Aryl and Super Aryl-Extended Calix[4]pyrroles: Synthesis and Applications

The research work described in this Thesis deals with the design and synthesis of molecular and supramolecular receptors based on the all-α isomers of two and four “wall” aryl and super aryl-extended calix[4]pyrrole scaffolds. The aims of the thesis included the preparation of organometallic receptors, water-soluble containers, self-assembled metallocages and metallocavitands. We explored the molecular recognition properties of the synthesized receptor containers towards ion pairs and neutral polar guests in organic solvents and in water solution. The formed inclusion complexes were characterized by NMR, ITC, UV/Vis and fluorescence/phosphorescence techniques. The characterization of the thermodynamic and kinetic stabilities of the inclusion complexes, as well as the metal-organic coordination interactions involved, should pave the way for the development of container receptors with more advanced functions.

Specifically, we disclosed the synthesis of an organometallic aryl-extended calix[4]pyrrole (AE-C[4]P) receptor from its parent “two-wall” calix[4]pyrrole α,α-isomer. We compared the binding affinities of the two receptors with tetraalkylammonium chloride salts in dichloromethane and acetone solution. Both receptors formed 1:1 host-guest complexes. The obtained results demonstrated that the 1:1 inclusion complexes of the organometallic receptor are energetically less stable than those of its parent counterpart. The reduction in binding stability was ascribed to the stronger repulsive anion-π interactions that existed between the organometallic meso-substituent and the bound anion.

Next, we investigated the application of a water-soluble super aryl-extended calix[4]pyrrole (SAE-C[4]P) receptor in the acid-catalyzed desymmetrization hydrolysis reaction of aliphatic bis-isonitriles. We also studied the binding properties of the water-soluble SAE-C[4]P receptor in the recognition of difunctional bis-isonitriles, mono-isonitrile-mono-formamides, and bis-formamides in water solution. The terminal formamide group of the mono-reacted compound existed in solution as two conformational isomers: trans and cis. We observed a high receptor’s selectivity in the exclusive binding of the cis-formamide isomer. The analyses of the kinetic data of the hydrolysis reactions revealed that the detected reduction in rate and yield enhancement for the mono-reacted species were due to the formation of thermodynamically and kinetically stable inclusion complexes with the substrates. These results demonstrated that the SAE-C[4]P acted as both a sequestering and protecting group in the mono-functionalization reaction.

We became interested in the development of self-assembled water-souble mono-metallic cages based on a water-soluble SAE-C[4]P ligand. The prepared metallocages feaured two endohedrally functionalized polar binding sites. The efficient self-assembly of the metallocages requires the encapsulation of sizeable mono- or di-functionalized guests complementing the hydrogen-bonding characteristics of the two distal binding sites of the cage. Interestingly, we observed a conformational selectivity in the binding of the metallocage with aliphatic bis-formamides. We also discovered the co-inclusion of a water molecule in the efficient self-assembly of the cage using mono-functionalized guests. Our findings augur well for the potential applications of the water-souble metallocages in on-demand catch and release processes of their molecular cargo.

Finally, we described the design and synthesis of an uncommon tetra-oxazolo[4,5-b]pyrazinyl SAE-C[4]P scaffold. We investigated the self-assembly of the synthesized SAE-C[4]P ligand into a bis-metallocavitand using Pt(II) salts as metal precursors and in the presence of suitable polar guests. The included guests fix the cone-conformation of the ligands and preorganize the pyrazinyl substituents for coordination to the metals. We found that only two equivalents of the metals were incorporated at the upper rim of the ligand through chelation to adjacent pyrazinyl units. The produced bis-metallocavitand inclusion complexes featured C2v symmetry in solution and in the solid-state.

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