tetra-tert-butylammonium tetrachloroaurate(III) | 1352401-76-3

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: tetra-tert-butylammonium tetrachloroaurate(III)
• 英文别名: Tetratert-butylazanium;tetrachlorogold(1-)；tetratert-butylazanium;tetrachlorogold(1-)
• CAS: 1352401-76-3
• 化学式: AuCl₄*C₁₆H₃₆N
• 分子量: 581.247
• InChiKey: YQEUMFIGBOLVFG-UHFFFAOYSA-J

计算性质

• 辛醇/水分配系数(LogP)：
  7.75
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  0
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  二甲基丙二胺 、 tetra-tert-butylammonium tetrachloroaurate(III) 、 2,3-bis(5'-formylpyrrol-2'-yl)quinoxaline 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 生成
  参考文献：
  名称：

  Gold(III) Macrocycles: Nucleotide-Specific Unconventional Catalytic Inhibitors of Human Topoisomerase I

  摘要：

  Topoisomerase IB (Top 1) is a key eukaryotic nuclear enzyme that regulates the topology of DNA during replication and gene transcription. Anticancer drugs that block Top1 are either well-characterized interfacial poisons or lesser-known catalytic inhibitor compounds. Here we describe a new class of cytotoxic redox-stable cationic Au3+ macrocycles which, through hierarchical cluster analysis of cytotoxicity data for the lead compound, 3, were identified as either poisons or inhibitors of Top1. Two pivotal enzyme inhibition assays prove that the compounds are true catalytic inhibitors of Top1. Inhibition of human topoisomerase 11 alpha (Top2 alpha) by 3 was 2 orders of magnitude weaker than its inhibition of Top1, confirming that 3 is a type I-specific catalytic inhibitor. Importantly, Au3+ is essential for both DNA intercalation and enzyme inhibition. Macromolecular simulations show that 3 intercalates directly at the 5'-TA-3' dinucleotide sequence targeted by Top1 via crucial electrostatic interactions, which include pi-pi stacking and an Au center dot center dot center dot O contact involving a thymine carbonyl group, resolving the ambiguity of conventional (drug binds protein) vs unconventional (drug binds substrate) catalytic inhibition of the enzyme. Surface plasmon resonance studies confirm the molecular mechanism of action elucidated by the simulations.

  DOI：

  10.1021/ja412350f

文献信息

• GOLD COMPLEXES FOR USE IN THE TREATMENT OF CANCER
  申请人：Munro Orde Quentin

  公开号：US20130090472A1

  公开（公告）日：2013-04-11

  The invention provides compounds of the Formula (I), in which W is independently selected from W 1 , W 2 , W 3 , W 4 , W 5 , or W represents a pair of substituents independently selected from H, alkyl, aryl or amide in which the amide is optionally part of a linking chain, and the Z n —Z n bonds (n=4-17; n′=n+1) are optionally of any whole or partial bond order, Y is Y 1 or Y represents a pair of substituents independently selected from H, C- 1 -C 6 alkyl, Z 5 or Z 6 aryl, or Y is optionally a bridging structure that may comprise one or more C- 1 -C 6 amide, C- 1 -C 6 ether, or C- 1 -C 6 ester groups, R-R 39 are independently selected from no substituent, a lone pair of electrons, H, halogen, C 5 -C 6 aryl, C 1 - C- 12 alkyl, amine, C- 1 -C 6 alkylamine, C- 1 -C 6 amide, nitro, cyano, carboxyl, C- 1 -C 6 ester, phosphane, thiol, C- 1 -C 6 thioether, OR′, and suitable pairs of adjacent R groups (R-R 39 ) may optionally together form part of a C 5 or C 6 aryl ring, a Z 5 or Z 6 ring, R′ is independently selected from H, C- 1 -C 6 alkyl, Z 5 or Z 6 aryl, C- 1 -C 6 ester, poly(—C 2 O—), amine, and C- 1 -C 6 alkylamine, Z-Z 24 are independently selected from C, N, P, O, and S, and X − is a pharmaceutically acceptable anion, for the treatment of cancer.

  该发明提供了Formula (I)中的化合物，其中W独立地选自W1、W2、W3、W4、W5，或W代表从H、烷基、芳基或酰胺中独立选择的一对取代基，其中酰胺可选作为连接链的一部分，Zn—Zn键（n=4-17；n′=n+1）可选为任何整数或部分键序，Y为Y1或Y代表从H、C-1-C6烷基、Z5或Z6芳基中独立选择的一对取代基，或Y可选作为可能包含一种或多种C-1-C6酰胺、C-1-C6醚或C-1-C6酯基团的桥接结构，R-R39独立选择自无取代基、孤立的一对电子、H、卤素、C5-C6芳基、C1-C12烷基、胺、C-1-C6烷基胺、C-1-C6酰胺、硝基、氰基、羧基、C-1-C6酯基、膦、硫醇、C-1-C6硫醚、OR′，以及适当的相邻R基（R-R39）可选地共同形成C5或C6芳基环、Z5或Z6环，R′独立选择自H、C-1-C6烷基、Z5或Z6芳基、C-1-C6酯基、聚（—C2O—）、胺，和C-1-C6烷基胺，Z-Z24独立选择自C、N、P、O和S，X-为药用可接受的阴离子，用于治疗癌症。
• US9346832B2
  申请人：——

  公开号：US9346832B2

  公开（公告）日：2016-05-24
• Gold(III) Macrocycles: Nucleotide-Specific Unconventional Catalytic Inhibitors of Human Topoisomerase I
  作者：Kate J. Akerman、Alexander M. Fagenson、Vidusha Cyril、Michael Taylor、Mark T. Muller、Matthew P. Akerman、Orde Q. Munro

  DOI：10.1021/ja412350f

  日期：2014.4.16

  Topoisomerase IB (Top 1) is a key eukaryotic nuclear enzyme that regulates the topology of DNA during replication and gene transcription. Anticancer drugs that block Top1 are either well-characterized interfacial poisons or lesser-known catalytic inhibitor compounds. Here we describe a new class of cytotoxic redox-stable cationic Au3+ macrocycles which, through hierarchical cluster analysis of cytotoxicity data for the lead compound, 3, were identified as either poisons or inhibitors of Top1. Two pivotal enzyme inhibition assays prove that the compounds are true catalytic inhibitors of Top1. Inhibition of human topoisomerase 11 alpha (Top2 alpha) by 3 was 2 orders of magnitude weaker than its inhibition of Top1, confirming that 3 is a type I-specific catalytic inhibitor. Importantly, Au3+ is essential for both DNA intercalation and enzyme inhibition. Macromolecular simulations show that 3 intercalates directly at the 5'-TA-3' dinucleotide sequence targeted by Top1 via crucial electrostatic interactions, which include pi-pi stacking and an Au center dot center dot center dot O contact involving a thymine carbonyl group, resolving the ambiguity of conventional (drug binds protein) vs unconventional (drug binds substrate) catalytic inhibition of the enzyme. Surface plasmon resonance studies confirm the molecular mechanism of action elucidated by the simulations.