Phenalenyl Chemistry Revisited: Stable and Bioactive Multisubstituted Phenalenyl Radicals Synthesized via a Protection–Oxidation–Protection Strategy

Phenalenyl chemistry has flourished for decades but currently faces bottlenecks related to synthetic challenges and stability issues. In this study, we introduced an iterative protection-oxidation-protection (POP) strategy to synthesize stabilized phenalenyl radicals (PRs) with multiple substitutions at the α-positions. The applicability of this POP strategy was verified using triisopropylsilylthyl and phenyl substituents to generate trisubstituted <b>PR1</b> and hexasubstituted <b>PR2</b>. In particular, both oxidation and dimerization were observed during the synthesis involving phenyl substituents. Both <b>PR1</b> and <b>PR2</b> were bench-stable, with half-lives in solution of up to 46 d and thermal decomposition temperatures of up to 300 °C. X-ray crystallographic analysis revealed that <b>PR1</b> existed as a distinct 12-center-2-electron π-dimer, whereas <b>PR2</b> existed as a monomer. The properties associated with monomer-dimer equilibrium both in the solid state and in solution were systematically investigated via variable-temperature spectroscopy, and the results revealed a small singlet-triplet energy gap and concentration-dependent absorption and electrochemical behaviors. Remarkably, both <b>PR1</b> and <b>PR2</b> formed biocompatible nanoparticles, with the latter capable of depleting reactive oxygen species in liver cells. This study thus demonstrated the applicability of the POP strategy for the construction of stable, functionalized PR derivatives with practical applications as spin functional materials.