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

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1HNMR和ESMS进行了结构表征,化合物15N-1的2D[1H,15N]HSQCNMR发现,该化合物在水溶液中存在同分异构体。2D[1H,15N]HSQCNMR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0.5h内将化合物1还原,而GSH在6h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。

A dinuclear Pt （IV） complex {[cis-Pt （NH3）2Cl （OH）212 （4,4＇ -methylene-dianiline）} （NO3）2 （compound 1） was synthesized by the oxidation of {[cis-Pt（NH3）2C1]2 （4,4＇-methylenedianiline）}（NO3）2, a potent anti-tumor active Pt（ll） 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（ll） 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.