Iron, the most abundant transition metal in the human body, plays critical roles in numerous physiological processes and pathological pathways. Labile iron, defined as protein-free or weakly protein-bound iron, is essential for iron metabolism and oxidative stress regulation. Our research demonstrated that N-oxide undergoes selective deoxygenation upon reaction with Fe(II) ions.
Heme, a metal complex consisting of iron and protoporphyrin IX (PPIX), functions as a vital signaling molecule and enzyme cofactor in maintaining homeostasis. Despite their importance, the cellular trafficking mechanisms of labile iron and heme, along with their contributions to pathological processes, remain poorly understood.
Our laboratory has developed fluorescent probes for detecting Fe(II) ions—the predominant oxidation state of labile iron—and labile heme based on N-oxide chemistry. These probes function effectively in living cells and have revealed crucial roles of labile iron during disease progression. Recently, we developed a novel chemical probe capable of monitoring labile heme levels in tissue samples. This probe reacts with heme to induce self-activation, forming covalent bonds with surrounding biomolecules. Using this approach, we successfully monitored the upregulation of heme biosynthesis in mouse brain. Furthermore, by exploiting this covalent bond formation, we have applied the probe to three-dimensional imaging using tissue-clearing techniques and single-cell analysis in mouse brains.
In this presentation, I will discuss the design principles of our fluorescent probes and highlight their applications in understanding iron and heme biology.