<i>In Vitro</i> Multiwavelength PDT with ³IL States: Teaching Old Molecules New Tricks

The purpose of the present investigation was to ascertain whether ³IL excited states with microsecond lifetimes are universally potent for photodynamic applications, and if these long-lived states are superior to their ³MLCT counterparts as <i>in vitro</i> PDT agents. A family of blue-green absorbing, Ru­(II)-based transition metal complexes derived from the π-expansive dppn ligand was prepared and characterized according to its photodynamic activity against HL-60 cells, and toward DNA in cell-free media. Complexes in this series that are characterized by low-energy and long-lived ³IL excited states photocleaved DNA with blue, green, red, and near-IR light. This panchromatic photodynamic effect translated to <i>in vitro</i> multiwavelength photodynamic therapy (PDT) with red-light cytotoxicities as low as 1.5 μM (EC₅₀) for the parent complex and 400 nM for its more lipophilic counterpart. This potency is similar to that achieved with Ru­(II)-based dyads containing long-lived ³IL excitons located on appended pyrenyl units, and appears to be a general property of sufficiently long-lived excited states. Moreover, the red PDT observed for certain members of this family was almost 5 times more potent than Photofrin with therapeutic indices 30 times greater. Related Ru­(II) complexes having lowest-lying ³MLCT states of much shorter duration (≤1 μs) did not yield DNA photodamage or <i>in vitro</i> PDT with red or near-IR light, nor did the corresponding Os­(II) complex with a submicrosecond ³IL excited state lifetime. Therefore, metal complexes that utilize highly photosensitizing ³IL excited states, with suitably long lifetimes (≫ 1 μs), are well-poised to elicit PDT at wavelengths even where their molar extinction coefficients are very low (<100 M^–1 cm^–1). Herein we demonstrate that such unexpected reactivity gives rise to very effective PDT in the typical therapeutic window (600–850 nm)

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