Acetonitrile appears as a colorless limpid liquid with an aromatic odor. Flash point 42°F. Density 0.783 g / cm3. Toxic by skin absorption. Less dense than water. Vapors are denser than air.
颜色/状态：
Colorless, limpid liquid
气味：
Aromatic odor
味道：
Burning sweetish taste
蒸汽密度：
1.42 (NTP, 1992) (Relative to Air)
蒸汽压力：
88.8 mm Hg at 25 °C
亨利常数：
Henry's Law constant = 3.45X10-5 atm-cu m/mole at 25 °C
When heated to decomposition, emits highly toxic fumes of /cyanides and nitrogen oxides/.
粘度：
0.35 cP at 20 °C
腐蚀性：
Liquid acetonitrile will attack some forms of plastics, rubber, and coatings.
燃烧热：
31.03X10+6 J/kg at 25 °C
汽化热：
72.7X10+4 J/kg at 80 °C
表面张力：
29.04 dynes/cm at 20 °C
电离电位：
12.20 eV
聚合：
A mixture of acetonitrile and sulfuric acid on heating (or self-heating) to 53 °C underwent an uncontrollable exothermic reaction to 160 °C in a few seconds. The presence of 28 mol% of sulfur trioxide reduces the initiation temperature to about 15 °C. Polymerization of the nitrile is suspected.
Inorganic cyanide has long been known to react with trivalent iron of cytochrome oxidase in mitochondria and block the reduction of oxygen needed for cellular respiration, thus leading to cytotoxic anoxia. The toxicity of acetonitrile (ACN) is believed to be mediated, in part, through this mechanism. ACN is metabolized to inorganic cyanide, but the conversion occurs slowly compared to other nitriles (which may explain the delay in onset of acute symptoms). /Previous studies/ suggest that the conversion to cyanide is oxygen- and NADPH-dependent, possibly mediated by P450 isozyme (2E1 or P-450j). Some /studies/ suggest that ACN produces cyanohydrin by a P450 reaction, which is then decomposed by catalase to release cyanide. Formaldehyde and formic acid are also postulated to be by-products of ACN metabolism. Cyanide can be further oxidized to thiocyanate, a less toxic compound that is excreted in urine, but one that may interfere with thyroid function. Conversion is mediated by rhodanese, a sulfurtransferase found in liver and human nasal respiratory mucosa. A minor urinary metabolite that has been detected after administration of ACN in drinking water to rats is 2-aminothiolazine-4-carboxylic acid. Cyanide also can be oxidized to cyanate ion with further oxidation to formic acid).
/Male Wistar/ rats given 2340 or 1500 mg/kg died within 3 to 28 hr after the intraperitoneal injection, but rats given 600 mg/kg survived with no apparent symptoms. After administration of 2340 mg/kg, concentrations of acetonitrile and free and combined cyanide in various organs ranged from 900 to 1700 mg/kg, 200 to 3500 ug/kg, and 3.5 to 17 mg/kg tissue, respectively. Mean total urinary acetonitrile and free and combined cyanide (essentially all thiocyanate) excreted during the 11 days following an intraperitoneal injection of 600 mg/kg were 28, 0.2 and 12 mg, respectively. These values were equivalent to 3, 0.035 and 2.3% of the acetonitrile dose, respectively. Urinary acetonitrile was detectable for 4 days after dosing, whereas free and combined cyanide were detectable until 11 days, at which time the animals were sacrificed.
Thiocyanate was measured as index of cyanide ion release in urine of rats given equimolar doses of nitriles. More thiocyanate was excreted after oral administration than after ip administration. Oral administration of acetonitrile yielded 37% of dose as thiocyanate (SCN-), whereas after ip injection, 4.5% of dose was excreted as thiocyanate. /nitriles/
When rat liver microsomes were incubated with glycolonitrile or acetonitrile, cyanide was liberated without the formation of formaldehyde. Based on the amount of cytochrome P450 in the microsomal preparation and the rates of cyanide formed, the action of an enzyme system was postulated in the metabolism of both compounds.
Organic nitriles are converted into cyanide ions through the action of cytochrome P450 enzymes in the liver. Cyanide is rapidly absorbed and distributed throughout the body. Cyanide is mainly metabolized into thiocyanate by either rhodanese or 3-mercaptopyruvate sulfur transferase. Cyanide metabolites are excreted in the urine. (L96)
IDENTIFICATION AND USE: Acetonitrile is a liquid with an ether like odor. It is a volatile highly polar solvent used in many different industrial applications including use for the hydrocarbon extraction processes, especially for butadiene; intermediate; catalyst; separation of fatty acids from vegetable oils; and manufacturing of synthetic pharmaceuticals. It is also the starting material for many types of nitrogen-containing compounds, It can be metabolized to produce hydrogen cyanide, which is the source of the observed toxic effects. HUMAN EXPOSURE AND TOXICITY: Symptoms and signs of acute acetonitrile intoxication include chest pain, tightness in the chest, nausea, emesis, tachycardia, hypotension, short and shallow respiration, headache, restlessness and seizures. The systemic effects appear to be attributable to the conversion of acetonitrile to cyanide. Blood cyanide and thiocyanate levels are elevated during acute intoxication. Fatalities after exposure to acetonitrile in the workplace and fatal cases of a child ingesting an acetonitrile containing cosmetic have been reported. Elevated tissue cyanide concentrations were found in postmortem examination of these cases. Acetonitrile is readily absorbed from the gastrointestinal tract, through the skin and the lungs. All three routes of exposure have been reported to lead to systemic effects. No epidemiological study of cancer incidence could be located. ANIMAL STUDIES: There are substantial data to suggest that most of the systemic toxic effects of acetonitrile are mediated through its metabolism to cyanide, which is catalyzed by the cytochrome P450 monooxygenase system. Cyanide is subsequently conjugated with thiosulfate to form thiocyanate which is eliminated in the urine. Peak concentrations of cyanide in the blood of rats following administration of near lethal doses of acetonitrile approximate concentrations observed following the administration of a lethal dose of potassium cyanide. The peak concentration of cyanide after administration of acetonitrile is delayed by up to several hours as compared to other nitriles. The more rapid rate at which cyanide is produced in the mouse appears to account for the much greater sensitivity of this species to the toxic effects of acetonitrile. A portion of the acetonitrile is also eliminated unchanged in expired air and in the urine. Guinea pigs are also another sensitive species to acetonitrile intoxication. The main symptoms in animals appear to be prostration followed by seizures. Dermal application of acetonitrile causes systemic toxicity in animals. Rats were given gavage doses of 125, 190, or 275 mg acetonitrile/kg from gestational days 6 through 19. An increase in post-implantation loss, with a decrease in viable fetuses, was seen at 275 mg/kg. There were no structural abnormalities in the fetuses derived from acetonitrile-exposed rats. Developmental study in pregnant Syrian golden hamsters exposed up to 8,000 ppm acetonitrile for 1 hour on gestational day 8 and then sacrificed on gestational day 14 demonstrated maternal toxixity and fetotoxicity. Abnormal fetuses exhibiting exencephaly and rib fusions were recovered; surviving litters at 8,000 ppm developed severe axial skeletal dysraphic disorders; one 8,000-ppm fetus exhibited extrathoracic ectopia cordis with accompanying defects in the sternum of the heart. Acetonitrile was not mutagenic in Salmonella typhimurium strain TA97, TA98, TA100, TA1535, or TA1537, with or without metabolic activation. In cultured Chinese hamster ovary cells, acetonitrile produced a weakly positive response in the sister chromatid exchange test without, but not with metabolic activation. A small increase in chromosomal aberrations was observed in cultured Chinese hamster ovary cells treated with acetonitrile in the presence, but not in the absence, of metabolic activation. A significant increase in micronucleated normochromatic erythrocytes was observed in peripheral blood samples from male mice treated with acetonitrile for 13 weeks; the frequency of micronucleated erythrocytes in female mice was not affected by exposure to acetonitrile.
Organic nitriles decompose into cyanide ions both in vivo and in vitro. Consequently the primary mechanism of toxicity for organic nitriles is their production of toxic cyanide ions or hydrogen cyanide. Cyanide is an inhibitor of cytochrome c oxidase in the fourth complex of the electron transport chain (found in the membrane of the mitochondria of eukaryotic cells). It complexes with the ferric iron atom in this enzyme. The binding of cyanide to this cytochrome prevents transport of electrons from cytochrome c oxidase to oxygen. As a result, the electron transport chain is disrupted and the cell can no longer aerobically produce ATP for energy. Tissues that mainly depend on aerobic respiration, such as the central nervous system and the heart, are particularly affected. Cyanide is also known produce some of its toxic effects by binding to catalase, glutathione peroxidase, methemoglobin, hydroxocobalamin, phosphatase, tyrosinase, ascorbic acid oxidase, xanthine oxidase, succinic dehydrogenase, and Cu/Zn superoxide dismutase. Cyanide binds to the ferric ion of methemoglobin to form inactive cyanmethemoglobin. (L97)
Weight-of-Evidence Characterization Under the current Risk Assessment Guidelines (US EPA, 1987), ACN is assigned carcinogen class D, not classifiable as to human carcinogenicity. There is an absence of human evidence and the animal evidence is equivocal. Under the Proposed Guidelines for Carcinogen Risk Assessment (US EPA, 1996), the carcinogenic potential of ACN following inhalation, oral, or dermal exposure is best characterized as "cannot be determined because the existing evidence is composed of conflicting data (e.g., some evidence is suggestive of carcinogenic effects, but other equally pertinent evidence does not confirm any concern)." /Based on former classification guidelines/
来源:Hazardous Substances Data Bank (HSDB)
毒理性
致癌性证据
A4：不能归类为人类致癌物。
A4: Not classifiable as a human carcinogen.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
致癌物分类
对人类不具有致癌性（未被国际癌症研究机构IARC列名）。
No indication of carcinogenicity to humans (not listed by IARC).
Like hydrogen cyanide (HCN), acetonitrile (ACN) is readily absorbed from the lungs and gastrointestinal tract, and is distributed throughout the body in both humans and laboratory animals. In a group of male and female test subjects, 74% of inhaled ACN was absorbed when cigarette smoke was held in the mouth for 2 seconds (and not inhaled), and 91% was absorbed when smoke was inhaled. Autopsy of an individual who died 2 days following inhalation of ACN vapors showed that cyanide reaches the spleen, lungs, and kidneys, but was not detected in the liver
The kinetics of distribution were studied in mice following intravenous dosing. After 5 minutes, the highest levels of radioactivity were found in the liver and kidney with levels declining with time. At 24 and 48 hours, radioactivity was found highest in the gastrointestine, thymus, liver, and testes. Covalent binding studies showed approximately one-half of the radioactivity in the liver bound to macromolecular fractions. The radioactivity in other organs was primarily in the lipid fractions. Acetonitrile was shown to be converted to cyanide by rat nasal and liver tissues with the maximum rate being ten times higher per gram of protein in the nasal tissue than in any other tissue monitored.
Whole body autoradiography in male mice injected intravenously with acetonitrile (ACN) radiolabeled with (14)C in the methyl group indicated that radioactivity was widely distributed throughout the body (e.g., liver, thymus, and reproductive organs). Interestingly, nonvolatile radioactivity was also observed in nasal secretions, mouth cavity, esophagus, and stomach contents. One could infer from these observations that ACN could also distribute to the stomach upon inhalation exposure.
Absorption of acetonitrile (ACN) is rapid in beagle dogs exposed to 16,000 ppm ACN (26,880 mg/cu m) vapors for 4 hours, based on blood cyanide concentrations peaking and reaching steady-state concentrations of 305-433 ug/100 mL after approximately 3 hours.
Heterochiral vs. Homochiral Linkage of Emissive Iridium(III) Complexes with
<scp>D</scp>
‐Penicillaminate: Drastic Change in Emission Induced by Silver(I) Linkage
bands. Whereas the (ppy)Ir III Ag I Ir IIIcomplex produced the heterochiral Δ D Λ D isomer, the ppy-CF 3 complex gave the homochiral Δ D Λ D and A D A D isomers that could completely be separated by crystallization. It was found that the quantum efficiency of the emission band for the Δ D Δ D isomer is much lower than that for the A D A D isomer.
[Ir(ppy or ppy-CF 3 ) 2 } 2 (μ-Cl) 2 ] Hppy = 2-苯基吡啶，Hppy-CF 3 = 2-[3,5-双(三氟甲基)苯基]-吡啶的反应) 与 D-青霉胺 (DH 2 pen) 提供发射性 Ir III 单核复合物 [Ir(ppy 或 ppy-CF 3 ) 2 (D-Hpen-N,S)] 作为 Δ D /Λ D 的 1:1 混合物异构体。这些复合物在 [AgIr(D-pen-N,S)(ppy or ppy-CF 3 ) 2 }Ir(D-Hpen-N,S)(ppy或 ppy-CF 3 ) 2 }] 通过用 AgNO 3 处理，导致发射带发生剧烈蓝移。(ppy)Ir III Ag I Ir III 复合物产生异手性 Δ D Λ D 异构体，而 ppy-CF 3 复合物产生可通过结晶完全分离的同手性 Δ D Λ D 和 ADAD 异构体。
[EN] COMPOUNDS AND COMPOSITIONS COMPRISING CDK INHIBITORS AND METHODS FOR THE TREATMENT OF CANCER<br/>[FR] COMPOSÉS ET COMPOSITIONS COMPRENANT DES INHIBITEURS DES CDK ET MÉTHODES DE TRAITEMENT DU CANCER
申请人：UNIV GEORGIA STATE RES FOUND
公开号：WO2010129858A1
公开（公告）日：2010-11-11
Disclosed herein are compounds suitable for use as antitumor agents, methods for treating cancer wherein the disclosed compounds are used in making a medicament for the treatment of cancer, methods for treating a tumor comprising, administering to a subject a composition comprising one or more of the disclosed cytotoxic agents, and methods for preparing the disclosed antitumor agents.
SULFONAMIDE, SULFAMATE, AND SULFAMOTHIOATE DERIVATIVES
申请人：Wang Zhong
公开号：US20120077814A1
公开（公告）日：2012-03-29
The disclosure provides biologically active compounds of formula (I):
and pharmaceutically acceptable salts thereof, compositions containing these compounds, and methods of using these compounds in a variety applications, such as treatment of diseases or disorders associated with E1 type activating enzymes, and with Nedd8 activating enzyme (NAE) in particular.
construction of carbon–sulfur bonds has been achieved via halogen-free Cs2CO3-promoted cross dehydrogenative coupling (CDC) of thiophenols with acetonitrile. This transformation provides a straightforward route to the synthesis of sulfenylated acetonitriles in up to 80% yield.
通过无卤的Cs 2 CO 3促进的硫酚与乙腈的交叉脱氢偶联（CDC），实现了构建碳-硫键的新方法。这种转化为亚磺酰化乙腈的合成提供了一条简单的途径，产率高达80％。
