Engineering of relevant photodynamic processes through structural modifications of metallotetrapyrrolic photosensitizers

Applications of metalloporphyrins and related molecules have been extensively pursued in the context of photodynamic therapy of cancer (PDT) and other biomedical applications. This review discusses photophysical and photochemical properties of metalloporphyrins and their analogues, such as metallochlorins, metallobacteriochlorins and metallophthalocyanines that are relevant for photodynamic processes. We specially emphasize the search for sensitizers strongly absorbing in phototherapeutic window (650–850 nm), the most penetrating and least harmful radiation to human tissues. Molecular engineering is guided by the understanding of the influence of the central metal ion and substituents on the electronic structure and photophysical properties of these compounds. The effects of the structural modifications are elucidated via studies of the electronic absorption and emission spectra, fluorescence and triplet state lifetimes and quantum yields, as well as quantum yields of singlet oxygen generation. The interaction between electronically excited (metallo)porphyrin derivatives and molecular oxygen is specially highlighted, because it leads to the generation of reactive oxygen species (ROS), the major players in photomedicine and photocatalysis. The parameters analysed and correlated encompass photophysical and electrochemical properties, cellular uptake and localization of the photosensitizer, as well as the mechanism of photodynamically induced cell death. The factors that determine the efficacy of PDT (drug and light doses, drug to light interval, oxygen concentration and tumour margin) are also emphasized. This review explores the most recent research performed on metalloporphyrin-based materials in photodynamic therapy, photodynamic inactivation of microorganisms, photodiagnosis and drug delivery, demonstrating their perspectives for biomedical applications.