The polymersomes were prepared using poly(ethylene glycol)-polystyrene (PEG-PS) block copolymers with azide functionality in the side chain, which self-assembled in water in well-defined vesicles. A bisoxazoline ligand 17 with two alkyne moieties was used to stabilize the polymer membrane via a crosslinking reaction and which simultaneously introduced binding sites for the metal catalyst Cu(I) (Figure 2a-2b). In order to achieve a high catalyst loading the cross-linked polymersomes were incubated twice with Cu(I) (Cu(I)-PLs, detailed synthetic procedure, and characterization are given in the supporting information), leading to a Cu(I) content of 0.035 mol/L. The polymersome morphology (Figure 2c-2d), copper distribution (Figure 2e), and oxidation state were determined (Figure 2f). Due to the presence of Cu(I), the polymersomes were visualized as dark spheres.
Figure 2. (a), (b) Schematic representation of block copolymer structures and cross-linked Cu(I) polymersomes (Cu(I)-PLs). (c) TEM picture of Cu(I)-PLs after first loading with Cu(I); (d) TEM picture of Cu(I)-PLs after second Cu(I) loading. (e) Copper distribution in the membrane of Cu(I)-PLs (indicated in pink), derived by SEM-EDX measurements. (f) XPS analysis on Cu(I)-PLs, to confirm the oxidation state of Cu(I).
Firstly, after preliminary stability tests of Cu(I)-PLs under different conditions (in the supporting information), the CuAAC reaction was optimized in batch using the Cu(I)-PLs with the synthesized 2,6-difluorobenzyl azide and the 2 alkynes (R2, 2M) at 65 oC, and compared with CuI powder and the homogeneous CuI-ligand complex (Cu(I): 0.05M, Table 2).
Table 2. Optimization of the batch reaction conditions.