A pH-Cascaded DNA Hydrogel Mediated by Reconfigurable A-motif Duplex, i-Motif Quadruplex, and T·A-T Triplex Structures

Governed by pH-configurable A-motif, i-motif and T·A-T triplex configurations, a cascaded DNA hydrogel subjecting to diverse pH values is presented. Under highly acidic conditions (pH 1.1), N1 protonation of adenine (pK_a 3.5) in A-strands generates AH⁺-H⁺A units, resulting in a parallel A-motif duplex crosslinked hydrogel. Under mild acid conditions (pH 5.2), the dissociation of A-motif duplex into single A-strands occurs due to the deprotonation of adenine, while N3 protonation of cytosine (pK_a 6.5) in C-strands creates hemi-protonated C:C⁺ units, resulting in i-motif bridged hydrogel. At neutral pH (pH 7.2), deprotonation of cytosine separates i-motif crosslinkers. Simultaneously, the addition of auxiliary T-strands results in the N3 protonation of thymine (pK_a 10), generating T·A-T triplex stabilized hydrogel. Under mildly alkaline conditions (pH 10.2), T·A-T triplex separates into single T-stands and A-T duplex, resulting in the disassembly of DNA hydrogel. Therefore, a stepwise pH-cascaded DNA hydrogel dictates the formation of structures following the pH steps 1.1 → 5.2 → 7.2 → 10.2 where pH-triggered DNA secondary structures, including A-motif, i-motif and T·A-T triplex, stabilize the hydrogel. The study advances DNA hydrogels from single pH-responsiveness to multiple cascaded pH values, which opens up new possibilities for the development of smart hydrogels capable of adapting to various environmental conditions.