Combinatorial Construction of a NIR-II Polymethine Dye Library

Abstract A comprehensive NIR-II polymethine dye library is essential for unraveling reliable structure-property relationships, enabling rational design, and supporting biomedical research. Yet current libraries lack the diversity and systematicity needed to establish reliable structure–property relationships, let alone to enable effective probe design and screening. Here, we develop a combinatorial NIR-II polymethine dye library comprising 18 structurally distinct members through the modular combination of three building blocks with three linkers, via an efficient tandem one-pot synthesis that is compatible with diverse structural units and delivers the library with significantly enhanced synthetic efficiency. Systematic photophysical characterization, combined with theoretical calculations, identifies the molecular planarity parameter (MPP) and the change in dipole moment relative to the ground state (Δμ) as two principal descriptors that rationalize the structure–property trends, providing valuable insights for guiding dye design within this polymethine library. The library further enables rapid screening of suitable dyes for intravital multichannel imaging, demonstrating its practical utility. This work demonstrates that our combinatorial dye library, together with the synthetic methodology and structure–property relationships, constitutes a platform that offers insights relevant to future NIR-II polymethine dye development.