Photocrosslinking of Polyacrylamides Using [2 + 2] Photodimerisation of Monothiomaleimides

The [2 + 2] photocycloaddition of monothiomaleimides (MTMs) has been exploited for the photocrosslinking of polyacrylamides. Polymer scaffolds composed of dimethylacrylamide and varying amounts of d,l-homocysteine thiolactone acrylamide (5, 10, and 20 mol %) were synthesized via free-radical polymerization, whereby the latent thiol functionality was exploited to incorporate MTM motifs. Subsequent exposure to UV light (λ = 365 nm, 15 mW cm–2) triggered intermolecular crosslinking via the photodimerization of MTM side chains, thus resulting in the formation of polyacrylamide gels. The polymer scaffolds were characterized using Fourier transform infrared spectroscopy, UV–visible spectroscopy, 1H NMR spectroscopy, and size exclusion chromatography, confirming the occurrence of the [2 + 2] photocycloaddition between the MTM moieties. The mechanical and physical properties of the resulting gels containing various MTM mol % were evaluated by rheology, compression testing, and swelling experiments. In addition, scanning electron microscopy was used to characterize the xerogel morphology of 5 and 10 mol % MTM hydro- and organo-gels. The macro-porous morphology obtained for the hydrogels was attributed to phase separation due to the difference in solubility of the PDMA modified with thiolactone side chains, provided that a more homogeneous morphology was obtained when the photo-gels were prepared in DMF as the solvent.

UV-Vis spectra were recorded on an Agilent Technologies Cary 60 UV-Vis in the range of 200-800 nm using a cuvette with a 10 mm optical path length.
Mass spectrometry was conducted using Agilent 6130B ESI-Quad containing an autosampler and isocratic pump from an Agilent 1100 to deliver the samples and the solvent used. In this system, the solvent was 80:20 methanol: water (HPLC grade).
Size exclusion chromatography was performed using Agilent Infinity II MDS instruments equipped with differential refractive index (DRI), viscometry (VS), dual angle light scatter (LS) and multiple wavelength UV detectors. The system was equipped with 2 x PLgel Mixed C columns (300 x 7.5 mm) and a PLgel 5 µm guard column. The eluent used was DMF with a 5 mmol NH 4 BF 4 additive to reduce column interactions. Samples were run at 1 ml/min at 50 °C. Poly(methyl methacrylate) standards (Agilent EasiVials) were used for calibration between 955,000 -550 g/mol. Analyte samples were filtered through a GVHP membrane with 0.22 μm pore size before injection. Respectively, experimental number average molecular weights (M n, SEC ) and dispersity (Đ) values of synthesized polymers were determined by conventional calibration using Agilent GPC/SEC software.
[2+2]-photocycloaddition reactions were performed using a 365 nm Lumidox II 96-Position LED array set at 45 mW. Irradiance (mW cm -2 ) was estimated by using an S142C Integrating Sphere Power Sensor Head with Silicon Detector, connected to a ThorLabs PM400 optical power meter at a wavelength set to 365 nm.
Rheological analysis was performed in an Anton Paar MCR 302 rheometer equipped with a parallel plate configuration (25 mm diameter). The data was analysed using the RheoCompass software.
Compression tests were carried out using a Shimadzu EZ-LX Universal Testing Instrument equipped with a 50 N load cell.
Scanning Electron Microscopy (SEM) was conducted using Zeiss SUPRA 55VP-23-99 scanning electron microscope (SEM) with a field emission electron gun (FEG). Accelerating voltage used was at 5 kV and both SE2 and nLens detectors were utilised depending on the sample. Unless otherwise stated, hydrogels were frozen in liquid nitrogen and freeze dried to remove water. Freeze dried gels were then casted on carbon tabs (9 mm) attached to aluminium specimen stubs. To improve the sample imaging, gold (Au) sputter coating was applied for 30 seconds prior imaging.

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The reaction was adopted from previous literature. 1 DL-homocysteine thiolactone hydrochloride (14 g, 91 mmol) was dissolved in 100 mL 1,4-dioxane and 100 mL water. Sodium hydrogen carbonate (76.5 g, 910 mmol) was added to the solution. After immersing the solution flask in an ice bath, the reaction was allowed to reach 0 °C and acryloyl chloride (9 g, 100 mmol) was added dropwise for 30 minutes and the reaction was carried out overnight. 200 mL water was added to the reaction mixture and the solution was extracted by ethyl acetate (3 x 200 mL). The organic layer was collected and the solvent removed under reduced pressure. The product was then recrystallized from dichloromethane to obtain the title compound as a white solid in 70 % yield (10.9 g, 63.7 mmol). 1

N-Propyl-3-bromomaleimide
The reaction was adopted from previous literature. 2 Bromomaleic anhydride (8.0 g, 45.4 mmol) was dissolved in acetic acid (200 mL) and propylamine (3.8 mL, 45.4 mmol) was slowly added to the solution. The reaction mixture was stirred and heated at 130 °C for 6 hours. Acetic acid was removed by the addition of toluene followed by azeotropic distillation, which was repeated several times. The

General procedure for aminolysis reaction
The reaction was adopted from previous literature. 3 The polymer (10 g) was dissolved in THF (500 mL).
The solution was stirred and degassed for 30 minutes. Then, propylamine (20 eq with respect to TLA repeating units) was slowly added directly to the polymeric solution. The reaction was carried out at ambient temperature for 24 h. The solution was then concentrated by removing some solvent under reduced pressure, and the concentrated polymeric solution was precipitated in diethyl ether. The solid was collected and filtrated by suction filtration and dried. The dried polymer was characterised by 1 H NMR, SEC, UV-Vis, and FT-IR techniques.

General procedure for the synthesis of poly(dimethyl acrylamide-monothiomaleimide)
The reaction was adopted from previous literature. 1 The polymer was dissolved in methanol (250 mL).
Then, a solution of N-propylmonobromomaleimide (3 eq with respect to TLA repeating unit) and anhydrous sodium acetate (1 eq with respect to N-propylmonobromomaleimide) in 50 mL methanol was added to the polymeric solution. The reaction mixture was carried out for 10 minutes at room temperature. Eventually, the solution was concentrated and precipitated in diethyl ether. The brown solid was dissolved in THF and precipitated in diethyl ether three time, and filtrated by suction filtration. The solid was characterised by 1 H NMR, SEC, UV-Vis, and FT-IR techniques.