Calorimetric titrations have been performed at 25 OC in an aqueous solution (pH 7.20) to give the complex stability constants and thermodynamic parameters for the 1 : 1 complexation of 2-naphthalenesulfonate with various 8-cyclodextrin (CD) derivatives 1-15. All of the derivatizations examined led to substantial decreases in complex stability, which are discussed from the thermodynamic point of view. Except for methylated CD 2 and bridged CDs 14 and 15, the marked stability drops caused by derivatizations are solely attributable to the highly negative entropy changes (TAS) that exceed the increased enthalpic gains (-AH) arising from the enhanced hydrophobic interaction with lipophilic 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 accommodated in the CD cavity. This is probably rationalized by the decreased 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 and 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 stabilities for 14 and 15 are mainly attributed to the decreased enthalpic gain, while the entropic gain is kept unchanged for 15 or becomes more positive for 14. As was the case with the parent CDs, the AH-TAS plot for modified CDs 2-16 shows an excellent linear relationship, affording a very large slope (a 1.07) and intercept (TA& 5.0). Interestingly, similar analyses of the thermodynamic parameters reported for quinone-receptor porphyrin 17, metalloporphyrins 18-29, and cyclophanes/calixarenes 30-43 also afford compensatory AH-TAS relationships with distinctly different slopes a and intercepts TASo. As proposed previously for the host-guest complexations with various ionophores and CDs, the a and TAS, values nicely interpret the complexation behavior of all host categories as measures of the conformational changes and the extent of desolvation caused upon complexation, respectively. Thus, the enthalpy- entropy compensation effect is demonstrated to be a convenient, versatile tool for analyzing a wide variety of host-guest complexations involving weak forces such as dipoledipole, ion-dipole, van der Waals, and hydrogen-bonding interactions.