Design and Synthesis of Fluorescent Sulfonamide-Based Sequence-Defined Oligomer with Sequence-Controlled Properties and Postsynthetic Modification: A Scalable Support-Free Iterative Approach

Sulfonamides are essential functional groups in both materials and biomedical sciences; however, their controlled integration into a polymer backbone remains challenging using conventional synthetic methods. Herein, we developed a scalable, support-free, protection/deprotection-free strategy for the synthesis of a class of fluorescent sulfonamide-based sequence-defined oligomers (SDOs). For a proof-of-concept, two sequence-defined oligomers (SDO-1 and SDO-2) were synthesized. The monomer composition of the SDOs was kept constant, while the monomer sequence was varied to investigate sequence–property relationships. The dansyl monomer imparts fluorescence characteristics and probe photophysical tunability. Furthermore, the synthetic strategy was advanced toward versatile postsynthetic modification. SDOs were characterized via 1H/13C NMR, 1H–1H COSY, and LC-MS. Sequencing of SDOs was validated by tandem MS. Comparative analysis of SDO-1 and SDO-2 revealed significant sequence-dependent variations: SDO-1 exhibited a quantum yield of 35.8%, lifetime of 20.68 ns, and Tg of 49.3 °C, while SDO-2 showed 16.7% quantum yield, 8.75 ns lifetime, and Tg of 87.2 °C.