Synthesis, Spectroscopic, and O Sensitization Characteristics of Extended Pd(II) 10,10-Dimethylbiladiene Complexes Bearing Alkynyl-Aryl Appendages.

Photodynamic therapy (PDT), which involves the photoinduced sensitization of singlet oxygen, is an attractive treatment for certain types of cancer. The development of new photochemotherapeutic agents remains an important area of research. Macrocyclic tetrapyrrole compounds including porphyrins, phthalocyanines, chlorins, and bacteriochlorins have been pursued as sensitizers of singlet oxygen for PDT applications but historically are difficult to prepare/purify and can also suffer from high nonspecific dark toxicity, poor solubility in biological media, and/or slow clearance from biological tissues. In response to these shortcomings, we have developed a series of novel linear tetrapyrrole architectures complexed to late transition metals as potential PDT agents. We find that these dimethylbiladiene () tetrapyrrole complexes can efficiently photosensitize generation of O oxygen upon irradiation with visible light. To extend the absorption profile of the platform, alkynyl-aryl groups have been conjugated to the periphery of the tetrapyrrole using Sonogashira methods. Derivatives of this type containing ancillary phenyl (), naphthyl (), and anthracenyl () groups have been prepared and characterized. In addition to structurally characterizing and , we find that extension of the tetrapyrrole conjugation successfully red-shifts the absorption of the family of biladienes further into the phototherapeutic window (i.e., 600-900 nm). Photochemical sensitization studies demonstrate that our series of new palladium biladiene complexes () can sensitize the formation of O with quantum yields in the range Φ = 0.59-0.73 upon irradiation with light of λ ≥ 650 nm. The improved absorption properties of the complexes in the phototherapeutic window, together with their high O quantum yields, highlight the promise of these compounds as potential agents for PDT.