Estudos computacionais sobre substâncias fotoativas: de aplicações fotodinâmicas a fototérmicas

Abstract

The study and development of photoactive substances for application in photodynamic and photothermal therapy are essential for advancing alternative cancer treatments. Computational calculations play a fundamental role in investigating the photophysical properties of these substances, significantly contributing to the evaluation of their applicability in phototherapies. This work is divided into two chapters. The first chapter is dedicated to the description of a novel substance, a candidate photosensitizer for photothermal therapy. The photophysical properties of the TB-TDPP compound, derived from 2,5-Dihydropyrrolo[3,4]pyrrole-1,4-dione (TDPP) and toluidine blue (TB), were investigated, and the results indicated favorable characteristics for its application as a photothermal agent. To assess the influence of structural modifications on its properties, an dimethylamino group was inserted into the thiophene ring of TB-TDPP. This modification resulted in a bathochromic shift in the maximum absorption wavelength, which is desirable for photosensitizers to act in deeper tissue regions. The second chapter presents the study of the photophysical properties of resveratrol, a natural substance found in fruits and peanuts, widely known for its antioxidant properties. Non-adiabatic molecular dynamics simulations indicated that, after excitation, trans-resveratrol, its most stable isomer, may undergo photoisomerization to the cis conformation or cyclization. After studying the deactivation pathways of resveratrol, the singlet oxygen generation capacity of both the cis and trans isomers of resveratrol, as well as other photoproducts described in the literature, 2,4,6-trihydroxy-phenanthrene (THP) and resveratrone, was evaluated. The intersystem crossing and fluorescence rates of these substances were calculated. The results showed that transand cis-resveratrol do not exhibit photophysical characteristics indicative of direct singlet oxygen generation. However, the photoproducts THP and resveratrone presented intersystem crossing rates competitive with their respective fluorescence rates when excited at the same wavelength as the precursor. It was also verified that singlet oxygen formation is thermodynamically favorable for these two photoproducts. As experimental results demonstrate a higher yield of THP formation compared to resveratrone upon resveratrol excitation under identical conditions, THP may be the primary species responsible for singlet oxygen generation. Additional studies are underway to investigate the occurrence of competing processes. Thus, this study suggests a potential new application of resveratrol in photodynamic therapy, expanding its possible uses.