valinomycin | 2001-95-8

• 物质功能分类: 原料药 - 抗生素类药物 - 其它抗生素类药
• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: valinomycin
• 英文别名: (3S,6S,9R,12R,15S,18S,21R,24R,27S,30S,33R,36R)-6,18,30-trimethyl-3,9,12,15,21,24,27,33,36-nona(propan-2-yl)-1,7,13,19,25,31-hexaoxa-4,10,16,22,28,34-hexazacyclohexatriacontane-2,5,8,11,14,17,20,23,26,29,32,35-dodecone
• CAS: 2001-95-8
• 化学式: C₅₄H₉₀N₆O₁₈
• 分子量: 1111.34
• InChiKey: FCFNRCROJUBPLU-DNDCDFAISA-N

物化性质

• 熔点：
  187-190 °C
• 比旋光度：
  D20 +31.0° (c = 1.6 in benzene)
• 沸点：
  821.74°C (rough estimate)
• 密度：
  1.060
• 闪点：
  87℃
• 溶解度：
  二甲基亚砜：≥10 mg/mL
• 物理描述：
  Shiny crystalline solid. Used as an insecticide and nematocide. Not registered as a pesticide in the U.S. (EPA, 1998)
• 颜色/状态：
  Shiny rectangular plates
• 碰撞截面：
  327.4 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]
• 稳定性/保质期：
  如果按照规格使用和储存，则不会分解，没有已知的危险反应，应避免与氧化物接触。

计算性质

• 辛醇/水分配系数(LogP)：
  9.1
• 重原子数：
  78
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  332
• 氢给体数：
  6
• 氢受体数：
  18

ADMET

毒理性

• 副作用

神经毒素 - 其他中枢神经系统神经毒素

Neurotoxin - Other CNS neurotoxin

来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases

毒理性

• 相互作用

果糖-1,6-二磷酸盐在体外对抗了氯化钾诱导的兔心肌收缩力抑制和瓦利诺霉素诱导的膜去极化。

Fructose-1,6-disphosphate counteracts the inhibition of contractile strength of rabbit cardiac muscle induced by potassium chloride in vitro and valinomycin induced depolarization. ...

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• TSCA：
  Yes
• 危险等级：
  6.1(a)
• 危险品标志：
  Xn
• 安全说明：
  S26,S28,S36,S36/37,S37/39,S45
• 危险类别码：
  R27/28
• WGK Germany：
  1,3
• 海关编码：
  29419090
• 危险品运输编号：
  UN 2811 6
• RTECS号：
  YV9468000
• 包装等级：
  I
• 危险类别：
  6.1(a)
• 储存条件：
  密封，在2°C至-8°C下保存

SDS

Name:	Valinomycin 96% (HPLC) Material Safety Data Sheet
Synonym:	None Known
CAS:	2001-95-8

Section 1 - Chemical Product MSDS Name:Valinomycin 96% (HPLC) Material Safety Data Sheet
Synonym:None Known

---

Section 2 - COMPOSITION, INFORMATION ON INGREDIENTS

CAS#	Chemical Name	content	EINECS#
2001-95-8	Valinomycin	96%	217-896-6

Hazard Symbols: T+
Risk Phrases: 27/28

---

Section 3 - HAZARDS IDENTIFICATION
EMERGENCY OVERVIEW
Very toxic in contact with skin and if swallowed.Highly toxic.
Potential Health Effects
Eye:
May cause eye irritation.
Skin:
May cause skin irritation. May be fatal if absorbed through the skin.
Ingestion:
May be fatal if swallowed. May cause irritation of the digestive tract. May cause cardiac disturbances. May cause central nervous system depression.
Inhalation:
May cause respiratory tract irritation. May cause cardiac abnormalities. Inhalation at high concentrations may cause CNS depression and asphixiation.
Chronic:
Effects may be delayed.

---

Section 4 - FIRST AID MEASURES
Eyes: Immediately flush eyes with plenty of water for at least 15 minutes, occasionally lifting the upper and lower eyelids. Get medical aid.
Skin:
Get medical aid immediately. Immediately flush skin with plenty of water for at least 15 minutes while removing contaminated clothing and shoes. Wash clothing before reuse. SPEEDY ACTION IS CRITICAL! Ingestion:
Never give anything by mouth to an unconscious person. Get medical aid immediately. SPEED IS ESSENTIAL. A DOCTOR MUST BE NOTIFIED AT ONCE. Do NOT induce vomiting. If conscious and alert, rinse mouth and drink 2-4 cupfuls of milk or water.
Inhalation:
Get medical aid immediately. Remove from exposure and move to fresh air immediately. If breathing is difficult, give oxygen. Do NOT use mouth-to-mouth resuscitation. If breathing has ceased apply artificial respiration using oxygen and a suitable mechanical device such as a bag and a mask.
Notes to Physician:

---

Section 5 - FIRE FIGHTING MEASURES
General Information:
As in any fire, wear a self-contained breathing apparatus in pressure-demand, MSHA/NIOSH (approved or equivalent), and full protective gear. During a fire, irritating and highly toxic gases may be generated by thermal decomposition or combustion. Containers may explode when heated. Non-combustible, substance itself does not burn but may decompose upon heating to produce irritating, corrosive and/or toxic fumes.
Extinguishing Media:
Substance is noncombustible; use agent most appropriate to extinguish surrounding fire.

---

Section 6 - ACCIDENTAL RELEASE MEASURES
General Information: Use proper personal protective equipment as indicated in Section 8.
Spills/Leaks:
Vacuum or sweep up material and place into a suitable disposal container. Clean up spills immediately, observing precautions in the Protective Equipment section. Avoid generating dusty conditions.
Provide ventilation.

---

Section 7 - HANDLING and STORAGE
Handling:
Wash thoroughly after handling. Use with adequate ventilation.
Minimize dust generation and accumulation. Avoid contact with eyes, skin, and clothing. Keep container tightly closed. Avoid ingestion and inhalation.
Storage:
Store in a tightly closed container. Store in a cool, dry, well-ventilated area away from incompatible substances. Poison room locked/refrigerator.

---

Section 8 - EXPOSURE CONTROLS, PERSONAL PROTECTION
Engineering Controls:
Facilities storing or utilizing this material should be equipped with an eyewash facility and a safety shower. Use adequate ventilation to keep airborne concentrations low.
Exposure Limits CAS# 2001-95-8: Personal Protective Equipment Eyes: Wear appropriate protective eyeglasses or chemical safety goggles as described by OSHA's eye and face protection regulations in 29 CFR 1910.133 or European Standard EN166.
Skin:
Wear appropriate protective gloves to prevent skin exposure.
Clothing:
Wear appropriate protective clothing to minimize contact with skin.
Respirators:
Follow the OSHA respirator regulations found in 29 CFR 1910.134 or European Standard EN 149. Use a NIOSH/MSHA or European Standard EN 149 approved respirator if exposure limits are exceeded or if irritation or other symptoms are experienced.

---

Section 9 - PHYSICAL AND CHEMICAL PROPERTIES

Physical State: Solid
Color: white
Odor: None reported.
pH: Not available.
Vapor Pressure: Not available.
Viscosity: Not available.
Boiling Point: Not available.
Freezing/Melting Point: 187.00 - 189.00 deg C
Autoignition Temperature: Not applicable.
Flash Point: Not applicable.
Explosion Limits, lower: Not available.
Explosion Limits, upper: Not available.
Decomposition Temperature:
Solubility in water: practically insoluble
Specific Gravity/Density:
Molecular Formula: C54H90N6O18
Molecular Weight: 1111.35

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Section 10 - STABILITY AND REACTIVITY
Chemical Stability:
Stable under normal temperatures and pressures.
Conditions to Avoid:
Incompatible materials, dust generation, excess heat, strong oxidants.
Incompatibilities with Other Materials:
Oxidizing agents.
Hazardous Decomposition Products:
Carbon monoxide, irritating and toxic fumes and gases, carbon dioxide.
Hazardous Polymerization: Has not been reported.

---

Section 11 - TOXICOLOGICAL INFORMATION
RTECS#:
CAS# 2001-95-8: YV9468000 LD50/LC50:
CAS# 2001-95-8: Oral, mouse: LD50 = 2500 ug/kg; Oral, rat: LD50 = 4 mg/kg; Skin, rabbit: LD50 = 5 mg/kg.
Carcinogenicity:
Valinomycin - Not listed by ACGIH, IARC, or NTP.
Other:
See actual entry in RTECS for complete information.

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Section 12 - ECOLOGICAL INFORMATION

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Section 13 - DISPOSAL CONSIDERATIONS
Dispose of in a manner consistent with federal, state, and local regulations.

---

Section 14 - TRANSPORT INFORMATION

IATA
Shipping Name: TOXIC SOLID, ORGANIC, N.O.S.*
Hazard Class: 6.1
UN Number: 2811
Packing Group: I
IMO
Shipping Name: TOXIC SOLID, ORGANIC, N.O.S.
Hazard Class: 6.1
UN Number: 2811
Packing Group: I
RID/ADR
Shipping Name: TOXIC SOLID, ORGANIC, N.O.S.
Hazard Class: 6.1
UN Number: 2811
Packing group: I

---

Section 15 - REGULATORY INFORMATION

European/International Regulations
European Labeling in Accordance with EC Directives
Hazard Symbols: T+
Risk Phrases:
R 27/28 Very toxic in contact with skin and if
swallowed.
Safety Phrases:
S 26 In case of contact with eyes, rinse immediately
with plenty of water and seek medical advice.
S 45 In case of accident or if you feel unwell, seek
medical advice immediately (show the label where
possible).
WGK (Water Danger/Protection)
CAS# 2001-95-8: 3
Canada
CAS# 2001-95-8 is listed on Canada's NDSL List.
CAS# 2001-95-8 is not listed on Canada's Ingredient Disclosure List.
US FEDERAL
TSCA
CAS# 2001-95-8 is listed on the TSCA inventory.

---

SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

概述

缬氨霉素是一种脂溶性的抗菌素，其化学结构包含3个D-缬氨酸、3个L-乳酸、3个L-缬氨酸和3个D-羟基异戊酸盐序列，并形成环状肽。它作为一种离子载体，对钾离子（K+）具有特异性亲和力，能够结合钾离子并轻易将其带入膜内，从而产生膜的极化，在膜两侧形成膜电位。

氨基酸及寡肽是有效的光学活性固定相，在气相、液相色谱以及毛细管电泳的手性分离中广泛应用。研究还发现，缬氨霉素可以作为杀虫剂或植物生长调节剂，并可能成为微生物代谢物的潜在药物。

生物学 产生膜电位

在没有加入缬氨霉素时，囊泡内外的一价离子总浓度保持基本不变，但囊泡外含有钾离子而囊泡内不含。当向0.1 mol, pH 5.0的醋酸钠溶液中添加0.2 mmol的pH 5.0氯化钾溶液，并加入缬氨霉素后，囊泡膜两侧会产生明显的膜电位。在外边有氯化钾存在的条件下，缬氨霉素将外侧的钾离子带入囊泡内，从而产生极化现象，在囊泡膜两侧形成一定膜电位。随着缬氨霉素浓度增加，膜电位也随之增加，这一过程反过来促使更多的钾离子进入囊泡内部，最终达到平衡状态。

光电响应信号

在0.1 mol NaCl溶液中，缬氨霉素对光电响应信号的影响不如K+明显，但同样逐渐变小。光电响应信号部分源自跨膜梯度差，另一部分是质子泵产生的质子梯度。关于缬氨霉素影响光电响应的具体机制，可能是因为离子渗透性的增加导致跨膜梯度崩溃，或者直接影响到紫膜碎片中菌紫质的质子泵功能，亦或两者同时存在。此外，即使质子流没有变化，由于膜电阻下降，光电压也会下降。

药用 抗生素药物

通过对一种非典型的灰色链霉菌（Streptomyces griseus）菌株分离，发现其培养液具有强烈的抗蚊幼虫活性。化学分析揭示存在一种杀虫抗生素——缬氨霉素（Valinomycin），它已报道为极赤黄链霉菌（S. fulvissimus）、玫瑰产色链霉菌（S. roseochromogenes）的产物，可用于杀虫、杀线虫和抗蜡。

脂质体离子载体

中性环状缩酚酸肽类药物缬氨霉素主要作用于细胞膜。作为流动的离子载体，它可以与单价或双价阳离子结合，并具有不同的特性。阳离子—离子载体复合物通过细胞膜进行扩散。尽管脂质体用作药物载体能降低VM（Valinomycin）的毒性，同时保持甚至加强抗肿瘤作用，但由于它们对重要器官如中枢神经组织、外周神经组织、心脏和肾的毒性问题限制了其广泛使用。

用途

缬氨霉素能够选择性地与钾离子（K+）结合形成脂溶性复合物，使钾离子容易通过膜脂双层。它作为呼吸链离子载体抑制剂的作用机制是通过增加线粒体内膜对钾离子的通透性，从而抑制氧化磷酸化作用。此外，它由链霉菌（Bacterium streptomyces）产生。

参考文献

1. Rod M.Heisey, 邵玲. 灰色链霉菌产生的杀虫抗生素——缬氨霉素 [J]. 农药译丛, 1990(1):37-39+34.
2. 胡坤生, 谈曼琪, 石志远, 彭程航. 缬氨霉素对紫膜碎片双层平板脂膜(BLM)光电响应的影响 [J]. 生物物理学报, 1991(2):179-182.
3. 杨力. 脂质体中掺入离子载体药物缬氨霉素能降低细胞毒性并加强抗肿瘤效应 [J]. 国外医学(肿瘤学分册), 1987(4):255-256.
4. 方培生. 以缬氨霉素为活性物质的微型钾离子敏感器件的研究 [J]. 西安交通大学学报, 1987(3):95-101.
5. 杨力. 缬氨霉素作为脂溶性复合物选择性地与K+结合 [J]. 生物化学杂志, 1986(2):123-127.

反应信息

• 作为反应物：
  描述：

  valinomycin 在 potassium chloride 作用下， 以 甲醇 为溶剂， 生成
  参考文献：
  名称：

  带有可衍生羟基位点的缬氨霉素类似物的位点生物活性。

  摘要：

  Valinomycin（VLM，1）是一种K +离子载体环二肽，能够使线粒体去极化并诱导多种哺乳动物细胞类型（包括多种肿瘤细胞系）的凋亡。为了创建可选择性地将VLM传递至病理细胞的基于VLM的，针对配体的抗癌药物，我们先前已将可衍生的羟基手柄引入VLM结构，从而可以访问带有三聚体的单羟基VLM（HyVLM）三元文库。d- Hyi，d -Val或l的异丙基侧链上的OH基-Val残基（分别为模拟量2-4）。在本文中，已根据其可改变分离的大鼠肝脏线粒体功能的能力评估了可缀合的HyVLM保留的生物活性水平。在1-10 nM的HyVLM和20或125 mM KCl介质中进行的实验表明，羟基相对于VLM降低HyVLM的效力，其程度取决于羟基化涉及的分子位点。另一方面，估计每个类似物与Na +，K +和Cs +的配合物的稳定常数（在25°C的甲醇中）表明，HyVLM很好地保留了VLM结合特征，除了Na

  DOI：

  10.1002/psc.2571
• 作为产物：
  描述：

  D-Hiv-D-Val-L-Lac-L-Val-SNAC 在 recombinant terminal CesB thioesterase 作用下， 以 aq. buffer 为溶剂， 反应 14.0h， 生成 valinomycin
  参考文献：
  名称：

  来自脑脑苷脂生物合成的硫酯酶负责线性四肽的寡聚化和大环化。

  摘要：

  Cereulide 是一种有毒的环状 depsidodecapeptide，由两种非核糖体肽合成酶 CesA 和 CesB在蜡样芽孢杆菌中产生。虽然在结构上与缬氨霉素高度相似，并具有同源的生物合成基因簇，但最近的工作表明，脑蓝素是通过一种不同的机制产生的，该机制依赖于两个二缩肽-肽基载体蛋白 (PCP) 结合中间体的非规范偶联。最终，这种替代机制产生了一种四肽-PCP 结合中间体，它不同于根据 CesA 和 CesB 的规范活性预测的四肽-PCP 中间体。为了区分机制，将两种四肽制备为N-乙酰半胱胺硫酯 (SNAC)，以及纯化的重组末端 CesB 硫酯酶 (CesB TE) 寡聚化和大环化每种底物的能力。只有经典底物被转化为脑脑苷脂，排除了替代机制。结果表明，CesB TE 可以使用相关的四肽底物，如缬氨霉素四肽和混合脑苷脂-缬氨霉素四肽与其天然底物结合产生嵌合天然产物。这项工作阐明了脑苷

  DOI：

  10.1021/acs.jnatprod.0c00333

文献信息

• Isopropenyl chlorocarbonate (IPCC)1 in amino acid and peptide chemistry: Esterification of N-protected amino acids; Application to the synthesis of the depsipeptide valinomycin
  作者：Choukri Zeggaf、Joël Poncet、Patrick Jouin、Marie-Noëlle Dufour、Bertrand Castro

  DOI：10.1016/s0040-4020(01)81083-8

  日期：1989.1

  Esterification of N-protected α-amino acids was achieved via isopropenyl chlorocarbonate (IPCC) activation. In situ alcoholysis of the unstable mixed anhydride intermediate was catalyzed by 4-(dimethylamino)pyridine (DMAP). Competing isopropenyl ester formation was negligible when using methylene chloride as the solvent. A variety of esters from primary and secondary alcohols were obtained with good

  N-保护的α-氨基酸的酯化反应是通过异丙烯基氯碳酸酯（IPCC）活化来实现的。不稳定的混合酸酐中间体的原位醇解反应是通过4-（二甲基氨基）吡啶（DMAP）催化的。当使用二氯甲烷作为溶剂时，竞争性异丙烯基酯的形成可忽略不计。从伯醇和仲醇获得的各种酯均具有良好的收率（60％至96％），即使在更剧烈的条件下，即使受阻更严重的叔丁醇也可提供可接受的收率。通过使用IPCC进行酯键形成，使用BOP试剂进行肽偶联和最后一步环化反应，制备抗生素瓦利霉素，可以说明depsipeptide合成方法的改进。
• Antineoplastic Agents. 570. Isolation and Structure Elucidation of Bacillistatins 1 and 2 from a Marine <i>Bacillus silvestris</i>^,
  作者：George R. Pettit、John C. Knight、Delbert L. Herald、Robin K. Pettit、Fiona Hogan、Venugopal J. R. V. Mukku、John S. Hamblin、Michael J. Dodson、Jean-Charles Chapuis

  DOI：10.1021/np800603u

  日期：2009.3.27

  cyclodepsipeptide strongly inhibited growth of a human cancer cell line panel, with GI50’s of 10−4−10−5 μg/mL, and each compound was active against antibiotic-resistant Streptococcus pneumoniae. The structures were elucidated by a combination of X-ray diffraction and mass and 2D NMR spectroscopic analyses, together with chemical degradation.

  已从从太平洋（智利南部）螃蟹获得的Bacillus silvestris样品的培养物中分离出两种新的环缩肽，称为杆菌抑制素 1 ( 1 ) 和 2 ( 2 ) 。每个 12 单位环缩肽强烈抑制人类癌细胞系面板的生长，GI 50为 10 -4 -10 -5 μg/mL，并且每种化合物对抗生素耐药性肺炎链球菌具有活性。通过结合 X 射线衍射和质量和 2D NMR 光谱分析以及化学降解来阐明结构。
• Selective Synthesis of Hydroxy Analogues of Valinomycin using Dioxiranes
  作者：Cosimo Annese、Immacolata Fanizza、Cosima D. Calvano、Lucia D’Accolti、Caterina Fusco、Ruggero Curci、Paul G. Williard

  DOI：10.1021/ol201971v

  日期：2011.10.7

  A synthesis of representative monohydroxy derivatives of valinomycin (VLM) was achieved under mild conditions by direct hydroxylation at the side chains of the macrocyclic substrate using dioxiranes. Results demonstrate that the powerful methyl(trifluoromethyl)dioxirane 1b should be the reagent of choice to carry out these key transformations. Thus, a mixture of compounds derived from the direct dioxirane

  缬氨霉素 (VLM) 的代表性单羟基衍生物的合成是在温和条件下通过使用二环氧乙烷在大环底物的侧链上直接羟基化来实现的。结果表明，强大的甲基（三氟甲基）二环氧乙烷1b应该是进行这些关键转化的首选试剂。因此，可以获得衍生自二环氧乙烷直接攻击一个 Hyi 残基（化合物3a）或一个 Val 部分（化合物3b和3c）的 β-(CH 3 ) 2 C- H烷基链的化合物的混合物。在方便的混合物分离后，每个新的氧官能化大环都得到了完全的表征。
• The crystal structure of a valinomycin•2Ca²⁺ complex and the multi-step solution equilibria in acetonitrile characterised by ¹H NMR, UV–Vis, and mass spectrometry
  作者：Alisha A. Contractor、Amaan M. Kazerouni、Anna R. Michmerhuizen、Margaret L. Falkenberry、Rigoberto Segovia、Nicholas M. Blair、SeongEun Kim、Douglas A. Vander Griend、John Bacsa、Farooq A. Khan、Megumi Fujita

  DOI：10.1080/10610278.2016.1186276

  日期：2017.2.1

  valinomycin–calcium complex, which crystallises exclusively as a 1:2 valinomycin:Ca2+ complex, [VCa2(OTf)2(H2O)2]2+ in the solid state (V = valinomycin, OTf = triflate). Along with the 1:2 complex, the solution phase 1:1 and 2:1 complexes have been characterised in acetonitrile by 1H NMR and UV–Vis titration experiments. The molar absorptivity curves and binding equilibrium constants for these complexes have been

  摘要 缬氨霉素是一种众所周知的钾选择性离子载体，但它与钙离子（另一种重要的生物学阳离子）直接相互作用的性质也引起了人们极大的兴趣。我们已经确定了缬氨霉素-钙复合物的第一个晶体结构，该复合物仅以 1:2 缬氨霉素:Ca2+ 复合物结晶，[VCa2(OTf)2(H2O)2]2+ 处于固态（V = 缬氨霉素，OTf = 三氟甲磺酸）。与 1:2 配合物一起，溶液相 1:1 和 2:1 配合物已通过 1H NMR 和 UV-Vis 滴定实验在乙腈中表征。这些复合物的摩尔吸光度曲线和结合平衡常数是通过使用程序 SIVVU™ 对 UV-Vis 滴定数据的全局分析确定的。
• Wearable technology with sensors integrated into clothing fibers
  申请人：HFT Smart Sensors, Incorporated

  公开号：US11344230B2

  公开（公告）日：2022-05-31

  Embodiments of the invention disclosed herein are directed to articles of clothing that allow for monitoring of different analytes (e.g., electrolytes and molecules) in human sweat during fitness activity, while training, or simply in everyday life. The clothing includes a sensor system completely integrated in textile such that every sensing part is made of textile fibers. The clothing is able to control, collect, analyze, and expel the sweat over time. The textile sensor allows a spontaneous absorption of body sweat directly from the skin, while it is produced, using the hydrophilic natural properties of the textile. Then, once adsorbed, the flux of sweat is controlled and guided through the textile using a gradient of the textile's hydrophilic properties. The sweat guided through the textile is analyzed through an electrochemical sensor woven into the textile. Finally, the sweat is collected in a reservoir and expelled for evaporation.

  本文公开的本发明实施例针对的是可在健身活动、训练或日常生活中监测人体汗液中不同分析物（如电解质和分子）的服装。这种服装包括一个完全集成在纺织品中的传感器系统，每个传感部件都由纺织纤维制成。服装能够控制、收集、分析和排出汗液。纺织品传感器利用纺织品的亲水性天然特性，可在人体出汗时直接从皮肤自发吸收汗液。吸附后，利用纺织品的亲水性能梯度控制和引导汗液流经纺织品。通过纺织品中编织的电化学传感器对引导通过纺织品的汗液进行分析。最后，汗液被收集到一个储存器中，并排出蒸发。