Aryl-Extended Calix[4]Pyrrole Receptors with Metal Centers: Organometallic Receptors and Metallo-Macrocycles Based on Coordination Bonds

In this thesis, we describe the design and synthesis of unprecedented organometallic calix[4]pyrrole receptors. We also investigated the influence of the inclusion of the organometallic moieties on their binding properties towards anions and electron-rich neutral molecules.

More precisely, we based our designs on α,α- and α,β-isomers of “two wall” aryl-extended calix[4]pyrroles featuring a metallo-ethynyl (metal-acetylide) unit connected to the para-position of one or both of their meso-phenyl substituents. We expected that the unique structural features displayed by the organometallic calix[4]pyrrole receptors would have an impact on their molecular recognition and binding properties towards tetraalkylammonium chloride salts (as a source of chloride) and pyridine N-oxide derivatives.

We designed symmetric and non-symmetric α,α-“two wall” calix[4]pyrrole receptors bearing one or two metal centers at their upper rim (e.g. Au(I), Pt(II)). Initially, we evaluated the binding properties of the organometallic mono-acetylide Au(I) calix[4]pyrrole with tetraalkylammonium chloride salts using ¹H NMR titration experiments. We observed a decrease in the binding affinities of the mononuclear Au(I) substituted calix[4]pyrrole in comparison with those of its synthetic precursors (iodo and ethynyl substituted derivatives).

We also synthesized and fully characterized symmetric di-nuclear “two-wall” aryl-extended calix[4]pyrroles containing platinum(II)–ethynyl substituents at their upper rims. We studied the self-assembly of the symmetric bis-Pt(II)-ethynyl ”two wall” calix[4]pyrroles into di-nuclear metallo-macrocycles using di(pyridinyl)pyridine-2,6-dicarboxamide derivatives as strap ligands. We used NMR spectroscopic titrations (¹H and ³¹P) to probe and thermodynamically characterize the interactions of the self-assembled metallo-macrocycles and its “two wall” calix[4]pyrrole synthetic precursors (non-metalated and di-nuclear Pt(II), respectively) with pyridine N-oxide and 4,4’-bipyridine N,N’-dioxide. We observed a reduction in the binding affinities of the metallo-macrocycles for the N-oxide derivatives in comparison to those of the “two wall” calix[4]pyrrole synthetic precursors.

We synthesized and fully characterized a non-symmetric mono-nuclear organometallic α,β-calix[4]pyrrole bearing a Au(I)-acetylide unit in the para-position of one of its meso-phenyl substituents. We aimed at using the compound as a supra-molecular conformational balance to quantify chloride-π interactions. We investigated the complexes formed by the mono-nuclear Au(I)-acetylide α,β-calix[4]pyrrole receptor and tetraalkylammonium chloride salts using ¹H-NMR spectroscopic titrations and variable temperature experiments. We also used computational methods to investigate the electronic properties of the receptor, as well as the structures and energies of its complexes. The chloride complexes of the Au(I)-acetylide calix[4]pyrrole and its acetylene synthetic precursor were present in solution as a mixture of two conformers (folded and unfolded). At low temperatures, the two conformers were involved in an equilibrium displaying slow-exchange dynamics on the chemical shift timescale. The presence of different chloride-π interactions in the two conformers was expected to produce a population ratios different from 1. We planned to use the observed changes in the ratio of conformers to quantify the strength of the chloride-π interaction. We observed that the two conformers of the chloride complex of the p-ethynyl α,β-calix[4]pyrrole receptor were present in solution in equimolar amounts. In contrast, for the p-Au(I)-acetylide α,β-calix[4]pyrrole derivative we were not able to unequivocally determine the composition of the mixture.

During this work we also discovered the existence of interchangeability and disorder in the solid state structures of the α,β-“two wall” calix[4]pyrrole receptors equipped with iodine and ethynyl para-substituents.