Metal (M = Cr, Mo, W, Re) carbonyl complexes with porphyrin and carborane isocyanide ligands: light-induced oxidation and carbon oxide release for antitumor efficacy

Abstract

The tetrapyrrolic macrocycle as a scaffold for various chemical modifications provides broad opportunities for the preparation of complex multifunctional conjugates suitable for binary antitumor therapies. Typically, illumination with monochromatic light triggers the photochemical generation of reactive oxygen species (ROS) (photodynamic effect). However, more therapeutically valuable effects can be achieved upon photoactivation of tetrapyrrole derivatives. Herein we report the novel porphyrin-based complexes of transition metals with isocyanide and carbonyl ligands. Synthesis of complexes presumed the use of 5-(p-isocyanophenyl)-10,15,20-triphenylporphyrin as a ligand in reactions with metal carbonyl complexes, M(CO)₆ (M = Cr, Mo, W), Re₂(CO)₁₀ and Re(CO)₅Cl. Based on these complexes and isocyanocarborane, the heteroleptic carbonyl complexes with porphyrin and carborane isocyanide ligands were prepared. In cell-free systems, the new compounds retained photochemical characteristics of the parental porphyrin derivative, such as triplet state formation and ROS generation, upon light-induced activation. In the cell culture, the carborane-containing derivatives demonstrated a more pronounced intracellular accumulation than their nonboronated counterparts. As expected, illumination at the Soret band (405 nm) of cells loaded with the new complexes caused photodynamic cell damage. In contrast, illumination at 530 nm instead initiated the release of carbon oxide (CO) followed by cell death independently of the photodynamic effect. Light-induced CO release was analyzed using second derivatives of UV-Vis spectra and our originally developed Spectrophotometric elimiNAtion of Photoinduced Side reactions (SNAPS) method. The yield of CO release decreased in the raw depending on metals in the carbonyl moiety: Mo ≥ Cr > W > Re ≥ Re₂. Overall, our novel metal carbonyl complexes with porphyrin and carborane isocyanide ligands emerge as potent bi-functional conjugates for combined photodynamic and photoinducible CO-releasing antitumor agents.