p-nitrosojulolidine | 33949-11-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: p-nitrosojulolidine
• 英文别名: 9-nitroso-2,3,6,7-tetrahydro-1H,5H-pyrido[3,2,1-ij]quinoline；9-Nitrosojulolidin；1H,5H-benzo[ij]quinolizine, 2,3,6,7-tetrahydro-9-nitroso-；7-nitroso-1-azatricyclo[7.3.1.05,13]trideca-5,7,9(13)-triene
• CAS: 33949-11-0
• 化学式: C₁₂H₁₄N₂O
• 分子量: 202.256
• InChiKey: MHPUSHOOMBFVSD-UHFFFAOYSA-N

物化性质

• 沸点：
  401.1±44.0 °C(Predicted)
• 密度：
  1.32±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  32.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  p-nitrosojulolidine 在 茴香硫醚 、 三氟乙酸 、 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 18.0h， 生成 (S,Z)-2-amino-3-(3-oxo-2-((2,3,6,7-tetrahydro-1H,5H-pyrido[3,2,1-ij]quinolin-9-yl)imino)-2,3-dihydrobenzo[b]thiophen-7-yl)propanoic acid
  参考文献：
  名称：

  Iminothioindoxyl Donors with Exceptionally High Cross Section for Protein Vibrational Energy Transfer

  摘要：

  摘要 各种蛋白质功能都与振动能量转移（VET）这一重要机制有关。通过在蛋白质中加入一对非典型氨基酸（ncAAs）的供体-传感器，可利用超快可见光泵/红外探针光谱对其基本转移途径进行实验跟踪。然而，迄今为止只有一种供体 ncAA，即偶氮丙氨酸（AzAla），它的可见光消光系数相当低。在这里，我们介绍两种基于亚氨基硫代吲哚肟（ITI）发色团的新型供体 ncAA。二甲基氨基-ITI（DMA-ITI）和久洛尼定-ITI（J-ITI）分子克服了 AzAla 的局限性，其 Vis 消光系数比 AzAla 高 50 倍。众所周知，ITI 分子具有超快的光开关功能，而 DMA-ITI 和 J-ITI 则只能在亚 ps 时间尺度上形成热基态，这对它们用作振动能量供体至关重要。在供体传感器二肽的 VET 测量中，我们研究了新供体的性能。我们观察到的信号比现有的 AzAla 供体大 20 倍，这为研究蛋白质中的 VET 提供了前所未有的可能性。

  DOI：

  10.1002/anie.202317047
• 作为产物：
  描述：

  julolidine hydrochloride 在 盐酸 、 sodium nitrite 作用下， 生成 p-nitrosojulolidine
  参考文献：
  名称：

  Distinguishing Potassium Channel Resting State Conformations in Live Cells with Environment-Sensitive Fluorescence

  摘要：

  Ion channels are polymorphic membrane proteins whose high-resolution structures offer images of individual conformations, giving us starting points for identifying the complex and transient allosteric changes that give rise to channel physiology. Here, we report live-cell imaging of voltage-dependent structural changes of voltage-gated Kv2.1 channels using peptidyl tarantula toxins labeled with an environment-sensitive fluorophore, whose spectral shifts enable identification of voltage-dependent conformation changes in the resting voltage sensing domain (VSD) of the channel. We synthesize a new environment-sensitive, far-red fluorophore, julolidine phenoxazone (JP) azide, and conjugate it to tarantula toxin GxTX to characterize Kv2.1 VSD allostery during membrane depolarization. JP has an inherent response to the polarity of its immediate surroundings, offering site-specific structural insight into each channel conformation. Using voltage-clamp spectroscopy to collect emission spectra as a function of membrane potential, we find that they vary with toxin labeling site, the presence of Kv2 channels, and changes in membrane potential. With a high-affinity conjugate in which the fluorophore itself interacts closely with the channel, the emission shift midpoint is 50 mV more negative than the Kv2.1 gating current midpoint. This suggests that substantial conformational changes at the toxin-channel interface are associated with early gating charge transitions and these are not concerted with VSD motions at more depolarized potentials. These fluorescent probes enable study of conformational changes that can be correlated with electrophysiology, putting channel structures and models into a context of live-cell membranes and physiological states.

  DOI：

  10.1021/acschemneuro.0c00276

文献信息

• Method of producing azomethine dye compound
  申请人：Kimura Keiza

  公开号：US20070073059A1

  公开（公告）日：2007-03-29

  A method of producing a compound represented by formula (I), including reacting a compound represented by formula (II) with a compound represented by formula (III): wherein, in formulas (I) to (III), Ar 31 represents a divalent aromatic group or a divalent heterocyclic group; L 21 represents a single bond, —O—, or —N(R 26 )—; Z 21 represents —O— or —N(R 27 )—; R 21 , R 22 , R 23 , R 24 , and R 27 each independently represent a hydrogen atom or a substituent; R 25 , R 26 , R 31 , and R 32 each independently represent a hydrogen atom, an aliphatic group, an aromatic group, or a heterocyclic group bonding through its carbon atom; and n 21 represents 0 or 1, wherein any of R 21 , R 22 , R 23 , R 24 , and R 27 may bond to one another to form a ring, and any of Ar 31 , R 31 , and R 32 may bond to one another to form a ring.

  一种制备由公式（I）表示的化合物的方法，包括通过化合物（II）与化合物（III）反应来制备：其中，在公式（I）至（III）中，Ar31表示二价芳香基团或二价杂环基团；L21表示单键，-O-或-N（R26）-；Z21表示-O-或-N（R27）-；R21、R22、R23、R24和R27各自独立地表示氢原子或取代基；R25、R26、R31和R32各自独立地表示氢原子、脂肪基、芳香基或通过其碳原子键合的杂环基；n21表示0或1，其中R21、R22、R23、R24和R27中的任何一个可以相互键合形成环，Ar31、R31和R32中的任何一个可以相互键合形成环。
• Distinguishing Potassium Channel Resting State Conformations in Live Cells with Environment-Sensitive Fluorescence
  作者：Sebastian Fletcher-Taylor、Parashar Thapa、Rebecka J. Sepela、Rayan Kaakati、Vladimir Yarov-Yarovoy、Jon T. Sack、Bruce E. Cohen

  DOI：10.1021/acschemneuro.0c00276

  日期：2020.8.5

  Ion channels are polymorphic membrane proteins whose high-resolution structures offer images of individual conformations, giving us starting points for identifying the complex and transient allosteric changes that give rise to channel physiology. Here, we report live-cell imaging of voltage-dependent structural changes of voltage-gated Kv2.1 channels using peptidyl tarantula toxins labeled with an environment-sensitive fluorophore, whose spectral shifts enable identification of voltage-dependent conformation changes in the resting voltage sensing domain (VSD) of the channel. We synthesize a new environment-sensitive, far-red fluorophore, julolidine phenoxazone (JP) azide, and conjugate it to tarantula toxin GxTX to characterize Kv2.1 VSD allostery during membrane depolarization. JP has an inherent response to the polarity of its immediate surroundings, offering site-specific structural insight into each channel conformation. Using voltage-clamp spectroscopy to collect emission spectra as a function of membrane potential, we find that they vary with toxin labeling site, the presence of Kv2 channels, and changes in membrane potential. With a high-affinity conjugate in which the fluorophore itself interacts closely with the channel, the emission shift midpoint is 50 mV more negative than the Kv2.1 gating current midpoint. This suggests that substantial conformational changes at the toxin-channel interface are associated with early gating charge transitions and these are not concerted with VSD motions at more depolarized potentials. These fluorescent probes enable study of conformational changes that can be correlated with electrophysiology, putting channel structures and models into a context of live-cell membranes and physiological states.
• Iminothioindoxyl Donors with Exceptionally High Cross Section for Protein Vibrational Energy Transfer
  作者：Carolin Feid、Larita Luma、Tobias Fischer、Jan Gerrit Löffler、Nikolai Grebenovsky、Josef Wachtveitl、Alexander Heckel、Jens Bredenbeck

  DOI：10.1002/anie.202317047

  日期：2024.2.26

  Various protein functions are related to vibrational energy transfer (VET) as an important mechanism. The underlying transfer pathways can be experimentally followed by ultrafast Vis‐pump/IR‐probe spectroscopy with a donor‐sensor pair of non‐canonical amino acids (ncAAs) incorporated in a protein. However, so far only one donor ncAA, azulenylalanine (AzAla), exists, which suffers from a comparably low Vis extinction coefficient. Here, we introduce two novel donor ncAAs based on an iminothioindoxyl (ITI) chromophore. The dimethylamino‐ITI (DMA‐ITI) and julolidine‐ITI (J‐ITI) moieties overcome the limitation of AzAla with a 50 times higher Vis extinction coefficient. While ITI moieties are known for ultrafast photoswitching, DMA‐ITI and J‐ITI exclusively form a hot ground state on the sub‐ps timescale instead, which is essential for their usage as vibrational energy donor. In VET measurements of donor‐sensor dipeptides we investigate the performance of the new donors. We observe 20 times larger signals compared to the established AzAla donor, which opens unprecedented possibilities for the study of VET in proteins.

  摘要 各种蛋白质功能都与振动能量转移（VET）这一重要机制有关。通过在蛋白质中加入一对非典型氨基酸（ncAAs）的供体-传感器，可利用超快可见光泵/红外探针光谱对其基本转移途径进行实验跟踪。然而，迄今为止只有一种供体 ncAA，即偶氮丙氨酸（AzAla），它的可见光消光系数相当低。在这里，我们介绍两种基于亚氨基硫代吲哚肟（ITI）发色团的新型供体 ncAA。二甲基氨基-ITI（DMA-ITI）和久洛尼定-ITI（J-ITI）分子克服了 AzAla 的局限性，其 Vis 消光系数比 AzAla 高 50 倍。众所周知，ITI 分子具有超快的光开关功能，而 DMA-ITI 和 J-ITI 则只能在亚 ps 时间尺度上形成热基态，这对它们用作振动能量供体至关重要。在供体传感器二肽的 VET 测量中，我们研究了新供体的性能。我们观察到的信号比现有的 AzAla 供体大 20 倍，这为研究蛋白质中的 VET 提供了前所未有的可能性。