Photophysical and Biological Properties of Diprotic Ruthenium(II) Complexes with Extended π-Systems

Ruthenium(II) polypyridyl complexes can be harnessed for photodynamic therapy. In this work, diprotic ligands which can be deprotonated to change the metal complexes from dicationic to neutral are combined with extended π systems for light absorption at longer wavelengths. Herein, the diprotic ligands are 4,4'-dhbp = 4,4'-dihydroxybipyridine or 4,7-dhphen = 4,7-dihydroxy-1,10-phenanthroline and the π-expanded ligands are bphen = bathophenanthroline, dppz = dipyrido[3,2-a:2',3'-c]phenazine, and dppn = benzodipyrido[3,2-a:2',3'-c]phenazine. This report describes the synthesis and characterization of [(bphen)₂Ru(4,4'-dhbp)]Cl₂ (1 _A ), [(dppz)₂Ru(4,4'-dhbp)]Cl₂ (2 _A ), [(dppn)₂Ru(4,4'-dhbp)]Cl₂ (3 _A ), [(bphen)₂Ru(4,7-dhphen)]Cl₂ (4 _A ), [(dppz)₂Ru(4,7-dhphen)]Cl₂ (5 _A ), and [(dppn)₂Ru(4,7-dhphen)]Cl₂ (6 _A ). Single crystal X-ray diffraction data are reported for 1 _A , 2 _A , and two known precursor compounds: [(ղ⁶-p-cymene)RuCl(diprotic ligand)]Cl (P1, P2 where diprotic ligand = 4,4'-dhbp and 4,7-dhphen, respectively). Compounds 1 _A -6 _A have been studied for their photocytotoxicity vs. breast and melanoma cancer cells, lipophilic vs. hydrophilic properties, thermodynamic acidities (pK _a values), singlet oxygen quantum yields, and luminescence which is heavily influenced by the nature of the π expanded ligand. Four compounds (bearing bphen and dppn ligands) have promising photocytotoxicity including activity with green light and one compound has a phototherapeutic index (PI) as high as 145.