In Vitro Heavy-Atom Effect of Palladium(II) and Platinum(II) Complexes of Pyrrolidine-Fused Chlorin in Photodynamic Therapy

Abstract

Introduction of a heavy atom into photosensitizers generally facilitates intersystem crossing and improves the quantum yield (Phi(Delta)) of singlet oxygen ((1)O(2)), which is a key species in photodynamic therapy (PDT). However, little information is available about the physiological importance of this heavy-atom effect. The aim of this study is to examine the heavy-atom effect in simple metallochlorins in vitro at the cellular level. 1,3-Dipolar cycloaddition of azomethine ylide to 5,10,15,20-tetrakis(pentafluorophenyl)porphyrinato palladium(II) and platinum(II) afforded metallochlorins 4b and 4c in yields of 17.1 and 12.9%, respectively. The Phi(Delta) values increased in the order of 4a (0.28) < 4b (0.89) < 4c (0.92) in C(6)D(6). The photocytotoxicity of 4a, 4b, and 4c was evaluated in HeLa cells at a light dose of 16 J x cm(-2) with lambda > 500 nm and increased in the order of 4a < 4b < 4c at the concentration of 0.5 microM. The photocytotoxicity of 4b and 4c was significantly inhibited by addition of sodium azide, but not D-mannitol, suggesting that (1)O(2) is the major species causing cell death. Our results clearly indicate that 4b and 4c act as efficient (1)O(2) generators due to the heavy-atom effect in a cellular microenvironment as well as in nonphysiological media.

Theoretical investigation on quinoline-based platinum (II) complexes as efficient singlet oxygen photosensitizers in photodynamic therapy

“…These studies show that the reasons of Pt(II) mix-ligand complexes as efficient photosensitizers are that platinum atom facilitates intersystem crossing and improves the triplets yields and MLCT transition, and platinum(II) (d 8 ) always adopts to square planar coordination which enhances the rigidity of molecular structure and significantly decreases the nonradiation decay. Recently, Obata and co-workers have found that Pt (II) complexes with porphyrin-based ligands have higher singlet oxygen yields and bigger photocytotoxicity than porphyrin ligands [14]. Shavaleev et al also found that platinum (II) complexes with quinoline-based ligands can efficiently produce singlet oxygen [15].…”

Synthesis and photophysical studies of self-assembled multicomponent supramolecular coordination prisms bearing porphyrin faces

“…Porphyrins possess characteristic structural and photophysical properties that make them well suited for adaptation into artificial designs, not only for solar energy conversion but also for applications in photodynamic therapy (24)(25)(26)(27)(28)(29), enzyme mimics (30)(31)(32), catalysis (33)(34)(35)(36)(37), and molecular electronic devices (38,39). In the context of solar energy, many multiporphyrin light-harvesting designs have been developed ranging from organic polymers, metalorganic frameworks, and supramolecular ensembles.…”

Metal-based glycoconjugates and their potential in targeted anticancer chemotherapy

“…In particular, S-glycoconjugated porphyrin and pyrrolidinefused chlorin coordinated to the metal center (Pd-4 and Pd-5, respectively) were designed on purpose to combine the phototoxicity of the palladium(II)-based photosensitizer with an increased cellular uptake into tumor cells provided by the glucose-like moieties [96]. Interestingly, glucose functionalization proved effective to enhance cellular uptake (up to 4-fold higher than non-glycosylated analogues).…”