Dual-Responsive Material Based on Catechol-Modified Self-Immolative Poly(Disulfide) Backbones

Abstract

Functional materials engineered to degrade upon triggering are in high demand due their potentially lower impact on the environment as well as their use in sensing and in medical applications. Here, stimuli-responsive polymers are prepared by decorating a self-immolative poly(dithiothreitol) backbone with pendant catechol units. The highly functional polymer is fashioned into stimuli-responsive gels, formed through pH-dependent catecholato-metal ion cross-links. The gels degrade in response to specific environmental changes, either by addressing the pH responsive, non-covalent, catecholato-metal complexes, or by addition of a thiol. The latter stimulus triggers end-to-end depolymerization of the entire self-immolative backbone through end-cap replacement via thiol-disufide exchanges. Gel degradation is visualized by release of a dye from the supramolecular gel as it itself is converted into smaller molecules.

Keywords: catechol; hydrogel; polymers; self-immolative; stimuli-responsive.

Scheme 1

a) Functionalization of pDTT using EDC coupling of protected dihydrocaffeic acid, followed by deprotection to reveal the catecholic moiety. b) Thiol‐induced/base‐catalyzed depolymerization of catechol‐modified poly(dithiothreitol) to produce catechol‐modified cDTT via cyclization reactions upon end‐cap removal.

Figure 1

a) SEC traces of unmodified pDTT (blue), pDTT‐Ace‐DHCA₂₀ (orange), pDTT‐Ace‐DHCA₁₀₀ (yellow), and pDTT‐Cat₁₀₀ (purple) in 0.01 m LiBr/DMF. The small‐molecule peak at ca. 24 min is ascribed to solvent impurity as confirmed by ¹H NMR (Figure S5). b) SEC trace of pDTT‐Cat₁₀₀ (blue) and pDTT‐Cat₁₀₀ after addition of 1 equiv DTT and 0.5 equiv Et₃N w.r.t. end‐caps (orange) in 0.01 m LiBr/DMF. All sample concentrations were 4 mg mL⁻¹.

Figure 2

a) Chemical structure of depolymerization products from pDTT‐Cat₁₀₀. b) ¹H NMR of pDTT‐Cat₁₀₀ (blue) and pDTT‐Cat₁₀₀ depolymerized in presence of 1 equiv DTT and 0.5 equiv Et₃N with respect to polymer end‐caps (orange) in DMSO‐d ₆. c) Conversion of polymers, pDTT‐Cat₁₀₀ (green), and pDTT‐Cat₂₀ (black) to cyclic monomer in response to adding 1 equiv DTT and 0.5 equiv Et₃N, along with the response of adding only 0.5 equiv Et₃N to pDTT‐Cat₂₀ (blue), measured by ¹H NMR spectroscopy (lines to guide the eye). In all measurements the polymer concentration was 1.6 mm.

Figure 3

a) pDTT‐Cat₂₀, Al³⁺, and rhodamine 6G in solution and b) after inducing hydrogel formation by addition of NaOH to raise pH (>10). c) Mechanism of gel breakdown, induced either by depolymerization through decapping by addition of 10 equiv DTT and 5 equiv Et₃N w.r.t. end caps (top), or by cleavage of Al³⁺–catecholato cross‐links at low pH, by addition of 1 m HCl in MeOH (bottom). d) Resulting liquefaction of the hydrogel and concomitant release of rhodamine 6G into solution after 100 min (depolymerization) and 17 min (catecholato–metal cross‐link cleavage).

Figure 4

Dye release from pDTT‐Cat₂₀ gels in different environments measured as absorbance at 529 nm; 1 m HCl in MeOH (blue), 10 equiv DTT and 5 equiv Et₃N (with respect to end‐caps) in MeOH (yellow), MeOH without stimuli (orange). Dashed lines to guide the eye.