Synthesis of Ruthenium-Nitrosyl Complexes with PNP Pincer Ligands for Application in Photodynamic Therapy

Photodynamic therapy, the use of light to activate a photosensitizer and cause damage to cells has gained prominence as an avenue to treat cancer. Traditionally, porphyrins and chlorins are used as photosensitizers that generate toxic singlet oxygen upon irradiation by red or near infrared light, which is capable of penetrating skin. A more novel approach is the release of nitric oxide upon irradiation. While nitric oxide is an important diatomic molecule at sub-nanomolar concentrations for cell signaling and disease prevention, at micromolar concentrations NO causes cell necrosis and apoptosis. The purpose of this investigation is to synthesize a ruthenium-based compound with phosphorus-nitrogen-phosphorus binding moiety (PNP), which after binding nitric oxide can be irradiated with red light to photolabilize NO. 2,2’-dibromo-di-p-tolylamine was synthesized in 53% yield and reacted with butyllithium and chlorodiphenylphosphine to give 2,2’-di-diphenylphosphine-di-p-tolylamine (PNP) in 43% yield. 2,6-dibromomethylpyridine was synthesized in 73% yield and reacted with butyllithium, diphenylphosphine, and borane to give the borane-protected 2,6bis(diphenylphosphino)pyridine. Removal of the protecting group gave 2,6bis(diphenylphosphino)pyridine (PMP) in small yield. The direct synthesis of 2,6bis(diphenylphosphino)pyridine was also examined, although it was inconclusive as to which method is superior since improved purification methods are necessary.