Electronic Supplementary Information (ESI) For

Supplementary Materials

Synthesis, self-assembly, and formation of polymer vesicle hydrogels of thermoresponsive copolymers

Xudong Wang a, Yueqin Duan b, Chenxi Li a, Yan Lu b, *

[a] Key Laboratory of Functional Polymer Materials, Ministry of Education, Institute of Polymer Chemistry, Nankai University, Tianjin 300071, China [b] School of Materials Science & Engineering, Tianjin University of Technology, Tianjin 300384, China

Correspondence to: [email protected] (Y. Lu)

S1 Experimental Section

Monomer Synthesis

(4'-hydroxybutyl)-3α, 7α, 12α-trihydroxy-5β-cholanoate (2)

CA 1 (10.0 g) was dissolved in 1, 4-butanediol (80 ml). Conc. hydrochloride was added dropwise to acidify the reactant to pH 3. The mixture was stirred at 55 C for 10 h. Water was added to the reactant to precipitate the product. The white precipitates were filtered and washed thoroughly with water. After drying in a vacuum oven at 60 C for 24 h, the product 2 was obtained in 98% yield. 1H-NMR (DMSO-d6): δ=0.58 (s, H18), 0.81 (s, H19), 0.91-0.93 (d, H21), 3.18 (m, H3), 3.40 (t, H4'), 3.61 (s, H7), 3.78 (s, H12), 3.98-4.02 (m, H1' overlap with one OH group), 4.10, 4.31 and 4.42 are the other three OH groups.

(4'-methacryloyloxybutyl)-3α, 7α, 12α-trihydroxy-5β-cholanoate (3)

A solution of 2 (6.0 g), triethylamine (12.6 g) and DMAP (50 mg) in dry THF (40 ml) was cooled in an ice-water bath. A mixture of methacrylic anhydride (4.8 g) in dry THF (20 ml) was added dropwise to the solution. The mixture was stirred at the ice-water bath for 4 h. After removing THF under vacuum, ethyl acetate (60 ml) was added and washed with 2 M HCl in brine, then brine. The organic layer was dried over anhydrous magnesium sulfate and filtered. After removing the solvent, the product was purified by column chromatography on silica gel (100-200 meshes) with ethyl acetate as eluent. The

1 18 19 monomer, 3 was obtained in 56 % yield. H-NMR (CDCl3): δ=0.67 (s, H ), 0.88 (s, H ),

21 3 7 12 0.97-0.99 (d, H ), 1.94 (s, C(CH3)=CH2), 3.45 (m, H ), 3.84 (s, H ), 3.97 (s, H ), 4.08-

1' 4' 4.11 (t, H ), 4.16-4.18 (t, H ), 5.56 (s , C(CH3)=CH), 6.10 (s , C(CH3)=CH).

S2 Results and Discussion

Figure S1. DSC curves of P1–P5 obtained by a second heating process.

S3 Gelation of the Random Copolymers

The solubility of the copolymers decreases in water with increasing cholic acid contents, and 2 w/v% is the saturated concentration of P5 in water. The limpid solutions (< 6 w/v %) of P1 and P2 become turbid, then form white shrunk mass rapidly in the solutions at 32 °C. The gelation and shrinkage can be observed even at 60 °C, but the processes are very quick. No higher temperature is investigated. At the critical gelation concentration, the limpid solutions of P3–P5 become turbid first, then form white gels and shrunk gels, respectively, at the gel-forming temperature (Table S1). The gels and shrunk gels can re- dissolve directly upon cooling.

Table S1. The gelation and shrinkage of P3-P5 solutions upon heating

Sample Concn. Temp. Retain Shrunk

(wt.-%) (oC) time (min) gela P5 2.0 23 62 R

1.5 23 62 R

1.0 25 20 R P4 3.0 25 10 Ir

2.0 28 4 Ir P3 5.0 27 3 Ir

4.0 29 2 R aR = regular; Ir = irregular; the gel-shrinking rate increased from P5 to P3.

S4 Figure S2. SEM images of P5 xerogels.

S5 Figure S3. (a) Top view of the primary gel fiber of CA-4EG. The self-assembled structure of CA crystals: (b) top view and (c) side view of the fiber-layer structure. The proposed fiber-layer structures of membrane: (d) top view of the ladder-like primary polymer micelle fiber, (e) top view and (f) side view of the fiber-layer structure.

CA crystal belongs to C2 space group.1 Lattice parameters: a = 40.334(5) Å, b = 7.729(9) Å, c = 15.620 (18) Å, β = 90.602(3)o, V = 4869 (10) Å3, Z = 8. On the basis of the fiber-layer structures found in the self-assembled crystals of CA from aqueous solution (Figures S3a–S3c), the similar fiber-layer structures of the vesicle membrane are proposed. There are ca. 19 NIPAM units between the adjacent CA pendant groups which form the dimer to reduce the exposure of the hydrophobic faces to water when P5 is dispersed in cold water (Figure S3d). An increase in the solution temperature to 23 °C drives the dimers on two adjacent chains to form tetramers through the hydrophobic interaction; meanwhile, two C3-OH groups form H-bonds to stabilize the tetramer structures (Figure S3d indicated by arrows). Finally the two chains form the ladder-like fiber. The parallel arrangement of the fibers forms the fiber-layer (Figures S3e and S3f).

References

[1] Wang XD, Li CX, Duan YQ, Lu Y (2014) Cryst Growth Des 14: 23