| 180717-31-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• CAS: 180717-31-1
• 化学式: C₉H₂₀N₃O₃PtS
• 分子量: 447.409
• InChiKey: LNLSXSYRWGQKER-GGEWPAHBSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  None
• 重原子数：
  None
• 可旋转键数：
  None
• 环数：
  None
• sp3杂化的碳原子比例：
  None
• 拓扑面积：
  None
• 氢给体数：
  None
• 氢受体数：
  None

反应信息

• 作为产物：
  描述：

  在 水 作用下， 以 水 、 重水 为溶剂， 生成 、
  参考文献：
  名称：

  单功能铂-核苷酸加合物的稳定作用：N-乙酰基-L-蛋氨酸络合物与鸟苷5'-单磷酸和鸟苷基（3'-5'）鸟苷的反应

  摘要：

  [Pt（en）MeCO-Met- S）Cl] NO 3 1，[Pt（en）（MeCO-Met- S）2 ] [NO 3 ] 2 2（en =乙烷-1,2-二胺，已制备MeCO-Met = N-乙酰基-L-甲硫氨酸及其15 N类似物（1n和2n），并通过1 H，13 C和二维[ 1 H，15 N]光谱进行了表征。复合物1（在310 K下半衰期为3.9小时）的水解速度比[Pt（en）Cl 2 ]慢，而2在水中稳定。1n与鸟苷5'-单磷酸酯（5'-GMP）的反应产生了稳定的混合配体络合物[Pt（[ 15 N] en）{MeCO-Met（1 –）- S }（5'-GMP- N 7）] +，与鸟苷基（3'-5'）鸟苷（GpG）的反应产生了两个不同的单官能团加合物[Pt（[ 15 N] en）{MeCO-Met（1 –）- S }（GpG- N 7）] +，由于3'-G或5'-G的电镀反应，优先形成一

  DOI：

  10.1039/dt9960002867

文献信息

• Chelate-ring-opened adducts of [Pt(en)(Me-Mal-O,O′)] (en = ethane-1,2-diamine, Me-Mal = 2-methylmalonate) with methionine derivatives: relevance to the biological activity of platinum anticancer agents
  作者：Zijian Guo、Trevor W. Hambley、Piedad del Socorro Murdoch、Peter J. Sadler、Urban Frey

  DOI：10.1039/a604210d

  日期：——

  The anticancer drug carboplatin [Pt(cbdca-O,O′)(NH 3 ) 2 ] which contains the chelated dicarboxylate ligand cbdca, cyclobutane-1,1-dicarboxylate, may be activated in vivo by reaction with sulfur ligands. The reactions between the analogue [Pt(en)(Me-Mal-O,O′)] 1 (en = ethane-1,2-diamine, Me-Mal = 2-methylmalonate) and the methionine derivatives N-acetyl-L-methionine (Ac-Met), glycyl-L-methionine (Gly-Met) and L-methionylglycine (Met-Gly) have been studied at pH 7 and 4, 310 K, using 1 H and two-dimensional [ 1 H, 15 N] heteronuclear single quantum coherence NMR spectroscopy and HPLC. The ring-opened species [Pt(en)(Me-Mal-O)(L-S)] (L = Ac-Met, Gly-Met or Met-Gly) containing monodentate malonate and S-bound monodentate methionine ligands were predominant in solution after 2 h. The second-order rate constant for the ring-opening reaction of 1 with Ac-Met at pH 6.56 was determined to be (1.48 ± 0.03) × 10 - 1 s -1 M -1 , and was similar for reactions with Gly-Met. Methylmalonate α-CH deuteriation rates were determined to be free Me-Met > ring-opened complex 1. Molecular-mechanics modelling suggested that hydrogen bonding between the free carboxylate group of monodentate Me-Mal and the co-ordinated amine groups, and between the two ring-opened ligands may contribute to the stability of the mixed-ligand adducts. However, in the case of Met-Gly, the ring-opening rate [(5.26 ± 0.10) × 10 -2 s -1 M -1 ] was nearly three times slower than that for the reaction of 1 with Ac-Met. In contrast, the ring-closure rate of [Pt(en)(Me-Mal-O)(Met-Gly-S)] [k 1 = (1.37 ± 0.03) × 10 -4 s -1 ] to give the S,N-chelated adduct was faster than that of [Pt(en)(Me-Mal-O)(Ac-Met-S)] - 2 [(2.27 ± 0.04) × 10 -5 s -1 ]. The S,N-chelated adducts [Pt(en)(Ac-MetH -1 -S,N)] 3, [Pt(en)(Gly-MetH -1 -S,N)] + and [Pt(en)(Met-GlyH -1 -S,N)] + became the predominant products of the reactions after about 24 h. Ring-opened adducts of chelated dicarboxylate platinum anticancer complexes with methionine derivatives could play a significant role in their mechanism of action.

  抗癌药物卡铂[Pt(cbdca-O,O')(NH_3)_2]，其中包含螯合的二羧酸配体cbdca（环丁烷-1,1-二羧酸盐），可能通过与硫配体的反应在体内被激活。对类似物[Pt(en)(Me-Mal-O,O')]1（en = 乙烷-1,2-二胺，Me-Mal = 2-甲基丙二酸）与蛋氨酸衍生物N-乙酰-L-蛋氨酸（Ac-Met）、甘氨酰-L-蛋氨酸（Gly-Met）和L-蛋氨酰甘氨酸（Met-Gly）在pH 7和4，310 K下进行的反应进行了研究，使用了^1H和二维[^1H, ^15N]异核单量子相干NMR谱和HPLC。环开型物种[Pt(en)(Me-Mal-O)(L-S)]（L = Ac-Met、Gly-Met或Met-Gly），包含单齿丙二酸和S-结合单齿蛋氨酸配体，在2小时后成为溶液中的主要物种。环开反应的二级速率常数在pH 6.56下以1与Ac-Met的反应确定为（1.48 ± 0.03）× 10^-1 s^-1 M^-1，与Gly-Met的反应类似。甲基丙二酸α-CH氘化速率确定为自由Me-Met > 环开复合物1。分子力学建模表明，单齿Me-Mal的自由羧酸基团与配位胺基团之间的氢键，以及两个环开配体之间可能有助于混合配体加合物的稳定性。然而，对于Met-Gly，环开速率[(5.26 ± 0.10) × 10^-2 s^-1 M^-1]几乎比1与Ac-Met的反应慢三倍。相反，[Pt(en)(Me-Mal-O)(Met-Gly-S)]的环闭速率[k1 = (1.37 ± 0.03) × 10^-4 s^-1]比[Pt(en)(Me-Mal-O)(Ac-Met-S)]-2[(2.27 ± 0.04) × 10^-5 s^-1]快。S,N-螯合加合物[Pt(en)(Ac-MetH-1-S,N)]3、[Pt(en)(Gly-MetH-1-S,N)]+和[Pt(en)(Met-GlyH-1-S,N)]+在约24小时后成为反应的主要产物。螯合二羧酸铂抗癌复合物与蛋氨酸衍生物的环开加合物可能在它们的作用机制中发挥重要作用。