Host–guest interactions involving cyclodextrins: useful complementary insights achieved by polarimetry Paolo Lo Meo, * Francesca D’Anna, Serena Riela, Michelangelo Gruttadauria and Renato Noto * Dipartimento di Chimica Organica ‘E. Patern  o’, Universit  a degli Studi di Palermo, V.le delle Scienze, Parco d’Orleans II, Pad. 17—90128 Palermo, Italy Received 20 March 2007; revised 1 June 2007; accepted 21 June 2007 Available online 27 June 2007 Dedicated to Professor Domenico Spinelli on the occasion of his 75th birthday Abstract—By means of simple polarimetry, we studied the binding abilities of native a-, b-, and g-cyclodextrins toward a group of suitably chosen model guests. We were able to get reliable estimations of the binding constants K, spread over a wide range (from 3.7 to 12,300 M 1 ), allowing us to carry on interesting comparisons. A comprehensive discussion of polarimetric data, and in particular a detailed analysis of the variations DQ of molar optical activities consequent to inclusion, offered us the opportunity to get useful insights into the structure and dynamic behavior of host–guest complexes. Ó 2007 Elsevier Ltd. All rights reserved. 1. Introduction Owing to their ability to form inclusion complexes with a large number of suitably sized and structured organic guest molecules, 1 native and chemically modified cyclodextrins (CDs) are materials of enormous interest. They are em- ployed in widespread research and industrial applications, spanning from reaction microenvironments 2 and enzyme modeling 3 to separation technologies 4 and to additives for pharmaceutical, cosmetic, and food industries. 5 Studies on CDs are the object of an immense literature that is periodi- cally reviewed. 6 Under this perspective, a deep understand- ing of the microscopic features of the binding phenomenon, and of the factors affecting the thermodynamics of the inclu- sion process, is of fundamental importance. Despite the large amount of both experimental and com- putational work carried out during the last decades, the intimate mechanisms implied in molecular and chiral recog- nition by CDs are still object of an intense debate and, up to now, cannot be considered satisfactorily understood. A thor- ough analysis of available data shows that inclusion is af- fected by different factors (hydrophobic and dipolar/ electrostatic interactions, hydrogen bond or other specific in- teractions, release of steric strain, solvent reorganization), often working in opposition to each other, and with no obvi- ous hierarchy among them. 7 All these effects exert their own influence on both the DH o and TDS o parameters associated with the process. The intuitive idea that a stronger interac- tion should correspond with a more rigid inclusion complex, suggested the possibility of a DH o TDS o ‘isoequilibrium’ compensation effect, 8,9 a topic heavily debated until re- cently. 10–12 In general, the inclusion is mainly enthalpy- driven when ‘non-specific’ effects (hydrophobic, van der Waals or dipolar interactions, solvation effects) prevail. 9,12 However, when strong ‘specific’ interactions (such as multi- ple hydrogen bonding) occur, unfavorable entropy effects may overwhelm enthalpy contributions. 11 Furthermore, on some occasions, the molecular recognition properties of CDs have not been found as effective as reasonably ex- pected. For instance, enantioselectivities of native CDs toward simple chiral derivatives are modest, 9,13 whereas significant improvements may be achieved in constrained systems. 14 As a matter of fact, the possibility of an ‘induced fit’ effect for the CD host may allow the optimization of molecular interactions with both enantiomers of the chiral guest. 15 Indeed, the dynamic behavior of CDs as flexible objects 16 is a topic that probably deserves more attention now than in the past: in fact, the old image of CDs as rigid and symmetric buckets has been progressively abandoned and should now be considered obsolete. The need to investigate more deeply host–guest inclusion phenomena in general, and binding equilibria involving CDs in particular, has encouraged the search for new exper- imental methodologies and procedures, able to achieve more precise, reliable and detailed information, and more quickly. * Corresponding authors. Tel.: +39 091 596919; fax: +39 091 596825; e-mail: rnoto@unipa.it 0040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved. doi:10.1016/j.tet.2007.06.065 Tetrahedron 63 (2007) 9163–9171