Exploiting the B–N/C–C Isosterism Yields Nile‐Red Inspired Organoboron Dyes Capable of Singlet‐Oxygen Photosensitization

Small dyes are indispensable tools for probing biological processes. Among them, Nile Red (NR) is widely used for imaging lipid‐rich environments. However, the structural diversification of its phenoxazine core remains limited. Herein, we exploit B─N/C─C isosterism to connect the western and eastern fragments of NR through a B─N linkage, enabling the design of NR‐inspired boronic acid‐derived salicylidenehydrazone (NR‐BASHY) dyes with enhanced structural and functional versatility. This strategy allows the modular one‐pot synthesis of NR‐BASHY dyes, which exhibit promising photophysical properties. These include intense absorption ( ε up to 50,800 M ^–1 cm ^–1 ) and high brightness ( ε  ×  Φ _f up to 17,000 M ^–1 cm ^–1 ) and a pronounced solvatofluorochromism with emission spanning the red to near‐infrared spectral region. In strong contrast to NR, NR‐BASHY can act as photosensitizers, featuring efficient singlet‐oxygen generation ( Φ _Δ up to 0.8) and photoinduced cytotoxicity against the U87 glioblastoma cell line in the submicromolar range (IC ₅₀ ca. 0.5 μM), while maintaining low dark toxicity (>100 μM). Moreover, the modular architecture of NR‐BASHY dyes enables click‐reaction mediated bioconjugation with the GV1001 peptide, highlighting the potential of this platform for targeted bioimaging applications.