Photophysical characterisation and studies of the effect of palladium(Ⅱ) 5,10,15,20-tetrakis-(4-sulfonatophenyl)-porphyrin on isometric contraction of isolated human mesenteric artery: Good news for photodynamic therapy

摘要

Background: Considering the important roles of porphyrins in biological systems and their promising use in photodynamic therapy (PDT), the present work investigated the photophysical properties of palladium(Ⅱ) 5,10,15,20-tetrakis-(4-sulfonatophenyl)-porphyrin (PdTSPP) and the effects of non-activated by light form of this porphyrin on contractile behaviour of isolated healthy endothelium-denuded human mesenteric arteries. Methods: The photophysical characterisation of PdTSPP: the formation of the triplet states and the singlet oxygen were studied using laser flash photolysis. The effect of PdTSPP on the isometric contraction of artery segments from human mesentery was assessed utilising the precise method of artery isometric tension recording using Mulvany-Halpern wire myograph. Results: We found that PdTSPP had a high lifetime of the triplet states τ_T = 270 μs. The calculated Stern Volmer rate constant k_q = 1.7 × 10~9M~(-1) s~(-1) showed an efficient quenching by oxygen that indicated formation of singlet oxygen, O_2(~1Δ_g). The photophysical parameters of PdTSPP, in particular its ability to generate O_2(~1Δ_g) has defined it as an exceptionally interesting molecule for PDT. The results of the contraction study showed that PdTSPP applied in increasing concentrations (1-100 μM) had no effect on the basal tone of human mesenteric artery under isometric condition. Furthermore, PdTSPP failed to potentiate or to attenuate the isometric contraction of the artery preparations precontracted with high extracellular potassium (42 mM KCl) or with 1 nM endothelin-1. Conclusions: The excellent photophysical properties of PdTSPP as well as the lack of an effect on the contractility of human vasculature in vitro characterise PdTSPP as a suitable compound for potential medical applications.