Intramolecular complexation in modified beta-cyclodextrins: a preparative,nuclear magnetic resonance and pH titration study

The reactions of 4-nitrophenyl trinorbornane-2-acetate and 4-nitrophenyl no radamantane-1-carboxylate with 6(A)-(6-aminohexylamino)-6(A)-deoxy-beta-cyc lodextrin 1 produce 6(A)-{6-(bicyclo[2.2.1]heptan-2-ylacetylamino)hexylamin o}-6(A)-deoxy-beta-cyclodextrin 2 (pK(a) = 8.98) and 6(A)-deoxy-6(A)-{6-(tr icyclo[3.3.1.0(3,7)]nonan-3-ylcarbonylamino)hexylamino}-beta-cyclodextrin 4 (pK(a) = 8.47), respectively, in good yield together with 4-nitrophenolate . The reaction of 2,3-dimethyl-1,8-bis-(4-nitrophenoxycarbonyl)cubane with two moles of 1 produces dimeric 1,8-bis-[6-(6(A)-deoxy-beta-cyclodextrin-6( A)-ylamino)hexylaminocarbonyl]-2,3-dimethylcubane 7 (pK(a) = 8.80) in good yield together with two moles of 4-nitrophenolate. The pK(a)s in brackets a re those of the single protonated amine functions of 2 and 4, and of both p rotonated amine functions of 7 which have identical pK(a)s [in each case at 298.2 K and I = 0.10 mol dm(-3) (NaClO4)]. H-1 NMR ROESY studies are consi stent with the trinorbornyl, noradamantyl and dimethylcubyl entities of 2, 4 and 7 complexing inside the beta CD annuli in D2O at pD greater than or e qual to 11. Under the same conditions, adamantane-1-carboxylate forms inter molecular complexes with 2, 4 and 7 and displaces their trinorbornyl, norad amantyl and the dimethylcubyl entities from the beta-cyclodextrin annulus t o varying degrees depending on the relative size, shape and hydrophobicity of these groups. These data are compared with those for analogous modified beta-cyclodextrins.