Synthetic receptors for neutral nitro derivatives Umporn Athikomrattanakul a,b , Chamras Promptmas b , Martin Katterle a, * a Fraunhofer Institute for Biomedical Engineering, Am Mühlenberg 13, Potsdam 14476, Germany b Department of Clinical Chemistry, Faculty of Medical Technology, Mahidol University, Nakhon Pathom 73170, Thailand article info Article history: Received 14 August 2008 Revised 30 October 2008 Accepted 5 November 2008 Available online 8 November 2008 Keywords: Nitro derivatives Arylurea-based receptor Guanidine-based receptor Binding constants abstract Different arylurea-based receptors with similar substitution pattern and one guanidine-based receptor were synthesised and studied concerning their binding capability towards the title functional group; spe- cific binding of neutral nitro groups is revealed with relatively high binding constants in DMSO ranging from 470 to 1370 M 1 for urea and 730–990 M 1 for guanidine-based binding partners. Ó 2008 Elsevier Ltd. All rights reserved. The utilisation of host–guest chemistry for a target is a well- established area of research and currently directed towards tailor-made receptors to bind suitable substrates in polar and non-polar solvents, respectively. A large number of receptors have been described in particular for the selective binding of anionic fragments. 1 Oxoanionic substrates such as carboxylic acids and carboxylates are important functional groups in biological and in self-assembled supramolecular systems. 2 Several binding receptors in particular for both simple and complex carboxylic compounds have been developed, in non-polar as well as in polar solvents. 3 Aryl(thio)urea derivatives build up bifurcate hydrogen donor–acceptor interactions, and therefore they are used as excellent neutral receptors for these oxoanions. 4,5 Moreover, urea and thiourea can act as an organocatalyst to activate the alkylation of aromatic compounds with nitroalkenes via the bidentate hydro- gen bonding. 6 Various guanidium salts have also been successfully employed for the molecular recognition of carboxylates (amino acids) or phosphates (nucleotides). 7,8 Recently, guanidinocarbonyl pyrrole receptors were described as well, which displayed high affin- ities for carboxylates due to the combination of the electrostatic interaction and the binding via a bidentate hydrogen bonding. 3,9,10 The neutral nitro group is one of the isosters of the mono-anio- nic carboxylate because of structural similarity. 3,11 Therefore, this group should be able to build up hydrogen donor–acceptor net- works based on the nitro-urea and nitro-guanidine interactions. The combination of multiple weak interactions like in carboxyl- ate-receptor systems leads to high binding affinities in polar solvent systems. 9 Many synthetic receptors have been constructed for mono-anionic carboxylate moieties, but surprisingly there are only few examples of synthetic receptors for the recognition of its isosteric anions, for example, phosphates, sulfonates groups and only one for the specific molecular recognition of the neutral nitro group. 10 However, there is one previous report that revealed the interaction between the nitro anions compound (nitronate) via hydrogen bond with the 1,3-dimethylthiourea by weak binding (K a = 120 M 1 ), but quite strong binding with bicyclic guanidinium (K a = 3200 M 1 ) in DMSO. 12 For this reason, we designed chromo- genic receptor units and provided an assessment of their relative affinity in polar or non-polar solvent systems. We applied two strategies to the design of the receptors: one was based on aryl(thio)urea derivatives with increasing electron-deficient aryl moieties (1–3). In a second approach, we employed the zwitter- ionic guanidinium derivative 4, which has never been used for the neutral nitro group recognition. As before, the urea moiety is a capable host for oxoanions, 11 and the binding can be tuned up by increasing the acidity of the hydrogen bond donor site by using strong withdrawing substituents on the aromatic ring and/or by substitution of the oxygen atom by a sulfur atom in the urea unit. Therefore, the thiourea derivatives were designed and synthesised to use as receptors for this purpose. Herein, we report on the synthesis and binding characteristics of the nitro moiety of new unsymmetrically substituted aromatic (thio)urea derivatives, which were obtained by condensation of the corresponding aryl iso- and thioisocyanates with 4-vinylaniline in a single reaction step. These aryl(thio)urea-based receptors yield in chromogenic systems which are used as a signalling unit for the binding events. Compounds 1 and 4 were synthesised as described earlier, 9,13 and the novel compounds 2 and 3 were prepared in analogy with moderate to good yields (Fig. 1). 0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetlet.2008.11.015 * Corresponding author. Tel.: +49 0331 58187 503; fax: +49 0331 58187 299. E-mail address: martin.katterle@ibmt.fraunhofer.de (M. Katterle). Tetrahedron Letters 50 (2009) 359–362 Contents lists available at ScienceDirect Tetrahedron Letters journal homepage: www.elsevier.com/locate/tetlet