c,c,t-[Pt(NH₃)₂Cl₂(acetato)₂] | 1313200-37-1

• 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
• 英文名称: c,c,t-[Pt(NH₃)₂Cl₂(acetato)₂]
• 英文别名: azane;dichloroplatinum(2+);diacetate
• CAS: 1313200-37-1
• 化学式: C₄H₁₂Cl₂N₂O₄Pt
• 分子量: 418.136
• InChiKey: XKXXPKMRHDHUEQ-UHFFFAOYSA-J

计算性质

• 辛醇/水分配系数(LogP)：
  -8.16
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  82.3
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  c,c,t-[Pt(NH₃)₂Cl₂(acetato)₂] 在 维生素 C 作用下， 以 乙醇 为溶剂， 生成 cisplatin
  参考文献：
  名称：

  一系列基于顺铂的脂族双（羧基）Pt（IV）前药的生物活性：有机链应持续多长时间？

  摘要：

  一系列基于顺铂的Pt（IV）前药候选物的生物学特性，即反式，顺式，顺式-[Pt（羧基）2 Cl 2（NH 3）2 ]，其中羧基= CH 3（CH 2）n COO − [（1），n = 0; （2），n = 2; （3），n ＝ 4；（4），n ＝ 6]讨论了具有大的亲脂性间隔。配合物的稳定性在不同的pH条件下进行了测试（即（从1.0到9.0），以模拟口服给药的假设条件，显示出较高的稳定性（> 90％）。在抗坏血酸的存在下证明了向其活性Pt（II）代谢物的转化，具有拟一级动力学，其半衰期随着羧酸链长的增加而平稳降低。他们的抗增殖活性已在一大批人类癌细胞系中进行了体外评估。正如预期的那样，效力随着链长的增加而增加：3和4分别在大约一两个数量级的所有细胞系上比顺铂具有更高的活性。与非肿瘤细胞相比，两种复合物在顺铂耐药细胞系上也都保持了活性，并且显示出选择性的逐步提高。对多细胞肿瘤球体（MCTSs

  DOI：

  10.1016/j.jinorgbio.2014.07.018
• 作为产物：
  描述：

  乙酸酐 、 c,c,t-[Pt(NH₃)2Cl₂(OH)2] 反应 120.0h， 生成 c,c,t-[Pt(NH₃)₂Cl₂(acetato)₂]
  参考文献：
  名称：

  一个值得怀疑的教条：PtIV 配合物赤道配体在生理条件下的水解

  摘要：

  由于其高动力学惰性，从而减少与生物分子的副反应，Pt IV配合物被认为定义了抗癌铂类药物的未来。在生理相关条件下研究了一系列双羧基 Pt IV配合物的水稳定性。出乎意料的是，与目前的化学理解相反，特别是奥沙利铂和沙铂复合物在赤道位置经历了快速水解（甚至在细胞培养基和血清中）。值得注意的是，所得水解产物的还原动力学差异很大，这是激活 Pt IV药物的关键参数，这也改变了细胞培养物中化合物的抗癌潜力。完整的 Pt IV配合物可以在赤道位置水解的发现与 Pt IV化合物一般动力学惰性的教条相矛盾，在新型铂基抗癌药物的筛选和设计中需要考虑这一点。

  DOI：

  10.1002/anie.201900682

文献信息

• <i>trans</i>-Platinum(<scp>iv</scp>) pro-drugs that exhibit unusual resistance to reduction by endogenous reductants and blood serum but are rapidly activated inside cells:¹H NMR and XANES spectroscopy study
  作者：Catherine K. J. Chen、Peter Kappen、Dan Gibson、Trevor W. Hambley

  DOI：10.1039/d0dt01622e

  日期：——

  complexes that they do to cis-diam(m)ineplatinum complexes. The cis complexes exhibit resistance to reduction by L-ascorbate and human blood serum, but are readily reduced inside cancer cells. Studies of reduction monitored by 1H NMR revealed that oxidation of trans-diammineplatinum(II) complexes does not always result in significant stabilisation, but the complexes trans, trans, trans-[Pt(OAc)4(NH3)2]

  最近的结果证实，保护跨铂不受癌细胞通路反应的影响，从而大大增强了它们的活性，表明这种复合物的潜力比以前认为的要大。在这项研究中，我们研究了铂（IV）氧化态和四羧酸盐配位球的使用，以确定这些特征是否能赋予反式-diammineplatinum络合物与顺式-dimm（m）ineplatinum络合物相同的稳定性。所述顺式配合物表现出对通过还原性大号-ascorbate和人血清，但癌细胞内部容易降低。减量研究由1监控1 H NMR表明，反式-diammineplatinum（II）配合物的氧化并不总是导致稳定，但是该配合物反式，反式，反式-[Pt（OAc）4（NH 3）2 ]（OAc =乙酸盐）和反式，反式，反式-[Pt（OPr）2（OAc）2（NH 3）2 ]（OPr =丙酸酯）在十倍过量的L-存在下分别表现出33 h和5.9天的二级半衰期。抗坏血酸。血液模型减少的XANES光谱研究表明，反式
• PLATINUM COMPLEX, ITS PREPARATION AND THERAPEUTIC USE
  申请人：City University

  公开号：US20210371441A1

  公开（公告）日：2021-12-02

  A platinum complex comprises a chemical structure of Structure I: where L 1 and L 2 are independently selected from electron donor ligands, including but not limited to halogen ligands, hydroxo ligands, carboxylato ligands, and alkoxido ligands; R 1 , R 2 and R 3 are each independently selected from a hydrogen atom, hydrocarbon group, or heterocyclic group; wherein the hydrocarbon group is selected from: alkyl, alkenyl, cycloalkyl, phenyl, and naphthyl which may optionally be substituted by at least one functional group selected from the group consisting of: hydroxy, halogen, alkoxy, alkoxycarbonyl, carboxy, amido, amino, nitro, cyano, carbamate, urea, sulfonyl, sulfenyl, phosphenyl, phosphinyl, sulfide, thioether, thioester, sugar moiety, cyclodextrin, or porphyrin ring; and the heterocyclic group is selected from: pyridyl, piperidyl, azino, azolyl, imidazolyl, triazinyl, furyl or carbozolyl; or two adjacent R 1 , R 2 and R 3 groups form a heterocycle or a carbocycle with or without an intermediary hetero atom or intermediary hetero atoms.

  一种铂配合物包括化学结构I，其中L1和L2是独立选择的电子给体配体，包括但不限于卤素配体、羟基配体、羧基配体和烷氧基配体；R1、R2和R3分别是独立选择的氢原子、烃基或杂环基；其中烃基选自：烷基、烯基、环烷基、苯基和萘基，可选择地被至少一个官能团取代，所述官能团选自羟基、卤素、烷氧基、烷氧羰基、羧基、酰胺基、氨基、硝基、氰基、氨基甲酸酯、脲、磺酰基、烷基硫基、膦基、硫醚、硫酯、糖基、环糊精或卟啉环；所述杂环基选自：吡啶基、哌啶基、咪唑基、三嗪基、呋喃基或卡波佐基；或者相邻的R1、R2和R3基与中间的杂原子或杂原子形成杂环或碳环。
• Reduction of the anti-cancer drug analogue cis,trans,cis-[PtCl2(OCOCH3)2(NH3)2] by L-cysteine and L-methionine and its crystal structure †
  作者：Lie Chen、Peng Foo Lee、John D. Ranford、Jagadese J. Vittal、Siew Ying Wong

  DOI：10.1039/a900441f

  日期：——

  The complex cis,trans,cis-[PtCl2(OCOCH3)2(NH3)2] 1 has been synthesized as a simplified and more soluble model of the anticancer drug cis,trans,cis-[PtCl2(OCOCH3)2(NH3)(C6H11NH2)] (JM216). The crystal structure of 1 shows an octahedral co-ordination sphere around the PtIV with strong intramolecular and weak intermolecular hydrogen bonding. The kinetics of reduction of 1 by the divalent sulfur amino

  已合成了复杂的顺，反，顺-[PtCl 2（OCOCH 3）2（NH 3）2 ] 1作为抗癌药顺，反，顺-[PtCl 2（OCOCH 3）的简化模型和更易溶模型。2（NH 3）（C 6 H 11 NH 2）]（JM216）。1的晶体结构显示了Pt IV周围的八面体配位球具有强分子内和弱分子间氢键。已通过多核NMR在一定pH值范围内确定了二价硫氨基酸L-半胱氨酸和L-蛋氨酸还原1的动力学。还原强烈依赖于pH，与氨基酸的质子化状态和硫的碱度有关。降低速度比以前的铂（IV）药物系统模型要慢得多。
• The Effect of Ligand Lipophilicity on the Nanoparticle Encapsulation of Pt(IV) Prodrugs
  作者：Timothy C. Johnstone、Stephen J. Lippard

  DOI：10.1021/ic4010642

  日期：2013.9.3

  In an effort to expand the therapeutic range of platinum anticancer agents, several new approaches to platinum-based therapy, including nanodelivery, are under active investigation. To better understand the effect of ligand lipophilicity on the encapsulation of Pt(IV) prodrugs within polymer nanoparticles, the series of compounds cis,cis,trans-[Pt(NH3)(2)Cl2L2] was prepared, where L. acetate, propanoate, butanoate, pentanoate, hexanoate, heptanoate, octanoate, nonanoate, and decanoate. The " lipophilicities of these compounds, assessed by reversed-phase HPLC, correlate with the octanol/water partition coefficients of their respective free carboxylic acid ligands, which in turn affect the degree of encapsulation of the ", Pt(IV) complex within the hydrophobic core of poly(lactic-co-glycolic acid)Wock-poly(ethylene glycol) (PLGA-PEG-COOH) nanoparticles. The most " lipophilic compound investigated, cis,cis,trans-[Pt(NH3)(2)Cl-2(O2C-(CH2)8CH(3))(2)], displayed the best encapsulation. This compound was therefore selected to evaluate the effect of increased platinum concentration on encapsulation. As the platinum concentration was increased, there was an initial increase in encapsulation followed by a decrease due to macroscopic precipitation. Maximal loading occurred when the platinum complex was present at a 40% w/w ratio with respect to polymer during the nanoprecipitation step. Particles formed under these optimal conditions had diameters of approximately 50 nm, as determined by transmission electron microscopy.
• Glassy carbon electrodes deliver unpredictable reduction potentials for platinum(IV) antitumor prodrugs
  作者：Meghan C. McCormick、Franklin A. Schultz、Mu-Hyun Baik

  DOI：10.1016/j.poly.2015.09.040

  日期：2016.1

  Reductive activation of six-coordinate Pt(IV) complexes to afford square-planar Pt(II) complexes has exhibited surprisingly divergent and unpredictable cathodic peak potentials during cyclic voltammetry (CV) measurements under widely employed experimental conditions. A systematic, detailed investigation reveals that glassy carbon (GC) electrodes are responsible for this erratic behavior. More reproducible CVs are obtained with platinum metal electrodes, which display cathodic responses at much more positive potentials. The unreliable and negatively shifted peak potentials observed at GC are attributed to a non-uniform oxide layer that is formed on the electrode surface causing slow electron transfer. A simple procedure of repetitive scanning to reducing potentials is found to be effective for cleaning and activating the GC surface, such that it exhibits the more consistent and accurate peak potential responses seen with a Pt electrode. (C) 2015 Elsevier Ltd. All rights reserved.