Effect of Polyelectrolyte Charge Density on the Linear Viscoelastic Behavior and Processing of Complex Coacervate Adhesives

It is well-known that the phase behavior and physicochemical and adhesive properties of complex coacervates are readily tuneable with the salt concentration of the medium. For toxicity reasons, however, the maximum applicable salt concentration in biomedical applications is typically low. Consequently, other strategies must be implemented in order to optimize the properties of the resulting complex coacervates. In this work, the effect of the charge density of a strong polyanion on the properties of complex coacervates was studied. To control this charge density, statistical anionic/charge-neutral hydrophilic copolymers were synthesized by means of an elegant protection/deprotection strategy and subsequently complexed with a strong polycation. The resulting complexes were observed to have an increasing water content as well as faster relaxation dynamics, with either increasing salt concentration or decreasing charge density. Time–salt and time–salt–charge density superpositions could be performed and showed that the relaxation mechanism of the complex coacervates remained unchanged. When the charge density was decreased, lower salt concentration complexes became suitable for viscoelastic adhesion with improved injectability. Such complex coacervates are promising candidates for injectable biomedical adhesives.


Polyelectrolytes synthesis
Kinetic study of BSPMA homopolymerization CTBPA (1 eq, 10.3 mg, 36.9 μmol), BSPMA (85 eq, 943 mg, 3.14 mmol), AIBN (0.1 eq, 0.591 mg, 3.60 μmol, 110 μL of a stock solution of 21.5 mg AIBN in 4.00 mL DMF) and 1.50 mL DMF were charged in a round bottom flask equipped with a stirring egg.An aliquot was withdrawn for 1 H NMR conversion analysis before the reaction mixture was deoxygenated via argon bubbling for 5 min.The vessel was immersed into a pre-heated oil bath at 70 °C and aliquots were withdrawn under argon protection at preset time intervals (i.e., 1, 2, 4, 6, 8 and 24 hours). 1 H NMR samples (~ 2 drops) were directly diluted in CDCl 3 while SEC samples (~ 4 drops) were precipitated into cold 6:1 n-hexane:ethanol, dried in air and dissolved in SEC eluent.The remainder of the solution was discarded without further use.

Kinetic study of OEGMA homopolymerization
CTBPA (1 eq, 10.3 mg, 36.9 μmol), OEGMA (97 eq, 1.08 g, 3.61 mmol), AIBN (0.1 eq, 0.607 mg, 3.70 μmol, 113 μL of a stock solution of 21.5 mg AIBN in 4.00 mL DMF) and 1.50 mL DMF were charged in a round bottom flask equipped with a stirring egg.An aliquot was withdrawn for 1 H NMR conversion analysis before the reaction mixture was deoxygenated via argon bubbling for 5 min.The vessel was immersed into a pre-heated oil bath at 70 °C and aliquots were withdrawn under argon protection at preset time intervals (i.e., 1, 2, 4, 6, 8 and 24 hours). 1 H NMR samples (~ 2 drops) were directly diluted in CDCl 3 while SEC samples (~ 4 drops) were precipitated into cold 6:1 n-hexane:ethanol, dried in air and dissolved in SEC eluent.The remainder of the solution was discarded without further use.

Kinetic study of BSPMA/OEGMA copolymerization
CTBPA (1 eq, 10.2 mg, 36.6 μmol), BSPMA (50 eq, 479 mg, 1.81 mmol), OEGMA (50 eq, 543 mg, 1.81 mmol), AIBN (0.1 eq, 0.640 mg, 3.90 μmol, 119 μL of a stock solution of 21.5 mg AIBN in 4.00 mL DMF) and 1.50 mL DMF were charged in a glass vial and mixed thoroughly.An aliquot was withdrawn for 1 H NMR conversion analysis before the reaction mixture was transferred into six 2 mL HPLC glass vials (~ 400 μL each) equipped with stirring bars and sealed with rubber septa.The vials were deoxygenated individually via argon bubbling for 3 min each before immersion into a pre-heated oil bath at 70 °C and were removed at set time points (i.e., 1, 2, 4, 6, 8 and 24 hours). 1 H NMR conversion samples (~ 1 drop) were directly diluted in CDCl 3 and analysed.SEC samples (~ 4 drops) were precipitated into small volumes of cold 6:1 n-hexane:ethanol and dried in air before redissolving in eluent.The remainder of the aliquots (~ 350 μL) were precipitated into cold 6:1 n-hexane:ethanol, redissolved in THF and further precipitated into pure n-hexane before drying under high vacuum. 1H NMR spectra of these purified samples were used to determine the relative conversion of BSPMA and OEGMA monomers by comparing the signal of BSPMA (2H, CH 2 , 3.22 ppm) to that of OEGMA (3H, CH 3 , 3.78 ppm and 2H, CH 2 , 3.55 ppm).

Synthesis of poly(oligo[ethylene glycol] methyl ether methacrylate) (POEGMA)
CTBPA (1 eq, 10.3 mg, 36.9 μmol), OEGMA (98 eq, 1.08 g, 3.60 mmol), AIBN (0.1 eq, 0.637 mg, 3.88 μmol, 118 μL of a stock solution of 21.5 mg AIBN in 4.00 mL DMF) and 1.5 mL DMF were charged in a round bottom flask equipped with a stirring egg.An aliquot was withdrawn for 1 H NMR conversion analysis before the reaction mixture was deoxygenated via argon bubbling for 5 min.The vessel was immersed into a pre-heated oil bath at 70 °C.After 18 hours, the vessel was cooled down to room temperature and opened to air before withdrawal of an aliquot for 1 H NMR conversion analysis.The polymer was precipitated into cold 6:1 nhexane:ethanol, redissolved in minimal THF and further precipitated into pure n-hexane twice.
The product was redissolved in minimal acetone, transferred into a glass vial and dried in vacuo.

Table S1 :
Compositions of the reaction mixtures for the synthesis of P(BSPMA x -co-OEGMA y )

Table S2 :
Compositions of the reaction mixtures for the synthesis of P(SPMA x -co-OEGMA y )