Metal-Coumarin Derivatives as Promising Photosensitizers: Unlocking Their Cancer Phototherapy Potential

Abstract

The coumarin scaffold exhibits remarkable chemical adaptability, allowing modifications at nearly every position. This versatility enables precise customization of its photophysical, photochemical, physicochemical, and biological properties both for bioimaging and therapeutic applications. Transition metal complexes with photofunctional capabilities have also garnered significant attention as light-activated drugs due to their diverse and well-established photophysical and photochemical characteristics, facilitating numerous biomedical applications. In this context, both coumarin derivatives and transition metal complexes have been extensively employed in light-induced therapies, including photodynamic therapy (PDT) for cancer treatment. PDT, a clinically approved treatment modality for various medical conditions, relies on the use of light-activated drugs, known as photosensitizers (PSs), which are activated by specific wavelengths of light to generate cytotoxic reactive oxygen species (ROS) capable of eliminating cancer cells. This review offers a comprehensive analysis of the strategic development of advanced metal-based PSs incorporating coumarin derivatives, emphasizing the unique photophysical, photochemical and photobiological properties provided by the coumarin scaffold. The discussion is systematically divided into two major sections based on the integration approach of the coumarin within the metal complexes: 1. Metal complexes with coumarin attached via non-conjugated linkers. This section details cases where coumarin is indirectly linked to the metal center. 2. Metal complexes with coumarin integrated into ligands. This section explores systems where the coumarin is directly involved in the metal coordination sphere, either through direct bonding or via conjugated linkers that enhance electronic interactions with the metal center. This structured approach facilitates an in-depth comparison and analysis of design strategies for these innovative therapeutic agents. Special attention is given to metal-COUPY conjugates, featuring cyclometalated Ir(III) or Ru(II) complexes, and Ru(II)-COUBPY complexes, where the coumarin scaffolds are incorporated into Ru(II) polypyridyl complexes through a bipyridine ligand.