In vitro heavy-atom effect of palladium(II) and platinum(II) complexes of pyrrolidine-fused chlorin in photodynamic therapy.
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.
Obata
Makoto
M
Graduate School of Humanities and Sciences, Nara Women's University, Kitauoyanishimachi, Nara 630-8506, Japan. mobata@cc.nara-wu.ac.jp
Hirohara
Shiho
S
Tanaka
Rika
R
Kinoshita
Isamu
I
Ohkubo
Kei
K
Fukuzumi
Shunichi
S
Tanihara
Masao
M
Yano
Shigenobu
S
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D018360:Crystallography, X-Ray; D003624:Darkness; D006367:HeLa Cells; D006801:Humans; D009942:Organometallic Compounds / Q000737:chemistry* / Q000494:pharmacology*; D010165:Palladium / Q000737:chemistry*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry / Q000494:pharmacology; D010984:Platinum / Q000737:chemistry*; D011166:Porphyrins / Q000737:chemistry*; D011759:Pyrrolidines / Q000737:chemistry*; D013056:Spectrophotometry, Ultraviolet
D009942:Organometallic Compounds; D017319:Photosensitizing Agents; D011166:Porphyrins; D011759:Pyrrolidines; C006969:chlorin; D010984:Platinum; D010165:Palladium; C032519:pyrrolidine