Tuning chloride binding, encapsulation, and transport by peripheral substitution of pseudopeptidic tripodal small cages
| Autor: | Michael Bolte, Inés Martí, M. Isabel Burguete, Ignacio Alfonso, Roberto Quesada, Santiago V. Luis, Jenifer Rubio, Cristian Vicent |
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| Přispěvatelé: | Junta de Castilla y León, Ministerio de Economía y Competitividad (España), Ministerio de Ciencia e Innovación (España) |
| Rok vydání: | 2012 |
| Předmět: |
Models
Molecular Spectrometry Mass Electrospray Ionization Macrocyclic Compounds Stereochemistry Drug Compounding Lipid Bilayers Supramolecular chemistry Transport Protonation Chloride Catalysis Bridged Bicyclo Compounds Chlorides X-Ray Diffraction medicine Molecule Moiety Cage compounds Amino Acids Binding Sites Ion Transport Molecular Structure Chemistry Organic Chemistry Pseudopeptides General Chemistry Nuclear magnetic resonance spectroscopy Ethylenediamines Solutions Crystallography Cyclization Electrophile Liposomes SN2 reaction Peptidomimetics Chloride binding medicine.drug |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| ISSN: | 1521-3765 |
| Popis: | A highly efficient synthesis of small pseudopeptidic cages from simple precursors has been achieved by the triple SN2 reaction between tripodal tris(amido amines) and several 1,3,5-tris(bromomethyl)benzene electrophiles. The success of the macrobicyclization strongly depends on the central triamine scaffold, which dictates the correct preorganization of the intermediates. The chloride binding properties of the protonated pseudopeptidic cages have been studied in the solid state (by X-ray diffraction) as well as in solution (by NMR spectroscopy and ESI-MS) and in the gas phase (by collision-induced dissociation (CID)-MS). The crystal structure of the HCl salts of several cages show a chloride partially or completely caged within the cavity of the macrobicycle. Both the amino acid side chain and the substitution at the aromatic tripodal ring have an effect on the chloride binding ability. The cages derived from the 1,3,5-benzene moiety show low affinity, whereas the triple substitution in the ring (either with Me or Et) increases the chloride binding by one order of magnitude. Besides, the cages derived from aliphatic amino acids display a stronger interaction than those derived from phenylalanine. The basis for the different mode of binding depending on the receptor structure is proposed according to the structural data (X-ray and NMR spectroscopy). Finally, the transport of the chloride anion through lipid bilayers has been studied for selected cages. Despite the important differences in the chloride binding, the transport properties are better correlated with the lipophilicity of the molecules. Therefore, the pseudopeptidic cages sharing the same binding motif for chloride rendered very different interaction and transport properties depending on the peripheral substitution. Caging of chloride: A family of pseudopeptidic molecular cages has been synthesized. They bind chloride in the solid state (X-ray), in solution (ESI-MS and NMR spectroscopy), and in the gas phase (collision-induced dissociation (CID)-MS). Moreover, some of them are able to transport chloride ions through lipid bilayers. The chloride binding, encapsulation, and transport abilities of the cages strongly depend on the peripheral substitution, such as the residues on the tripodal aromatic cap or the amino acid side chain (see figure). Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. inancial support from the Spanish Ministerio de Ciencia e Innovación (MICINN) and the Ministerio de Economía y Competitividad (MINECO) is gratefully acknowledged (CTQ2009-14366-C02), as well as the Consejería de Educación de la Junta de Castilla y León (project BU337A12–2). I.M. (FPI), J.R. (FPU), and R.Q. (Ramón y Cajal) also thank the MICINN/MINECO for personal financial support. |
| Databáze: | OpenAIRE |
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