Journal of the Mexican Chemical Society ISSN: 1870-249X [email protected] Sociedad Química de México México Rosete-Luna, Sharon; Medrano, Felipe; Bernal-Uruchurtu, Margarita I.; Godoy-Alcántar, Carolina Crown Ether Ditopic Receptors for Ammonium Salts with High Affinity for Amino Acid Ester Salts Journal of the Mexican Chemical Society, vol. 53, núm. 4, octubre-diciembre, 2009, pp. 209-219 Sociedad Química de México Distrito Federal, México Available in: http://www.redalyc.org/articulo.oa?id=47512356002 How to cite Complete issue Scientific Information System More information about this article Network of Scientific Journals from Latin America, the Caribbean, Spain and Portugal Journal's homepage in redalyc.org Non-profit academic project, developed under the open access initiative J. Mex. Chem. Soc. 2009, 53(4), 209-219 Article © 2009, Sociedad Química de México ISSN 1870-249X Crown Ether Ditopic Receptors for Ammonium Salts with High Affinity for Amino Acid Ester Salts Sharon Rosete-Luna, Felipe Medrano, Margarita I. Bernal-Uruchurtu, and Carolina Godoy-Alcántar* Centro de Investigaciones Químicas, Universidad Autónoma del Estado de Morelos, 62209 Cuernavaca, Morelos, México. Tel/Fax: +52 777329 7997, [email protected] Received August 13, 2009; accepted November 19, 2009 Abstract. Two bis crown ether receptors were synthesized and Resumen. En este trabajo se sinterizaron dos receptores del tipo bis tested as host molecules for protonated forms of alkyl amines and eter corona y fueron estudiados como moléculas anfitrión de alqui- amino acid esters. Molecular recognition studies were conducted in laminas y ésteres de aminoácidos protonados. Se realizaron estudios CH2Cl2:MeOH (92:8) by spectrophotometric UV/Vis titrations and de reconocimiento molecular por titulaciones espectrofotométricas 1 by spectrometric H NMR titrations in CDCl3. The calculated binding UV/Vis en CH2Cl2:MeOH (92:8) y por titulaciones espectrométricas 2 5 -1 1 constants are in the range 10 -10 M . A high affinity for L-amino de RMN H en CDCl3. Las constantes de enlace calculadas están en acid methyl ester derivatives was found. A theoretical study at the el intervalo 102-105 M-1. Se encontró una alta afinidad por los ésteres DFT level of the synthesized receptor and some analog ligands with metílicos de los L-aminoácidos estudiados. Un estudio teórico a nivel three different ammonium ions helps to rationalize the experimentally DFT de los receptores sinterizados y algunos ligandos análogos con found trends. tres diferentes iones amonio permite explicar las tendencias experi- Key words: Ditopic Receptors, Binding Constant; Crown Ethers, mentales encontradas. Alkyl Ammonium, Amino Acid. Palabras clave: Receptores ditópicos, constante de enlace, éteres corona, alquilamonio, aminoácido. Introduction ments [14-17] and only some host-guest complex have been studied in solution by 1H NMR [8, 18, 19] or by calorimetric Molecular recognition of amines is an interesting field due to titrations [20, 21]. In Table 1 we summarize the analytical their widespread presence in nature. Many biogenic amines methods used for their study and their corresponding stability such as histamine, cadaverine, and putrescine are used as constants. probes to measure the quality of marine food products [1]. Functionalized benzocrown ethers are desirable can- Tyramine is a potent bacterial mutagen that induces tumors didates for amine receptor molecules because of their well at multiple sites in rodents [2]. Dopamine is a well-known known ability to form strong complexes with organic cations neurotransmitter, and epinephrine (adrenaline) is an adrenal [3d]. In this work we report the use of two ditopic bis(crown) hormone. The entire class of alkaloids comprises toxic amines ethers to detect protonated amine and amino acid derivatives while aliphatic amines have many applications in the chemical in solution. In Scheme 1 the general preparation method industry some of them are considered environmental hazards. used is presented and in Chart 1 the guest molecules used are The development of effective receptors for amines has indicated. The receptor molecules have in their structure two been an area of considerable interest for many years. Crown crown ether moieties linked by a conjugated aromatic bis azo- ethers and heterocrown ethers constituted the earliest hosts or methine unit. These structural units can bind the ammonium chemosensors for amines, which were recognized primarily in group of the guest molecule through H-bonds. The aromatic their ammonium forms [3]. and conjugated systems in the receptor molecules open the Metalloporphyrin hosts were developed to bind neutral possibility for additional �-� interactions or van der Waals amines by coordination to metal cations [4]. These hosts were contacts with the alkyl or aromatic groups of ammonium able to recognize amines in both organic solvents and water guest. The ionophores are electronically connected which [5]. Dynamic covalent chemistry added a new dimension to might introduce allosteric control over the recognition proper- amine recognition, for example, the reaction of neutral, pri- ties. This particular type of ditopic receptors has been used mary amines with carbonyl groups in dyes to form fluorescent as hosts for alkali and alkaline metals [22] but, to the best of imines [6]. Zimmerman and co-workers provided an element our knowledge, amine and amino acid complexes have not of selectivity by preparing a molecularly imprinted polymer been studied yet. In this work we report the affinity of the bis dye for the detection of amines [7]. However some of these crown ether receptors towards protonated amines and amino hosts have solubility problems, i.e., they are soluble in non- acid ester derivatives in solution. Using theoretical methods polar organic solvents while the ammonium ions require polar at the DFT level we propose the structure of these complexes solvents which limited the potential analytical procedures of and some insight on the origin of the trends of the selectivity study to liquid-liquid extractions [8-13] and transport experi- experimentally observed. 210 J. Mex. Chem. Soc. 2009, 53(4) Sharon Rosete-Luna et al. Table 1. Binding constants for selected host-guest complexes of ammonium organic cations. Host Guest K (M-1) Method Solvent Reference 5 1 chiral 18-crown-6 chiral ammonium 107-2.6 × 10 H NMR CD3CN 8 derivatives with picrates lipophilic chains 4 70-8.3 × 10 Extraction experiments CHCl3:H2O 4 calix(4)-crown ethers alkyl ammonium (1.08 – 1.4) × 10 Extraction experiments CH2Cl2:H2O 9 picrates 5 bis-crown ether bisammonium alkyl 2.56 × 10 - Extraction experiments CHCl3:H2O 10 peptidic receptors picrates 1.33 × 1010 a 18-crown-6 and a-amino acids 1-9 Extraction experiments CHCl3:H2O 11 a macrocyclic xanthone-based receptor 3 1 bis(crown-ether) monoammonium (6-7.4) × 10 H NMR CDCl3:MeOH-d4 18 analogue of Tröger’s and bisammonium (5-78) × 105 base chlorides 4 1 tetrazamacrocyclic bisammonium 550-9 × 10 H NMR CD3CN 19 (cyclidene) nickel(II) thiocyanates or complex bearing two perchlorates crown-ether residues 3 7 meso-ternaphthalene bisammonium picrates 5 × 10 -1.6 × 10 Extraction experiments CHCl3:H2O 12 bearing two crown ethers 18-crown-6 organic ammonium 50-1.9 × 104 Calorimetric titration MeOH 20 halides 18-crown-6 protonated amino acid 708-2400 Calorimetric titration MeOH 21 methyl esters benzo-18-crown-6 protonated amino acid 102 Calorimetric titration MeOH 21 methyl esters a Ratio between the two association constants of both diastereomeric complexes. 18 16 20 14 O O O 10 O O 12 8 Reflux 6h 22 O O O O O O 1 2 N N + Ethanol 23 O O 13 9 11 5 6 O O O O NH2 H H 21 O 15 7 O 3 4 O 19 17 1 18 16 O 20 O 14 O 10 O O O O 12 3 Reflux 6h 22 8 4 O O H H + 2 5 6 O O NH2 Ethanol 23 O O 13 9 N N O O O 11 7 1 O O 21 O 15 O 19 17 2 Scheme 1. Synthesis of the host molecules studied in this work. Crown Ether Ditopic Receptors for Ammonium Salts with High Affinity for Amino Acid Ester Salts 211 O O O - + - - Cl H3N CH C OCH3 NH4 Cl - Cl H3N CH C OCH3 Cl H3N CH C OCH3 CH2 D CH2 CH3 A HN NH Cl- - 3 NH3 Cl E B C F - NH3 Cl - NH3 Cl G H Chart 1. Chemical structures of the guest molecules studied in this work. Results and Discussion 0.5 Electronic spectra of receptors associated with ion binding 0.4 Using a mixture of methylene chloride and methanol (92:8) the absorption maxima of receptors 1 and 2 appears at 387 and 352 e nm, respectively. The observed transitions are of �-�* nature 0.3 anc b and are attributed to the extended � system formed by the three r aromatic rings connected by two imine groups present in the receptor structure. The band is highly sensitive to the polarity of Abso 0.2 the solvent, methanol addition to a CH2Cl2 solution of receptor 1, leads to a hypochromic effect of 380 nm band (Supplementary 0.1 material) This solvatochromic behaviour has been explained as due to a hydrogen bond formation between imine groups of the receptor molecule and the hydroxyl group of the methanol [23]. 0.0 Addition of the ammonium salts result in hypsochromic 250 300 350 400 450 500 550 and hypochromic shifts of the receptors bands as it is shown λ (nm) in Fig. 1. These shifts might be explained in terms of the Fig. 1. Changes of the absorption spectra during the titration of 1 -5 -4 conformational changes occurring upon complexation on the (1.5 × 10 M) with F (0-2.7 × 10 M) in CH2Cl2:MeOH (92:8). The N,N’-(p-phenylenedimethylidyne)dianiline structural unit that arrow indicates the direction of spectral changes occurring with the connects both crown ethers (vide infra).