THERMODYNAMICS OF MOLECULAR RECOGNITION BY CYCLODEXTRINS .2. CALORIMETRIC TITRATION OF INCLUSION COMPLEXATION WITH MODIFIED BETA-CYCLODEXTRINS - ENTHALPY-ENTROPY COMPENSATION IN HOST-GUEST COMPLEXATION - FROM IONOPHORE TO CYCLODEXTRIN AND CYCLOPHANE

Calorimetric titrations have been performed at 25-degrees-C in an aque ous solution (pH 7.20) to give the complex stability constants and the rmodynamic parameters for the 1:1 complexation of 2-naphthalenesulfona te with various beta-cyclodextrin (CD) derivatives 1-15. All of the de rivatizations examined led to substantial decreases in complex stabili ty, which are discussed from the thermodynamic point of view. Except f or methylated CD 2 and bridged CDs 14 and 15, the marked stability dro ps caused by derivatizations are solely attributable to the highly neg ative entropy changes (TDELTAS) that exceed the increased enthalpic ga ins (-DELTAH) arising from the enhanced hydrophobic interaction with l ipophilic side chain(s) in the modified CDs. The copper chelation in 4 , 6, 8, and 10 did not improve the complex stability, in spite of the presumed ion pairing of Cu2+ with the naphthalenesulfonate anion accom modated in the CD cavity. This is probably rationalized by the decreas ed hydrophobicity of the CD cavity caused by the closely located ionic species (Cu2+). Contrary to the pronounced enhancement reported for 1 -anilino-8-naphthalenesulfonate (ANS) as a guest, the capped CDs 14 an d 15 did not promote the binding of 2-naphthalenesulfonate, but rather reduced the binding constants by 2-3 orders of magnitude, as compared with the parent CD 1. Thermodynamically, the reduced complex stabilit ies for 14 and 15 are mainly attributed to the decreased enthalpic gai n, while the entropic gain is kept unchanged for 15 or becomes more po sitive for 14. As was the case with the parent CDs, the DELTAH-TDELTAS plot for modified CDs 2-16 shows an excellent linear relationship, af fording a very large slope (alpha 1.07) and intercept (TDELTAS0 5.0). Interestingly, similar analyses of the thermodynamic parameters report ed for quinone-receptor porphyfin 17, metalloporphyrins 18-29, and cyc lophanes/calixarenes 30-43 also afford compensatory DELTAH-TDELTAS rel ationships with distinctly different slopes alpha and intercepts TDELR AS0. As proposed previously for the host-guest complexations with vari ous ionophores and CDs, the alpha and TDELTAS(o) values nicely interpr et the complexation behavior of all host categories as measures of the conformational changes and the extent of desolvation caused upon comp lexation, respectively. Thus, the enthalpy-entropy compensation effect is demonstrated to be a convenient, versatile tool for analyzing a wi de variety of host-guest complexations involving weak forces such as d ipole-dipole, ion-dipole, van der Waals, and hydrogen-bonding interact ions.