Inclusion complexes and guest-induced color changes of pH-indicator-modified β-cyclodextrins

A methyl red-modified β-cyclodextrin (1) and a p-methyl red-modified one (2), both being the structural isomers with a positional difference of one substituent in the appending dye part, were synthesized in order to attain color changes induced by host-guest complexation as well as to investigate their conformations and binding properties. The structures of 1 and 2 were investigated by UV-visible absorption and induced circular dichroism spectroscopy in a 10% ethylene glycol aqueous solution. Host 1 accommodates the methyl red moiety in its own β-CD cavity with an orientation parallel to the CD axis, forming an intramolecular complex, while 2 partially includes the p-methyl red moiety in its own β-CD cavity with an orientation perpendicular to the CD axis. In neutral media, both 1 and 2 exist as azo forms, which have the dye part unprotonated. In acidic medium, 1 prefers the ammonium form, which is the form protonated on the dimethylamino group in the methyl red moiety, while 2 adopts the azonium form, which is the form protonated on the azo group. Their pK_a's are estimated to be 1.25 for 1 and 2.08 for 2. Upon addition of guest species, 1 and 2 in acidic media near their pK_a values (pH, 1.60 for 1; 2.52 for 2) changed the locations of the dye parts from inside to outside the cavities, forming 1:1 inclusion complexes with the guests. The guest-induced conformation changes of 1 and 2 caused the color changes from yellow to red for 1 and from orange to red for 2, which occur associated with the conversion of the dye parts of 1 and 2 from the azo form to the azonium one. The guest-binding properties, however, were markedly affected by structural difference of 1 and 2, as shown by the fact that the binding constants of 2 are larger than those of 1 in acidic media and 1 loses the binding ability in neutral medium, where 2 still has binding ability. The guest selectivity of 2 observed in acidic media is remarkable for the adamantane derivatives. These results demonstrated that various color changeable indicators for molecules may be constructed on the basis of the appropriate structural design of the dye part in chromophore-modified cyclodextrins.