Propriedades fotofísicas de porfirinas monocatiônicas de Pd(II), Pt(II) e Ru(II) e sua interação com a albumina sérica bovina

Abstract

Porphyrins are stable tetrapyrrole macrocycles with strong absorption in the visible region and high singlet oxygen generation efficiency, well established as photosensitizing agents in Photodynamic Therapy (PDT). Their monocationic derivatives often exhibit interactions with biological targets, although their interactions with albumins are not yet fully understood. In this work, a complete photophysical characterization of a set of monocationic porphyrins (H₂MPyP) and their Pd(II), Pt(II), and Ru(II) complexes was performed. For this purpose, spectroscopic techniques such as UV-vis, Laser Flash Photolysis, and fluorescence and phosphorescence emission were employed, from which parameters such as molar absorption coefficient, quantum yields of triplet state formation, fluorescence, and singlet oxygen were obtained. Furthermore, their interactions with bovine serum albumin (BSA) were investigated, including binding constant and its photo-oxidation under irradiation with a halogen lamp. Compared to tetracationic analogs, the monocationic porphyrins were more efficient in populating the triplet state and generating singlet oxygen. Among them, H₂MPyP, PdMPyP, and PtMPyP exhibited high triplet quantum yields (ΦT ≈ 0.85), with H₂MPyP showing the highest singlet oxygen yield (ΦΔ = 0.70). All compounds promoted BSA photo-oxidation, with the overall efficiency following the order PtMPyP > PdMPyP > H₂MPyP > RuMPyP; notably, PtMPyP exhibited the highest photodegradation rate constant (kpd = 0.286 min⁻¹). Molecular docking localized all porphyrins in site III (subdomain IB), stabilized by hydrophobic and π–cation interactions. No single descriptor (ΦΔ, lipophilicity, or affinity) alone explained the reactivity, supporting the concept of an "exposure–affinity window": effective protein photo-oxidation requires sufficient binding for colocalization with BSA, but also adequate exposure to O₂ near oxidizable residues. These findings demonstrate that metal coordination finely tunes both excited state deactivation and protein oxidation, offering practical guidelines for designing next-generation PDT photosensitizers with enhanced efficiency and selectivity.