Double Responsive Pentablock Terpolymers: Self-Assembly and Gelation

This study dealt with the utilization of the dual-responsive behavior of PDMAEMA for the construction of double responsive hydrogels. Here, the synthesized hydrogels were based on ABCBA pentablock terpolymers, where dual-responsive (temperature/pH) PDMAEMA B- blocks and temperature-responsive poly(di(ethylene glycol) methyl ether methacrylate) (PDEGMA) A-blocks can be separately switched water-insoluble by applying an external stimulus, while a poly(ethylene oxide) (PEO) middle C-block is merely responsible for the stabilization of the system.

The proposed self-assembly of this system is shown in Scheme 3. In dilute solutions the ABCBA pentablock terpolymers assemble into flower-like micelles upon heating initiated by the coil-to-globule phase transition (Ttr) of the outer PDEGMA A-blocks, which occurs at lower temperatures as compared to the phase transition temperature of the PDMAEMA B-blocks. The resulting flower-like micelles consist of a PDEGMA core, which is stabilized by looped PDMAEMA-b-PEO-b-PDMAEMA segments of the pentablock terpolymer. Since the PDMAEMA blocks are dual-responsive the micelles can undergo a further contraction depending on pH at Ttr(PDMAEMA)caused by the collapse of the PDMAEMA blocks. As a result, core (PDEGMA) – shell (PDMAEMA) – corona (looped PEO) micelles are obtained.

At high concentrations, the ABCBA pentablock terpolymers assemble into a physically cross-linked hydrogel network, which is induced by the collapsing PDEGMA A-blocks. The further contraction of PDMAEMA at higher temperatures should then lead to a change in the mechanical properties of the gel.

Scheme 3.Self-assembly of ABCBA pentablock terpolymers.

The synthesis of the PDEGMA-b-PDMAEMA-b-PEO-b-PDMAEMA-b-PDEGMA ABCBA pentablock terpolymers was performed by using a bifunctional PEO775 (DPn = 775, degree of functionality = 1.66) ATRP-macroinitiator for a sequential ATRP of DMAEMA and DEGMA.

This approach, however, was limited to relatively short blocks, i.e. DPn ≤ 90 and DPn ≤ 43 for the PDMAEMA B-blocks and the PDEGMA A-blocks, respectively. The synthesis of higher molecular weights resulted in broad molecular weight distributions caused, e.g., by transfer reactions during the polymerization. The PDMAEMA-b-PEO-b-PDMAEMA triblock copolymer intermediate with DPn(PDMAEMA) = 90 (ABA-90) revealed a reasonable PDMAEMA block length along with a low PDI and was then used for further polymerization of the ABCBA pentablock copolymers.

Temperature-dependent DLS measurements of dilute solutions (c = 2 g/L) were performed with both the PDMAEMA-b-PEO-b-PDMAEMA triblock copolymer intermediates (ABA) as well as the PDEGMA-b-PDMAEMA-b-PEO-b-PDMAEMA-b-PDEGMA pentablock terpolymers (ABCBA). The transition points for the PDMAEMA blocks in the ABA intermediates were shown to be dependent on pH and the molecular weight of the

Notably, no significant influence on the phase transition temperatures, which may be caused by the long hydrophilic PEO775 middle block, was observed. The introduction of the PDEGMA outer blocks led to a significant change in the aggregation behavior for the ABCBA pentablock terpolymers (denoted as ABCBA-x, where x = number average degree of polymerisation of PDEGMA block) in dilute solutions (Figure 5). Here, three different ABCBA pentablock terpolymers were studied via temperature-dependent DLS revealing two separate phase transitions upon heating, thus confirming that both responsive blocks can be triggered separately. The first transition is initiated by the pH-independent coil-to-globule phase transition of the PDEGMA outer blocks at low temperatures (Ttr = 29 – 33 °C) for the two systems with the highest molar fraction of DEGMA units (ABCBA-25 and ABCBA-43), and the second pH-dependent transition at higher temperatures (Ttr > 40 for pH < 10) corresponds to the collapse of the PDMAEMA blocks (Figure 5A-C). These transitions are indicated by a significant increase of the count rate caused by each collapse of the respective blocks, which can only be clearly observed for pH = 8 (Figure 5A) since the two separated phase transitions of PDEGMA and PDMAEMA start to merge for pH ≥ 9 (Figure 5B and C).

However, short PDEGMA blocks as shown for ABCBA-11 revealed a phase transition at drastically elevated temperatures (Ttr = 45 °C). The collapse of these short PDEGMA11 blocks showed a weak impact on the count rate and could only be observed for pH = 8 (Figure 5A) due to Ttr(PDEGMA11) > Ttr (PDMAEMA) for pH > 8 (Figure 5B and C).

Figure 5. Temperature-dependent scattering intensities at θ = 90° for ABCBA pentablock copolymers in different buffer solutions (c = 2 g/L) at A) pH 8, B) pH 9 and C) pH 10 (ABCBA-11 ( ), ABCBA-25 ( ) and ABCBA-43 ( )); the dashed line indicates the Ttr of the PDMAEMA block in the corresponding ABA triblock copolymer precursor (DPn(PDMAEMA) = 90) at the respective pH.

Hydrogel formation of concentrated solutions was initially shown for the ABA triblock copolymer intermediates, which revealed that a molar fraction of DMAEMA units of fDMAEMA

≥ 0.19 is needed to form free-standing gels. Furthermore, rheology measurements of these gels indicated higher gel strengths and that the sol-gel transition temperature (TSG) shifts to lower temperatures by increasing the molecular weight of the PDMAEMA blocks, concentration of the solution or pH. For instance, a 10 wt% solution of the ABA triblock copolymer carrying an average degree of polymerization of 90 (ABA-90) formed no gel at pH

= 9 and a 20 wt% solution at pH = 10 was necessary to form a strong freestanding gel (Figure 6A). A doubling of the molecular weight of the PDMAEMA blocks, however, led to gelation for any investigated solution and revealed already strong gels for a 10 wt% solution at pH 10.

Figure 6. Temperature-dependent storage and loss moduli for A) ABA-90 at pH 10 and a concentration of 10 wt% (G' ( ), G'' ( )) and 20 wt% (G' ( ), G'' ( )), respectively and B) for ABCBA-25 at pH 10 and a concentration of 10 wt% (G' ( ), G'' ( )) and 20 wt% (G' ( ), G'' ( )), respectively.

Gels from 10 and 20 wt% solutions of ABCBA-25 and ABCBA-43 were only investigated at pH 10 as ABA-90, which represents the precursor for all ABCBA pentablock terpolymers, forms only very weak gels at pH = 9. Even though the PDEGMA blocks lower the TSG by 8 – 10 °C, a change in the mechanical properties of the hydrogel, which could then be attributed to the second phase transition of the collapsing PDMAEMA at higher temperatures, was not observed (Scheme 3, Figure 6B). Notably, an approximately doubling of the PDEGMA block length (ABCBA-43) leads to similar results to those from the ABCBA-25. This might be attributed to the long PEO middle block, which may compensate for the second collapse of the PDMAEMA. Consequently, an increase of the molar fractions of DEGMA units above those presented in this study (fDEGMA ≤ 0.08) might be necessary to shift the sol-gel transitions of the ABCBA hydrogels to lower temperatures close to Ttr(PDEGMA) and, in addition, to realize two clearly separated phase transitions with a sufficient impact on the mechanical properties of the hydrogel at the point where PDMAEMA starts to collapse.