Synergistic Effects in PtII–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-PtII -porphyrin conjugates have been proposed as promising multitarget agents. To reveal the effect of the PtII center on the chemical and physical properties of the PS and to explore the effect of the PS on the activation mechanism of PtII ligand before reaching its biological target, we carried out a first-principle investigation on these tetra-PtII -porphyrin conjugates. To propose a further advance in this novel field and to gain useful insights for the design of new, more efficient PtII -PS conjugates, we introduced structural modifications into the porphyrin dye, which involved the synthesis of the tetra-PtII -chlorin and tetra-PtII -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 PtII moiety, the latter being a desirable feature to avoid many side reactions of the conjugate during their transport to the biological target.