One‐Pot Conversion of Acridines Into Phototherapeutic Near‐Infrared Spirocyanines

ABSTRACT As near‐infrared (NIR) bio‐imaging and phototherapeutic agents, polymethine cyanines have disadvantages in optical properties due to the fast nonradiative transition. Herein, we reported a small‐sized and spirocycle‐fused trimethine acridinocyanine (SpiroCY) via one‐pot oxidative trimerization using oxygen as the oxidant. Theoretical calculations using the Automated Design of Chemical Reaction (ADCR) program elucidate the formation of the O 2 ‐derived hydroperoxyl radical (HO 2 • ) and demonstrate a radical cascade reaction (RCR) mechanism for spirocyanine synthesis. The spiro‐functionalization effect greatly reshapes the photophysical properties of the parent acridinocyanine by improving brightness and suppressing H‐aggregation due to the three‐dimensional architecture and enhanced rigidity, which allows for mitochondria‐targeted NIR‐I and NIR‐II cell imaging at a very low dose (10−100 nM); and switches the parent acridinocyanine into a potential antitumor drug and Type‐I photosensitizer generating superoxide anion radical (O 2 •− ) and hydroxyl radical ( • OH) under 808 nm light irradiation for efficient photodynamic therapy. This work provides a new insight for dye functionalization, adds mechanistic understandings of the spirocyclic effect, and paves a way for developing spiro dyes as unique NIR‐I and NIR‐II imaging and phototherapeutic agents.