Prof. Pau Ballester

In the past 5 years, Ballester group has been especially active in the following research topics:

Study and synthesis of receptors featuring deep and polar aromatic cavities, functioning both in water and organic solvents

We demonstrated that aryl-extended calix[4]pyrrole (AE-C[4]Ps) cavitands are efficient receptors for the recognition of polar substrates in water by means of hydrogen bonding interactions Chem. Sci. 2019, 10, 2413-2423, Org. Chem. Front. 2023, 10, 4, 996, Acc. Chem. Res. 2023, 56, 4, 500.We introduced unprecedented water soluble tetra-α super aryl-extended calix[4]pyrroles (SAE-C[4]Ps) wit extended aromatic cavities functionalized with either eight ionizable or charged groups. Moreover, in combination with a series of pyridyl-N-oxides guests, we used them to set up a model system for quantifying the hydrophobic effect Org. Chem. Front. 2019, 6, 1738-1748 and aromatic and cation-pi interactions Chem. Sci. 2023, 14 (40), 11131-11140, Chem. Commun. 2023, 59, 14146-14148.

Development of self‐assembly processes (non-covalent synthesis) for the construction of capsular and cage-like architectures, as well as mechanically interlocked counterparts

We demonstrated that tetra-α super aryl-extended tetra-pyridyl calix[4]pyrroles self-assemble into mono-metallic Pd(II)-cages featuring two different and converging polar binding sites Chem. Commun. 2019, 55, 604-607. We studied the exchange dynamics of pyridine N-oxide guest in mono-metallic Pd(II)/Pt(II)-cages. A “French doors” mechanism, involving the rotation of the meso-phenyl walls of the cages allowed the passage of planar guests. A modification of the encapsulation mechanism for the quinuclidine N-oxide was postulated requiring the partial dissociation of the Pd(II)-cage Angew. Chem., Int. Ed. 2019, 58, 16105-16109. We discussed the effect of the solvent on the binding of anions and ion-pairs with a neutral [2]rotaxane having a bis-C[4]P cyclic component and bis-amide pyridinyl-N-oxide axle Org. Biomol. Chem. 2021, 19, 9986-9995. We introduced a SAE-C[4]P equipped with four oxazolo[4,5-b]pyrazinyl units at its upper rim and its Pt(II)/Pd(II)-metallobridged cavitand counterparts Angew. Chem., Int. Ed. 2022, n/a, e202202140. We worked on the self-assembly of shape-persistent [1+1] tetra-imine cages based on two different tetra-α aryl-extended calix[4]pyrrole scaffolds Chem. Sci., 2023, 14, 1, 186.

Application of supramolecular concepts to mediate chemical reactions and modify their typical regio- and stereo-selectivities

We showed that in the presence of an equimolar amount of a water-soluble SAE-C[4]P, the hydrolysis reaction of α,ω-alkyl-bis-isonitriles produced mixtures of non-statistical composition and a significant decrease in reaction rates. The selectivity for the mono-formamide product is specially enhanced in the case of the bis-isonitrile having a spacer with five methylene groups. The receptor acted both as a sequestering and supramolecular protecting group Angew. Chem., Int. Ed. 2021, 60, 10359-10365. We are currently working on the development of new containers to study the mediation of bimolecular cycloaddition reactions. The mediation of chemical reactions in synthetic nanocontainers is expected to produce relevant results for the rationalization and understanding of the high rate accelerations produced by enzymes.

Molecular recognition and sensing in organic and aqueous solvents (i.e. clinically relevant polar guests).

We described the synthesis of a tetra-pyridinium aryl extended calix[4]pyrrole that is soluble in neutral water and selectively binds the cis-(E) conformers of secondary and tertiary formamides with binding affinities larger than 103 M−1 Chem. Sci. 2018, 9, 7186-7192. We used calix[4]pyrrole phosphonate-cavitands as receptors for the design of supramolecular sensors for creatinine and its lipophilic derivative hexylcreatinine J. Am. Chem. Soc. 2020, 142, 4276-4284., Talanta 2022, 246, 123473, DOI: 10.1016/j.talanta.2022.123473. We examined, from an interdisciplinary perspective, the design and development of effective water-soluble synthetic receptors based on cyclic, oligo-cyclic, and concave-shaped architectures Chem. Rev. (Washington, DC, U. S.) 2021, 121, 2445-2514. We reported the efficient and template self-assembly of a tetra-cationic super aryl-extended calix[4]pyrrole tetra-pyridyl ligand into a water-soluble Pd(II)-cage featuring two endohedral polar binding sites Chem. Sci. 2021, 12, 13469-13476.

Controlled-release of encapsulated cargo (i.e. photo-controlled).

We synthesized and performed dimerization studies of lipophilic photo-responsive aryl-extended tetra-urea calix[4]pyrroles. We also investigated the photo-induced cargo-release of the assembled dimers. Chem.–Eur. J. 2018, 24, 2182-2191. We reported the synthesis of tetra-urea derivatives of calix[4]arene and calix[4]pyrrole containing four spiropyran (SP) units at their upper rims. We investigated the photo- and acid-induced cargo-release of the assembled dimers Chem.–Eur. J. 2021, 27, 12675-12685.

Trafficking of neutral and charged molecules through lipophilic membranes (i.e. amino acids and anions)

We investigated the influence that the insertion method of aryl-extended calix[4]pyrrole into liposomal membranes exerts on their properties as anion carriers Chem.–Eur. J. 2019, 25, 4775-4781. We described for the first time the use of calix[4]pyrrole receptors as synthetic carriers for the facilitated diffusion of amino acids across membranes of liposomes and living cells Chem 2020, 6, 3054-3070.