Advancing Meta-Selective C-H Amination through Non-Covalent Interactions.

Regioselective C-H amination of simple arenes is highly desirable, but accessing meta-sites of ubiquitous arenes has proven challenging due to the lack of both electronic and spatial preference. This study demonstrates the successful use of various privileged nitrogen-containing functionalities found in pharmaceutical compounds to direct meta-C-H amination of arenes, overcoming the long-standing requirement for a redundant directing group. The remarkable advancements in functional group accommodation for precise regiochemical control were achieved through the discovery of an unprecedented organo-initiator and the strategic utilization of non-covalent interactions. This protocol has been successfully applied in the concise synthesis and late-stage derivatization of drug molecules, which would have been otherwise challenging to achieve.

Rigidity Bridging Flexibility to Harmonize Three Excited-State Deactivation Pathways for NIR-II-Fluorescent-Imaging-Guided Phototherapy.

Small organic phototherapeutic molecules of the second near-infrared (NIR-II) window (1000-1700 nm) serve as promising candidates for theranostics. However, developing such versatile agents for fluorescence-guided photodynamic/photothermal therapy remains a demanding task stirred by competitive energy dissipation pathways, including radiative decay, internal conversion, and intersystem crossing. To the best of current knowledge, the current paradigm for addressing the issue has deliberately approached the optimum balance among three deactivation processes through offsetting from each other, possibly leading to a comprehensively compromised theranostic efficacy. Few reports aim to modulate the three deactivation pathways excluding sacrificing any one of them. Herein, a molecular design strategy to construct a phototherapeutic organic fluorophore CCNU-1060, armed with NIR-II luorescence-guided phototherapeutic properties, is rationally developed. With a flexible motor, tetraphenylethene, bridged to the rigidified coplanar core boron-azadipyrromethene, the desired CCNU-1060 is subsequently encapsulated into an amphiphilic matrix to form CCNU-1060 nanoparticles (NPs), which match or transcend its precursor NJ-1060 NPs in the three energy dissipation processes. CCNU-1060 NPs are utilized to realize high-spatial vessel imaging and effective NIR-II fluorescence-guided phototherapeutic tumor ablation. This study unlocks a viewpoint of molecular engineering that simultaneously regulates multiple energy dissipation pathways for the construction of versatile phototherapy agents.