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 (Φf, Φisc, Φic, ΦΔ, τS, τT, kf, kic, kisc, kq) 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 (Φisc = 0.80 – 0.90) and excellent singlet oxygen quantum yields in methanol and ethanol (ΦΔ = 0.60 – 0.85) and the free base analogues exhibited suitable triplet state yields (Φisc = 0.70 – 0.80) and singlet oxygen quantum yields (ΦΔ = 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 (Φf = 0.03 – 0.14) and moderate triplet state lifetimes (τT = 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.

Synthesis and spectral properties of gem-dimethyl chlorin photosensitizers

ACS Spring Meeting 2021

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