Synergistic Effects in Pt II -Porphyrinoid Dyes as Candidates for a Dual-Action Anticancer Therapy: A Theoretical Exploration.

The combination of a photosensitizer (PS) with a cisplatin-like unit represents a challenging strategy to increase the effectiveness of photodynamic therapy and to afford a dual-action anticancer treatment. Recently, new tetra-Pt-II-porphyrin conjugates have been proposed as promising multitarget agents. To reveal the effect of the Pt-II center on the chemical and physical properties of the PS and to explore the effect of the PS on the activation mechanism of Pt-II ligand before reaching its biological target, we carried out a first-principle investigation on these tetra-Pt-II-porphyrin conjugates. To propose a further advance in this novel field and to gain useful insights for the design of new, more efficient Pt-II-PS conjugates, we introduced structural modifications into the porphyrin dye, which involved the synthesis of the tetra-Pt-II-chlorin and tetra-Pt-II-bacteriochlorin derivatives. Results showed that the designed dyes better met the criteria to be successful in a dual-action therapy, as they displayed improved optical properties and reduced the hydrolysis rate of the Pt-II moiety, the latter being a desirable feature to avoid many side reactions of the conjugate during their transport to the biological target.