Functionalization of a Ru(<scp>ii</scp>) polypyridine complex with an aldehyde group as a synthetic precursor for photodynamic therapy

Photodynamic therapy has garnered significant attention over the past decades for its potential in treating various types of cancer, as well as bacterial, fungal, and viral infections. However, current clinically approved photosensitizers based on a tetrapyrrolic scaffold face notable limitations, including low water solubility, slow body clearance, and photobleaching. As a promising alternative, Ru(II) polypyridyl complexes have emerged due to their favorable photophysical and biological properties (<i>i.e.</i>, reactive oxygen species generation, high water solubility, and biocompatibility). Despite these attractive properties, the vast majority of compounds are associated with poor tumor accumulation, representing a major hurdle for therapeutic applications. To overcome this limitation, herein, the chemical synthesis and photophysical evaluation of the functionalization of a Ru(II) polypyridyl complex with an aldehyde group, as a synthetic precursor for further conjugation, is reported. To ensure that the intrinsic chemical reactivity of the aldehyde group remains unaffected by the coordination environment to the metal center, a phenyl spacer was strategically introduced between the central ligand framework and the aldehyde functionality. Computational studies indicated that upon excitation of the metal complex, an excited state electron from the ruthenium t_2g orbital is transferred to the π* ligand orbital in a metal-to-ligand charge transfer transition. The compound was found to be highly stable under physiological conditions as well as upon irradiation. Upon light exposure, the metal complex was found to efficiently convert molecular oxygen to singlet oxygen. These findings highlight the potential of the aldehyde functionalized Ru(II) polypyridyl complex as a versatile precursor for photodynamic therapy.