Metal-free synthesis of Pyrrolo[2,1-a]isoquinolines for type I photodynamic therapy and thermally activated delayed fluorescence materials.

Pyrrolo[2,1-a]isoquinoline is a privileged bioactive scaffold, yet its conventional synthesis typically relies on metal catalysis or pre-functionalized substrates. Developing efficient, metal-free synthetic routes is therefore crucial from both green chemistry and practical application perspectives. In this work, we report a metal-free, acid-promoted cascade cyclization that efficiently affords diverse pyrrolo[2,1-a]isoquinolines in good to excellent yields under mild conditions. This one-pot strategy features operational simplicity, broad substrate scope, and scalability for gram-scale preparation. The resulting compounds serve as acceptor units for constructing thermally activated delayed fluorescence (TADF) materials with aggregation-induced emission (AIE) properties, thus opening a new pathway toward multifunctional organic luminescent materials. Notably, using this approach, we have developed two green-fluorescent materials with good biocompatibility. Without requiring nanocarriers, these materials are efficiently endocytosed into HeLa cells and enable effective bioimaging. Furthermore, upon light irradiation, they generate significant levels of reactive oxygen species and achieve photodynamic therapy of HeLa cells via a Type I mechanism.