Chemical & Pharmaceutical Bulletin ( IF 1.5 ) Pub Date : 2023-07-01 , DOI: 10.1248/cpb.c23-00043 Yoshimi Ichimaru 1 , Koichi Kato 1 , Rina Nakatani 2 , Risa Isomura 2 , Kirara Sugiura 2 , Yoshihiro Yamaguchi 3 , Wanchun Jin 2 , Hideki Mizutani 2 , Masanori Imai 2 , Masaaki Kurihara 1 , Mikako Fujita 4 , Masami Otsuka 4, 5 , Hiromasa Kurosaki 2
We designed and synthesized a chiral ligand N-(anthracen-9-ylmethyl)-1-(pyridin-2-yl)-N-(pyridin-2-ylmethyl)ethanamine (APPE) DNA photocleavage agent to investigate the effects of chirality of bis(2-picolyl)amine on the DNA photocleavage activity of metal complexes. The structures of ZnII and CoII complexes in APPE were analyzed via X-ray crystallography and fluorometric titration. APPE formed metal complexes with a 1 : 1 stoichiometry in both the crystalline and solution states. Fluorometric titration was used to show that the ZnII and CoII association constants of these complexes (log Kas) were 4.95 and 5.39, respectively. The synthesized complexes were found to cleave pUC19 plasmid DNA when irradiated at 370 nm. The DNA photocleavage activity of the ZnII complex was higher than that of the CoII complex. The absolute configuration of the methyl-attached carbon did not affect DNA cleavage activity and, unfortunately, an achiral APPE derivative without the methyl group (ABPM) was found to perform DNA photocleavage more effectively than APPE. One reason for this may be that the methyl group suppressed the structural flexibility of the photosensitizer. These results will be useful for the design of new photoreactive reagents.
Fullsize Image中文翻译:
手性 N-(蒽-9-基)甲基-N,N-双(2-吡啶甲基)胺锌(II)/钴(II)配合物的结构表征及 DNA 光裂解活性评价
我们设计并合成了手性配体N- (蒽-9-基甲基)-1-(吡啶-2-基) -N- (吡啶-2-基甲基)乙胺(APPE) DNA光裂解剂,以研究手性的影响双(2-吡啶甲基)胺对金属配合物DNA光裂解活性的影响。通过X 射线晶体学和荧光滴定分析了 APPE 中Zn II和 Co II配合物的结构。APPE 在结晶状态和溶液状态下形成化学计量比为 1:1 的金属配合物。使用荧光滴定法显示这些配合物的 Zn II和Co II缔合常数 (log Kas) 分别为 4.95 和 5.39。发现合成的复合物在 370 nm 照射时可切割 pUC19 质粒 DNA。Zn II配合物的 DNA 光裂解活性高于 Co II配合物。甲基连接碳的绝对构型并不影响 DNA 裂解活性,不幸的是,发现不含甲基的非手性 APPE 衍生物 (ABPM) 比 APPE 更有效地进行 DNA 光裂解。造成这种情况的原因之一可能是甲基抑制了光敏剂的结构灵活性。这些结果将有助于设计新的光反应试剂。
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