Journal of Inclusion Phenomena and Macrocyclic Chemistry 40: 291–295, 2001. © 2001 Kluwer Academic Publishers. Printed in the Netherlands. 291 The Influence of β - and γ -Cyclodextrin Cavity Size on the Association Constant with Decanoate and Octanoate Anions MARCIA M. MEIER 1 , MARILDE T. BORDIGNON LUIZ 2 , PATRICK J. FARMER 3 and BRUNO SZPOGANICZ 1, ∗ 1 Chemistry Department, 2 Food Science and Technology Department Federal University of Santa Catarina, Florian´ opolis - SC 88040 - 900 - Brazil; 3 Department of Chemistry, University of California, Irvine, Irvine, California 92697-2025, USA (Received: 12 December 2000; in final form: 8 July 2001) Key words: cyclodextrin, decanoate anion, octanoate anion, fatty acids, association constant, phenolphthalein Abstract This work evaluates the influence of the β - and γ -cyclodextrin (CD) cavity size on the association constant (K CDA ) with decanoate (C 10 ) and octanoate (C 8 ) anions. The spectral displacement technique with phenolphthalein was used to obtain the 1:1 association constant (K CDA ) in NaHCO 3 /NaOH buffer pH 10.5 at 25 ◦ C. The K CDA value obtained were 2.6 (±0.2) × 10 3 , 2.5 (±0.5) × 10 2 , for β CD–C 10 and γ CD–C 10 inclusion complexes, and 5.1 (±0.2) × 10 2 and 4.7 (±0.2) × 10 1 for β CD–C 8 and γ CD–C 8 inclusion complexes, respectively. The K CDA values of either acid with β CD is approximately 10 times higher than for the same acid with γ CD, where as for the same cyclodextrin, the K CDA value is 5 times higher for the C 10 association than for the C 8 . The data demonstrate that the cyclodextrin cavity size exerts a greater influence on the association constant than the chain length of the acid for these compounds. 1 H NMR studies show that fatty acid protonation has a distinct effect on the chemical shift of CD protons. Introduction Cyclodextrins (CDs) are cyclic oligosaccharides containing 6 to 12 glucose units linked by α-1,4-glucosidic bonds. They have the shape of a hollow truncated cone, resulting in a hydrophobic cavity. The more common cyclodextrins are α- , β - and γ -CD with 6, 7 and 8 glucose units, respectively, each having a slightly larger cavity size [1]. The formation of inclusion complexes between small organic molecules and cyclodextrins has proven to be an excellent method for studying the nature of noncovalent binding forces in solution [2]. The principal factors involved in binding are believed to be van der Waals and hydrophobic interactions, although hydrogen bonding and steric effects may also play a role [3]. A number of experimental techniques have been em- ployed in the determination of the affinity between cyclo- dextrins and guest molecules. These include fluorescence spectroscopy [4], potentiometric titration, conductance [5, 6], NMR titration [7, 8] and UV-visible spectroscopy [9–11]. A spectral technique, using phenolphthalein (PH) as competitive chromophoric binder, can be used when the guest does not absorb in the visible region. This method is based on the displacement of the competitive agent upon complexation of the desired guest to the CD cavity, and allows a determination of the association constant [12]. This method has been used to investigate the association constant between β CD and a homologous series of fluoro- ∗ Author for correspondence. E-mail: bruno@qmc.ufsc.br carbon and hydrocarbon anionic surfactants [10] and the influence of tetrahydrofuran on the association between β CD-phenolphthalein [2]. Another technique applicable to the study of inclusion complexes in CD is 1 H NMR spectroscopy. The chemical shifts (δ) of both the interior protons of the CD (H 3 and H 5 ) and the guest protons can be analyzed to provide information about the inclusion mode and binding affinity between CD and guest [8]. Little studied is the influence of the cyclodextrin size on the association of different fatty acids, which may be of importance in optimizing hydrophobic interactions within the inclusion complex. Therefore, in this work the associ- ation constants of two cyclodextrins, β CD and γ CD, with octanoate (C 8 ) and decanoate (C 10 ) anions were determined by using phenolphthalein as a competitive agent. 1 H NMR spectra of β CD-C 10 and C 8 , γ CD-C 10 and C 8 systems were also obtained in order to measure the variation of chemical shift of cyclodextrin protons in the presence of fatty acids at different pHs. Experimental Reagents and solutions Decanoic acid 99% and octanoic acid 99% were purchased from Fluka. D 2 O, KOD and phenolphthalein were purchased from Aldrich. NaHCO 3 and NaOH were obtained from Nuc- lear. Cerestar (USA) donated β -CD and γ -CD and both