TPEN—Advanced Metal Chelator: From Characterization to Biomedical Applications

TPEN (N,N,N′,N′-tetrakis(2-pyridylmethyl)ethylenediamine) is a ligand containing six nitrogen donors. It is characterized by high structural flexibility, enabling the coordination of metals with various ionic radii and coordination numbers. It is an advanced metal chelator that demonstrates high selectivity, particularly towards “soft” and “medium” metal ions, and has a wide range of applications, from coordination chemistry, materials engineering, and nuclear energy to innovations in medicine. TPEN can cross cell membranes freely, which is important in cell biology. However, its presence is not neutral for healthy cells and can lead to apoptosis by depleting essential metals such as zinc, iron, and copper. Targeted delivery systems are therefore essential. This can be achieved, for example, by using nanoparticles that release TPEN upon ultrasound. This review systematizes the understanding of TPEN complexes. Methods for the coordination of various d-, p-, and f-block metals are presented, as well as the properties of these complexes, which are crucial to understanding the mechanisms of reaction with TPEN. This ligand may find applications both as a diagnostic tool (in sensors) and as a therapeutic tool (by inducing cancer cell death). This work also demonstrates the need to design new and more effective TPEN analogs that overcome problems with solubility and stability in acids.