Light exploitation as a source of selectivity in anticancer therapies is gaining interest in the last years.[1] The use of biocompatible wavelengths requires the administration of photoactive chromophores that must be distributed into cancerous cells in sufficient concentration to trigger clinically relevant photodamage upon irradiation of the ill area. Therefore, efficient photophysical and photochemical processes are a prerequisite for new photosensitizers to be candidates for clinical development. Traditionally, light-induced biological damage is exerted through the classical O2 mediated type I and/or type II photodynamic therapy (PDT) photoreactions. However, the physiological conditions of solid tumours often imply low levels of molecular dioxygen, limiting the outcome of the already clinically approved drugs.[1]
The present talk will describe recent approaches to circumvent the hypoxia problem from a multidisciplinary perspective, emphasising however the contributions of computational chemistry in the elucidation of the molecular mechanisms behind the photodamage. The photoprocesses that will be considered are mediated by molecules based on heavy transition metals[2,3] and by some metal-free chromophores[4,5] for instance by releasing nitric oxide (NO) upon excitation.[4] I will show recent results on how these non-canonical photosensitizers respond upon light absorption, and how this information reveals the photochemical mechanisms responsible of the biological damage.