Rhenium and Technetium Complexes Anchored by Phosphines and Scorpionates for Radiopharmaceutical Applications

Abstract

This review presents a comprehensive overview of the most significant developments in the chemistry of technetium and rhenium complexes anchored by heterofunctionalized phosphines and by hard and soft scorpionates. The main goal is to provide the reader with chemical, radiochemical and biological knowledge which is expected to enhance the application of these types of compounds in the development of target-specific radiopharmaceuticals. In the introductory section, a short historical outlook is presented to introduce the few 99mTc radiopharmaceuticals based on phosphorus- and boron-containing ligands already in clinical use. Generic considerations of the characteristics of these ligands are included in this section highlighting their potential usefulness in the design of biocomplexes for clinical applications. The following section deals with the chemistry of intermediate- and low-valent rhenium and technetium complexes anchored by polydentate phosphines, which combine soft phosphorus atoms with other hard or soft donors (N, O, S). Synthetic procedures involving phosphines with denticities adjustable to a given metal fragment are described. In the last section the coordination chemistry of rhenium and technetium with poly(pyrazolyl)borates and poly(mercaptoimidazolyl)borates (hard and soft scorpionates) is described, giving special attention to high-valent rhenium and technetium oxides and to low-valent carbonyl complexes. In all these sections, synthetic procedures, reactivity studies and structural characterization are discussed, with special emphasis on those inorganic and organometallic systems that allowed, or are expected to allow, the labeling of biomolecules (e.g., small peptides and central nervous system receptor ligands). In this context, the biological properties of the already achieved biocomplexes, anchored by phosphorus- or boron-containing ligands, are also briefly discussed.