KSEF RDE: Cytotoxic Photoactive Ruthenium(II) Complexes with Polypyridyl and N-Heterocyclic Carbene Ligands

Tris(2,2-bipyridyl)ruthenium(II) is the quintessential photoactive metal complex. Because of its ease of synthesis, stability, chirality, and rich photochemical and photophysical properties, it has myriad applications. [Ru(bpy)3]2+ and its derivatives been used extensively as photosensitizers for water splitting, chemiluminescent sensors for biodiagnostics, components of photovoltaic devices and organic light-emitting diodes, and photocatalysts for organic synthesis. Most relevant to this proposal, [Ru(bpy)2(dppz)]2+ (dppz = dipyrido[3,2-a:2’,3’-c]phenazine), serves as a luminescent DNA probe. The Glazer group has established methods to photochemically activate related Ru(II) complexes, developing excited-state chemistries designed to target specific biological entities, such as G-quadruplex DNA. N-heterocyclic carbenes and their metal complexes have undergone explosive growth since Arduengo reported the first stable NHC in 1991. Their powerful electron donor and weak electron-acceptor ability makes them strong bases, potent nucleophiles and robust ligands. In particular, NHCs demonstrate a strong trans-effect, i.e., cause the ligand across from them in a complex to be selectively lost. The anti-cancer activity of some NHC complexes of Ag(I), Au(I), Pd(II) and Cu(I) provides a precedent for using these ligand in biological media.