Two-dimensional 13C-1H heteronuclear correlation NMR spectroscopic studies for the inclusion complex of cyclomaltoheptaose (β-cyclodextrin) with a new Helicobacter pylori eradicating agent (TG44) in the amorphous state

Abstract The interaction of a newly developed Helicobacter pylori eradicating agent (TG44, 4-methylbenzyl-4′-[ trans -4-(guanidinomethyl)cyclohexylcarbonyloxy]-biphenyl-4-carboxlylate monohydrochloride) with cyclomaltoheptaose (β-cyclodextrin, β-CyD) in the solid state was studied by high-speed frequency-switched Lee-Goldburg (FSLG) 13 C– 1 H heteronuclear correlation (HETCOR) NMR experiments. The TG44/β-CyD solid complex in a 1:1 stoichiometry was prepared by the grinding method. Powder X-ray diffractometry confirmed that the complex is in an amorphous state. The solid-state 13 C signals of TG44 and β-CyD were significantly broadened by the complexation. As the temperature increased, the 13 C signals of the aromatic moieties of TG44 were insignificantly influenced, whereas those of the cyclohexyl moiety became sharper. The T 1 ρ H values of the aromatic moieties of TG44 were almost the same as those of the β-CyD carbons, whereas those of other TG44 carbons gave much smaller values. The 13 C– 1 H HETCOR spectra gave the intermolecular correlation peaks between the aromatic carbons of TG44 and the β-CyD protons or between the biphenyl protons of TG44 and the β-CyD carbons, when measured using longer contact times (500 and 1500 μs). On the basis of these solid NMR spectroscopic data together with aqueous NMR data, we assume that β-CyD includes predominantly the biphenyl moiety of TG44 in the solid state. 13 C– 1 H HETCOR spectroscopy is particularly useful for the determination of inclusion modes of the complexes that occurring in an amorphous form.