化学
钌
吡唑
脱质子化
配体(生物化学)
药物化学
光化学
亲脂性
单线态氧
光解
水溶液
立体化学
光敏剂
氧气
催化作用
有机化学
离子
生物化学
受体
作者
Masanari Hirahara,Aki Iwamoto,Yuden Teraoka,Yuki Mizuno,Yasushi Umemura,Takamasa Uekita
标识
DOI:10.1021/acs.inorgchem.3c03716
摘要
Ruthenium complexes bearing bis pyrazole (pzH) ligands, cis-[Ru(bpy)2(R-pzH)2]2+ (bpy = 2,2′-bipyridine, R = −H, −Cl), were examined as photoactivated anticancer prodrugs. A dicationic pyrazole complex deprotonated to give monocationic pyrazole–pyrazolate complexes, cis-[Ru(bpy)2(R-pz–)(R-pzH)]+, in an aqueous solution with pKa values of 9.5 and 7.2 for R = H and R = Cl, respectively. Upon deprotonation, relative quantum yields of photosubstitution decreased while lipophilicity of the complexes increased according to the measurements of water–octanol coefficients. The ruthenium complex with 4-chloropyrazole ligands displayed high cytotoxicity upon light irradiation (IC50 = 0.060 ± 0.016 μM) toward lung cancer cells, which was 7 times higher than that in the dark (IC50 = 0.44 ± 0.07 μM). Additional experiments for the ruthenium R-pyrazole complexes indicated that (1) selective photodissociation of the 4-chloropyrazole ligand occurs from cis-[Ru(bpy)2(4-Clpz–)(4-ClpzH)]+, (2) photoinduced ligand dissociation is dominant rather than photoinduced generation of singlet oxygen (1O2), and (3) induction of cell death occurs via the intrinsic pathway of apoptosis.
科研通智能强力驱动
Strongly Powered by AbleSci AI