TY - JOUR
T1 - In vitro heavy-atom effect of palladium(II) and platinum(II) complexes of pyrrolidine-fused chlorin in photodynamic therapy
AU - Obata, Makoto
AU - Hirohara, Shiho
AU - Tanaka, Rika
AU - Kinoshita, Isamu
AU - Ohkubo, Kei
AU - Fukuzumi, Shunichi
AU - Tanihara, Masao
AU - Yano, Shigenobu
PY - 2009/5/14
Y1 - 2009/5/14
N2 - Introduction of a heavy atom into photosensitizers generally facilitates intersystem crossing and improves the quantum yield (ΦΔ) of singlet oxygen (1O2), 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 ΦΔ values increased in the order of 4a (0.28) < 4b (0.89) < 4c (0.92) in C6D6. The photocytotoxicity of 4a, 4b, and 4c was evaluated in HeLa cells at a light dose of 16 J·cm-2 with λ > 500 nm and increased in the order of 4a < 4b < 4c at the concentration of 0.5 μM. The photocytotoxicity of 4b and 4c was significantly inhibited by addition of sodium azide, but not D-mannitol, suggesting that 1O 2 is the major species causing cell death. Our results clearly indicate that 4b and 4c act as efficient 1O2 generators due to the heavy-atom effect in a cellular microenvironment as well as in nonphysiological media.
AB - Introduction of a heavy atom into photosensitizers generally facilitates intersystem crossing and improves the quantum yield (ΦΔ) of singlet oxygen (1O2), 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 ΦΔ values increased in the order of 4a (0.28) < 4b (0.89) < 4c (0.92) in C6D6. The photocytotoxicity of 4a, 4b, and 4c was evaluated in HeLa cells at a light dose of 16 J·cm-2 with λ > 500 nm and increased in the order of 4a < 4b < 4c at the concentration of 0.5 μM. The photocytotoxicity of 4b and 4c was significantly inhibited by addition of sodium azide, but not D-mannitol, suggesting that 1O 2 is the major species causing cell death. Our results clearly indicate that 4b and 4c act as efficient 1O2 generators due to the heavy-atom effect in a cellular microenvironment as well as in nonphysiological media.
UR - http://www.scopus.com/inward/record.url?scp=65649091683&partnerID=8YFLogxK
U2 - 10.1021/jm8015427
DO - 10.1021/jm8015427
M3 - Article
C2 - 19378972
AN - SCOPUS:65649091683
SN - 0022-2623
VL - 52
SP - 2747
EP - 2753
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
IS - 9
ER -