Synthesis of bridged and metallobridged bis(β-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'-oxamido-bisbenzoyl linkers-that is, 6,6'-[2,2'-oxamidobis(benzoylamino)]ethyleneamino-6,6'-deoxy-bis(beta-CD) (2), 6,6'-[2,2'oxamidobis(benzoylamino)]diethylene- diamino-6,6'-deoxy-bis(P-CD) (3), 6,6'[4,4'-oxamidobis(benzoylamino)]ethyle- neamino-6,6'-deoxy-bis(P-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 Cull 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 (K-S 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 K-S 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.