Manipulation of Intramolecular and Intermolecular Noncovalent Conformational Locked Network via Side-Chain Isomerization for Constructing Planar NIR-II Phototheranostic Aggregates

The transition from molecular-scale intramolecular non-covalent conformational locking (NoCL) to hierarchically organized intra- and intermolecular NoCL in aggregates presents transformative potential for engineering photo-theranostic aggregates (PTAs) with enhanced rigidity and light-harvesting ability. Nevertheless, the simultaneous achievement of intra- and intermolecular NoCL in the aggregate state remains significant challenge, primarily due to the inherent complexity of intermolecular interactions and the lack of effective regulation strategies, rendering this frontier largely underexplored. Herein, we proposed a side-chain isomerization strategy to manipulate intra-/intermolecular NoCL for constructing high performance NIR-II multimodal PTAs with planar structures. Two pairs of isomers, whose alkyl side-chains are linear (l-series) and branched (b-series) configurations, were designed and syn-thesized. Crystals of b-series demonstrated planar structures attributed to robust S‧‧‧O interactions for intramolecular NoCL and multiple acceptor-acceptor intermolecular interactions for intermolecular NoCL, in contrast to those of l-series with twisted structures. Theoretic calculation and femtosecond transient absorption spectra revealed the dual NoCL effectively narrowed the energy gap and optimized excited-state energy dissipation pathway, resulting in com-prehensively enhancement in phototheranostic performance including superior ROS generation, higher NIR-II bright-ness and excellent photothermal properties compared to l-series NPs. Notably, the exceptional performance of b-3CPFIC NPs enabled it as an ideal candidate in multimodal NIR-II phototheranostics of tumors. The successful imple-mentation of this side-chain isomerization strategy has unveiled a novel design paradigm for developing high-performance multifunctional NIR-II PTAs and established fundamental structure-properties relationship at aggregate level.