Engineering Synergistic Intra‐/Intermolecular Conformational Locking via Side‐Chain Branching: A β‐Sheet‐Inspired Strategy for Planar NIR‐II Phototheranostic Aggregates

Engineering stable noncovalent conformational locks (NoCL) network at the aggregate level is essential for developing phototheranostic aggregates (PTAs) with enhanced rigidity and light-harvesting ability, but remains a challenge due to complex intermolecular interactions. Inspired by β-sheet proteins, where branched side chains act as steric directors to program backbones into interlocked architectures, a side-chain isomerization strategy is proposed to manipulate analogous NoCL networks for constructing planar-structured NIR-II multimodal PTAs. Two isomeric pairs with linear (l-series) and branched (b-series) alkyl side-chains are synthesized. Crystallographic analysis reveals that the b-series, driven by directional S···O/F interactions, adopts a fully planar conformation stabilized by a synergistic dual NoCL network, whereas l-series exhibits twisted conformations. Theoretical calculation and femtosecond transient absorption spectra confirm the dual NoCL network effectively narrows the energy gap and optimizes excited-state energy dissipation pathway, resulting in comprehensive enhancement in phototheranostic performance including superior ROS generation, higher NIR-II brightness and excellent photothermal properties compared to l-series NPs. Notably, the exceptional performance of b-3CPFIC NPs enables it to serve as an ideal candidate in multimodal NIR-II phototheranostics of tumors. This work establishes a novel design paradigm for multifunctional PTAs and elucidates aggregate-level structure-property relationships.