Molecular Design of Thermoresponsive Cellulose: How Graft Architecture Dictates Sol‐Gel Transitions

The development of polysaccharide‐peptoid hybrids represents a promising route toward sustainable, stimuli‐responsive biomaterials. However, achieving controlled synthesis and predictable thermal transitions, particularly reversible sol‐gel behavior, remains challenging. Herein, we report a systematic study on the synthesis of thermoresponsive carboxymethyl cellulose (CMC) graft polymers via the Ugi multicomponent polymerization of glycylglycine as a model dipeptide. Two distinct synthetic strategies, stepwise grafting of preformed n‐propylamine‐capped peptoids and one‐pot grafting, are employed to design graft architecture. Comprehensive characterizations reveal that graft length, density, and molecular weight dictate the thermal response. Notably, only graft polymers with short, dense grafts (CNP 80 (12.0) ) undergo a reversible sol‐gel transition upon heating, while long, sparse grafts (CNP 5 , CNP 20 ) lead to particulate aggregation without gelation. In situ variable‐temperature FTIR, coupled with two‐dimensional correlation spectroscopy, elucidates a sequential response mechanism: the dehydration of hydrophobic methyl groups precedes the rearrangement of amide hydrogen bonds, thereby driving aggregation. This work establishes a synthesis platform for cellulose‐g‐peptoid graft polymers and clarifies the molecular‐to‐macroscopic design principles for thermally triggered gelation.