Chemoadaptive Polymeric Assemblies by Integrated Chemical Feedback in Self-Assembled Synthetic Protocells

[Image: see text] The design and chemical synthesis of artificial material objects which can mimic the functions of living cells is an important ongoing scientific endeavor. A key challenge necessary for fulfilling the criteria for a system to be living currently regards evolution, which is derived from adaptivity. Integrated chemical loops capable of feedback control are required to achieve chemical systems which exhibit adaptivity. To explore this, we present an integrated, two-component orthogonal chemical process involving reversible addition–fragmentation chain transfer (RAFT) based polymerization-induced self-assembly (PISA) and a copper-catalyzed azide–alkyne click (CuAAC) coupling reaction. The chemical processes are linked through electron transfer from the activated chain-transfer agent (CTA) to the dormant Cu(II) precatalyst. We show that combining these complementary chemistries in a single reaction pot resulted in two primary outcomes: (i) simplification of the PISA process to synthesize the macro-CTA in situ from available nonamphiphilic components and (ii) routes to complexity and adaptation involving population dynamics, morphologies, and dissipative phenomena observed during in situ microscopy analysis.