CORDIS - EU research results

Dynamic Constitutional Chemistry for the Preparation of Receptors for Anions of Biological Interest

Final Report Summary - ANION_CAGES (Dynamic Constitutional Chemistry for the Preparation of Receptors for Anions of Biological Interest)

The project entitled ‘Anion_cages’ sought to develop efficient receptors for anionic species in aqueous media using dynamic combinatorial chemistry (DCC) methodologies and study their practical applicability. Negatively charged species have an enormous biological and environmental relevance. For example, chloride ion is the most abundant anion in living beings and it is implied in multiple biological processes. Abnormal levels of chloride are related to some pathologies like cystic fibrosis. Other relevant anionic species include phosphorylated macromolecules such as DNA or phosphorylated sugars. Anionic amino acids like aspartic and glutamic also play an important role as neurotransmitters.
The main goal of the project was to implement DCC methodologies in the anion recognition field. Despite some successful reports, the recognition of anions in water with good affinity represents a considerable challenge. Our approach was to use peptidic or pseudopeptidic building blocks (BBs) containing amino acid like information to generate dynamic libraries (DCL) through the formation of dynamic covalent bonds. We chose disulphide formation and disulphide metathesis as these reactions are compatible in aqueous media near neutral pH. DCC methodologies have previously shown great potential for the discovery of receptors in aqueous media.
We have succeeded in the preparation of a large family of building blocks with different functionalities and different number of thiol groups. We also were able to implement a range of reaction conditions in aqueous media (different pH, use of different co-solvents, etc.) that allowed the reproducible generation of dynamic libraries using our BBs. Although we have not been able to identify suitable receptors for anion recognition using our compounds we did some significant contributions to the field of systems chemistry. When combining building blocks with different valences an important increment of the complexity of the mixtures (in terms of structure and topology) is expected. However, due to self-recognition events in some cases one product arises from the virtual complex mixture almost exclusively. We have succeeded in identifying these interactions, which represent and effective recognition of an amino acid zwitterion in water. Furthermore we described the effect structural and environmental variations on the outcome of the libraries. Future work will be addressed to implement this knowledge to the preparation of selective sensors for amino acids suitable to work in water and study their use in vivo. Some preliminary results indicate the feasibility of this goal.
The fellow is now developing this new research line in the area of Supramolecular Chemistry and Systems Chemistry. With the help of the CIG he has been able to build a strong CV (see list of publications) and establish his own research group. During this time he has published several research papers as corresponding author, a book chapter, and has presented his work to a number of national and international conferences. Moreover he has joined a COST action which permitted to establish promising collaborations with other scientists within the EU. This period covered by the CIG grant has supposed a big leap forward to the fellow’s career allowing him to obtain a tenured position in the Spanish Research Council (CSIC, expected start Jan-Feb 2017).