Organometallic Ru(II) Photosensitizers Derived from π‑Expansive Cyclometalating Ligands: Surprising Theranostic PDT Effects

The purpose of the present study was to investigate the influence of π-expansive cyclometalating ligands on the photophysical and photobiological properties of organometallic Ru­(II) compounds. Four compounds with increasing π conjugation on the cyclometalating ligand were prepared, and their structures were confirmed by HPLC, 1D and 2D ¹H NMR, and mass spectrometry. The properties of these compounds differed substantially from their Ru­(II) polypyridyl counterparts. Namely, they were characterized by red-shifted absorption, very weak to no room temperature phosphorescence, extremely short phosphorescence state lifetimes (<10 ns), low singlet oxygen quantum yields (0.5–8%), and efficient ligand-centered fluorescence. Three of the metal complexes were very cytotoxic to cancer cells in the dark (EC₅₀ values = 1–2 μM), in agreement with what has traditionally been observed for Ru­(II) compounds derived from small C^N ligands. Surprisingly, the complex derived from the most π-expansive cyclometalating ligand exhibited no cytotoxicity in the dark (EC₅₀ > 300 μM) but was phototoxic to cells in the nanomolar regime. Exceptionally large phototherapeutic margins, exceeding 3 orders of magnitude in some cases, were accompanied by bright ligand-centered intracellular fluorescence in cancer cells. Thus, Ru­(II) organometallic systems derived from π-expansive cyclometalating ligands, such 4,9,16-triazadibenzo­[<i>a,c</i>]­napthacene (pbpn), represent the first class of potent light-responsive Ru­(II) cyclometalating agents with theranostic potential

Photophysics of Ru(II) Dyads Derived from Pyrenyl-Substitued Imidazo[4,5‑<i>f</i>][1,10]phenanthroline Ligands

The photophysics of a series of Ru­(II) dyads based on the 2-(1-pyrenyl)-1<i>H</i>-imidazo­[4,5-<i>f</i>]­[1,10]-phenanthroline ligand was investigated. The ability of these metal complexes to intercalate DNA and induce cell death upon photoactivation makes them attractive photosensitizers for a range of photobiological applications, including photodynamic therapy. In the present study, time-resolved transient absorption and emission spectroscopy were used to interrogate the photoinduced processes that follow metal-to-ligand charge transfer excitation of the complexes in solution. It was found that energy transfer to pyrene-localized intraligand triplet states, facilitated by torsional motion of the pyrene moiety relative to the imidazo­[4,5-<i>f</i>]­[1,10]­phenanthroline ligand, was an important relaxation pathway governing the photophysical dynamics in this class of compounds. Biphasic decay kinetics were assigned to spontaneous (pre-equilibrium) and delayed emission, arising from an equilibrium established between ³MLCT and ³IL states. TDDFT calculations supported these interpretations

Ru(II) Dyads Derived from 2‑(1-Pyrenyl)‑1<i>H</i>‑imidazo[4,5‑<i>f</i>][1,10]phenanthroline: Versatile Photosensitizers for Photodynamic Applications

Combining the best attributes of organic photosensitizers with those of coordination complexes is an elegant way to achieve prolonged excited state lifetimes in Ru­(II) dyads. Not only do their reduced radiative and nonradiative rates provide ample time for photosensitization of reactive oxygen species at low oxygen tension but they also harness the unique properties of ³IL states that can act as discrete units or in concert with ³MLCT states. The imidazo­[4,5-<i>f</i>]­[1,10]­phenanthroline framework provides a convenient tether for linking π-expansive ligands such as pyrene to a Ru­(II) scaffold, and the stabilizing coligands can fine-tune the chemical and biological properties of these bichromophoric systems. The resulting dyads described in this study exhibited nanomolar light cytotoxicities against cancer cells with photocytotoxicity indices exceeding 400 for some coligands employed. This potency extended to bacteria, where concentrations as low as 10 nM destroyed 75% of a bacterial population. Notably, these dyads remained extremely active against biofilm with light photocytotoxicities against these more resistant bacterial populations in the 10–100 nM regime. The results from this study demonstrate the versatility of these highly potent photosensitizers in destroying both cancer and bacterial cells and expand the scope of compounds that utilize low-lying ³IL states for photobiological applications