无机化学学报
無機化學學報
무궤화학학보
JOURNAL OF INORGANIC CHEMISTRY
2007年
7期
1206-1212
,共7页
抗肿瘤试剂%双核铂(Ⅳ)配合物%DNA%Guanosine-5'-Monophosphate(5'-GMP)%Glutathione(GSH)
抗腫瘤試劑%雙覈鉑(Ⅳ)配閤物%DNA%Guanosine-5'-Monophosphate(5'-GMP)%Glutathione(GSH)
항종류시제%쌍핵박(Ⅳ)배합물%DNA%Guanosine-5'-Monophosphate(5'-GMP)%Glutathione(GSH)
antitumor agent%dinuclear platinum( Ⅱ/Ⅳ) complexes%DNA%guanosine-5'-monophosphate(5'-GMP)%glutathione(GSH)
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.
閤成瞭一箇新型的雙覈Pt(Ⅳ)配閤物{[cis-Pt(NH3)2Cl(OH)2]2(4,4'-methylenedianiline)}(NO3)2(化閤物1)及相應的 15N標記化閤物{[cis-Pt(15NH3)2Cl(OH)2]2(4,4'-methylenedianiline)}(NO3)2(化閤物15N-1).利用1H NMR和ESMS進行瞭結構錶徵,化閤物15N-1的2D[1H,15N]HSQC NMR髮現,該化閤物在水溶液中存在同分異構體.2D[1H,15N]HSQC NMR技術跟蹤瞭化閤物15N-1與Guanosine-5'-Monophosphate(5'-GMP)和Glutathione(GSH)的反應.結果顯示,5'-GMP能在0.5 h內將化閤物1還原,而GSH在6 h以後纔能夠部分的將化閤物1還原.化閤物1所錶現齣來的反應性能將有利于提高其治療效果和降低毒副作用.
합성료일개신형적쌍핵Pt(Ⅳ)배합물{[cis-Pt(NH3)2Cl(OH)2]2(4,4'-methylenedianiline)}(NO3)2(화합물1)급상응적 15N표기화합물{[cis-Pt(15NH3)2Cl(OH)2]2(4,4'-methylenedianiline)}(NO3)2(화합물15N-1).이용1H NMR화ESMS진행료결구표정,화합물15N-1적2D[1H,15N]HSQC NMR발현,해화합물재수용액중존재동분이구체.2D[1H,15N]HSQC NMR기술근종료화합물15N-1여Guanosine-5'-Monophosphate(5'-GMP)화Glutathione(GSH)적반응.결과현시,5'-GMP능재0.5 h내장화합물1환원,이GSH재6 h이후재능구부분적장화합물1환원.화합물1소표현출래적반응성능장유리우제고기치료효과화강저독부작용.
A dinuclear Pt(Ⅳ) complex{[cis-Pt(NH3)2Cl(OH)2]2(4,4'-methylene-dianiline)}(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.
