DNA‐Targeted Complexes of Tc and Re for Biomedical Applications

Abstract

Due to their favorable chemical features, Re and Tc complexes have been widely used for the development of new therapeutic agents and imaging probes to solve problems of biomedical relevance. This review provides an update of the most relevant research efforts towards the development of novel cancer theranostic agents using Re and Tc‐based compounds interacting with specific DNA structures. This includes a variety of homometallic complexes, namely those containing M(CO)3 (M = Re, Tc) moieties, that exhibit different modes of interaction with DNA, such as covalent binding, intercalation, groove binding or G‐quadruplex DNA binding. Additionally, heterometallic complexes, designed to potentiate synergistic effects of different metal centers to improve DNA‐targeting, cytotoxicity and fluorescence properties, are also reviewed. Particular attention is also given to 99mTc‐ and 188Re‐labeled oligonucleotides that have been widely explored to develop imaging and therapeutic radiopharmaceuticals through the in vivo hybridization with a specific complementary DNA or RNA target sequence to provide useful molecular tools in precision medicine for cancer diagnosis and treatment. Finally, the need for further improvement of DNA‐targeted Re and Tc‐based compounds as potential therapeutic and diagnostic agents is highlighted, and future directions are discussed.

Two rhenium compounds with benzimidazole ligands: synthesis and DNA interactions

“…To balance the net charge, each [ReO 2 (Benzim) 4 ] + unit must have +1.5 average charge. To explain this situation in a reported similar structure, 9,10 it was postulated that there are shared protons between adjacent complex units such that one unit may be formulated as [ReO 2 (Benzim) 4 ] + and the other one as [ReO(OH)(Benzim) 4 ] 2+ . Although in our structure we do not have any direct evidence either of the presence of shared protons or of their location, we have assumed that the protons are in O1 and O2 close to the hydrophilic layer ( vide infra ), and close to O4 so that they are effectively delocalized between the two positions.…”

“…Several comprehensive reviews highlight the biological effects of different rhenium complexes according to their oxidation states. 8,9 The most active rhenium complexes reported to date contain Re( i ) carbonyl centers bound to mono-, di-, or tridentate ligands. It is proposed that such compounds induce their cytotoxic effects through covalent binding to DNA bases and/or protein side chains.…”