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

doi:10.7503/cjcu20180078

高等学校化学学报 ›› 2018, Vol. 39 ›› Issue (9): 1919.doi: 10.7503/cjcu20180078

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

王宁, 朱惠芳, 王璐, 张田田, 顾佳丽, 舒婕()

苏州大学材料与化学化工学部, 分析测试中心, 苏州 215123

收稿日期:2018-01-25 出版日期:2018-09-07 发布日期:2018-05-28
作者简介:
联系人简介: 舒婕, 女, 博士, 副教授, 主要从事固体核磁共振方法及其在材料科学中的应用研究. E-mail: shujie@suda.edu.cn
基金资助:
国家自然科学基金(批准号: 21673148, 21303111)资助.

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

WANG Ning, ZHU Huifang, WANG Lu, ZHANG Tiantian, GU Jiali, SHU Jie^*()

College of Chemistry, Chemical Engineering and Materials Science, Analysis and Testing Center, Soochow University, Suzhou 215123, China

Received:2018-01-25 Online:2018-09-07 Published:2018-05-28
Contact: SHU Jie E-mail:shujie@suda.edu.cn
Supported by:
† Supported by the National Natural Science Foundation of China(Nos.21673148, 21303111).

摘要/Abstract

摘要：

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.

关键词: 埃索美拉唑镁, 核磁共振波谱, 互变异构体, 动力学矩阵, 反应速率常数

Abstract:

EMD chloroform solution(1 mg/mL) was chosen as the research system. Based on the one-dimensional ¹H NMR spectrum, two-dimensional ¹H-¹H COSY spectrum, ¹H-¹H NOESY spectrum and ¹H-¹H 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 ¹H 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.

Key words: Esomeprazole magnesium, Nuclear magnetic resonance spectrum, Tautomer, Dynamic matrix, Reaction rate constant

中图分类号:

O657.61

TrendMD:

王宁, 朱惠芳, 王璐, 张田田, 顾佳丽, 舒婕. 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. 高等学校化学学报, 2018, 39(9): 1919.

WANG Ning,ZHU Huifang,WANG Lu,ZHANG Tiantian,GU Jiali,SHU Jie. Structural Identification and Asymmetric-exchange Dynamics Study of Esomeprazole Magnesium in Specific Solution as Probed by Using ¹H NMR Spectra^†. Chem. J. Chinese Universities, 2018, 39(9): 1919.

图/表 6

Fig.1 One-dimensional 1H NMR spectra(A, B) and two-dimensional 1H-1H COSY spectrum(C) of 1 mg/mL EMD chloroform solution and molecular structure scheme of EMD(D)(A) Peaks are assigned using alphabetic labels with respect to the structural scheme; (B) showing only the aromatic region(δ 6.8—7.8)

Fig.2 Schematic diagram of structure transformation in EMD chloroform solution(A) and schematic diagram of two possible tautomers A and B in 1 mg/mL EMD chloroform solution(B)

Fig.3 Two-dimensional 1H-1H NOESY spectrum(A) and two-dimensional 1H-1H ROESY spectrum(B) of 1 mg/mL EMD chloroform solution showing only the aromatic region(δ 6.5—8.5)

Table 1 1D1H NMR chemical shifts, J-coupling constants, assignments and correlation information of the 1 mg/mL EMD chloroform solution

Chemical shift, δ	J_HH/Hz	Integration^a	Assignment	COSY	ROESY
Chemical shift, δ	J_HH/Hz	Integration^a	Assignment	COSY	Correlation	Phase^b
11.08	—	0.95	—NH(A)	—	—	—
10.98	—		—NH(B)	—	—	—
8.25	—	1.00	f	g	g	-
7.68	8.0^c	0.64	d(A)	c(A)	d(B)	+
7.40	8.0^c	0.36	d(B)	c(B)	d(A)	+
7.26	—	—	b(B)	—	b(A)	+
7.01	—	1.63	c(B)	d(B)	a	-
6.98	—		c(A)	d(A)	a	-
6.95	—		b(A)	—	b(B)	+
4.78	13.5^c	1.00	e	i	e'; i	-
4.60	13.5^c	1.00	e'	i	e; i	-
3.87	—	3.08	a	—	c(A); cB)	-
3.73	—	3.04	h	—	i; g	-
2.26	—	6.03	g	f	h	-
2.24	—		i	e/e'	h; e; e'	-
1.57	—	8.16	DOH	—	—	—

Fig.4 Line shape analysis of the peaks at δ 11.08/10.98(A) and δ 7.01/6.98/6.95(B) The deduced relative weights are shown in the figures.

Fig.5 One-dimensional 1H NMR spectra of 1 mg/mL EMD chloroform solution recorded at different temperatures (25—55 ℃) showing δ range of 7—8(A) and 6.8—7.1(B)

参考文献 26

[1]	Pensabene L., Davidson G., Proton Pump Inhibitors, Springer, Berlin, Heidelberg, 2017
[2]	Teng M., Khoo A. L., Zhao Y. J., Lin L., Lim B. P., Wu T. S., Dan Y. Y., J. Clin. Pharm. Ther., 2015, 40, 368—375
[3]	Koch T. R., Petro A., Darrabie M., Opara E. C., Dig. Dis. Sci., 2005, 50(1), 86—93
[4]	Tamura T., Sakaeda T., Kadoyama K., Okuno Y., Int. J. Med. Sci., 2012, 99(5), 322—326
[5]	Kan S. L., Lu J., Liu J. P., Zhao Y., Drug Deliv., 2014, 23(3), 1—8
[6]	Cho H. G., Andrews L., J. Phys. Chem. A, 2017, 121(45), 8583—8595
[7]	Ren B. Y., Huang D., Xu Q., Sun Y. G., Chem. J. Chinese Universities, 2017, 38(9), 1584—1589
	(任保轶, 黄丹, 徐钦, 孙亚光. 高等学校化学学报, 2017, 38(9), 1584—1589)
[8]	Xie Y., Chen J., Xu B., Yan L., Tang J. J., Xie J. W., Chem. J. Chinese Universities, 2017, 38(5), 758—763
	(谢琰, 陈佳, 徐斌, 闫珑, 唐吉军, 谢剑炜. 高等学校化学学报, 2017, 38(5), 758—763)
[9]	Chapyshev S. V., Chernyak A. V., Ushakov E. N., Magn. Reson. Chem., 2017, 55(2), 99—105
[10]	Hameed I. H., Al-Rubaye A. F., Kadhim M. J., Int. J. Pharm. Rev. Res., 2017, 8(2), 79—84
[11]	Zhong J., Jiang X. M., Spectrosc. Spect. Anal., 2015, 35(1), 282—286
	(钟军, 蒋雪梅. 光谱学与光谱分析, 2015, 35(1), 282—286)
[12]	Claramunt R. M., Lopez C., Alkorta I., Elguero J., Yang R., Schulman S., Magn. Reson. Chem., 2004, 42(8), 712—714
[13]	Gomez-Calvario V., Garduno-Ramirez M. L., Leon-Rivera I., Rios M. Y., Magn. Reson. Chem., 2016, 54(4), 268—290
[14]	Romanuk C. B., Garro-Linck Y., Alves de Santana M. S., Manzo R. H., Ayala A. P., Monti G. A., Chattah A. K., Olivera M. E., J. Pharm. Sci., 2017, 106(10), 3033—3040
[15]	Baumann R., Wider G., Ernst R. R., Wuthrich K., J. Magn. Reson., 1981, 44(2), 402—406
[16]	Bax A., Freeman R., J. Magn. Reson., 1981, 44(3), 542—561
[17]	Keeler J., Understanding NMR Spectroscopy, John Wiley & Sons, Chichester, 2010
[18]	Wagner R., Berger S., J. Magn. Reson., 1996, 123(1), 119—121
[19]	Bax A., Davis D. G., J. Magn. Reson., 1985, 63(1), 207—213
[20]	Hwang T. L., Shaka A. J., J. Am. Chem. Soc., 1992, 114(8), 3157—3159
[21]	Levitt M. H., Spin Dynamics-Basics of Nuclear Magnetic Resonance, John Wiley & Sons, Chichester, 2008
[22]	Massiot D., Fayon F., Capron M., King I., Calve L. S., Alonso B., Durand J. O., Bujoli B., Gan Z., Hoatson G., Magn. Reson. Chem., 2002, 40(1), 70—76
[23]	Perrin C. L., Dwyer T. J., Chem. Rev., 1990, 90(6), 935—967
[24]	Jeener J., Meier B. H., Bachmann P., Ernst R. R., J. Chem. Phys., 1979, 71(11), 4546—4553
[25]	Dwyer T. J., Norman J. E., Jasien P. G., J. Chem. Ed., 1998, 75(12), 1635—1640
[26]	Lu X., Wang B. Y., Chen S., Badjic J. D., Molecules, 2014, 19(9), 292—303

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^†

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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†

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