palladium-bacteriopheophorbide | 274679-00-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四吡咯及其衍生物
• 英文名称: palladium-bacteriopheophorbide
• 英文别名: WST09；WSTO9；Tookad(R)；Tookad；3-[(3R,11R,12R,21S,22S)-16-acetyl-11-ethyl-3-methoxycarbonyl-12,17,21,26-tetramethyl-4-oxo-23,25-diaza-7,24-diazanidahexacyclo[18.2.1.15,8.110,13.115,18.02,6]hexacosa-1(23),2(6),5(26),8,10(25),13,15,17,19-nonaen-22-yl]propanoic acid;palladium(2+)
• CAS: 274679-00-4
• 化学式: C₃₅H₃₆N₄O₆*Pd
• 分子量: 715.114
• InChiKey: GPIVNYFDHQDTDZ-GDUCSYRESA-L

计算性质

• 辛醇/水分配系数(LogP)：
  5.89
• 重原子数：
  46
• 可旋转键数：
  7
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  125
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  palladium-bacteriopheophorbide 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 生成
  参考文献：
  名称：

  Distribution of Chlorophyll- and Bacteriochlorophyll-derived Photosensitizers in Human Blood Plasma

  摘要：

  AbstractChlorophylla and, in particular, bacteriochlorophyll a derivatives are promising candidates for photosensitizers in photodynamic therapy. The distribution of 21 (bacterio)chlorophyll derivatives among human blood plasma fractions was studied by iodixanol gradient ultracentrifugation and in situ absorption spectroscopy. Modifications of the natural pigments involved the central metal (Mg2+, Zn2+, Pd2+, none), the isocyclic ring (closed, open and taurinated), substituents at C‐3 (vinyl, acetyl, 1‐hydroxyethyl) and C‐173 (phytyl ester, free acid). Cellular blood components bound only a small fraction of the pigments. Distribution among low‐density lipoproteins (LDL), high‐density lipoproteins (HDL) and high‐density proteins (HDP) of the plasma was influenced as follows: (1) application in Cremophor® EL slightly altered pigment distribution by lipoprotein modification, (2) only very polar pigments with multiple hydrophilic substituents showed substantial HDP binding, (3) the presence of the esterifying alcohol at C‐173 caused enrichment in LDL, this was more pronounced with bacteriochlorophylls than with chlorophylls, (4) substituents at C‐3 had only little influence on the distribution, (5) Zn2+‐complexes were enriched in HDL compared to Mg2+ and Pd2+ complexes, indicating specific binding of the former. Equilibration of pigments among the different fractions was largely complete within 3 h.

  DOI：

  10.1111/j.1751-1097.2009.00621.x
• 作为产物：
  描述：

  palladium diacetate 、 bacteriopheophorbide-a 在 sodium ascorbate 作用下， 以 甲醇 、 氯仿 为溶剂， 反应 15.0h， 生成 palladium-bacteriopheophorbide
  参考文献：
  名称：

  [EN] SYNTHESIS AND COMPOSITION OF PHOTODYNAMIC THERAPEUTIC AGENTS FOR THE TARGETED TREATMENT OF CANCER
  [FR] SYNTHÈSE ET COMPOSITION D'AGENTS THÉRAPEUTIQUES PHOTODYNAMIQUES POUR LE TRAITEMENT CIBLÉ DU CANCER

  摘要：

  本发明描述了一种新的化合物，可用于图像引导手术和光动力疗法。特别是，化合物可以通过使用针对表达在患病组织上的受体的配体将化合物输送到疾病组织（如癌症），然后通过受体介导的内吞作用定位到细胞核或线粒体，并对癌细胞以及其他疾病提供有效的活性。同时还描述了使用该化合物的方法和组合物。

  公开号：

  WO2017044443A1

文献信息

• Fast, facile, base-free microwave-assisted metallation of bacteriochlorophylls and corresponding high yield synthesis of TOOKAD
  作者：Miffy. H. Y. Cheng、Alberto Cevallos、Maneesha A. Rajora、Gang Zheng

  DOI：10.1142/s1088424621500656

  日期：2021.7

  synthetic challenges associated with bacteriochlorophyll metallation; specifically, a slow reaction rate and necessity of complex purification procedures remain barriers towards metalated bacteriochlorophyll synthesis. Here, these limitations are overcome through the development of a new fast, facile, efficient, base-free microwave heating metallation method for the synthesis of a series of metallo (Pd

  天然衍生的金属细菌叶绿素自从临床批准用于癌症光动力治疗以来就引起了广泛关注。它们的治疗特性植根于细菌叶绿素的金属络合，这赋予它们有利于生物光子和生物医学应用的光学特性，包括在治疗水平上产生近红外光活化的活性氧。尽管有这些优点，但这些发色团的效用受到与细菌叶绿素金属化相关的合成挑战的限制。具体而言，缓慢的反应速率和复杂纯化程序的必要性仍然是金属化细菌叶绿素合成的障碍。在这里，通过开发一种新的快速、简便、高效、无碱微波加热金属化法合成了一系列金属（Pd、Cu、Zn、Cd、Sn、In、Mn、Co）细菌焦脱镁叶绿素。介绍了这些配合物的制备以及结构和光谱表征。然后将这种微波合成方法应用于有效且高效地生成临床光敏剂 Pd-细菌脱镁叶绿素 (TOOKAD)，然后验证其金属化增强的 ROS 生成。
• Modulation of Reactive Oxygen Species Photogeneration of Bacteriopheophorbide <i>a</i> Derivatives by Exocyclic E-Ring Opening and Charge Modifications
  作者：Áron Roxin、Juan Chen、Andrew S. Paton、Timothy P. Bender、Gang Zheng

  DOI：10.1021/jm401538h

  日期：2014.1.9

  With the knowledge that the dominant photodynamic therapy (PDT) mechanism of la (WST09) switched from type 2 to type 1 for 1b (WST11) upon taurine-driven E-ring opening, we hypothesized that taurine-driven E-ring opening of bacteriochlorophyll derivatives and net-charge variations would modulate reactive oxygen species (ROS) photogeneration. Eight bacteriochlorophyll a derivatives were synthesized with varying charges that either contained the E ring (2a-5a) or were synthesized by taurine-driven E-ring opening (2b-513). Time-dependent density functional theory (TDDFT) modeling showed that all derivatives would be type 2 PDT-active, and ROS-activated fluorescent probes were used to investigate the photogeneration of a combination of type 1 and type 2 PDT ROS in organic- and aqueous-based solutions. These investigations validated our predictive modeling calculations and showed that taurine-driven E-ring opening and increasing negative charge generally enhanced ROS photogeneration in aqueous solutions. We propose that these structure activity relationships may provide simple strategies for designing bacteriochlorins that efficiently generate ROS upon photoirradiation.
• [EN] CATIONIC BACTERIOCHLOROPHYLL DERIVATIVES AND USES THEREOF<br/>[FR] DERIVES DE BACTERIOCHLOROPHYLLES CATIONIQUES ET UTILISATION DE CEUX-CI
  申请人：YEDA RES & DEV

  公开号：WO2005120573A3

  公开（公告）日：2006-01-26
• Novel Water-soluble Bacteriochlorophyll Derivatives for Vascular-targeted Photodynamic Therapy: Synthesis, Solubility, Phototoxicity and the Effect of Serum Proteins¶
  作者：Alexander Brandis、Ohad Mazor、Eran Neumark、Varda Rosenbach-Belkin、Yoram Salomon、Avigdor Scherz

  DOI：10.1562/2004-12-01-ra-389r1.1

  日期：——

  New negatively charged water-soluble bacteriochlorophyll (Bch1) derivatives were developed in our laboratory for vascular-targeted photodynamic therapy (VTP). Here we focused on the synthesis, characterization and interaction of the new candidates with serum proteins and particularly on the effect of serum albumin on the photocytotoxicity of WST11, a representative compound of the new derivatives. Using several approaches, we found that aminolysis of the isocyclic ring with negatively charged residues markedly increases the hydrophilicity of the Bch1 sensitizers, decreases their self-association constant and selectively increases their affinity to serum albumin, compared with other serum proteins. The photocytotoxicity of the new candidates in endothelial cell culture largely depends on the concentration of the serum albumin. Importantly, after incubation with physiological concentrations of serum albumin (500-600 mu M), WST11 was found to be poorly photocytotoxic (> 80% endothelial cell survival in cell cultures). However, in a recent publication (Mazor, O. et aL [2005] Photochem. Photobiol. 81,342-351) we showed that VTP of M2R melanoma xenografts with a similar WST11 concentration resulted in similar to 100% tumor flattening and > 70% cure rate. We therefore propose that the two studies collectively suggest that the antitumor activity of WST11 and probably of other similar candidates does not depend on direct photointoxication of individual endothelial cells but on the vascular tissue response to the VTP insult.