Rational Design of Organic Chromophores for Simultaneously Trig-gering Redox Imbalance and Tracking Organelles in Biological Sys-tems Under Near-Infrared Light Irradiation.

Abstract

The design of organic photosensitizers that operate efficiently in the near-infrared (NIR) region remains challenging due to the need to balance electronic delocalization, stability, and biological compatibility. Here we report a rational, electronegativity-guided strategy for engineering (donor-π)₃-acceptor pyrylium-based chromophores capable of concurrent NIR phototherapy and subcellular imaging. Density functional theory calculations identified pyrylium (PYR) as the optimal acceptor for narrowing the HOMO-LUMO gap and enhancing intramolecular charge transfer (ICT). The resulting octupolar chromophores, PYR-OMe and PYR-NPh₂, display intense absorption in the 600-800 nm range, large Stokes shifts (>100 nm), and excellent photostability. Under NIR irradiation, PYR-NPh₂ catalyzes efficient NADH photooxidation and generates multiple reactive oxygen species (ROS), even under hypoxic conditions. In cancer cells (e.g., MDA-MB-231), PYR-NPh₂ induces redox imbalance and pronounced phototoxicity while enabling high-fidelity lysosomal imaging at ∼100 nm resolution using structured illumination microscopy. This work introduces a unified molecular design principle for NIR organic chromophores that integrate redox modulation, ROS generation, and organelle-level visualization, advancing the frontier of precision phototheranostics.