Transition Metals Coordination by Bis-imidazole-calix[4]arene Ligands with and Without Pyrene Units Grafted at the Large Rim

Abstract

Herein, the presented results show that previously studied DNA/RNA-interacting bis-imidazole-calix[4]arene systems can, in aqueous solutions, efficiently bind a series of biorelevant transition metal cations by coordination with the two imidazole arms at the small rim of their macrocyclic basket. The SCXRD and NMR results structurally characterised the complexes formed by referent bis-imidazole-calix[4]arene with Cu²⁺ and Zn²⁺. In solid-state (crystal), the bis-anilino derivative/Cu²⁺ complex, only upon exposure to the air, undergoes intramolecular dehydrogenative coupling of two neighbouring aniline units, yielding an azo bridge at the large rim of the calix[4]arene basket. In the biorelevant aqueous solution, the comparison of fluorometric titrations of referent calix[4]arene, with its analogues having one or two pyrene units grafted at the opposite (large) rim, revealed moderate-to-strong affinity towards transition metal cations, and, more importantly, a strong impact of pyrene on the binding affinity towards some cations. The pyrene arm(s) significantly diminished the affinity of the calix[4]arene-imidazole ligand towards Cu⁺ and strongly increased the affinity towards divalent Co²⁺ and Cd²⁺ cations. Moreover, the fluorometric response of some studied derivatives was strappingly sensitive to cation type. Since the counter-anion plays only a marginal role, such a change in selectivity is attributed to the intramolecular interaction of pyrene(s) with the calix[4]arene-imidazole system, sterically controlling the metal cation binding site.

Keywords: X-ray structures; calix[4]arene; dehydrogenative coupling; fluorescence; metal coordination; pyrene excimer/exciplex.

Scheme 1

Synthesis of compounds 2, 3, and 4 from the parent compound 1.

Scheme 2

Preparation and crystallization of complexes 1a, 1b, and 1c. In the diagram of 1c, blue bubbled “w” stands for coordinated water molecules. Blue marked Zn is penta-coordinated, red-marked is tetra-coordinated.

Figure 1

Molecular structure of 1a with atom numbering. H atoms are omitted for clarity.

Figure 2

Unit cell content in 1b. Only atoms discussed in the structure description are labelled. H-atoms are omitted for clarity. Only one orientation of the disordered tert-butyl group at C45 is shown.

Figure 3

Molecular structure of 1c with partial atom labelling and with H-bonds depicted. H-atoms are excluded for clarity. Only atoms involved in H-bonding and in Zn coordination are labelled, as well as the Zn ions. Only one (majoritarian) position of the disordered NO₃⁻ group (N7, O5, O6, O7) is depicted for clarity.

Figure 4

Coordination environment of four Zn ions with atom labelling. Only atoms from one asymmetric unit are labelled. H-atoms are omitted.

Figure 5

¹H NMR spectra (600 MHz, 300 K, CD₃CN) in the aromatic region of (a) 2 and (b) 2 with two equivalents of added ZnCl₂.

Figure 6

Normalised fluorescence spectra of studied 1 (λ_exc = 300 nm, water), 2 (λ_exc = 350 nm, water), and 3 (λ_exc = 350 nm). Normalisation was performed by dividing the complete spectrum by the maximal intensity of emission.

Figure 7

Comparison of stability constants and relative intensity values (ΔInt = Int_{(100% complex)}/Int₀) from fluorometric titrations of 1 with different cations in water.

Figure 8

MD structures of (a) calix[4]arene-pyrene conjugates 2 (left) and 3 (right) and (b) their Zn²⁺-complexes, 2/Zn²⁺ (left) and 3/Zn²⁺ (right); after 100 ns at T = 303 K. Water molecules and chlorine counterions are omitted for clarity.