Tuning the Photophysical Properties of Ru(II) Photosensitizers for PDT by Protonation and Metallation: A DFT Study

Due to their activity, photosensitizers with the Ru(II)–polypyridyl complex structure represent an intriguing class of photodynamic therapy agents used to treat neoplasms. However, their solubility is poor, intensifying experimental research into improving this property. One recently proposed solution is to attach a polyamine macrocycle ring. In this paper, the density functional theory (DFT) and time-dependent DFT (TD-DFT) studies on such derivative were performed to assess the impact of the protonation-capable macrocycle and its ability to chelate transition state metals, as illustrated by the Cu(II) ion, on the expected photophysical activity. These properties were determined by examining ultraviolet–visible (UV–vis) spectra, intersystem conversion, and type I and II photoreactions of all species possibly present in a tumor cell. For comparison purposes the structure devoid of the macrocycle was also examined. The results show that the subsequent protonation of amine groups improves the reactivity, with [H₂L]⁴⁺/[H₃L]⁵⁺ being borderline, whereas complexation appears to weaken the desired photoactivity.