Session: Heterocycles & Aromatics:

Photodynamic therapy (PDT) is a developing non-invasive targeted therapy which involves systemic or topical administration of a photosensitizer (PS), which after irradiation of a specific wavelength of light reacts with the coexisting molecular oxygen. As a result, highly reactive singlet oxygen (¹O₂) and other reactive oxygen species (ROS) can be formed leading to specific apoptotic or necrotic cell death of the cancer cells.

In this study we aim to develop novel non-toxic PSs, i.e., chlorins which bear a gem-dimethyl group, attributing to their resistance to oxidation. These compounds have potential use as anticancer or antimicrobial agents and their photophysical properties are described herein.

Synthesis was performed following a method reported by Lindsey and co-workers. A complete characterization of their spectral and photophysical properties (Φ_f, Φ_isc, Φ_ic, Φ_Δ, τ_S, τ_T, k_f, k_ic, k_isc, k_q) is accompanied by density functional calculations (DFT) and time dependent (TD) DFT to investigate the features of the frontier molecular orbitals. The metallochlorins exhibit high triplet state yields (Φ_isc = 0.80 – 0.90) and excellent singlet oxygen quantum yields in methanol and ethanol (Φ_Δ = 0.60 – 0.85) and the free base analogues exhibited suitable triplet state yields (Φ_isc = 0.70 – 0.80) and singlet oxygen quantum yields (Φ_Δ = 0.40 – 0.70). Results show that the chlorins can be potential PS candidates for PDT, given that they display high singlet oxygen quantum yields in polar solvents, modest fluorescence quantum yields (Φ_f = 0.03 – 0.14) and moderate triplet state lifetimes (τ_T= 150 – 220 ns) upon photoexcitation.

Future work includes the optimization of the photophysical properties of the chlorins (red-shifted absorption, high triplet state yields, long triplet lifetimes and high singlet oxygen quantum yields) and enhancing the water solubility through modification of the periphery with a variety of substituents. Additionally, in vitro evaluation will be employed in future.

René Williams

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