对称四甲基六元瓜环与卡培他滨通过主客体作用构筑的超分子药物包结配合物（英文）
|
摘要
使用了核磁共振波谱、基质辅助激光解吸电离飞行时间质谱、等温滴定量热和荧光光谱等表征手段考察了对称四甲基六元瓜环(TMeQ[6])与抗癌性药物分子卡培他滨(CAP)之间的主客体超分子作用,实验结果表明:CAP分子的烷基链部分进入到了瓜环的空腔内部,而其余的部分则处于瓜环的端口外侧.该结论为今后TMeQ[6]在医学领域上作为药物分子载体方面的应用提供了理论依据.
A novel supramolecular host-guest complex of the anticancer drug capecitabine(CAP) with symmetrical α,α′,δ,δ′-tetramethyl-cucurbit[6]uril(TMeQ[6]) has been characterized using nuclear magnetic resonance spectroscopy, MALDI-TOF mass spectrometry, isothermal titration calorimetryand fluorescence spectroscopy analyses. The result revealed that the alkyl chain of CAP is located inside the cavities of TMeQ[6], whereas the other part of CAP remains outside the portal. Our results suggest that TMeQ[6] could be a promising candidate for use as an excipient in the pharmaceutical and medical research fields.
A novel supramolecular host-guest complex of the anticancer drug capecitabine(CAP) with symmetrical α,α′,δ,δ′-tetramethyl-cucurbit[6]uril(TMeQ[6]) has been characterized using nuclear magnetic resonance spectroscopy, MALDI-TOF mass spectrometry, isothermal titration calorimetryand fluorescence spectroscopy analyses. The result revealed that the alkyl chain of CAP is located inside the cavities of TMeQ[6], whereas the other part of CAP remains outside the portal. Our results suggest that TMeQ[6] could be a promising candidate for use as an excipient in the pharmaceutical and medical research fields.
引文
[1]Greef,T.F.A.;Smulders,M.M.J.;Wolffs,M.;Schenning,A.P.H.J.;Sijbesma,R.P.;Meijer,E.W.Chem.Rev.2009,109,5687.
[2]Webber,M.J.;Langer,R.Chem.Soc.Rev.2017,46,6600.
[3]Webber,M.J.;Appel,E.A.;Meijer,E.W.;Langer,R.Nat.Mater.2016,15,13.
[4]Schmaljohann,D.Adv.Drug Delivery Rev.2006,58,1655.
[5]Meng,F.H.;Zhong,Z.Y.;Feijen,J.Biomacromolecules 2009,10,197.
[6]Rosler,A.;Vandermeulen,G.W.M.;Klok,H.A.Adv.Drug Delivery Rev.2012,64,270.
[7]Allen,T.M.;Cullis,P.R.Adv.Drug Delivery.Rev.2013,65,36.
[8]Yang,Y.;Wang,S.P.;Wang,Y.T.;Wang,X.H.;Wang,Q.;Chen,M.W.Biotechnol.Adv.2014,32,1301.
[9]Davis,M.E.;Brewster,M.E.Nat.Rev.Drug Discovery 2004,3,102.
[10]Brewster,M.E.;Loftsson,T.Adv.Drug Delivery Rev.2007,59,645.
[11]Hirayama,F.;Uekama,K.Adv.Drug Delivery Rev.1999,36,125.
[12]Liu,Q.Y.;Yang,Y.T.;Li,H.;Zhu,R.R.;Shao,Q.;Yang,S.G.;Xu,J.J.Biosens.Bioelectron.2015,64,147.
[13]Liu,Q.Y.;Yang,Y.T.;Lv,X.T.;Ding,Y.A.;Zhang,Y.Z.;Jing,J.J.;Xu,C.X.Sens.Actuators,B 2017,240,726.
[14]Liu,Q.Y.;Chen,P.P.;Xu,Z.;Chen,M.M.;Ding,Y.A.;Yue,K.;Xu,J.Sensor Actuators,B 2017,251,339.
[15]Liu,Q.Y.;Zhu,J.Q.;Sun,T.;Zhou,H.Y.;Shao,Q.;Li,G.J.;Liu,X.D.;Yin,Y.S.RSC Adv.2013,3,2765.
[16]Zhou,Y.;Li,H.;Yang,Y.W.Chin.Chem.Lett.2015,26,825.
[17]Wheate,N.J.;Dickson,K.A.;Kim,R.R.;Nematollahi,A.;Macquart,R.B.;Kayser,V.;Yu,G.C.;Church,W.B.Marsh,D.J.J.Pharm.Sci.2016,105,3615.
[18]Veesar,I.A.;Memon,S.;Syed,M.N.Biochem.Eng.J.2013,79,71.
[19]Duan,Q.;Cao,Y.;Li,Y.;Hu,X.;Xiao,T.;Lin,C.;Pan,Y.;Wang,L.J.Am.Chem.Soc.2013,135,10542.
[20]Gokel,G.W.;Leevy,W.M.;Weber,M.E.Chem.Rev.2014,104,2723.
[21]Zhang,M.;Saha,M.L.;Wang,M.;Zhou,Z.;Song,B.;Lu,C.;Yan,X.;Li,X.;Huang,F.;Yin,S.;Stang,P.J.J.Am.Chem.Soc.2017,139,5067.
[22]Chi,X.;Ji,X.;Shao,L.;Huang,F.Macromol.Rapid Commun.2017,38,1600626.
[23]Yu,G.;Yu,W.;Shao,L.;Zhang,Z.;Chi,X.;Mao,Z.;Gao,C.;Huang,F.Adv.Funct.Mater.2016,26,8999.
[24]Yao,Y.;Wang,Y.;Zhao,R.;Shao,L.;Tang,R.;Huang,F.J.Mater.Chem.B 2016,4,2691.
[25]Yu,G.;Zhou,J.;Shen,J.;Tang,G.;Huang,F.Chem.Sci.2016,7,4073.
[26]Jie,K.;Zhou,Y.;Yao,Y.;Huang,F.Chem.Soc.Rev.2015,44,3568.
[27]Yu,G.;Jie,K.;Huang,F.Chem.Rev.2015,115,7240.
[28]Yu,G.;Yu,W.;Mao,Z.;Gao,C.;Huang,F.Small 2015,11,919.
[29]Wang,Q.;Cheng,M.;Cao,Y.;Jiang,J.;Wang L.Acta Chim.Sinica2016,74,9(in Chinese).(王其,程明,曹逸涵,强琚莉,王乐勇,化学学报,2016,74,9.)
[30]Gao,Y.;Hu J.;Ju Y.Acta Chim.Sinica 2016,74,312(in Chinese).(高玉霞,胡君,巨勇,化学学报,2016,74,312.)
[31]Li,W.;Qu,W.;Zhang,H.;Li,X.;Lin,Q.;Yao,H.;Zhang,Y.;Wei,T.Chin.J.Org.Chem.2017,37,2619(in Chinese).(李文婷,曲文娟,张海丽,李翔,林奇,姚虹,张有明,魏太保,有机化学,2017,37,2619.)
[32]Li,B.;Li,X.;Sun,X.;Wang,N.Chin.J.Chem.2016,34,1114.
[33]Kim,J.;Jung,I.S.;Kim,S.Y.;Kang,E.;Sakamoto,J.K.;Yamaguchi,S.;Kim,K.;Am,K.J.Chem.Soc.2000,122,540.
[34]Day,A.I.;Blanch,R.J.;Arnold,A.P.Angew.Chem.2002,114,285.
[35]Cheng,X.J.;Liang,L.L.;Chen,K.;Ji,N.N.;Xiao,X.;Zhang,J.X.;Zhang,Y.Q.;Xue,S.F.;Zhu,Q.J.;Ni,X.L.;Tao,Z.Angew.Chem.,Int.Ed.2003,52,7393.
[36]Li,Q.;Qiu,S.C.;Zhang,J.;Chen,K.;Huang,Y.;Xiao,X.;Zhang,Y.;Li,F.;Zhang,Y.Q.;Xue,S.F.;Zhu,Q.J.;Tao,Z.;Lindoy,L.F.;Wei,G.Org.Lett.2016,18,4020.
[37]Gao,R.H.;Chen,L.X.;Chen,K.;Tao,Z.;Xiao,X.Coord.Chem.Rev.2017,348,1.
[38]Gao,Z.Z.;Kan,J.L.;Chen,L.X.;Bai,D.;Wang,H.Y.;Tao,Z.;Xiao,X.ACS Omega 2017,2,5633.
[39]Wang,X.X.;Chen,K.;Shen,F.F.;Hua,Z.Y.;Qiu,S.C.;Zhang,Y.Q.;Cong,H.;Liu,Q.Y.;Tao,Z.;Xiao,X.Chem.-Eur.J.2017,23,16953.
[40]Barrow,S.J.;Kasera,S.;Rowland,M.J.;Del Barrio,J.;Scherman,O.A.Chem.Rev.2015,115,12320.
[41]Gao,Z.Z.;Bai,D.;Chen,L.X.;Tao,Z.;Xiao,X.;Priorb,T.J.;Redshaw,C.RSC Adv.2017,7,461.
[42]Assaf,K.I.;Nau,W.M.Chem.Soc.Rev.2015,44,394.
[43]Kaifer,A.E.Acc.Chem.Res.2014,47,2160.
[44]Gao,Z.Z.;Yang,L.G.;Bai,D.;Chen,L.X.;Tao,Z.;Xiao,X.Chem.J.Chin.Univ.2017,38,212(in Chinese).(高中政,杨立国,白东,陈丽霞,陶朱,肖昕,高等学校化学学报,2017,38,212.)
[45]Chen,L.X.;J.L.Kan,Cong,H.;Prior,T.J.;Tao,Z.;Xiao,X.;Redshaw,C.Molecules 2017,22,1147.
[46]Ji,L.;Yang,L.;Yu,Z.Y.;Tan,C.S.Y.;Parker,R.M.;Abell,C.;Scherman,O.A.Acc.Chem.Res.2017,50,208.
[47]Xiao,X.;Sun,J.S.;Jiang,J.Z.Chem.-Eur.J.2013,19,16891.
[48]Yang,B.;Gao,Z.Z.;Lu,J.H.;Zhu,Q.J.;Xue,S.F.;Tao,Z.;Prior,T.J.;Redshaw,C.;Wei,G.;Xiao,X.Cryst Eng Comm 2016,18,5028.
[49]Uzunova,V.D.;Cullinane,C.;Brix,K.;Nau,W.M.;Day,A.I.Org.Biomol.Chem.2010,8,2037.
[50]Walker,S.;Oun,R.;Mc Innes,F.J.;Wheate,N.J.Isr.J.Chem.2011,51,616.
[51]Wheate,N.J.;Limantoro,C.Supramol.Chem.2016,28,849-856.
[52]Walker,S.;Oun,R.;Mc Innes,F.J.;Wheate,N.J.Isr.J.Chem.2011,51,616.
[53]Saleh,N.I.;Ghosh,I.;Nau,W.M.Supramolecular Systems in Biomedical Fields,RSC Publishing,Cambridge UK,2013,pp.164~212.
[54]Zhao,Y.J.;Xue,S.F.;Zhu,Q.J.;Tao,Z.;Zhang,J.X.;Wei,Z.B.;Long,L.S.;Hu,M.L.;Xiao,H.P.;Day,A.I.Chin.Sci.Bull.2004,49,1111.
[55]Gao,Z.Z.;Bai,D.;Xiao,Z.Y.;Zhu,Q.J.;Xue,S.F.;Tao,Z.;Xiao,X.Inorg.Chem.Commun.2016,71,68.
[56]Bai,D.;Wang,X.;Gao,Z.;Qiu,S.;Tao,Z.;Zhang,J.;Xiao,X.Chin.J.Org.Chem.2017,37,2022(in Chinese).(白东,王鑫,高中政,邱胜超,陶朱,张建新,肖昕,有机化学,2017,37,2022.)
[57]Negreira,N.;Mastroianni,N.;Alda,M.L.;de Barcelo,D.Talanta2013,116,290.
[58]Walko,C.M.;Lindley,C.Clin.Ther.2005,27,23.
[2]Webber,M.J.;Langer,R.Chem.Soc.Rev.2017,46,6600.
[3]Webber,M.J.;Appel,E.A.;Meijer,E.W.;Langer,R.Nat.Mater.2016,15,13.
[4]Schmaljohann,D.Adv.Drug Delivery Rev.2006,58,1655.
[5]Meng,F.H.;Zhong,Z.Y.;Feijen,J.Biomacromolecules 2009,10,197.
[6]Rosler,A.;Vandermeulen,G.W.M.;Klok,H.A.Adv.Drug Delivery Rev.2012,64,270.
[7]Allen,T.M.;Cullis,P.R.Adv.Drug Delivery.Rev.2013,65,36.
[8]Yang,Y.;Wang,S.P.;Wang,Y.T.;Wang,X.H.;Wang,Q.;Chen,M.W.Biotechnol.Adv.2014,32,1301.
[9]Davis,M.E.;Brewster,M.E.Nat.Rev.Drug Discovery 2004,3,102.
[10]Brewster,M.E.;Loftsson,T.Adv.Drug Delivery Rev.2007,59,645.
[11]Hirayama,F.;Uekama,K.Adv.Drug Delivery Rev.1999,36,125.
[12]Liu,Q.Y.;Yang,Y.T.;Li,H.;Zhu,R.R.;Shao,Q.;Yang,S.G.;Xu,J.J.Biosens.Bioelectron.2015,64,147.
[13]Liu,Q.Y.;Yang,Y.T.;Lv,X.T.;Ding,Y.A.;Zhang,Y.Z.;Jing,J.J.;Xu,C.X.Sens.Actuators,B 2017,240,726.
[14]Liu,Q.Y.;Chen,P.P.;Xu,Z.;Chen,M.M.;Ding,Y.A.;Yue,K.;Xu,J.Sensor Actuators,B 2017,251,339.
[15]Liu,Q.Y.;Zhu,J.Q.;Sun,T.;Zhou,H.Y.;Shao,Q.;Li,G.J.;Liu,X.D.;Yin,Y.S.RSC Adv.2013,3,2765.
[16]Zhou,Y.;Li,H.;Yang,Y.W.Chin.Chem.Lett.2015,26,825.
[17]Wheate,N.J.;Dickson,K.A.;Kim,R.R.;Nematollahi,A.;Macquart,R.B.;Kayser,V.;Yu,G.C.;Church,W.B.Marsh,D.J.J.Pharm.Sci.2016,105,3615.
[18]Veesar,I.A.;Memon,S.;Syed,M.N.Biochem.Eng.J.2013,79,71.
[19]Duan,Q.;Cao,Y.;Li,Y.;Hu,X.;Xiao,T.;Lin,C.;Pan,Y.;Wang,L.J.Am.Chem.Soc.2013,135,10542.
[20]Gokel,G.W.;Leevy,W.M.;Weber,M.E.Chem.Rev.2014,104,2723.
[21]Zhang,M.;Saha,M.L.;Wang,M.;Zhou,Z.;Song,B.;Lu,C.;Yan,X.;Li,X.;Huang,F.;Yin,S.;Stang,P.J.J.Am.Chem.Soc.2017,139,5067.
[22]Chi,X.;Ji,X.;Shao,L.;Huang,F.Macromol.Rapid Commun.2017,38,1600626.
[23]Yu,G.;Yu,W.;Shao,L.;Zhang,Z.;Chi,X.;Mao,Z.;Gao,C.;Huang,F.Adv.Funct.Mater.2016,26,8999.
[24]Yao,Y.;Wang,Y.;Zhao,R.;Shao,L.;Tang,R.;Huang,F.J.Mater.Chem.B 2016,4,2691.
[25]Yu,G.;Zhou,J.;Shen,J.;Tang,G.;Huang,F.Chem.Sci.2016,7,4073.
[26]Jie,K.;Zhou,Y.;Yao,Y.;Huang,F.Chem.Soc.Rev.2015,44,3568.
[27]Yu,G.;Jie,K.;Huang,F.Chem.Rev.2015,115,7240.
[28]Yu,G.;Yu,W.;Mao,Z.;Gao,C.;Huang,F.Small 2015,11,919.
[29]Wang,Q.;Cheng,M.;Cao,Y.;Jiang,J.;Wang L.Acta Chim.Sinica2016,74,9(in Chinese).(王其,程明,曹逸涵,强琚莉,王乐勇,化学学报,2016,74,9.)
[30]Gao,Y.;Hu J.;Ju Y.Acta Chim.Sinica 2016,74,312(in Chinese).(高玉霞,胡君,巨勇,化学学报,2016,74,312.)
[31]Li,W.;Qu,W.;Zhang,H.;Li,X.;Lin,Q.;Yao,H.;Zhang,Y.;Wei,T.Chin.J.Org.Chem.2017,37,2619(in Chinese).(李文婷,曲文娟,张海丽,李翔,林奇,姚虹,张有明,魏太保,有机化学,2017,37,2619.)
[32]Li,B.;Li,X.;Sun,X.;Wang,N.Chin.J.Chem.2016,34,1114.
[33]Kim,J.;Jung,I.S.;Kim,S.Y.;Kang,E.;Sakamoto,J.K.;Yamaguchi,S.;Kim,K.;Am,K.J.Chem.Soc.2000,122,540.
[34]Day,A.I.;Blanch,R.J.;Arnold,A.P.Angew.Chem.2002,114,285.
[35]Cheng,X.J.;Liang,L.L.;Chen,K.;Ji,N.N.;Xiao,X.;Zhang,J.X.;Zhang,Y.Q.;Xue,S.F.;Zhu,Q.J.;Ni,X.L.;Tao,Z.Angew.Chem.,Int.Ed.2003,52,7393.
[36]Li,Q.;Qiu,S.C.;Zhang,J.;Chen,K.;Huang,Y.;Xiao,X.;Zhang,Y.;Li,F.;Zhang,Y.Q.;Xue,S.F.;Zhu,Q.J.;Tao,Z.;Lindoy,L.F.;Wei,G.Org.Lett.2016,18,4020.
[37]Gao,R.H.;Chen,L.X.;Chen,K.;Tao,Z.;Xiao,X.Coord.Chem.Rev.2017,348,1.
[38]Gao,Z.Z.;Kan,J.L.;Chen,L.X.;Bai,D.;Wang,H.Y.;Tao,Z.;Xiao,X.ACS Omega 2017,2,5633.
[39]Wang,X.X.;Chen,K.;Shen,F.F.;Hua,Z.Y.;Qiu,S.C.;Zhang,Y.Q.;Cong,H.;Liu,Q.Y.;Tao,Z.;Xiao,X.Chem.-Eur.J.2017,23,16953.
[40]Barrow,S.J.;Kasera,S.;Rowland,M.J.;Del Barrio,J.;Scherman,O.A.Chem.Rev.2015,115,12320.
[41]Gao,Z.Z.;Bai,D.;Chen,L.X.;Tao,Z.;Xiao,X.;Priorb,T.J.;Redshaw,C.RSC Adv.2017,7,461.
[42]Assaf,K.I.;Nau,W.M.Chem.Soc.Rev.2015,44,394.
[43]Kaifer,A.E.Acc.Chem.Res.2014,47,2160.
[44]Gao,Z.Z.;Yang,L.G.;Bai,D.;Chen,L.X.;Tao,Z.;Xiao,X.Chem.J.Chin.Univ.2017,38,212(in Chinese).(高中政,杨立国,白东,陈丽霞,陶朱,肖昕,高等学校化学学报,2017,38,212.)
[45]Chen,L.X.;J.L.Kan,Cong,H.;Prior,T.J.;Tao,Z.;Xiao,X.;Redshaw,C.Molecules 2017,22,1147.
[46]Ji,L.;Yang,L.;Yu,Z.Y.;Tan,C.S.Y.;Parker,R.M.;Abell,C.;Scherman,O.A.Acc.Chem.Res.2017,50,208.
[47]Xiao,X.;Sun,J.S.;Jiang,J.Z.Chem.-Eur.J.2013,19,16891.
[48]Yang,B.;Gao,Z.Z.;Lu,J.H.;Zhu,Q.J.;Xue,S.F.;Tao,Z.;Prior,T.J.;Redshaw,C.;Wei,G.;Xiao,X.Cryst Eng Comm 2016,18,5028.
[49]Uzunova,V.D.;Cullinane,C.;Brix,K.;Nau,W.M.;Day,A.I.Org.Biomol.Chem.2010,8,2037.
[50]Walker,S.;Oun,R.;Mc Innes,F.J.;Wheate,N.J.Isr.J.Chem.2011,51,616.
[51]Wheate,N.J.;Limantoro,C.Supramol.Chem.2016,28,849-856.
[52]Walker,S.;Oun,R.;Mc Innes,F.J.;Wheate,N.J.Isr.J.Chem.2011,51,616.
[53]Saleh,N.I.;Ghosh,I.;Nau,W.M.Supramolecular Systems in Biomedical Fields,RSC Publishing,Cambridge UK,2013,pp.164~212.
[54]Zhao,Y.J.;Xue,S.F.;Zhu,Q.J.;Tao,Z.;Zhang,J.X.;Wei,Z.B.;Long,L.S.;Hu,M.L.;Xiao,H.P.;Day,A.I.Chin.Sci.Bull.2004,49,1111.
[55]Gao,Z.Z.;Bai,D.;Xiao,Z.Y.;Zhu,Q.J.;Xue,S.F.;Tao,Z.;Xiao,X.Inorg.Chem.Commun.2016,71,68.
[56]Bai,D.;Wang,X.;Gao,Z.;Qiu,S.;Tao,Z.;Zhang,J.;Xiao,X.Chin.J.Org.Chem.2017,37,2022(in Chinese).(白东,王鑫,高中政,邱胜超,陶朱,张建新,肖昕,有机化学,2017,37,2022.)
[57]Negreira,N.;Mastroianni,N.;Alda,M.L.;de Barcelo,D.Talanta2013,116,290.
[58]Walko,C.M.;Lindley,C.Clin.Ther.2005,27,23.