1,4,8,11-Tetraazacyclotetradecane-4,11-di(methylphosphonic acid) | 309252-30-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机膦酸及其衍生物
• 英文名称: 1,4,8,11-Tetraazacyclotetradecane-4,11-di(methylphosphonic acid)
• 英文别名: 1,4,8,11-tetraazacyclotetradecaner-1,8-bis(methylphosphonic) acid；[8-(Phosphonomethyl)-1,4,8,11-tetrazacyclotetradec-1-yl]methylphosphonic acid
• CAS: 309252-30-0
• 化学式: C₁₂H₃₀N₄O₆P₂
• 分子量: 388.341
• InChiKey: AIOKOIXRGYKZKR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -8.1
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  146
• 氢给体数：
  6
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  cobalt(II) chloride hexahydrate 、 1,4,8,11-Tetraazacyclotetradecane-4,11-di(methylphosphonic acid) 在 sodium hydroxide 作用下， 以 水 为溶剂， 以62%的产率得到trans-Co(1,4,8,11-tetraazacyclotetradecaner-1,8-bis(methylphosphonic) acid)*6H2O
  参考文献：
  名称：

  钴（III）与1,4,8,11-四氮杂环十四烷-1,8-双（甲基膦酸）配合物的顺/反异构

  摘要：

  摘要X射线结构测定表明1,4,8,11-四氮杂环十四烷-1,8-双（甲基膦酸）酸H4L与Co（III）形成顺式和反式O，O异构体。其他供体原子的取向表明顺式-O1，O2-反式-N1，N8-顺式-O1，N4- [Co（HL）]的形成。由于相邻的膦酸基团之间的强氢键，容易形成动力学上优选的顺式异构体。水溶液中氢键的存在由pKa的值证实，与反式异构体相比，pKa的值增加了四个数量级。反式[Co（HL）]的形成仅在惰性条件下在惰性气氛下长时间加热Co（II）溶液与配体后才发生氧化，这可以通过将Co（II）离子插入氮原子平面来解释。 1,4,8,11-四氮杂环十四烷

  DOI：

  10.1016/s0020-1693(01)00348-6
• 作为产物：
  描述：

  Tetraethyl 4,11-dibenzyl-1,4,8,11-tetraazacyclotetradecane-1,8-di(methylphosphonate) 在 palladium on activated charcoal 甲酸 、 氢溴酸 、 氢气 作用下， 以 乙醇 、 溶剂黄146 为溶剂， 生成 1,4,8,11-Tetraazacyclotetradecane-4,11-di(methylphosphonic acid)
  参考文献：
  名称：

  Bis(methylphosphonic Acid) Derivatives of 1,4,8,11-Tetraazacyclotetradecane (Cyclam). Synthesis, Crystal and Molecular Structures, and Solution Properties

  摘要：

  1,8位具有甲基膦酸基团和取代基R=H，Me，CH2Ph的4和11位环戊二胺衍生物，通过适当的环戊二胺衍生物、甲醛和膦酸/二乙基膦酸酯的Mannich反应合成，然后从氮原子去除保护苄基。类似的方法可以得到环戊二胺的单(甲基膦酸)衍生物。四种膦酸衍生物的晶体结构显示相同的环状构象和取向，由于磷酸根氧原子和邻近乙烯链上的质子化氮原子之间的强分子内氢键，导致挂链的稳定性。即使在水溶液中，氢键也是稳定的。通过温度依赖的NMR测量，估计了构象不稳定化的激活参数。确定的质子化常数证实了化合物的高碱性及其对氮原子取代基的依赖性。非配位于甲基膦酸基团上的氮原子的增强碱性是由于强氢键的存在。

  DOI：

  10.1135/cccc20001289

文献信息

• Peptide purification by means of hard metal ion affinity chromatography
  申请人：Hearn Milton Thomas William

  公开号：US20090143529A1

  公开（公告）日：2009-06-04

  A polymer substrate functionalized with a functionality comprising at least one cyclic, metal ion coordinating ligand group which comprises at least 3 nitrogen donor atoms in the ring of the cyclic group, at least one of the nitrogen atoms having an optionally substituted carboxy(lower alkyl) or optionally substituted phosphono(lower alkyl) group covalently attached thereto, is well suited for use in conjunction with “hard” metal ions of low toxicity (such as Ca 2+ , Mg 2+ or Fe 3+ ) in the separation/purification of appropriately “tagged” polypeptides by Immobilized Metal ion Affinity Chromatography (IMAC).

  一种聚合物基底，其功能化包括至少一个环状金属离子配位配体基团，该基团在环状结构中至少包含3个氮供体原子，其中至少一个氮原子具有可选择性取代的羧酸（较低烷基）或可选择性取代的膦酸（较低烷基）基团共价连接，非常适合与低毒性的“硬”金属离子（例如Ca2+，Mg2+或Fe3+）一起在固定金属离子亲和层析（IMAC）中用于分离/纯化适当“标记”的多肽。
• TUMOR AND IMMUNE CELL IMAGING BASED ON PD-L1 EXPRESSION
  申请人：The Johns Hopkins University

  公开号：US20190314531A1

  公开（公告）日：2019-10-17

  The presently disclosed subject matter provides compositions, kits, and methods comprising imaging agents that can detect Programmed Death Ligand 1 (PD-L1). The presently disclosed imaging agents can be used to detect diseases and disorders, such as cancer, infection, and inflammation, in a subject.
• ADHESIVE/ADSORPTION SWITCH ON NANOPARTICLES TO INCREASE TUMOR UPTAKE AND DELAY TUMOR CLEARANCE
  申请人：The Johns Hopkins University

  公开号：US20220118116A1

  公开（公告）日：2022-04-21

  Lipid-based nanocarriers (liposomes) loaded with a chemotherapeutic agent and exhibiting interstitial drug release and intratumoral adhesion are disclosed. The lipid-based nanocarriers disclosed herein include an ‘adsorptive/adhesive switch’ on the nanocarriers surface with the aim to increase the tumor residence times of the drug delivery nanocarriers and to slow down their tumor clearing kinetics. The switch is designed to promote nanoparticle adsorption on cancer cells and/or the extracellular matrix (ECM) while keeping their internalization by cells to a minimum. This approach of drug delivery is key for interstitial release of highly-diffusive forms of therapeutics.
• LOW MOLECULAR WEIGHT AND POLYAMIDOAMINE (PAMAM) DENDRIMER BASED PSMA-SPECIFIC DUAL CONTRAST AGENTS FOR OPTICAL AND PHOTOACOUSTIC IMAGING AND THERANOSTIC AGENTS FOR TREATING PROSTATE CANCER
  申请人：The Johns Hopkins University

  公开号：US20220401592A1

  公开（公告）日：2022-12-22

  Poly(amidoamine) [PAMAM] dendrimers for use as PSMA-targeted contrast agents for optical and photoacoustic imaging (PA) and theranostic agents for treating prostate cancer are disclosed.
• Bis(methylphosphonic Acid) Derivatives of 1,4,8,11-Tetraazacyclotetradecane (Cyclam). Synthesis, Crystal and Molecular Structures, and Solution Properties
  作者：Jan Kotek、Pavel Vojtíšek、Ivana Císařová、Petr Hermann、Petr Jurečka、Jan Rohovec、Ivan Lukeš

  DOI：10.1135/cccc20001289

  日期：——

  Cyclam derivatives with methylphosphonic acid arms in position 1,8 and substituent R = H, Me, CH₂Ph in positions 4 and 11 are synthesised by Mannich reaction of an appropriate cyclam derivative, formaldehyde and phosphonic acid/diethyl phosphite followed by removal of protecting benzyl groups from nitrogen atoms. Mono(methylphosphonic acid) derivative of cyclam can be obtained by a similar route. Crystal structures of four phosphonic acid derivatives show the same ring conformation and orientation pendants due to strong intramolecular hydrogen bonds between phosphonate oxygen atoms and protonated nitrogen atoms adjacent over ethylene chains. The hydrogen bonds are stable even in aqueous solution. Activation parameters for destabilisation of the conformation are estimated from temperature-dependent NMR measurement. The protonation constants determined confirm the expected high basicity of the compounds and its dependence on the nitrogen atom substituents. The enhanced basicity of the nitrogen atoms non-bonded to methylenephosphonic acid moiety, is explained by the presence of the strong hydrogen bonds.

  1,8位具有甲基膦酸基团和取代基R=H，Me，CH2Ph的4和11位环戊二胺衍生物，通过适当的环戊二胺衍生物、甲醛和膦酸/二乙基膦酸酯的Mannich反应合成，然后从氮原子去除保护苄基。类似的方法可以得到环戊二胺的单(甲基膦酸)衍生物。四种膦酸衍生物的晶体结构显示相同的环状构象和取向，由于磷酸根氧原子和邻近乙烯链上的质子化氮原子之间的强分子内氢键，导致挂链的稳定性。即使在水溶液中，氢键也是稳定的。通过温度依赖的NMR测量，估计了构象不稳定化的激活参数。确定的质子化常数证实了化合物的高碱性及其对氮原子取代基的依赖性。非配位于甲基膦酸基团上的氮原子的增强碱性是由于强氢键的存在。