Department of Applied Chemistry, China Agricultural University, Beijing 100193, China.
Chirality. 2012 Apr;24(4):283-8. doi: 10.1002/chir.21993. Epub 2012 Jan 25.
Hexaconazole [(RS)-2-(2,4-dichlorophenyl)-1-(1H-1,2,4-triazol-1-yl) hexan-2-ol] is a potent triazole fungicide and consists of a pair of enantiomers. Enantioselective degradation of hexaconazole was investigated in rat hepatic microsomes in vitro. Concentrations of (-)- and (+)-hexaconazole and enantiomer fraction were determined by high performance liquid chromatography with a cellulose-tris-(3,5-dimethylphenylcarbamate)-based chiral stationary phase. The t(1/2) of (-)-hexaconazole and (+)-hexaconazole were 23.70 and 13.95 min for rac- hexaconazole and 44.18 and 23.54 for enantiomers examined separately. Furthermore, hexaconazole is configurationally stable in rat hepatic microsomes, demonstrating no chiral inversion from the (-)-hexaconazole to (+)-hexaconazole or vice versa. Intrinsic metabolic clearance of (+)-hexaconazole is 1.12 times than that of (-)-hexaconazole. Interaction study revealed that there was competitive inhibition between (-)-hexaconazole and (+)-hexaconazole. In addition, there was a significant difference between the inhibitory concentration (IC(50)) of (-)- to (+)-hexaconazole and (+)- to (-)-hexaconazole [IC(50)(-)/(+)/IC(50)(+)/(-) = 1.88]. These results may have potential implications for better environmental and ecological risk assessment for hexaconazole.
(RS)-2-(2,4-二氯苯基)-1-(1H-1,2,4-三唑-1-基)己-2-醇]是一种有效的三唑类杀菌剂，由一对对映异构体组成。在大鼠肝微粒体体外实验中研究了(RS)-己唑醇的对映体选择性降解。(-)-和(+)-己唑醇及对映体分数的浓度通过高效液相色谱法用纤维素三-(3,5-二甲基苯基氨基甲酸酯)手性固定相测定。rac-己唑醇中(-)-己唑醇和(+)-己唑醇的 t(1/2)分别为 23.70 和 13.95 min，单独检测时对映体的 t(1/2)分别为 44.18 和 23.54。此外，己唑醇在大鼠肝微粒体中构型稳定，(-)-己唑醇向(+)-己唑醇或反之的对映体反转没有发生。(+)-己唑醇的内在代谢清除率是(-)-己唑醇的 1.12 倍。相互作用研究表明，(-)-己唑醇和(+)-己唑醇之间存在竞争性抑制。此外，(-)-己唑醇与(+)-己唑醇和(+)-己唑醇与(-)-己唑醇的抑制浓度(IC(50))之间存在显著差异[IC(50)(-)/(+)/IC(50)(+)/(-) = 1.88]。这些结果可能对更好地评估己唑醇的环境和生态风险具有潜在意义。
