Journal of Inclusion Phenomena and Macrocyclic Chemistry 38: 199–206, 2000. © 2000 Kluwer Academic Publishers. Printed in the Netherlands. 199 Interplay between Molecular Recognition and Redox Properties: A Theoretical Study of the Inclusion Complexation of β -Cyclodextrin with Phenothiazine and its Radical Cation LEI LIU, XIAO-SONG LI, TING-WEI MU, QING-XIANG GUO ⋆ and YOU-CHENG LIU Department of Chemistry, University of Science and Technology of China, Hefei 230026, P.R. China and National Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou, 730000, P.R. China (Received: 20 July 1999; in final form: 4 October 1999) Abstract. The PM3 molecular orbital method was employed in the conformational analysis of the in- clusion complexation of β -cyclodextrin with phenothiazine and its radical cation from a complete and unrestricted geometry optimization. Ab initio calculations at the level of HF/3-21G(d) and B3LYP/3- 21G(d) were utilized to determine the electronic structures of the host, guest and their complexes. The results indicated that the complexation of β -cyclodextrin with the phenothiazine radical cation was significantly more favorable than that with the neutral one, in good agreement with the experimental observation. The charge-transfer interaction was proposed as a physical reason for such behavior. It is suggested that caution should be given when extrapolating one oxidation state behavior to the supramolecular systems in their other oxidation states. Key words: cyclodextrin, inclusion, phenothiazine, radical cation, theoretical study. 1. Introduction α-, β - and γ -Cyclodextrins (CDs) are cyclic oligomers of six, seven and eight α-D-glucose units connected through glycosidic α-1,4 bonds [1]. These com- pounds, usually characterized as a doughnut or wreath-shaped truncated cones, have a hydrophobic cavity of appropriate dimensions and hence can form inclusion complexes with a variety of organic compounds in aqueous solution [2]. Model studies on the inclusion complexation of CD with various substrates offer important insights into molecular recognition and enzyme-substrate interactions [3]. Theoretical calculations [4] help illustrate the driving forces for the compl- exation [5] and the inclusion regioselectivity in CD-catalyzed reactions [6]. Due to its large size, most studies on CD chose molecular mechanics (MM) calcula- tion [7] and molecular dynamics (MD) simulation [8] based on various empirical ⋆ Author for correspondence.