Insights into bovine serum albumin (BSA) photooxidation mediated by mono-cationic porphyrins with Pd(II), Pt(II), and Ru(II) bipyridyl complexes

Abstract

Porphyrins are well-established photosensitizers for photodynamic therapy (PDT), and mono-cationic derivatives often display enhanced interactions with biological targets; however, their interactions with albumins remain insufficiently understood. In this study, we investigated the interaction between bovine serum albumin (BSA) and the photooxidative behavior (halogen-lamp irradiation) of a mono-cationic free-base porphyrin (H₂MPyP) and its Pd(II), Pt(II), and Ru(II) complexes, alongside comprehensive electrochemical, photophysical, and protein-binding characterizations. Compared with tetra-cationic analogues, the mono-cationic porphyrins were more efficient at 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 photooxidation, with the overall efficiency following PtMPyP > PdMPyP > H₂MPyP > RuMPyP; notably, PtMPyP displayed the highest photodegradation rate constant (kpd = 0.286 min−1). Molecular docking located all porphyrins at site III (IB subdomain), stabilized by hydrophobic and π–cation interactions. No single descriptor (ΦΔ, lipophilicity, or affinity) alone accounted for reactivity, supporting an “exposure–affinity window”: productive protein photooxidation requires sufficient binding for colocalization with BSA but adequate exposure to O₂ near oxidizable residues. These findings show that metal coordination fine-tunes both excited-state deactivation and protein oxidation, offering actionable guidelines for designing next-generation PDT photosensitizers with improved efficiency and selectivity.