| 双核Pt(Ⅳ)配合物与Guanosine-5′-Monophosphate和Glutathione反应的核磁共振光谱研究(英文) |
| NMR Studies on Reactivity of Dinuclear Platinum(Ⅳ) Complex Towards Guanosine-5′-Monophosphate and Glutathione |
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| 摘要: 合成了一个新型的双核Pt(Ⅳ)配合物{[cis-Pt(NH3)2Cl(OH)2]2(4,4′-methylenedianiline)}(NO3)2(化合物1)及相应的 15N标记化合物{[cis-Pt( 15NH3)2Cl(OH)2]2 (4,4′-methylenedianiline)}(NO3)2(化合物 15N-1)。利用 1H NMR和ESMS进行了结构表征，化合物 15N-1的2D[ 1H, 15N]HSQC NMR发现，该化合物在水溶液中存在同分异构体。2D[ 1H, 15N]HSQC NMR技术跟踪了化合物 15N-1与Guanosine-5′-Monophosphate(5′-GMP)和Glutathione(GSH)的反应。结果显示，5′-GMP能在0.5 h内将化合物1还原，而GSH在6 h以后才能够部分的将化合物1还原。化合物1所表现出来的反应性能将有利于提高其治疗效果和降低毒副作用。 |
| 关键词: 抗肿瘤试剂 双核铂(Ⅳ)配合物 DNA Guanosine-5′-Monophosphate(5′-GMP) Glutathione(GSH) |
| 基金项目: |
| Abstract: A dinuclear Pt(Ⅳ) complex{[cis-Pt(NH3)2Cl(OH)2]2(4,4′-methylenedianiline)}(NO3)2(compound 1) was synthesized by the oxidation of {[cis-Pt(NH3)2Cl]2 (4,4′-methylenedianiline)}(NO3)2, a potent anti-tumor active Pt(Ⅱ) complex. The formation of compound 1 was verified by 1H NMR and ES-MS spectroscopy. Compound 1 shows good water solubility. The 15N-labelled compound 1 ( 15N-1) was synthesized in order to investigate the reactivity of compound 1 towards guanosine-5′-monophosphate(5′-GMP) and glutathione (GSH) by 2D [ 1H, 15N] HSQC NMR spectroscopy. It was revealed from the 2D [ 1H, 15N] HSQC NMR spectra that compound 1 could exist in different isomers in aqueous solution. The reactivity of 15N-1 towards 5′-GMP and GSH was followed by 1H NMR and 2D [ 1H, 15N] HSQC NMR spectroscopy. The Pt(Ⅳ) isomers of compound 1 can be fully reduced to Pt(Ⅱ) species by 5′-GMP within 0.5 h, while they can only be partly reduced by GSH after 6 h. The reduction products were compared to those of compound 1 and ascorbate incubated for 48 h. The unique reactivity of compound 1 may be desirable for achieving enhanced therapeutic effects and decreased toxic side effects. |
| Keywords: antitumor agent dinuclear platinum(Ⅱ/Ⅳ) complexes DNA guanosine-5′-monophosphate(5′-GMP) glutathione(GSH) |
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| 范大民,杨晓亮,郭子建.双核Pt(Ⅳ)配合物与Guanosine-5′-Monophosphate和Glutathione反应的核磁共振光谱研究(英文)[J].无机化学学报,2007,23(7):1206-1212. |
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