (T5), the temperature of 10% weight loss (T10) and the char yields of polymers were observed from TGA curves recorded at heating rate of 20 °C/min under nitrogen atmosphere (Table S6). It was observed that the weight loss in homopolymer and block copolymers is a three-step process (Figs. S8 and S9). The first stage of weight loss appeared in the range of 300–325 °C due to the degradation of the aliphatic groups (ester C⚌O and C—O bonds) connected to the ferrocene units into a large amount of carbon dioxide. The aryl boronic acid moieties and Fe—C bonds were broken up to 450 °C, which constitute the second stage of weight loss. The release of Fe atoms can catalyse the degradation of the polymer due to its good catalytic effect. The small weight loss in the third stage represented degradation of the ferrocene units present in the polymer. The weight loss stopped after 500 °C and the main components of the residue (8.40–19.19%) were carbon and iron (Amer et al., 2013; Derue et al., 2014; Patrícia et al., 2006).

4

4 Conclusion

Ferrocene-containing methacrylate homopolymer, and poly(2-methacryloyloxy)ethyl ferrocenecarboxylate) (PMAEFc) was synthesized by RAFT. Using PMAEFc as a macroinitiator, three novel diblock copolymers (PMAEFc-b-PVAPBA, PMAEFc-b-PMVAPBA and PMAEFc-b-PSBA) were prepared through chain extension. The synthesized block copolymers were characterized by FTIR, 1H NMR and GPC. Thermal properties of homopolymers and block copolymers were investigated by DSC and TGA. Detailed micellization behaviour of PMAEFc-b-PMVAPBA (in binary organic solvents mixture and in aqueous solution) was also studied. The saccharide binding/sensing properties of PMAEFc-b-PVAPBA were also explored by 11B NMR and 1H NMR spectroscopy.

On binding with diols, the disappearance of hydroxyls signal of boronic acid in 1H NMR spectrum, and peak shifting of boron in 11B NMR spectrum of PMAEFc-b-PVAPBA, clearly depicted the free and bound forms of block copolymers. Comparative studies of micellization in binary organic solvents systems and in aqueous medium, showed that the larger aggregates (Rh = 179–264 nm) were obtained in binary organic solvents system than during dialysis in aqueous medium (Rh = 110–140 nm). PMAEFc-b-PMVAPBA block copolymer contains both boronic acid (BA) moiety and ferrocenyl (redox-active) groups in which BA can bind with glucose, while ferrocene moiety can undergo a reversible redox- triggered change in micelles size. It was also found that the increase in polarity and swelling of PMAEFc-b-PMVAPBA micelles was due to the redox behaviour of ferrocene and binding of glucose with boronic acids hydroxyls led to unimers or smaller aggregates. Results from TGA and DSC showed that block copolymers exhibited higher thermal stability than homopolymers.

Compliance with ethical standards

Funding: This study was funded by the National Natural Science Foundation of China (51673170, 21472168, 21372200 and 21272210), the Science and technology innovation team of Ningbo (2011B82002), the Fundamental Research Funds for the Central Universities (2016FZA4018).

Conflict of interest

The authors declare that they have no conflict of interest.

Acknowledgements

Financial supports from the National Natural Science Foundation of China (51673170, 21472168, 21372200 and 21272210), the Science and technology innovation team of Ningbo (2011B82002), the Fundamental Research Funds for the Central Universities (2016FZA4018) are gratefully acknowledged.

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Appendix A

Supplementary material

Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.arabjc.2017.05.018.

Appendix A

Supplementary material

Supplementary data 1

Supplementary data 1


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