盐酸四环素中可交换氢和氢键的核磁共振波谱研究

doi:10.11938/cjmr20202874

摘要/Abstract

摘要：

四环素类抗生素是一类广谱抗生素，对革兰氏阳性菌、革兰氏阴性菌、支原体、衣原体和立克次体感染均具有抗菌活性.本文运用一维（1D）和二维（2D）核磁共振（NMR）技术对盐酸四环素中可交换氢和氢键进行研究，并将研究结果与RNA和蛋白质结合的四环素以及游离药物的晶体结构进行比较，进一步讨论了药物中的氢键构架与药物活性的相关性.最后对盐酸四环素及其同系物的¹H和¹³C NMR信号进行了全归属和分析，并对文献归属结果进行了细微校正.这些结果有助于进一步探索该类药物在更复杂的生物或环境系统中的构效关系.

关键词: 核磁共振, 四环素, 交换氢, 氢键

Abstract:

Tetracyclines are a class of broad-spectrum antibiotics that have antibacterial activities against Gram-positive and Gram-negative bacteria, including Mycoplasma, Chlamydia, and Rickettsia. In this paper, we report the one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR) studies on the exchangeable protons and hydrogen bound in tetracycline hydrochloride (TC). The NMR results were compared with the results obtained from the crystal structures of free tetracycline and RNA- and protein-bound complexes. The H-bonding frameworks in the drug and their correlation with drug activity were discussed. The¹H and ¹³C NMR signals of TC and its derivatives were fully assigned and interpreted, and the misassigned signals in previous reports were corrected. The results of this study could be conducive to further exploration of the structure-function correlation of this drug family in more complex biological and environmental systems.

Key words: NMR, tetracycline, exchangeable protons, hydrogen bond

中图分类号:

O482.53

谢金华,王乐,刘盼,苏稀琪,MINGLi-June. 盐酸四环素中可交换氢和氢键的核磁共振波谱研究[J]. 波谱学杂志, 2021, 38(3): 313-322.

Jin-hua XIE,Le WANG,Pan LIU,Xi-qi SU,Li-June MING. An NMR Spectroscopy Study on the Exchangeable Protons and Hydrogen Bonds in Tetracycline Hydrochloride[J]. Chinese Journal of Magnetic Resonance, 2021, 38(3): 313-322.

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Position	1A/δ_H (J/HZ)	1A/δ_C	1B/δ_H (J/HZ)	1B/δ_C	1C/δ_H(J/HZ)	1C/δ_C
1	/	192.7	/	193.7	/	194.0
2	/	95.4	/	96.0	/	96.2
3	/	187.8	/	187.6	/	187.8
4	4.71(s)	65.8	4.58 (s)	65.4	4.34 (s)	68.7
4a	3.02 (d, J=11.4 Hz)	41.5	2.79~2.88 (m)	42.3	2.84~2.90 (m)	35.5
5	3.76 (dd, J=10.4/9.6 Hz)	64.5	3.72 (dd, J=10.2/9.4 Hz)	64.9	2.21 (dd, J=8.9/3.1 Hz, H-5eq) 1.79 (q, J=13.2 Hz, H-5ax)	27.5
5a	3.60 (d, J=8.9 Hz)	44.7	2.79~2.88 (m)	50.4	2.84~2.90 (m)	42.2
6	/	141.2	/	69.5	/	68.5
6a	/	143.7	/	149.3	/	148.5
7	7.12 (d, J=7.2 Hz)	116.9**	7.07 (d, J=7.6 Hz)	115.4**	7.12 (d, J=7.6 Hz)	115.7**
8	7.57 (dd, J=8.0/8.0 Hz)	137.6	7.52 (dd, J=8.0/8.0 Hz)	137.0	7.56 (dd, J=8.0/8.0 Hz)	137.1
9	6.95 (d, J=8.4 Hz)	117.8**	6.90 (d, J=8.3 Hz)	117.5**	6.94 (d, J=8.3 Hz)	117.5**
10	/	161.3	/	161.7	/	161.9
10a	/	114.9	/	115.0	/	115.0
11	/	194.0	/	194.3	/	193.5
11a	/	105.7	/	105.9	/	107.4
12	/	174.2	/	174.2	/	175.6
12a	/	74.1	/	73.1	/	73.7
OH-3	7.57*	/	7.52*		7.47*	/
OH-10	11.48	/	11.61		11.81 (s)	/
OH-12	15.02	/	15.06		15.13 (s)	/
OH-12a	10.21*	/	10.09*		10.48*	/
CONH₂	9.57, 9.02	172.2	9.52, 9.06	172.6	9.56 (s), 9.12 (s)	172.6
NH⁺	15.83*		16.28*		16.41*
NMe₂	2.80 (s)	42.3	2.79~2.88 (m)	42.7	2.84~2.90 (m)	40.0
R¹	6.34*	/	5.92*	/	/	/
R²	5.54, 5.42	114.3	1.68 (s)	25.2	1.53 (s)	23.1
R³	5.54, 5.42	114.3	5.00*	/	5.05*	/

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