Dynamic Constitutional Chemistry for the Preparati.. (Anion_cages)
Dynamic Constitutional Chemistry for the Preparation of Receptors for Anions of Biological Interest
Start date: Oct 1, 2012,
End date: Sep 30, 2016
From chloride to DNA, over 75% of the cofactors and bio-molecules have negative charge at physiological pH. However, efficient syntheticreceptors for anionic entities in aqueous solution have attracted lesser attention than ligands for cationic or neutral species. The intrinsicphysicochemical problems of anion binding and the molecular diversity of anionic species have often hampered this research field. In this project,the identification and synthesis of new molecular receptors for anions with biological relevance is proposed. To this aim, we will use aconstitutional dynamic chemistry approach, a conceptually new methodology based on the molecular evolution idea. Thus, we will prepare adynamic library of components interconnected through exchange by chemical equilibriums. These building blocks will bear a molecular recognitionmoiety able to bind anions, and the required functional group(s) for the establishment of a covalent bond under reversible conditions. In thepresence of the target entity (an anionic template), the dynamic system will evolve to efficiently interact with the template and the best binder willbe amplified and identified. As the building blocks, we will use peptide-like molecular architectures, since they can bear different potential anionbinding functions (amide, ammonium, etc…), show large molecular and structural diversity and, in general, display good biological tolerance.Additionally, their synthetic, isolation and characterization procedures are quite straightforward. Using this rationale with anionic templates ofbiological importance, this methodology will allow us to synthesize new receptors of biologically interesting molecules with increased bindingabilities, which will be finally tested for the corresponding biological functions. Therefore, if successful, this project will mean an importantmethodological breakthrough in anion recognition chemistry.
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