1. Ru(II) Dyads Derived from 2-(1-Pyrenyl)-1H-imidazo[4,5-f][1
Ru(II) Dyads Derived from 2-(1-Pyrenyl)-1H-imidazo[4,5-f][1.10]phenanthroline: Versatile Photosensitizers for Photodynamic Applications
Raymond Twumasi

2. Photosensitizers Therapeutic agents and diagnostic tools
Utilize light as an external trigger for temporal and spatial selectivity in various applications
PDT and PDI
Applications include photodynamic therapy (PDT) of cancer and age-related macular degeneration to photodynamic inactivation (PDI) of microorganisms.

3. Advantages Minimization of collateral damage
Localized and immediate burst of cytotoxic agents
Rapid cellular destruction
Less chance for resistance
Minimization of collageral damage to healthy tissue and off-shite toxicity
Key advantage PDT holds over traditional cancer chemotherapy
Less chance for the development of intrinsic or acquired resistance
Particularly important when considering prolonged treatment of the widespread use of targeted antibiotics
Periodontology , 55,

4. Disadvantages Tendency to photobleach Poor aqueous solubility
Prolonged retention in tissues
Organic-porphyrin based systems employ triplet excited states to photogenerate cytotoxic singlet oxygen and other ROS upon light activation
Dalton Trans. 2009, – 10701

5. Organic PSs vs Metal Complexes
Capable of photochemistry with wider breadth of wavelengths of light
Metal complexes have a variety of excited state configuration
MLCT, MC, LC, IL, ILCT, MMCT
Combinations
Low-lying 3IL excited states
Metal complexes have a variety of excited state configurations that can easily be accessed through rational changes to their scaffolds.
Wavelengths of light ranging from UV to near-IR
Low-lying 3IL excited states with slow kinetics are of immense interest because they can prolong the lifetimes of Ru(II) coordination complexes
Does this through equilibrium with MLCT states or by acting as distinct states.
Isr. J. Chem. 2013, 53, 391 – 400

6. Other work in field Wrighton and coworkers:
Organic chromophores + metal complexes = extend excited state lifetimes
Ford & Rogers applied this concept to Ru(II) complexes
Lifetimes above 150 µs have been reported for pure 3IL states.
Wrighton and coworkers demonstrated in the 70s that organic chromophores could be tethered to metal complexes to extend their excited state lifetimes 5-8..
Ford & Rogers later applied this concept to Ru(II) complexes 9.
In order to lengthen their typical 1 µs lifetimes 100-fold

7. Previous work 3IL states with lifetimes as long as 240 µs (from 22 µs)
5-(puren-1-ylethynyl)-1,10-phenantholine (5-EPP)
They did this by changing the attachment point between the pyrenyethnyl group and the coordinating [1,10]-phenanthroline (phen) ligand in complexes of the type [Ru(LL)2(EPP)]2+ or the number of EPP ligands
All structural isomers gave very potent PDT effect in cancer cells.
Potency derives from ligands that impart low-lying 3IL states and long excited state lifetimes.
JACS. 2013, 135, – 17175

8. Problem
Blue/green-absorbing PSs can be activated despite no absorption of light at these wavelengths
PSs can be activated in the PDT window despite no absorption of light at these wavelengths, which underscores the efficiency of such highly photosensitizing excited states.
Problem holds for both contiguously fused π–systems and true tethered dyads, where π–expansive organic chromophore is attached to a coordinating ligand such as bpy of phen.
Inorg. Chem. 2014, 53, 4548 – 4559

9. Purpose: outline photophysical properties and photodynamic potency of another type of metal-organic dyad with a low-lying 3IL state.
Goal: To expand the repertoire of Ru (II) complexes that exhibit unusual potency due to low-lying 3IL excited states

10. Compound 1 = previously studied in the context of remarkable luminescent oxygen sensing
Compound 2 = DNA affinity and photocleavage
J. Phys. Chem. A 2014, 118, – 10521

11. Results – UV Vis
Bpy or phen LC (or IL) transitions (1LC π to π* - based on extinction coefficients)
Ippy LC or pyrene-based transitions (1LC π to π*)
Typical MLCT transitions – metal with ippy ligand (1MLCT dπ to ippy π*)
J. Phys. Chem. A 2014, 118, – 10521

12. Results – Resonance Raman
Recorded at 458, 476, 488 nm
In order to confirm MLCT transition involved ippy
All spectra were normalized to the intensity of bpy band at 1490 cm-1
Bands associated with the vibrational modes of ippy ligand are highlighted
As longer excitation wavelengths were employed, the contribution of the ippy-related vibrational modes to the RR spectra increased, as expected if the lowest-energy MLCT transition was Ru (dπ) to ippy (π*)
J. Phys. Chem. A 2014, 118, – 10521

13. Compounds 1-4 were weakly emissive
Compound 2 was most red-shifted and compound 1 was least
Emission resolved into two components τ1 and τ2
Measured using stroboscopic detection
Measured using a gated detector and constrained in the fit of the stroboscopic biexponential decay (done for precise determination of τ2)
Contribution of τ2 is minor.

14. Electronic absorption signatures
Dyads are weakly coupled systems with distinct chromophores
3MLCT state can exist in equilibrium with 3IL state of ippy
Decay via a double exponential process
Decay should be linear combination of deactivation rates for both states
2 possible reasons:
luminescence from both states or
luminescence from single state in which τ1 represents pre-equilibrium relaxation and τ2 involves decay from equilibrated mixture
Gated emission measurements couldn’t isolate τ2. Could only find monoexponential decay (between 5 and 10 µs) suggesting the second reason
1MLCT
3MLCT
3IL
1Ground state

15. Emission decay kinetics
Biexponential decay kinetics also observed in water
τ2 plays more important role in excited state quenching by O2
High O2 quantum yields attributed to 3IL
Potent photobiological agents for PDT

16. Absorption titration - DNA binding
Binding constant (Kb):
nonintercalating metal complex [Ru(phen)3]2+ is 1.65 x 104 M-1
intercalating complex [Ru(phen)2dppz]2+ is >10 M-1
Increasing Steric bulk = increasing DNA affinity

17. Photodynamic Activity
Nanomolar light toxicities and PIs > 100
Highly photosensitizing excited states
Such potency typical for low-lying 3IL states or 3IL-3MLCT equilibrium mixtures
Prolonged lifetimes are particularly attractive features because they make complexes particularly sensitive to quenching by molecular oxygen. Very good for retaining activity in cancer cells

18. Conclusion
Ru(II) dyads containing ippy can be used to achieve highly photosensitizing states
Common factor among dyads is low-lying, long-lived 3IL state
High light cytotoxicity against both cancer and bacteria cells
Dark toxicities influenced by ancillary ligands
Would’ve liked to see PSs that could be used for multiwavelength PDT which may be useful in specialized application (future)

19. Questions?