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

doi:10.7503/cjcu20180078

Abstract

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

CLC Number:

O657.61

TrendMD:

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^†[J]. Chem. J. Chinese Universities, 2018, 39(9): 1919.

Figures/Tables 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)

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

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