Monochromophore-Based Phosphorescence and Fluorescence from Pure Organic Assemblies for Ratiometric Hypoxia Detection

Abstract

Hypoxia is a parameter related to many diseases. Ratiometric hypoxia probes often rely on a combination of an O₂ -insensitive fluorophore and an O₂ -sensitive phosphor in a polymer matrix, which require high cost and multi-step synthesis of transition metal complexes. The two-chromophore hypoxia probes encounter unfavorable energy transfer processes and different stabilities of the chromophores. Reported herein is a pure organic ratiometric hypoxia nanoprobe, assembled by a monochromophore, naphthalimide ureidopyrimidinone (BrNpA-UPy), bridged by a bis-UPy-functionalized benzyl skeleton. The joint factors of quadruple hydrogen bonding, the rigid backbone of UPy, and bromine substitution of the naphthalimide derivative facilitate bright phosphorescence (Φ_P =7.7 %, τ_P =3.2 ms) and fluorescence of the resultant nanoparticles (SNPs) at room temperature, which enable accurate, ratiometric, sensitive oxygen detection (K_sv =189.6 kPa^-1 ) in aqueous solution as well as in living HeLa cells.

Keywords: hypoxia detection; organic phosphorescence and fluorescence; ratiometric imaging; self-assembly; supramolecular chemistry.