Chiral Diaminopyrrolic Receptors for Selective Recognition of Mannosides, Part 1: Design, Synthesis, and Affinities of Second-Generation Tripodal Receptors

Authors

  • Prof. Cristina Nativi,

    1. Dipartimento di Chimica, Università di Firenze, Polo Scientifico e Tecnologico, 50019 Sesto Fiorentino, Firenze (Italy)
    2. Centro Risonanze Magnetiche (CERM), Polo Scientifico e Tecnologico, 50019 Sesto Fiorentino, Firenze (Italy)
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  • Dr. Oscar Francesconi,

    1. Dipartimento di Chimica, Università di Firenze, Polo Scientifico e Tecnologico, 50019 Sesto Fiorentino, Firenze (Italy)
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  • Gabriele Gabrielli,

    1. Dipartimento di Chimica, Università di Firenze, Polo Scientifico e Tecnologico, 50019 Sesto Fiorentino, Firenze (Italy)
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  • Prof. Alberto Vacca,

    1. Dipartimento di Chimica, Università di Firenze, Polo Scientifico e Tecnologico, 50019 Sesto Fiorentino, Firenze (Italy)
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  • Dr. Stefano Roelens

    Corresponding author
    1. Istituto di Metodologie Chimiche (IMC), Consiglio Nazionale delle Ricerche (CNR), Dipartimento di Chimica, Polo Scientifico e Tecnologico, 50019 Sesto Fiorentino, Firenze (Italy), Fax: (+39) 055-457-3570
    • Istituto di Metodologie Chimiche (IMC), Consiglio Nazionale delle Ricerche (CNR), Dipartimento di Chimica, Polo Scientifico e Tecnologico, 50019 Sesto Fiorentino, Firenze (Italy), Fax: (+39) 055-457-3570
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Abstract

A new generation of chiral tripodal receptors for recognition of carbohydrates, featuring trans-1,2-diaminocyclohexane as a key structural element, and their recognition properties toward a set of glycosides of biologically relevant monosaccharides is described. The introduction of a chelating diamino unit into the pyrrolic tripodal architecture markedly enhanced their binding abilities compared with the parent aminopyrrolic receptors previously reported by our group. In addition, the chirality of the structure had a clear impact on affinities, as well as on selectivities, displaying high enantiodiscrimination levels. These second-generation diaminopyrrolic tripodal receptors are highly selective for mannose among other monosaccharides, with two members of the family being selective for the α and the β anomers respectively. The measured affinities in acetonitrile, 83 μM of (S)-7 for the β mannoside and 127 μM of (R)-5 for the α mannoside, make them the most effective synthetic receptors for mannosides reported to date. The affinity assessment required a further evolution of the equation image parameter, a previously developed binding descriptor, which in its ultimate formulation has now been extended to include, with no restrictions, complexes of any stoichiometry, and can thus be generally employed to rank affinity data from heterogeneous systems on a common scale.

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