Host-guest Interaction Between Cucurbit[8]uril and Baicalin and Its Effect on the Properties of Baicalin†

doi:10.7503/cjcu20180337

Abstract

Abstract:

The interaction between cucurbit[8]uril(Q[8]) and baicalin(BAL) was investigated by ultraviolet-visible absorption spectrometry and nuclear magnetic resonance spectroscopy. The results showed that Q[8] and BAL formed an inclusion complex with molar ratio of 1:1. The inclusion stability constant was 2.8×10⁴ L/mol. The phase solubility experiments revealed that the solubility of BAL in water increased 4.5 fold by interacting with Q[8] at 100 μmol/L. The effect of Q[8] on antioxidant activity of BAL was investigated by 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonate acid)(ABTS) method. Both the BAL-Q[8] inclusion complex and BAL had the scavenging ability for ABTS free radicals, and the IC₅₀ values were 5.48 and 5.07 μmol/L, respectively. BAL and BAL-Q[8] were stable in artificial intestinal juice. BAL was degraded rapidly in 6 h, but BAL-Q[8] was not degraded basically in artificial gastric juice, which indicated that Q[8] significantly improved the stability of BAL in artificial gastric juice. In vitro cumulative release results showed that Q[8] increased the cumulative release of BAL in artificial gastric juice by 2 times. The cumulative release rate of BAL-Q[8] was significantly slower than the cumulative release rate of BAL in artificial intestinal juice, which indicated that Q[8] had sustained release effect on BAL.

Key words: Baicalin, Cucurbit[8]uril, Inclusion complex, Stability, Antioxidant activity

CLC Number:

O624
O641.3

TrendMD:

HUANG Jingjing, XU Zhiling, LIAN Xiaowei, ZHANG Xiaodong, TAO Zhu, ZHOU Qingdi, ZHANG Qianjun, WEI Gang. Host-guest Interaction Between Cucurbit[8]uril and Baicalin and Its Effect on the Properties of Baicalin^†[J]. Chem. J. Chinese Universities, 2018, 39(11): 2425.

Figures/Tables 9

Fig.1 Structures of baicalin(BAL, A) and cucurbit[8]uril(Q[8], B)

Fig.2 UV-Vis absorption spectra of BAL with Q[8] in aqueous solution(A) or hydrochloric acid solution(C) and UV-Vis Job’s plot of ΔA against n(Q[8])/[n(Q[8])+n(BAL)] at 275 nm (B,D)c(BAL)=20 μmol/L; (A,C)n(Q[8])/n(BAL): a. 0; b. 0.2; c. 0.4; d. 0.6; e. 0.8; f. 1.0; g. 1.2;h. 1.4; i. 1.6; j. 1.8; k. 2.0. Insets in (A, C) are the plot of absorbances at 275 nm of BAL.

Scheme 1 Interaction model of Q[8] with BAL

Table 1 1H NMR and 1H-1H COSY spectra of BAL and BAL-Q[8]

Position	¹H NMR[400 MHz, V(DCl):V(D₂O)=5:1], δ		¹H-¹H COSY of BAL-Q[8]
Position	BAL	BAL-Q[8]	¹H-¹H COSY of BAL-Q[8]
3	4.19(1H, s)	3.93(1H, s)
8	4.04(1H, s)	4.63(1H, s)
2'	4.77(1H, d)	3.68(1H, m)	2'-H/ 1',3'-H
3'	4.32(1H, t)	3.32(1H, m)	3'-H/ 2', 4'-H
4'	4.49(1H, t)	3.63(1H, m)	4'-H/ 3', 5'-H
5'	4.32(1H, t)	3.08(1H, m)	5'-H/ 4',6'-H
6'	4.77(1H, d)	3.83(1H, m)	6'-H/ 1',5'-H
1″	2.25(1H, d)	2.35(1H, brs)	1″-H/ 2″-H
2″	0.76(1H, t)	0.99(1H, t)	2″-H/ 1″,3″-H
3″	0.62(1H, t)	0.92(1H, t)	3″-H/ 2″, 4″-H
4″	0.49(1H, t)	0.78(1H, t)	4″-H/ 3″ , 5″-H
5″	1.43(1H, d)	1.25(1H, brs)	5″-H/ 4″-H

Fig.3 IR spectra of Q[8](a), BAL(b), physical mixture of BAL-Q[8] (c), BAL-Q[8] inclusion complex(d)

Fig.4 UV spectra of saturated BAL in the presence of different concentrations of Q[8](A) and phase solubility graph of BAL in Q[8] at λ=275 nm(B)c(Q[8])/(μmol·L-1): a. 0; b. 10; c. 30; d. 50; e. 70; f. 90.

Fig.5 Changes of UV absorption intensity of BAL and BAL-Q[8] inclusion complex over time at pH=1.2(A) and 6.8(B)

Fig.6 Scavenging activity of BAL, BAL-Q[8] inclusion complex and L(+)-ascorbic acid at different concentrations

Fig.7 Release curves of BAL and BAL-Q[8] inclusion complex at pH=1.2(A) and 6.8(B)

References 25

[1]	Motoo Y., Sawabu N., Cancer Letters, 1994, 28(1), 91—93
[2]	Qin X. W., Zheng M. R., Mou X. L., Su J. H., Chinese J. Dermatol., 1998, 31(2), 116—117
	(秦小卫, 郑茂荣, 牟贤龙, 孙君红. 中华皮肤科杂志, 1998, 31(2), 116—117)
[3]	Kitamura K., Honda M., Yoshizaki H., Yamamoto S., Nakane H., Fukushima M., Ono K., Tokunaga T., Antiviral Res., 1998, 37(2), 131—133
[4]	Gong M. T., Yu L. F., Chen Q. H., Xie B. Y., Lu W. G., Chinese Pharm. J., 2008, 43(17), 1332—1335
	(龚明涛, 虞丽芳, 陈庆华, 谢保源, 陆伟根. 中国药学杂志, 2008, 43(17), 1332—1335)
[5]	Wang H., Chen J. M., Zhang Q. M., J. Shenyang Pharm. Univ., 2000, 17(2), 105—106
	(王弘, 陈济民, 张清民. 沈阳药科大学学报, 2000, 17(2), 105—106)
[6]	Saleh N., Koner A. L., Nau W. M., Angew. Chem. Int. Ed. Engl., 2008, 47(29), 5398—5401
[7]	Zhang L. X., Zhao W. X., Synthetic Materials Aging and Application, 2015, 44(1), 109—112
	(张来新, 赵卫星. 合成材料老化与应用, 2015, 44(1), 109—112)
[8]	Day A. I., Arnold A. P., Method for Synthesis Cucurbiturils, WO 068232,2000-11-16
[9]	Day A. I., Blanck R. J., Amold A. P., Angew. Chem. Int. Ed., 2002, 41(2), 275—277
[10]	Kim J., Jung I. S., Kim S. Y., Lee E., Kang J. K., Sakamoto S., Yamaguchi K., Kim K., J. Am. Chem. Soc., 2000, 122(3), 540—541
[11]	Zhao Y., Bali M. S., Cullinane C., Day A. I., Collins J. G., Dalton Trans., 2009, (26), 5190—5198
[12]	Mock W. L., Shih N. Y., J. Org. Chem., 1986, 51(23), 4440—4446
[13]	Jeon Y. M., Kim H., Whang D., Kim K., J. Am. Chem. Soc., 1996, 118(40), 9790—9791
[14]	Mou L., Xue S. F., Du Y., Zhao Y. J., Zhu Q. J., Tao Z., Chem. J. Chinese Universities, 2006, 27(4), 654—659
	(牟兰, 薛赛凤, 杜莹, 赵云洁, 祝黔江, 陶朱. 高等学校化学学报, 2006, 27(4), 654—659)
[15]	Jiang P. Y., Xue S. F., Wu M. Q., Xiao X., Zhu Q. J., Tao Z., Chem. J. Chinese Universities, 2008, 29(8), 1573—1577
	(姜平月, 薛赛凤, 吴明强, 肖昕, 祝黔江, 陶朱. 高等学校化学学报, 2008, 29(8), 1573—1577)
[16]	Li G. P., Yu F. Q., Lin J. H., Chen Y. Z., Chinese J. Applied Chem., 2010, 27(5), 563—566
	(李国平, 俞芳琴, 林金鹤, 陈银枝. 应用化学, 2010, 27(5), 563—566)
[17]	Dong N., Wang X. L., Pan J. P., Tao Z., Acta Chim. Sinica, 2011, 69(12), 1431—1437
	(董南, 王秀林, 盘金品, 陶朱. 化学学报, 2011, 69(12), 1431—1437)
[18]	Li L. F., Lin Y. W., Huang Z. W., Luo H. B., Chem. J. Chinese Universities, 2012, 33(2), 282—287
	(李立凡, 林友文, 黄智文, 罗红斌. 高等学校化学学报, 2012, 33(2), 282—287)
[19]	Huang Z., Lin Y., Lai K., J. Fujian Medical Univ., 2010, 44(5), 347—350
	(黄智文, 林友文, 赖楷贤, 李光文. 福建医科大学学报, 2010, 44(5), 347—350)
[20]	Lian X. W., Huang J. J., Tao Z., Zhou H. D., Zhang Q. J., Wei G., Chem. J. Chinese Universities, 2018, 39(2), 226—233
	(练小卫, 黄净净, 陶朱, 周清娣, 张前军, 卫钢. 高等学校化学学报, 2018, 39(2), 226—233)
[21]	Mou L., Xue S. F., Zhu Q. J., Tao Z., Zeng X., Chem. J. Chinese Universities, 2005, 26(10), 1835—1839
	(牟兰, 薛赛凤, 祝黔江, 陶朱, 曾晞. 高等学校化学学报, 2005, 26(10), 1835—1839)
[22]	Xu Z. L., Lian X. W., Li M. J., Zhang X. D., Wang Y., Zhang Q. J., Tao Z., Chem. Res. Chinese Universities, 2017, 33(15), 1—6
[23]	Xu H., Chen L., Ma L. H., Analysis and Testing Technology and Instruments, 2002, 8(2), 72—80
	(续浩, 陈亮, 马丽花. 分析测试技术与仪器, 2002, 8(2), 72—80)
[24]	Li P. Y., Huo L. N., Su W., Lu R. M., Deng C. C., Lü Y. G., Chinese J. Expe. Trad. Med. Form, 2011, 17(1), 162—164
	(李培源, 霍丽妮, 苏炜, 卢汝梅, 邓超澄, 吕友国. 中国实验方剂学杂志, 2011, 17(1), 162—164)
[25]	Chinese Pharmacopoeia Commission, Chinese Pharmacopoeia, 2015, Section Two, China Medical Science and Technology Press, Beijing, 2015, 85—86
	(国家药典委员会. 中国药典2015年版二部, 北京: 中国医药科技出版社, 2015, 85—86)