新型硝基苯胺衍生化β-环糊精键合SBA-15液相色谱手性固定相的制备及评价

doi:10.7503/cjcu20140131

摘要/Abstract

摘要：

合成了一种新型6-单硝基苯胺衍生化β-环糊精配体, 将该手性配体键合到SBA-15有序介孔材料表面, 制备了手性液相色谱固定相(NCDSP), 采用红外光谱、元素分析、热重分析、质谱、扫描电子显微镜、透射电子显微镜和X射线衍射分析对其结构进行了表征. 评价了新固定相的基本色谱性能, 并将其用于β-受体阻滞剂和二氢黄烷酮类手性药物对映体的拆分. 结果表明, 14种β-受体阻滞剂和6种二氢黄烷酮类药物在NCDSP上均可实现手性分离, 其中美托洛尔的分离度达到1.75, 2'-羟基黄烷酮的分离度达到5.21, 并且分析时间一般不超过20 min. 通过与苯胺衍生化β-环糊精固定相(PCDSP)进行对比研究, 探讨了新固定相的手性分离机理.

关键词: 高效液相色谱法, β-环糊精类SBA-15固定相, 手性分离, β-受体阻滞剂, 二氢黄烷酮, 手性药物

Abstract:

A mono-nitrophenylamino-β-cyclodextrin was synthesized and bonded to the surface of ordered mesoporous SBA-15 for high performance liquid chromatography(HPLC), which obtained a novel 6-mono-nitrophenylamino-β-cyclodextrin bonded SBA-15 chiral stationary phase(NCDSP). Its structure and morphology were characterized by infrared spectroscopy, elemental analysis, thermal gravimetric analysis, mass spectrometry, scanning electron microscopy, transmission electron microscopy and X-ray diffraction. The basic chromatographic property of new NCDSP was evaluated and used for enantioseparations of chiral drugs such as β-blockers and dihydroflavanones. The fourteen kinds of β-blockers and six kinds of dihydroflavanones chiral drugs can be separated on NCDSP. The resolutions of metoprolol enantiomers and 2'-hydroxy flavanone enantiomers reached 1.75 and 5.21 within 20 min, respectively. By comparative study with PCDSP, some enantio-separation mechanisms of the new stationary phase were also discussed.

Key words: High performance liquid chromatography, β-Cyclodextrin-bonded SBA-15 stationary phase, Chiral separation, β-Blocker, Dihydroflavanone, Chiral drug

中图分类号:

O657

TrendMD:

周仁丹, 李来生, 程彪平, 聂桂珍, 张宏福. 新型硝基苯胺衍生化β-环糊精键合SBA-15液相色谱手性固定相的制备及评价. 高等学校化学学报, 2014, 35(6): 1152.

ZHOU Rendan, LI Laisheng, CHENG Biaoping, NIE Guizhen, ZHANG Hongfu. Preparation and Evaluation of a Novel 6-mono-Nitrophenylamino-β-cyclodextrin Bonded SBA-15 Chiral Stationary Phase for HPLC^†. Chem. J. Chinese Universities, 2014, 35(6): 1152.

图/表 9

参考文献 20

[1]	Chen L.R., Chiral Separation in Liquid Chromatography, Science Press, Beijing, 2006, 1—15
	(陈立仁. 液相色谱手性分离, 北京: 科学出版社, 2006, 1—15)
[2]	Guo J. H., Chin. J. Cardiac Pacing and Electrophysiology, 2005, 19(5), 331—334
	(郭继鸿.中国心脏起搏与心电生理杂志, 2005,19(5), 331—334)
[3]	Pei J. X., Wu P. S., Chin. J. Hypertens, 2011, 19(7), 608—610
	(裴静娴, 吴平生.中华高血压杂志, 2011,19(7), 608—610)
[4]	Ali I., Gaitonde V. D., Aboul-Enein H. Y., Hussain A., Talanta, 2009, 78(2), 458—463
[5]	Yu X. Y., Gu X. J., Xie Y., Qu S. L., Shen B. C., PTCA(Part B: Chem. Anal.), 2012, 48, 884—886
	(余小燕, 谷晓娟, 谢宇, 屈尚蓝, 沈报春. 理化检验-化学分册, 2012, 48, 884—886)
[6]	Szente L., Szemán J., Anal. Chem., 2013, 85(17), 8024—8030
[7]	Lai X. H., Ng S. C., J. Chromatogr. A, 2004, 1031, 135—142
[8]	Poon Y. F., Muderawan I. W., Ng S. C., J. Chromatogr. A, 2006, 1101, 185—197
[9]	Zhao D. Y., Huo Q. S., Feng J. L., Chmelka B. F., Stucky G. D., J. Am. Chem. Soc., 1998, 120(24), 6024—6036
[10]	Li L. S., Ma H. P., Fang Y. S., Chen H., Chin. J. Anal. Lab., 2011, 30(11), 20—25
	(李来生, 马海萍, 方奕珊, 陈红.分析试验室, 2011,30(11), 20—25)
[11]	Gao F., Zhao J. W., Zhang S., Zhou F., Jin W., Zhang X. M., Yang P. Y., Zhao D. Y., Chem. J. Chinese Universities, 2002, 23(8), 1494—1497
	(高峰, 赵建伟, 张松, 周峰, 金婉, 张祥民, 杨芃原, 赵东元.高等学校化学学报, 2002,23(8), 1494—1497)
[12]	Zhou Z. M., Li X., Chen X. P., Hao X. Y., Anal. Chim. Acta, 2010, 678, 208—214
[13]	Liu Y., Zhang Y.M., Sun S. X., Li Y. M., Chen R. T., J. Chem. Soc., Perkin Trans. 2, 1997, 1609—1613
[14]	Wang Y., Young D. J., Tan T. T. Y., Ng S. C., J. Chromatogr. A, 2010, 1217, 5103—5108
[15]	Jin Z.Y., Xu X. M., Chen H. Q., Li X. H., Cyclodextrin Chemistry-Preparation and Application, Chemical Industry Press, Beijing, 2009, 300—301
	(金征宇, 徐学明, 陈寒青, 李学红. 环糊精化学-制备与应用, 北京: 化学工业出版社, 2009, 300—301)
[16]	Armstrong D. W., Chen S., Chang C., Chang S., J. Liq. Chromatogr. Rel. Technol., 1992, 15(3), 545—556
[17]	Chang S. C., Reid Ⅲ G. L., Chen S., Chang C. D., Armstrong D. W., Trac-trend. Anal. Chem., 1993, 12(4), 144—153
[18]	Li L. S., Zhou R. D., Cheng B. P., Nie G. Z., Zhang Y., J. Nanchang Univ.(Nat. Sci.), 2013, 37(2), 145—151
	(李来生, 周仁丹, 程彪平, 聂桂珍, 张扬. 南昌大学学报(理科版), 2013, 37(2), 145—151)
[19]	Armstrong D. W., Chang C. D., Less S. H., J. Chromatogr. A, 1991, 539, 83—90
[20]	Armstrong D. W., Li W., Chromatography, 1987, 2, 43—48

Compound	k₁	k₂	k₃	α	R_s	V(ACN)∶V(MeOH)∶V(TEA)∶V(HOAc)	λ/nm
Metoprolol	1.93	2.28		1.18	1.75	95∶5∶2∶2	275
Alprenolol	1.96	2.12		1.08	0.91	95∶5∶1∶1	270
Atenolol	4.07	4.76		1.17	1.56	95∶5∶4∶4	275
Propranolol	2.22	2.59		1.17	1.51	95∶5∶1.5∶1.5	290
Esmolol	1.76	2.11		1.20	1.67	95∶5∶2∶2	275
Pindolol	2.91	3.09		1.06	0.80	97∶3∶2∶2	263
Labetalol	2.36	2.59	2.86			95∶5∶4∶4	306
Nadolol	2.91	3.10	3.46			95∶5∶4∶4	276
Bisoprolol	2.92	3.16		1.08	0.68	95∶5∶1∶1	272
Sotalol	1.66	1.72		1.04	0.85	95∶5∶4∶4	275
Carteolol	2.67	2.84		1.06	0.76	95∶5∶2∶2	254
Celiprolol	1.99	2.10		1.06	0.84	95∶5∶2∶2	332
Arotinolol	2.97	3.41		1.15	1.21	95∶5∶4∶4	316
Carvedilol	2.43	2.84		1.17	1.58	95∶5∶2∶2	285

Compound	k₁	k₂	k₃	α	R_s	V(ACN)∶V(MeOH)∶V(TEA)∶V(HOAc)	λ/nm
Metoprolol	1.93	2.28		1.18	1.75	95∶5∶2∶2	275
Alprenolol	1.96	2.12		1.08	0.91	95∶5∶1∶1	270
Atenolol	4.07	4.76		1.17	1.56	95∶5∶4∶4	275
Propranolol	2.22	2.59		1.17	1.51	95∶5∶1.5∶1.5	290
Esmolol	1.76	2.11		1.20	1.67	95∶5∶2∶2	275
Pindolol	2.91	3.09		1.06	0.80	97∶3∶2∶2	263
Labetalol	2.36	2.59	2.86			95∶5∶4∶4	306
Nadolol	2.91	3.10	3.46			95∶5∶4∶4	276
Bisoprolol	2.92	3.16		1.08	0.68	95∶5∶1∶1	272
Sotalol	1.66	1.72		1.04	0.85	95∶5∶4∶4	275
Carteolol	2.67	2.84		1.06	0.76	95∶5∶2∶2	254
Celiprolol	1.99	2.10		1.06	0.84	95∶5∶2∶2	332
Arotinolol	2.97	3.41		1.15	1.21	95∶5∶4∶4	316
Carvedilol	2.43	2.84		1.17	1.58	95∶5∶2∶2	285

Compound	k₁	k₂	α	R_s	V(1%TEAA)∶V(ACN)	λ/nm
Flavanone	3.97	4.26	1.07	0.69	80∶20	254
6-Methoxy flavanone	3.77	3.95	1.05	0.54	80∶20	256
7-Methoxy flavanone	3.69	3.95	1.07	0.86	80∶20	276
6-Hydroxy flavanone	2.61	2.61	1.00	0.00	80∶20	256
2'-Hydroxy flavanone	2.48	3.23	1.30	3.50	80∶20	254
4'-Hydroxy flavanone	2.91	3.33	1.14	1.63	80∶20	254

Compound	k₁	k₂	α	R_s	V(1%TEAA)∶V(ACN)	λ/nm
Flavanone	3.97	4.26	1.07	0.69	80∶20	254
6-Methoxy flavanone	3.77	3.95	1.05	0.54	80∶20	256
7-Methoxy flavanone	3.69	3.95	1.07	0.86	80∶20	276
6-Hydroxy flavanone	2.61	2.61	1.00	0.00	80∶20	256
2'-Hydroxy flavanone	2.48	3.23	1.30	3.50	80∶20	254
4'-Hydroxy flavanone	2.91	3.33	1.14	1.63	80∶20	254

Compound	k₁	k₂	α	R_s	V(1%TEAA)∶V(MeOH)	λ/nm
Flavanone	4.40	4.64	1.05	0.54	60∶40	254
6-Methoxy flavanone	4.74	5.16	1.09	0.97	60∶40	256
7-Methoxy flavanone	4.87	5.50	1.13	1.56	60∶40	276
6-Hydroxy flavanone	2.78	2.99	1.08	0.85	60∶40	256
2'-Hydroxy flavanone	3.03	4.25	1.40	5.21	60∶40	254
4'-Hydroxy flavanone	3.40	3.40	1.00	0.00	60∶40	254