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

Abstract

The reactions of 4-nitrophenyl trinorbornane-2-acetate and 4-nitrophenyl noradamantane-1-carboxylate with 6^A-(6-aminohexylamino)-6^A-deoxy-β-cyclodextrin 1 produce 6^A-{6-(bicyclo[2.2.1]heptan-2-ylacetylamino)hexylamino}-6^A-deoxy-β-cyclodextrin 2 (pK_a = 8.98) and 6^A-deoxy-6^A-{6-(tricyclo[3.3.1.0]nonan-3-ylcarbonylamino)hexylamino}-β-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-β-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_as in brackets are those of the single protonated amine functions of 2 and 4, and of both protonated amine functions of 7 which have identical pK_as [in each case at 298.2 K and I = 0.10 mol dm⁻³ (NaClO₄)]. ¹H NMR ROESY studies are consistent with the trinorbornyl, noradamantyl and dimethylcubyl entities of 2, 4 and 7 complexing inside the βCD annuli in D₂O at pD ≥ 11. Under the same conditions, adamantane-1-carboxylate forms intermolecular complexes with 2, 4 and 7 and displaces their trinorbornyl, noradamantyl and the dimethylcubyl entities from the β-cyclodextrin annulus to varying degrees depending on the relative size, shape and hydrophobicity of these groups. These data are compared with those for analogous modified β-cyclodextrins.