Towards Recognition of Polar Molecules in Water Using Calix[4]pyrrole Based Receptors

Identifier:  TDX:3383

Handle: https://hdl.handle.net/20.500.11797/TDX3383

Authors:  Peñuelas Haro, Guillem

Abstract:
This thesis deals with the design, synthesis and binding studies of water-soluble amphiphilic receptors for the selective binding of polar neutral molecules or residues related to human health. To do so, we selected aryl-extended calix[4]pyrrole based receptors. These scaffolds deliver a concave cavity closed at one end by four polar groups (pyrrole NHs) and opened at their opposite end. These features allow polar and non-polar interactions to operate synergistically to obtain high levels of affinity and selectivity. Specifically, we describe the design, synthesis and binding studies of three generations of a novel family of phosphonate cavitands based on aryl-extended calix[4]pyrrole scaffolds for the selective binding of creatinine. The structural modifications and the conclusions extracted from each generation are described. Although the expected selectivity was not accomplished, large binding constants were obtained for some of the studied receptors (Ka ≈ 1000 M-1). In order to better understand how these types of receptors function in water, we performed a thorough study of their binding properties using a series of polar neutral guests. The results derived from this studies showed that calix[4]pyrroles are excellent hosts for amides, ureas and N-oxides in water, reaching binding constant values larger than 100000 M-1. We could demonstrate that calix[4]pyrrole receptors are better hydrogen bonding donors than bulk water. We also report the design and synthesis of two novel strapped calix[4]pyrroles featuring ionizable dendritic terminations for the selective binding of mono-saccharides. The optimized synthetic strategy is discussed in detail. We performed binding studies with one of the synthesized receptors in organic media with octyl-D-glucoside. The extracted results from these experiments augur well for its transfer to aqueous solution.