Light‐ and pH‐Gated Reversible Modulation of Peptide Coacervates via Noncovalent Integration of Spiropyran Photoswitches

Peptide coacervates formed via liquid-liquid phase separation (LLPS) have emerged as versatile cell-like compartments for protocell studies and spatially confined catalysis. However, achieving remote, noninvasive modulation of their assembly‒disassembly lifecycle remains a key challenge. Here, we report a supramolecular design that enables light- and pH-gated reversible coacervation of peptides through non-covalent integration of spiropyran photoswitches. The mechanism relies on photoisomerization-induced charge shift in spiropyran, which consequently modulates interpeptide electrostatic interactions to drive coacervate formation. Dissociation occurs reversibly via thermal relaxation upon the cessation of light, a process further regulated by pH, thereby enabling distinct on-demand on- and off-coacervation regimes. We validate this principle through systematic structural variations of both components, establishing a direct link between molecular design and phase behavior. Exploiting their reversible sequestration capability, we demonstrate that these coacervates serve as efficient light‑ and pH-activated microreactors with OR logic gate functions that are capable of accelerating cascade reactions under dilute conditions and as dynamic reusable templates with cascaded OR-AND logic gate functions for recyclable synthesis of nanogels with tunable dimensions. This work establishes a versatile approach for dual-mode regulation of peptide coacervates, opening avenues for the development of photo- and pH-responsive microreactors and adaptive templates for material synthesis.