Synthesis of bridged and metallobridged bis(beta-cyclodextrin)s containing fluorescent oxamidobisbenzoyl linkers and their selective binding towards bile salts.
A series of beta-cyclodextrin (beta-CD) dimers containing fluorescent 2,2'-oxamidobisbenzoyl and 4,4'-oxamidobisbenzoyl linkers--that is, 6,6'-[2,2'-oxamidobis(benzoylamino)]ethyleneamino-6,6'-deoxy-bis(beta-CD) (2), 6,6'-[2,2'-oxamidobis(benzoylamino)]diethylenediamino-6,6'-deoxy-bis(beta-CD) (3), 6,6'-[4,4'-oxamidobis(benzoylamino)]ethyleneamino-6,6'-deoxy-bis(beta-CD) (4), and 6,6'-[4,4'-oxamidobis(benzoylamino)]diethylenediamino-6,6'-deoxy- bis(beta-CD) (5)--were synthesized from the corresponding oxamidobis(benzoic acid)s through treatment with mono[6-aminoethyleneamino-6-deoxy]-beta-CD or mono[6-diethylenetriamino-6-deoxy]-beta-CD. Further treatment of 2-5 with copper perchlorate gave their Cu(II) complexes 6-9 in satisfactory yields. The conformation and binding behavior of 2-9 towards two bile salt guests--sodium cholate (CA) and sodium deoxycholate (DCA)--was comprehensively investigated by circular dichroism, 2D NMR spectroscopy, and fluorescence spectroscopy in Tris-HCl buffer solution (pH 7.2) at 25 degrees C. Thanks to the cooperative host-linker-guest binding mode, the stoichiometric 1:1 complexes formed by bis(beta-CD)s 2-5 with bile salts gave high stability constants (KS values) of up to 10(3)-10(4) M(-1). Significantly, benefiting from the intramolecular 1:2 or 2:4 binding stoichiometry, the resulting complexes of metallobis(beta-CD)s 6-9 with bile salts gave much higher KS values of up to 10(6)-10(7) M(-2). The enhanced binding abilities of bis(beta-CD)s and metallobridged bis(beta-CD)s are discussed from the viewpoints of induced-fit interactions and multiple recognition between host and guest.
Liu
Yu
Y
Department of Chemistry, State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, PR China. yuliu@nankai.edu.cn
Yu
Hong-Mei
HM
Chen
Yong
Y
Zhao
Yan-Li
YL
D001565:Benzoates / Q000737:chemistry; D001647:Bile Acids and Salts / Q000737:chemistry / Q000378:metabolism*; D001671:Biochemistry / Q000379:methods*; D003300:Copper / Q000737:chemistry; D005456:Fluorescent Dyes / Q000737:chemistry* / Q000378:metabolism; D008670:Metals / Q000737:chemistry; D008968:Molecular Conformation; D013050:Spectrometry, Fluorescence; D017186:Titrimetry; D047392:beta-Cyclodextrins / Q000737:chemistry* / Q000378:metabolism*
D001565:Benzoates; D001647:Bile Acids and Salts; D005456:Fluorescent Dyes; D008670:Metals; D047392:beta-Cyclodextrins; D003300:Copper; C031215:betadex