Design of a phosphinate-based bioluminescent probe for superoxide radical anion imaging in living cells

Superoxide radical anion (O₂ ˙^- ) as an important member of reactive oxygen species (ROS) plays a vital role both in physiology and pathology. Herein we designed and synthesized a novel phosphinate-based bioluminescence probe for O₂ ˙^- detection in living cells, which exhibited good sensitivity for capturing O₂ ˙^- at the nanomole level and high selectivity against other ROS. The probe was further found to be of low toxicity for living cells and was then successfully employed for sensing endogenous O₂ ˙^- by using phorbol-12-myristate-13-acetate (PMA) as a traditional O₂ ˙^- stimulator in Huh7 cells. Moreover, the increasing production and use of nanoparticles, has given rise to many concerns and debates among the public and scientific authorities regarding their safety and final fate in biological systems. Herein it was found that mondisperse polystyrene particles could stimulate O₂ ˙^- generation in Huh7 cells. Overall, the probe was demonstrated to have a great potential as a novel bioluminescent sensor for detecting O₂ ˙^- in living cells. To our knowledge, this is the first small-molecule phosphinate-based bioluminescence probe that will open up great opportunities for unlocking the mystery of O₂ ˙^- in human health and disease.