Novel behavior of O-methylated β-cyclodextrins in inclusion of meso-tetraarylporphyrins

The mechanism for formation of extremely stable 1:2 inclusion complexes of water-soluble mesotetraarylporphyrins with heptakis(2,3,6-tri-O-methyl)-beta-cyclodextrin (TMe-beta-CD) in aqueous solutions has been studied by means of NMR spectroscopy and isothermal titration calorimetry. To simplify the system, 5,10,15-tris(3,5-dicarboxylatophenyl)-20-phenylporphyrin (1) was used as a guest porphyrin, because 1 forms only a 1:1 inclusion complex with cyclodextrin (CD). As host compounds, native beta-CD and the O-methylated-beta-CDs such as heptakis(2,3-di-O-methyl)- (2,3-DMe-beta-CD), heptakis(2,6-di-O-methyl)- (2,6-DMe-beta-CD), and TMe-beta-CDs were used. The thermodynamic parameters for complexation such as binding constants (K) and enthalpy (Delta H degrees) and entoropy changes (AS') were determined by means of isothermal titration calorimetry. The K value for complexation of 1 with CD increases in the order beta-CD (K = (1.2 +/- 0.1) x 10(3) M-1) < 2,6-DMe-beta-CD ((1.2 +/- 0.1) x 10(4) M-1) << TMe-beta-CD ((6.9 +/- 0.4) x 10(6) M-1) < 2,3-DMe-beta-CD ((8.5 +/- 0.5) x 10(6) M-1), indicating participation of the secondary OCH3 groups in extremely strong complexation of 1 with CD. Complex formation of 1 with beta-CD and 2,6-DMe-beta-CD is an enthalpically and entropically favorable process, while that with TMe-beta-CD and 2,3-DMe-beta-CD is an enthalpically much more favorable but an entropically less favorable process. The thermodynamic parameters suggest that inclusion of 1 into the cavities of TMe-beta-CD and 2,3-DMe-beta-CD is promoted by van der Waals interactions, which are stronger than those in the cases of beta-CD and 2,6-DMe-beta-CD. C-13 NMR spectra show that the conformations of both TMe-beta-CD and 2,3-DMe-beta-CD are altered upon inclusion of 1, while those of beta-CD and 2,6-DMe-beta-CD are mostly retained. On the basis of these results, it can be concluded that induced-fit type complexation of 1 with TMe-beta-CD and 2,3-DMe-beta-CD causes extremely strong binding of the host to the guest.