Thermoresponsive Copolymer Microgels Synthesized via Single‐Step Precipitation Polymerization: Random or Block Structure?

Abstract The inner structure of polymeric microgels critically influences their responsiveness and potential applications, yet remaining challenging to resolve at molecular resolution. In this work, a structural characterization of thermoresponsive copolymer microgels is provided by integrating small‐angle neutron scattering (SANS), dynamic light scattering (DLS), and nuclear magnetic resonance (NMR) measurements with multi‐scale simulations. Specifically, Poly(N‐isopropylacrylamide‐ co ‐N‐isopropylmethacrylamide), P(NIPAM‐ co ‐NIPMAM), copolymer microgels, in which a random monomer distribution is conventionally assumed, are considered. By synthesizing different samples, including isotopically labeled microgels via selective deuteration, the microgels swelling behavior is probed and distinct polymer‐specific signatures are revealed. To elucidate their internal distribution, monomer‐resolved microgel simulations are performed across different copolymer models. A direct comparison between experimental and numerical form factors provides evidence of preferential organization into block structures, challenging the prevailing view of random distribution. ¹³ C‐NMR experiments confirm NIPAM‐rich blocks and atomistic simulations link this unexpected block‐like architecture to distinct local hydrogen‐bonding patterns. This integrated approach provides the first direct evidence of preferential block formation in P(NIPAM‐ co ‐NIPMAM) microgels. Beyond this system, these results establish a generalizable strategy for unveiling hidden structural order in copolymer microgels, offering new strategies to tailor their design and to enhance control of material responsivity.