Evaluation of Chiral Recognition Ability of a Novel Uranyl±Salophen-Based Receptor: An Easy and Rapid Testing Protocol Antonella Dalla Cort,* [a] Josÿ Ignacio Miranda Murua, [b] Chiara Pasquini, [a] Miquel Pons,* [b] and Luca Schiaffino [a, b] Introduction The development of artificial receptors able to bind prefer- entially one of the two enantiomers of a given substrate is an essential target in bioorganic and supramolecular chemis- try. [1] The fundamental role played by stereochemistry in chemical interactions is clearly envisioned, for example, in the context of drug/receptor chemistry. Moreover, enantio- meric recognition is a key feature of many enzyme-catalysed reactions and is the basis of asymmetric catalysis. In recent years much work has been devoted to the development of chiral supramolecular receptors devoid of the classical ele- ments of chirality. This wide field encloses purely covalent structures such as inherently chiral calixarenes, [2] and nonco- valent assemblies whose chirality arises from desymmetris- ing interactions between achiral molecular components. [3] In many of these cases synthetic procedures lead to racemic mixtures, whose resolution is not always a simple task. In a time-saving and low-cost perspective, the ability of the host to achieve chiral recognition should conveniently be as- sessed at the racemic mixture level. Also, efficient tools for rapid determination of enantioselectivity are a requirement for the application of combinatorial methods to the synthe- sis of artificial receptors. [4] In the present work we describe a NMR-based protocol to evaluate the chiral recognition ability of synthetic hosts directly from their racemic mixture. The method described here has been applied to a novel derivative of nonsymmetri- cally substituted uranyl±salophen complexes (1,R ¼6 R’). [5] In these compounds the uranyl dication employs four of its co- ordination positions for complexation with the salophen ligand. [6] The fifth site is free and has been widely used for complexation of anions [7] and neutral molecules endowed with a hard donor site. [5,8] For this reason uranyl±salophen complexes have found applications as receptors, [9] cata- lysts, [10] carriers [11] and sensors. [12] [a] Dr. A. Dalla Cort, Dr. C. Pasquini, Dr. L. Schiaffino IMC-CNR and Dipartimento di Chimica Universit‡ La Sapienza, Box 34, Roma 62 00185 Rome (Italy) Fax: (+ 39)06490421 E-mail: antonella.dallacort@uniroma1.it [b] Dr. J. I. M. Murua, Prof. M. Pons, Dr. L. Schiaffino Dept de Quimica Organica Universitat de Barcelona, Facultat de Quimica Marti i Franques, 1, 08028 Barcelona (Spain) and Laboratory of Biomolecular NMR Parc CientÌfic de Barcelona Josep Samitier, 1±5, 08028 Barcelona (Spain) E-mail: mpons@qo.ub.es Abstract: A novel member of a new class of chiral uranyl±salophen com- plexes has been synthesised. The chiral recognition ability of this receptor toward the enantiomers of two primary amines, a sulfoxide, and a quaternary ammonium chloride has been evaluat- ed for the first time. The enantioselec- tivities obtained are encouraging. The NMR method developed for this pur- pose allows a fast, quantitative deter- mination of the enantioselectivity of the host directly from its racemic mix- ture and could find application as a preliminary screening tool in the search for new receptors using combi- natorial methods. The experiments car- ried out in this context demonstrated also that the activation barrier for the racemisation of such chiral uranyl±salo- phen receptors is much higher than the lower limit of 21 kcalmol 1 previously reported. Keywords: chirality ¥ enantioselec- tive recognition ¥ high-throughput screening ¥ host±guest systems ¥ NMR spectroscopy Chem. Eur. J. 2004, 10, 3301±3307 DOI: 10.1002/chem.200400016 ¹ 2004 Wiley-VCH Verlag GmbH&Co. KGaA, Weinheim 3301 FULL PAPER