Ru(II)-perylenediimide complexes for activation of singlet oxygen: photodynamic therapy and cellular imaging for treatment of Melanoma Cancer

• Grant number: 18/03424-0
• Support type: Scholarships in Brazil - Doctorate
• Effective date (Start): August 01, 2018
• Effective date (End): July 31, 2021
• Field of knowledge: Physical Sciences and Mathematics - Chemistry
• Principal Investigator: Rose Maria Carlos
• Grantee: Isabele Aparecida Soares de Campos
• Home Institution: Centro de Ciências Exatas e de Tecnologia (CCET). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil
• Associated research grant: 14/50918-7 - INCT 2014: for the Biorational Control of Pest-Insect and Phytopathogens, AP.TEM

Abstract

We have recently prepared the [Ru(phen)2(pPDIp)]2+ complex which is capable to mimic key features of the photosynthetic center (cumulative absorption of photons to separate charges by electron transfer) to promote challenging chemical. The interplay between the two chromophores Ru(II)-pPDIp coordination and p-p stacking of the pPDIp arrays in the dyad is markedly influenced by the medium that affects the photochemical and photophysical processes. A direct consequence of this effect is that we can use solvent and irradiation wavelength to tune the excited state energy and, consequently, select the desired product. For example, in DMSO, the photolysis produces the radical anion of the pPDIp*- whereas in RPMI solution both the pPDIp*- and dianion pPDIp2- moieties are produced. In contrast, in buffer solution (pH 7.4) and immobilized in films the 3*pPDIp is reached, which sensitizes the activation of singlet oxygen through an energy transfer process with molecular oxygen in the ground state. We explored the potential application of this complex in PDT in vitro experiments using the B16F10-Nex2 murine Melanoma cells. Neither significant effects on cell viability nor apparent changes in the morphology of cells were observed in the dark. However, under green LED illumination (dose = 0.41 J.cm-2) the complex exhibits strong photocytotoxic effect, displaying IC50 values of 1.2 mmolL-1. These findings have encouraged us to design a new dyad by introduction of electro-donating groups in the bay region of perylenediimide showing higher spectral absorption in the visible region that decays efficiently to produce the triplet state of perylene. This novel compounds opened the possibility to achieve high efficiency to activate oxygen singlet from the triplet of perylene, which prompt us to investigate photosentized oxygen reactions that lead to in vitro suppression of cancer cells. Moreover, to achieve an easy removal of the sensitizer after the photodynamic action, we plan to immobilize the optimized photosensitizers proposed in this work in polymeric films. Additionally, since the precise mechanism by which the [Ru(phen)2(pPDIp)]2+ complex promotes singlet oxygen activation and reduction of the pPDIp moiety by one and/or two electron has not been investigated we intend to carry out a detailed investigation of the geometries and electronic structures of the excited energy states of lesser energy triplet spin for the complexes using (fs- and ps-) time resolved techniques. (AU)