258 Letters in Organic Chemistry, 2009, 6, 258-263 1570-1786/09 $55.00+.00 © 2009 Bentham Science Publishers Ltd. Chiral Recognition of 2-Hydroxypropyl-alpha-cyclodextrin Towards DL- Tryptophan Luiz Fernando B. Malta a , Jaqueline D. Senra b , Luzineide W. Tinoco b , M.E. Medeiros a and Octavio A.C. Antunes* ,a a Instituto de Química,Universidade Federal do Rio de Janeiro, CT Bloco A 641, Cidade Universitária, Rio de Janeiro RJ 21941-909, Brazil; b Núcleo de Pesquisas em Produtos Naturais, Universidade Federal do Rio de Janeiro, Cidade Universitária CCS Bloco H Rio de Janeiro RJ 21941-590, Brazil Received March 27, 2008: Revised November 14, 2008: Accepted November 14, 2008 Abstract: In this report, the recognition points of tryptophan by 2-hydroxypropyl-alpha-cyclodextrin (HPCD) are pre- sented. This cyclodextrin exhibited greater thermodynamic chiral selectivity towards DL-tryptophan than the hydroxypro- pylated beta form. FTIR spectroscopy was used to tentatively evidence this chiral discrimination in solid state HPCD- Trp complexes. An inclusion complex was only detected for the HPCD-DTrp sample, while HPCD-LTrp immediately decomposed after crystallization, which left a mechanical mixture of tryptophan and cyclodextrin. Keywords: Chiral recognition, NMR, FTIR, cyclodextrin, tryptophan, thermodynamic chiral selectvity. INTRODUCTION Cyclodextrins (CDs) have been employed by our re- search group as chiral selectors [1], phase transfer agents [2a] and metallic nanoparticles stabilizers [2b]. This wide range of applying fields seems to be a result of its multifunc- tional cavity, which allows, for example, to increase water solubility of lypophillic molecules due to supramolecular inclusion phenomenum [3]; and to discriminate optical iso- mers, following the “lock and Key” model [4]. Besides, the possibility to chemically modify cyclodextrins may enhance some of their properties. For example, hydroxypropylation of OH groups situated nearby the cavity rims leads to modi- fied CDs with increased water solubility [5]. Chiral recognition has been the subject of our research efforts [1,6]. In previous work, we managed to establish the effect the cavity size of hydroxypropylated cyclodextrins (HPCD) has on enantiomeric discrimination of DL- tryptophan [1]. Inclusion topologies and encapsulation free energies were sufficient to explain why the alpha-HPCD was the unique CD form tested to efficiently discriminate D - and L-tryptophan during a capillary electrophoresis run [1]. However, the recognition points in both host and guest chemical structures were missed. Lipkowitz et al. [7] had already reported these sites for native alpha-CD and amino acids, but, as far as we known, solid-state chiral recognition in cyclodextrin systems by means of infrared spectroscopy has never been reported so far. In the present work, the site-specific recognition points of hydroxypropylated alpha-cyclodextrin and tryptophan (Fig. 1) were obtained by means of 1 H NMR spectroscopy. The effects on both host and guest proton resonances caused by *Address correspondence to this author at the Instituto de Química, Univer- sidade Federal do Rio de Janeiro, CT Bloco A 641, Cidade Universitária, Rio de Janeiro RJ 21941-909, Brazil; Tel: 55 21 25627248; Fax: 55 21 25627559; E-mai: oacantunes@gmail.com Trp inclusion in hydroxypropilated CDs were disclosed. In addition, the thermodynamic chiral selectivity of HPCD towards Trp racemate was shown using visible electronic spectroscopy technique and methyl orange as an inclusion probe. This was then compared with our past results con- cerning other TCS determination methid and beta- cyclodextrin-tryptophan system [1, 8]. Finally, the Fourier- transform infrared spectroscopy (FTIR) was applied to char- acterize powdered HPCD-Trp samples in search of signs of chiral discrimination in the solid state. N H NH 2 O OH 1 2 3 4 6   O HO H 2 H 4 H 1 O O H 3 HO H 5 O HO H 6 H 6 (A) (B) Fig. (1). Molecular structure of (A) tryptophan; and (B) hy- droxypropylated cyclodextrin. RESULTS AND DISCUSSION Fig. (2) shows NMR spectra of DL-tryptophan aromatic region, with and without hydroxypropylated cyclodextrins, which were added using a 20-fold molar excess with respect to the amino acid. According to the previously calculated stability constants [1], 90% of the tryptophan content is complexed when such excess is added. For the complex with 2-hydroxypropyl-beta-cyclodextrin, Fig. (2B), indole H2, H3 and H4 resonances were shifted to high field when compared to the correspondent signals in DL-Trp spectrum (Fig. 2A), which means that these hydrogens were inside the cavity. As stablished in the literature [9], shielding is associated to the inclusion phenomenum. In Fig. (2C), on the other hand, it was shown that the addition of 2-hydroxypropyl-alpha-