埃索美拉唑镁在特定溶液中的分子互变异构体结构表征及互变动力学的核磁共振波谱研究

Structural Identification and Asymmetric-exchange Dynamics Study of Esomeprazole Magnesium in Specific Solution as Probed by Using ~1H NMR Spectra

选取浓度为1 mg/mL的埃索美拉唑镁二水合物(EMD)的氯仿溶液作为研究体系,通过对溶液的一维~1H NMR谱、二维~1H-~1H COSY谱、~1H-~1H NOESY谱和~1H-~1H ROESY谱的分析,发现EMD在氯仿溶液中存在2种互变异构体(分别命名为A和B),2种结构的相对含量分别为64%和36%.结合变温一维~1H NMR谱和二维交换谱(2D EXSY谱)技术,通过动力学矩阵的计算得出了A→B和B→A的一级反应速率常数k_(AB)和k_(BA)分别为1.04和1.91 s^(-1).使用上述两组数据可分别计算出A→B的反应平衡常数K_c分别为0.56和0.54,2组数值相近,证明了测试结果的准确性.

EMD chloroform solution(1 mg/mL)was chosen as the research system.Based on the one-dimensional 1 H NMR spectrum,two-dimensional 1 H-1 H COSY spectrum,1 H-1 H NOESY spectrum and 1 H-1 H ROESY spectrum,it is revealed that there are two tautomers coexisting in the EMD chloroform solution,named as A and B,with relative content of 64%and 36%.Furthermore,by analyzing the data of two-dimensional exchange spectra(2D EXSY)and temperature-dependent 1 H NMR spectra,the reaction rate constants k AB and k BA of A→B and B→A were deduced,which are 1.04 and 1.91 s-1,respectively.Using these two sets of data,the equilibrium constant K c of A→B was calculated,which are 0.56 and 0.54,respectively.The K c value derived from the relative concentration is matched with the value deduced from the reaction rate constants,proving the accuracy of the test results.