A spectrofluorimetric study of binary fluorophore–cyclodextrin complexes used as chiral selectors Francesca D’Anna, * Serena Riela, Michelangelo Gruttadauria, Paolo Lo Meo and Renato Noto * Dipartimento di Chimica Organica ‘E. Paterno `’, Universita ` degli Studi di Palermo, Viale delle Scienze, Parco d’Orleans II, 90128 Palermo, Italy Received 10 December 2004; revised 14 February 2005; accepted 3 March 2005 Available online 31 March 2005 Abstract—Six binary complexes between three fluorophores (pyrene, xanthone and anthraquinone) and b-cyclodextrin (b-CD) or heptakis- (6-amino)-(6-deoxy)-b-cyclodextrin (am-b-CD) were tested at two pH values (8.0 and 9.0) as chiral selectors for three a-amino acids chosen as model. The conditional constant (b 2T ) values for ternary complexes (fluorophore-CD-amino acid), determined by means of fluorescence spectroscopy, showed that the binary complexes are suitable receptors for chiral recognition. The effect of a-amino acids on stability and stoichiometric ratio of the binary complexes has also been studied. The binary complexes were in most cases stabilized by adding the ternary agent. The trend of stoichiometric ratios found is supported by variations in fluorescence spectra. Those relative to pyrene (Py) show little changes going from binary to ternary complexes, while those recorded in the presence of xanthone (Xan) give the most significant variations underlining a deep reorganization of guest. Anthraquinone (Aq) shows an intermediate behavior. q 2005 Elsevier Ltd. All rights reserved. 1. Introduction Chiral recognition is one of the most fundamental aims in stereochemistry. Many authors, such as Ogston, 1 Cramer, 2 and more recently Davankov, 3 have tried to understand the nature of interactions that are needed for a chiral selector to recognize enantiomers. The importance of this topic is also due to the fact that the activity of most biological molecules, indeed in protein recognition phenomena, seems to be due to ability of receptors to interact with amino acid residues in order to give inclusion complexes or supramolecular species. 4 As amino acids are the main constituents of proteins and, as they show a marked trend to form complexes with a wide variety of molecules, in the last three decades many researchers have attempted to find artificial receptors for these chiral molecules. In fact a better understanding of interactions working in chiral recognition processes can be useful, not only because most therapeutic drugs are developed from chiral amino acid intermediates and are required in an enantiomerically pure form, but also because it can allow the development of new methods of asymmetric synthesis and chromatographic resolution of enantiomers. Several papers have been published on the synthesis of chiral macrocyclic compounds and their ability to recognize enantiomers. 5 On this subject Cram et al. have reported the synthesis of macrocycles having binaphthyl units, which are able to selectively interact with enantiomers of amino acids. 6 More recently Escuder et al. 7 have reported the synthesis of molecular receptors able to selectively interact with enantiomers of tyrosine, phenylalanine and tryptophan. Among semi-natural receptors, cyclodextrins are very important. Thanks to their intrinsically chiral cavity, cyclodextrins have been used in chiral recognition of both L/D amino acids 8 and small peptide segments. 9 Very often the chiral recognition of a-amino acids results from a ternary complex, formed between a functionalised cyclo- dextrin, a metal ion and the chiral molecule; 10 in other cases, as recently reported by Liu et al., 11 the high L-enantioselectivity for leucine is due to the presence of a functional group on the primary rim of cyclodextrin that changes its ability towards molecular and chiral recognition. Among enantioselective sensors, fluorescent ones are particularly interesting, due to the high sensitivity and selectivity of the detection method. 12 Until now, little attention has been addressed to the possibility of using fluorescent binary host/guest complexes, formed by cyclo- dextrin, in studying chiral recognition processes. On this subject, some years ago, Yang and Bohne 13 reported results concerning the interaction of the complex pyrene/ b-cyclodextrin with the enantiomers of tryptophan. The 0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.tet.2005.03.013 Tetrahedron 61 (2005) 4577–4583 Keywords: Cyclodextrins; Chiral recognition; Fluorescence. * Corresponding authors. Tel.: C39 091596919; fax: C39 091596825 (R.N.); e-mail: rnoto@unipa.it