SUPRAMOLECULAR CHEMISTRY .46. MOLECULAR RECOGNITION OF NUCLEOTIDES, NUCLEOSIDES, AND SUGARS BY AMINOCYCLODEXTRINS

beta-Cyclodextrins bearing two or seven aminomethyl groups in the 6-position (compounds 1a,b) are shown to act as polytopic receptors for nucleotides, la discriminates the guest compounds on the basis of nucleobase nature, sugar type (oxy- or deoxyriboses), and position of the phosphate groups (3' or 5'). For the first time such selectivity toward different moieties of nucleotides is realized by one artificial receptor simultaneously and in water as a solvent. 1b, although considerably less selective, exhibits very high sensitivities with binding constants of up to 3 X 10(6) M(-1). Comparison between complexes with inorganic phosphates, ribose phosphates, riboses, and nucleotides allows quantification of the different binding contributions: up to 20 kJ/mol for ionic interactions (as a function of the number of salt bridges) and 10-13 kJ/mol for the ribose unit. The nucleobases, although discriminated, are shown to contribute repulsive rather than attractive forces to complex formation. Complexation-induced NMR chemical shifts and intermolecular NOEs allow insight into the supramolecular structures. These results are in line with molecular mechanics simulations (CHARMm) which also show that the strong electrostatic interactions with Ib draw the substrate further away from the secondary interaction sites and thus lower the selectivity.: The sugar moiety is shown by NOE to rest in the cyclodextrin cavity. This complexation, in;contrast to usual expectations, is stronger for the more hydrophilic ribose derivatives in comparison to the deoxy compounds. Selective broadening of some proton signals is ascribed, on the basis of T-1 measurements, to complex dissociation processes rather than slow tumbling effects.