Crystal structure of the inclusion complex of the antibacterial agent triclosan with cyclomaltoheptaose and NMR study of its molecular encapsulation in positively and negatively charged cyclomaltoheptaose derivatives Original Research Article

The inclusion complexes of triclosan with native cyclomaltoheptaose (β-cyclodextrin, βCD) as well as with negatively and positively charged derivatives are studied. The structure of the inclusion complex βCD/triclosan in the crystalline state [P1, a = 15.189(5), b = 15.230(6), c = 16.293(6), α = 91.07(4), β = 91.05(3) γ = 100.71(3)] comprises two crystallographically independent host macrocycles A and B. The packing results in βCD dimers that align head-to-head and form infinite channels along the c-axis. Only one guest molecule statistically disordered over two positions, (the dichlorophenyl ring in the cavities of either A or B) corresponds to each dimer (a 2:1 host/guest complex). The enclosed dichlorophenyl ring enters the dimer through the primary side, whereas the hydrophilic chlorophenol ring extends in the space between dimers. Water molecules in five positions are also enclosed in the intradimer region, arranged on a plane perpendicular to the sevenfold axis of βCD. The NMR spectroscopic studies in aqueous solution show the presence of both 1:1 and 2:1 βCD/triclosan complexes. In the first case, two different 1:1 complexes are simultaneously present, each with either ring entering the narrow primary side of one βCD molecule. In the 2:1 complex both rings of triclosan are included in two independent βCD hosts, a precursor to the supramolecular arrangement found in the crystalline form. In the case of the negatively charged sodium heptakis[6-deoxy-6-(3-thiopropionate)]-βCD, the NMR studies at pH 7.9 show a complete inclusion of triclosan inside the host in two orientations, one for the non-ionized (phenol) and reverse for the ionized (phenolate) form. Finally, for the positively charged heptakis(6-aminoethylamino-6-deoxy)-βCD, inclusion of triclosan is possible only when the pH is raised to 10 and it is concluded that both aromatic rings are alternatively inside the cavity. However in that case also, inclusion of the entire guest in the elongated cavity is suggested.