Luminescent Cyclometalated Iridium(III) Polypyridine Complexes Modified with a Dendritic Guanidinium Moiety as...

We report herein three cyclometalated iridium(III) polypyridine complexes appended with a dendritic guanidinium unit [Ir(N^C)₂(bpy-Gu₉)](Cl)₁₀ (bpy-Gu₉ = 4-(N-(3,4,5-tris(2-(2-(2-(4-((3,4,5-tris(2-(2-(2-guanidinoethoxy)ethoxy)ethoxy)benz-amido)methyl)-1H-1,2,3-triazol-1-yl)ethoxy)ethoxy)ethoxy)phenylcarbonyl)aminomethyl)-4'-methyl-2,2'-bipyridine; HN^C = 2-phenylpyridine (Hppy) (1a), 2-phenylquinoline (Hpq) (2a), and 2-(1-naphthyl)benzothiazole (Hbsn) (3a)) as molecular glues. Their guanidinium-free counterparts [Ir(N^C)₂(bpy-C4)](Cl) (bpy-C4 = 4-(N-(n-propylcarbonyl)aminomethyl)-4'-methyl-2,2'-bipyridine; HN^C = Hppy (1b), Hpq (2b), and Hbsn (3b)) were also isolated. Irradiation of the complexes led to intense greenish-yellow to red emission. Additionally, the cellular uptake and (photo)cytotoxic effects of the complexes were investigated. Protein-binding studies showed that the decacationic complexes 1a-3a exhibited high binding affinity toward bovine serum albumin (BSA). Complex 1a was utilized to modify doxorubicin (DOX)-loaded, glutathione (GSH)-responsive BSA nanoparticles (DOX/^SSBNPs), affording Ir-DOX/^SSBNPs. Notably, functionalization of DOX/^SSBNPs with the complex reversed the surface charge from negative to positive. The size of Ir-DOX/^SSBNPs decreased significantly upon incubation with GSH as a result of efficient DOX release. The positively charged Ir-DOX/^SSBNPs showed efficient cellular uptake in HeLa cells, which proved to be crucial for their effectiveness in combined chemo-photodynamic therapy. These results showed that iridium(III)-based molecular glues can be employed for drug delivery and combined chemo-photodynamic therapy.