Wu Shuchun, Yu Miao, Zhang Hu, Han Jianzhong, Qian Mingrong
College of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, China; Zhejiang Medical College, Hangzhou, China.
Chirality. 2015 May;27(5):344-8. doi: 10.1002/chir.22440. Epub 2015 Mar 28.
Paclobutrazol, with two stereogenic centers, but gives only (2R, 3R) and (2S, 3S)-enantiomers because of steric-hindrance effects, is an important plant growth regulator in agriculture and horticulture. Enantioselective degradation of paclobutrazol was investigated in rat liver microsomes in vitro. The degradation kinetics and the enantiomer fraction were determined using a Lux Cellulose-1 chiral column on a reverse-phase liquid chromatography-tandem mass spectrometry system. The t1/2 of (2R, 3R)-paclobutrazol is 18.60 min, while the t1/2 of (2S, 3S)-paclobutrazol is 10.93 min. Such consequences clearly indicated that the degradation of paclobutrazol in rat liver microsomes was stereoselective and the degradation rate of (2S, 3S)-paclobutrazol was much faster than (2R, 3R)-paclobutrazol. In addition, significant differences between the two enantiomers were also observed in enzyme kinetic parameters. The Vmax of (2S, 3S)-paclobutrazol was more than 2-fold of (2R, 3R)-paclobutrazol and the Clint of (2S, 3S)-paclobutrazol was higher than that of (2R, 3R)-paclobutrazol after incubation in rat liver microsomes. These results may have potential implications for better environmental and ecological risk assessment for paclobutrazol.
多效唑有两个手性中心，但由于空间位阻效应，只产生(2R, 3R)和(2S, 3S)对映体，它是农业和园艺领域一种重要的植物生长调节剂。体外研究了大鼠肝微粒体中多效唑的对映体选择性降解。在反相液相色谱 - 串联质谱系统上使用Lux Cellulose - 1手性柱测定降解动力学和对映体分数。(2R, 3R)-多效唑的t1/2为18.60分钟，而(2S, 3S)-多效唑的t1/2为10.93分钟。这些结果清楚地表明，大鼠肝微粒体中多效唑的降解具有立体选择性，且(2S, 3S)-多效唑的降解速率比(2R, 3R)-多效唑快得多。此外，在酶动力学参数方面，两种对映体之间也观察到显著差异。在大鼠肝微粒体中孵育后，(2S, 3S)-多效唑的Vmax是(2R, 3R)-多效唑的2倍多，且(2S, 3S)-多效唑的Clint高于(2R, 3R)-多效唑。这些结果可能对多效唑更好的环境和生态风险评估具有潜在意义。
