Thiol-Substituted Poly(2-oxazoline)s with Photolabile Protecting Groups—Tandem Network Formation by Light

Herein, we present a novel polymer architecture based on poly(2-oxazoline)s bearing protected thiol functionalities, which can be selectively liberated by irradiation with UV light. Whereas free thiol groups can suffer from oxidation or other spontaneous reactions that degrade polymer performance, this strategy with masked thiol groups offers the possibility of photodeprotection on demand with spatio-temporal control while maintaining polymer integrity. Here, we exploit this potential for a tandem network formation upon irradiation with UV light by thiol deprotection and concurrent crosslinking via thiol-ene coupling. The synthesis of the novel oxazoline monomer 2-{2-[(2-nitrobenzyl)thio]ethyl}-4,5-dihydrooxazole (NbMEtOxa) carrying 2-nitrobenzyl-shielded thiol groups and its cationic ring-opening copolymerization at varying ratios with 2-ethyl-2-oxazoline (EtOxa) is described. The tandem network formation was exemplarily demonstrated with the photoinitator 2-hydroxy-2-methylpropiophenone (HMPP) and pentaerythritol tetraacrylate (PETA), a commercially available, tetrafunctional vinyl crosslinker. The key findings of the conducted experiments indicate that a ratio of ~10% NbMEtOxa repeat units in the polymer backbone is sufficient for network formation and in-situ gelation in N,N-dimethylformamide.


Methods
The molar masses and the molar mass distribution (Đ) of the synthesized poly(2-oxazoline)s were measured using a PSS system (Agilent 1260) equipped with an autosampler, RI detector and an UV-detector type Agilent VWD Series 1260. The absorption was measured at λ = 280 nm. A so-called Gram Linear M column, equipped with a 10 µm particle size precolumn was utilized at T ≈ 60 °C. As eluent dimethylacetamide (DMAc) mixed with 1 g l -1 LiBr was used and 20 µl of the polymer-samples were injected. The flow rate of the system was 1 ml min -1 . The calibration curve was measured using PMMA standards (PSS, Mainz). Other gel permeation chromatography (SEC) experiments were carried out on an Agilent 1200-System consisting of a degasser, an isocratic pump, an autosampler, a RI-detector, a UVdetector (Lambda 1010, Bischoff), and a SDV Linear M column. THF was used as eluent with a flow rate of 1 ml min -1 . Calibration was performed with polystyrene standards (PSS, Mainz).
The UV/Vis measurements were performed using an Evolution 220 UV-Visible spectrophotometer and a PCCU 1 Peltier control and cooling unit from Thermo Scientific. NMR spectroscopy was performed using a Bruker AV 400 spectrometer or a Joel ECZ 500 spectrometer. All measurements were performed at room temperature. The 1 H NMR spectra were recorded at 400 or 500 MHz and 13 C NMR spectra at 101 or 126 MHz. Chemical shifts (δ) are given in ppm and are referenced to the undeuterated signal of the used solvent.
Polymerizations were performed using a Discover SP Microwave System equipped with an Explorer 12 Hybrid Autosampler from CEM. Crosslinking and photodeprotection experiments were carried out in a UV-crosslinker UVP-CL1000, operating at λ = 365 nm (He = 12.0 J cm -² per 1 h).
The obtained yellowish, highly viscous residue was stirred with hexanes (60 ml) for 30 min to obtain a yellowish-white powder as product. The title compound was filtered-off
The aqueous phases were combined and extracted with DCM (30 ml). The solvent was evaporated and the crude product was directly used for preparation of compound 3.

Deprotection Procedure
The corresponding copolymer (100 mg, 6.7 µmol) was filled into a microwave vial and dissolved in MeCN (30 ml). The vial was sealed with a silicone cap and the mixture was purged with Ar for 15 min. Afterwards, the vial was placed in a UV crosslinking chamber with a wavelength of λ = 365 nm for 2 h (He = 24 J cm -²). Then the polymer was recovered by precipitation into ice-cold diethyl ether. The precipitate was collected and thoroughly washed with diethyl ether. Finally, the product was dried in vacuum overnight.

Kinetics of Photodeprotection
Solutions of different polymer concentrations were prepared in MeCN. Each solution was added to a 1 cm square quartz cell. The cells were irradiated at λ = 365 nm in a UV crosslinking chamber (He = 12 J cm -² per 1 h). After 5 min, the irradiation was stopped and the cells immediately transferred to a UV spectrometer, where the absorbance was recorded at λ = 310 nm.
The vial was sealed and remaining oxygen was removed by a freeze-pump-thaw cycle.

Attempts to synthesize a NbMEtOxa Homopolymer
MeOTf and MeOxa were dissolved in anhydrous MeCN and stirred for 15 minutes in the microwave oven at 120 °C with an initial power of 140 W. Then, NbMEtOxa was added in a glovebox to the reaction mixture. The reaction vial was transferred back to the microwave oven 7 and further stirred for 90 min (120°C, initial power 140 W). Subsequently, the polymerization was quenched by adding water (0.2 ml) and stirred for 4 hours at room temperature. The polymer was precipitated into ice-cold diethyl ether, dissolved in 1,4-dioxane and dried via lyophilization. The individual reaction parameters are listed in the following table.                 Figure S22: Images of reaction vials before (upper picture) and after irradiation (lower picture, vial numbers are marked with a prime). The vial numbers correspond to numbering in Table S2.

Gel Formation
The concentration of polymer was 15 wt% in DMF. Vials 1 and 2 were used as control.
Successful network formation in vial 6' is corroborated by the triangular shape of the rigid gel after irradiation of the tilted vial.