Pyrrole-based photosensitisers for photomedicine

Photodynamic therapy (PDT) is a light activated therapy which involves the administration of a drug-photosensitiser (PS), the application of light, and molecular oxygen. The therapeutic effect is associated with the ability of the PS to generate its triplet excited state configuration upon excitation. This state can react with the coexisting molecular oxygen and trigger the production of highly reactive singlet oxygen (¹O_²) and other reactive oxygen species (ROS).
In this thesis, the development of novel pyrrole-based PSs was envisioned. First, chlorins which bear a gem-dimethyl group were synthesised and their photophysical and photobiological properties were investigated. The results showed that the chlorins can be potential PS candidates for PDT, given that they display very good phototoxicity against the colon carcinoma cell line, high singlet oxygen quantum yields, modest fluorescence quantum yields and moderate triplet state lifetimes upon photoexcitation. Second, one of the zinc(II) chlorins was used for the development of novel porphyrin-chlorin 1,4-phenylene linked arrays. Their excited state properties, their singlet oxygen generation and the in vitro studies shed light on the processes occurring upon photoexcitation. Third, a library of novel tris(dipyrrinato)aluminium(III) complexes was developed. These chelates show excitonic states (Davydov splitting) in their absorption spectra and are weakly fluorescent emitters. They displayed short-lived singlet excited states, accompanied by long-lived triplet excited states, and they generate singlet oxygen upon irradiation in moderate yields. The in vitro phototoxicity studies deemed half of the complexes as promising PDT agents since they exhibited great phototoxicity at low and safe concentrations. Time-dependent density functional theory calculations and single-crystal X-ray analysis are provided.