Host–guest complexation of antioxidative caffeic and ferulic acid amides with a functionalized cyclophane

Host−guest complexation has been studied by 1H NMR on the benzyl and phenethyl amides of ferulic and caffeic acids as the guests in chloroform and acetonitrile; the counter host is a cyclophane which integrates four phenylene rings, amino and amide groups in the macrocyclic framework and bears four pendant methyl acetate ester arms. CAPE, one of the best known natural antioxidants, also has been studied for comparison. Among the guests studied, ferulic acid benzyl amide shows NMR shifts due to the formation of a host−guest complex in chloroform. The complexation occurs in two steps with the formation constants K1 = [HG]/[H][G] = 6 M−1 and β2 = [HG2]/[H][G]2 = 87 M−2. Two guest molecules are bound on the surface of the macrocyclic framework of a host molecule by two hydrogen bonds, NH(host amide)···O=C(guest amide) and C=O(host ester)···HO(guest phenol). The latter hydrogen bond may protect the bioactive site, i.e., phenol OH, of guest molecules captured in the complex against undesirable oxidation. This feature is observed only for ferulic acid benzyl amide in chloroform; the cyclophane ester interacts with this amide, distinctively from the other hydroxycinnamic acid derivatives.