New Ru(II) Complexes for Dual Photoreactivity: Ligand Exchange and ¹O₂ Generation

Abstract

CONSPECTUS Uncovering the factors that govern the electronic structure of Ru(II)–polypyridyl complexes is critical in designing new compounds for desired photochemical reactions, and strategies to tune excited states for ligand dissociation and 1O2 production are discussed herein. The generally accepted mechanism for photoinduced ligand dissociation proposes that population of the dissociative triplet ligand field (3LF) state proceeds through thermal population from the vibrationally cooled triplet metal-to-ligand charge transfer (3MLCT) state; however, temperature-dependent emission spectroscopy provides varied activation energies using the emission and ligand exchange quantum yields for [Ru(bpy)2(L)2]2+ (bpy = 2,2′-bipyridine; L = CH3CN or py). This suggests that population of the 3LF state proceeds from the vibrationally excited 3MLCT state. Because the quantum yield of ligand dissociation for nitriles is much more efficient than that for py, steric bulk was introduced into the ligand set to distort the pseudo-octahedral geometry and lower the energy of the 3LF state. The py dissociation quantum yield with 500 nm irradiation in a series of [Ru(tpy)(NN)(py)]2+ complexes (tpy = 2,2′:6′,2″-terpyridine; NN = bpy, 6,6′-dimethyl-2,2′-bipyridine (Me2bpy), 2,2′-biquinoline (biq)) increases by 2–3 orders of magnitude with the sterically bulky Me2bpy and biq ligands relative to bpy. Ultrafast transient absorption spectroscopy reveals population of the 3LF state within 3–7 ps when NN is bulky, and density functional theory calculations support stabilized 3LF states. Dual activity via ligand dissociation and 1O2 production can be achieved by careful selection of the ligand set to tune the excited-state dynamics. Incorporation of an extended π system in Ru(II) complexes such as [Ru(bpy)(dppn)(CH3CN)2]2+ (dppn = benzo[i]dipyrido[3,2-a:2′,3′-c]phenazine) and [Ru(tpy)(Me2dppn)(py)]2+ (Me2dppn = 3,6-dimethylbenzo[i]dipyrido[3,2-a:2′,3′-c]phenazine) introduces low-lying, long-lived dppn/Me2dppn 3ππ* excited states that generate 1O2. Similar to [Ru(bpy)2(CH3CN)2]2+, photodissociation of CH3CN occurs upon irradiation of [Ru(bpy)(dppn)(CH3CN)2]2+, although with lower efficiency because of the presence of the 3ππ* state. The steric bulk in [Ru(tpy)(Me2dppn)(py)]2+ is critical in facilitating the photoinduced py dissociation, as the analogous complex [Ru(tpy)(dppn)(py)]2+ produces 1O2 with near-unit efficiency. The ability to tune the relative energies of the excited states provides a means to design potentially more active drugs for photochemotherapy because the photorelease of drugs can be coupled to the therapeutic action of reactive oxygen species, effecting cell death via two different mechanisms. The lessons learned about tuning of the excited-state properties can be applied to the use of Ru(II)–polypyridyl compounds in a variety of applications, such as solar energy conversion, sensors and switches, and molecular machines.

Unusual Role of Excited State Mixing in the Enhancement of Photoinduced Ligand Exchange in Ru(II) Complexes

“…1–33 In contrast, the efficient photoinduced ligand dissociation for the release of drugs or biological probes with spatiotemporal control necessitates the population of the dissociative metal-centered, ligand field states ( 3 LF), known to lead to nonradiative deactivation of the emissive 3 MLCT state. 14,34–41 Therefore, understanding the interplay between the 3 MLCT and 3 LF states is important to improve the function of Ru(II) complexes, both when the long-lived 3 MLCT state is desired, as well as for cases where increased 3 LF population is required. 14,42 Therefore, the improvement of agents for this wide range of applications requires understanding of the molecular and electronic factors that result in 3 MLCT deactivation and ligand photodissociation through population of the 3 LF state(s).…”

Photo-induced cytotoxicity and anti-metastatic activity of ruthenium(ii)–polypyridyl complexes functionalized with tyrosine or tryptophan

“…22 On the other hand, Ru(II)-polypyridyl complexes are known to generate reactive oxygen species (ROS) up on irradiation into their MLCT band in the visible region of the spectrum. [23][24][25][26] As outlined above, such ROS species damage biomolecules and are therefore cytotoxic to living cells. [27][28][29] Since these two complexes are functionalized with amino acid moieties to enhance cellular internalization and possess well-defined photophysical/physicochemical properties, their capability to photo-induced damage to the DNA and function as cytotoxic agents was investigated.…”

“…41 Spheroids exhibit the phenomena of multicellular resistance (MCR), which is manifested in the diminished efficacy of chemotherapeutics similar to in-vivo activities. 42 Thus, to examine the cytotoxicity of these two photo-responsive Ru(II)-polypyridyl complexes towards such 3D tumors under more biologically relevant conditions, treatment efficacy was examined with 3D tumor model by generating tumor spheroids with A549 and Hct116 cells. Spheroids of ca.…”

Excited‐State Dynamics of a Two‐Photon‐Activatable Ruthenium Prodrug

“…Owing to the lack of early time data (<5 ps) for TPA, we are unable to elucidate critical ultrafast timescales that affect the evolution of the initially excited states and branching ratios. Certainly, we cannot fully rule out other deactivation pathways that compete with intersystem crossing of the 1 MLCT to 3 MLCT, for example, 1 MLCT→ 3 MC→GS 21. However, we can still compare the final GSB recovery of both OPA and TPA.…”