S-ethyl hexahydro-1H-azepine-1-carbothioate S,S-dioxide | 54404-54-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氮杂环庚烷
• 英文名称: S-ethyl hexahydro-1H-azepine-1-carbothioate S,S-dioxide
• 英文别名: S-ethyl-hexahydro-1H-azepine-1-carbothioate sulfone；molinate sulphone；molinate sulfone；Molinate-sulfone；azepan-1-yl(ethylsulfonyl)methanone
• CAS: 54404-54-5
• 化学式: C₉H₁₇NO₃S
• 分子量: 219.305
• InChiKey: YDGVBAZMNPWLGE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  62.8
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  S-ethyl hexahydro-1H-azepine-1-carbothioate S,S-dioxide 、 L-cysteine 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 24.0h， 生成 S-(hexahydro-1H-azepine-1-carbonyl)cysteine
  参考文献：
  名称：

  Identification of a S-Hexahydro-1H-azepine-1-carbonyl Adduct Produced by Molinate on Rat Hemoglobin β₂ and β₃ Chains in Vivo

  摘要：

  Molinate is a thiocarbamate herbicide used in the rice industry for over 25 years, and regulatory reports have shown that administration of molinate results in reproductive toxicity in male rats. Previous in vitro studies indicate that molinate undergoes oxidative metabolism, forming reactive electrophilic intermediates capable of undergoing nucleophilic addition by protein nucleophiles. On the basis of in vitro studies, carbamylation of an active site serine residue in Hydrolase A has been proposed to be the mechanism responsible for the observed testicular toxicity. The experiments presented here utilize hemoglobin to characterize covalent protein modifications produced in vivo by molinate. Rats were dosed intraperitoneally with molinate as a function of exposure duration, Examination of globin from molinate-treated rats by HPLC demonstrated a new peak in the isolated samples and, when collected and analyzed using MALDI-TOF MS, revealed a 126 Da increase in mass relative to the native beta(3) chain. Digestion of the globin using Glu-C and analysis by MALDI-TOF MS revealed two modified peptide fragments at m/z 2743 and 4985 consistent with a 126 Da increase to peptide fragments [122-146] and [102-146] in the unmodified beta(2) and beta3 chains of globin. Using selected reaction monitoring LC/MS/MS, S-hexahydro-1H-azepine-1-carbonyl cysteine HHAC-Cys) was identified in the globin hydrolysates isolated from the molinate-treated rats, but not in the control samples, and the quantity of adduct exhibited a cumulative dose response. These experiments demonstrate the ability of molinate to covalently modify proteins in vivo in a dose dependent manner. For hemoglobin this modification was a carbamylation at Cys-125 similar to the modification produced by disulfiram and NIV-diethyldithiocarbamate. The ability of molinate to covalently modify cysteine residues provides a potential mechanism to account for enzyme inhibition following molinate exposure and suggests that enzymes with cysteine residues in their active site may be inhibited by molinate.

  DOI：

  10.1021/tx015564a
• 作为产物：
  描述：

  禾草敌 生成 S-ethyl hexahydro-1H-azepine-1-carbothioate S,S-dioxide
  参考文献：
  名称：

  TILLES, H.

  摘要：

  DOI：

文献信息

• TILLES, H.
  作者：TILLES, H.

  DOI：——

  日期：——
• Identification of a <i>S</i>-Hexahydro-1<i>H</i>-azepine-1-carbonyl Adduct Produced by Molinate on Rat Hemoglobin β₂ and β₃ Chains in Vivo
  作者：Lisa J. Zimmerman、Holly S. Valentine、Kalyani Amarnath、William M. Valentine

  DOI：10.1021/tx015564a

  日期：2002.2.1

  Molinate is a thiocarbamate herbicide used in the rice industry for over 25 years, and regulatory reports have shown that administration of molinate results in reproductive toxicity in male rats. Previous in vitro studies indicate that molinate undergoes oxidative metabolism, forming reactive electrophilic intermediates capable of undergoing nucleophilic addition by protein nucleophiles. On the basis of in vitro studies, carbamylation of an active site serine residue in Hydrolase A has been proposed to be the mechanism responsible for the observed testicular toxicity. The experiments presented here utilize hemoglobin to characterize covalent protein modifications produced in vivo by molinate. Rats were dosed intraperitoneally with molinate as a function of exposure duration, Examination of globin from molinate-treated rats by HPLC demonstrated a new peak in the isolated samples and, when collected and analyzed using MALDI-TOF MS, revealed a 126 Da increase in mass relative to the native beta(3) chain. Digestion of the globin using Glu-C and analysis by MALDI-TOF MS revealed two modified peptide fragments at m/z 2743 and 4985 consistent with a 126 Da increase to peptide fragments [122-146] and [102-146] in the unmodified beta(2) and beta3 chains of globin. Using selected reaction monitoring LC/MS/MS, S-hexahydro-1H-azepine-1-carbonyl cysteine HHAC-Cys) was identified in the globin hydrolysates isolated from the molinate-treated rats, but not in the control samples, and the quantity of adduct exhibited a cumulative dose response. These experiments demonstrate the ability of molinate to covalently modify proteins in vivo in a dose dependent manner. For hemoglobin this modification was a carbamylation at Cys-125 similar to the modification produced by disulfiram and NIV-diethyldithiocarbamate. The ability of molinate to covalently modify cysteine residues provides a potential mechanism to account for enzyme inhibition following molinate exposure and suggests that enzymes with cysteine residues in their active site may be inhibited by molinate.