Cyclo[2]carbazole[2]pyrrole: a preorganized calix[4]pyrrole analogue

Abstract

A cyclo[2]carbazole[2]pyrrole (2) consisting of two carbazoles and two pyrroles has been synthesized by directly linking the carbazole 1- and 8-carbon atoms to the pyrrole α-carbon atoms. Macrocycle 2 is an extensively conjugated 16-membered macrocyclic ring that is fixed in a pseudo-1,3-alternate conformation. This provides a preorganized anion binding site consisting of two pyrrole subunits. ¹H NMR spectroscopic analysis revealed that only the two diagonally opposed pyrrole NH protons, as opposed to the carbazole protons, take part in anion binding. Nevertheless, cyclo[2]carbazole[2]pyrrole 2 binds representative anions with higher affinity in CD₂Cl₂ than calix[4]pyrrole (1), a well-studied non-conjugated tetrapyrrole macrocycle that binds anions via four pyrrolic NH hydrogen bond interactions. On the basis of computational studies, the higher chloride anion affinity of receptor 2 relative to 1 is rationalized in terms of a larger binding energy and a lower host strain energy associated with anion complexation. In the presence of excess fluoride or bicarbonate anions, compound 2 loses two pyrrolic NH protons to produce a stable dianionic macrocycle [2-2H]^2- displaying a quenched fluorescence.

Fig. 1. General synthetic schemes for a calix[4]pyrrole and a porphyrin.

Fig. 2. Chemical structures of receptors 1 and 2.

Scheme 1. Synthesis of receptor 2.

Fig. 3. Two different views of the X-ray crystal structure of receptor 2. Most hydrogen atoms and solvent molecules have been removed for clarity. Displacement ellipsoids are scaled to the 30% probability level.

Fig. 4. Partial ¹H NMR spectra of (a) 2 (3 mM) only, (b) 2 + excess TBAF (tetrabutylammonium fluoride), (c) 2 + excess TBACl, (d) 2 + excess TBABr, (e) 2 + excess TBAI, (f) 2 + excess TEAHCO₃, (g) 2 + excess TBAHSO₄, (h) 2 + excess (TBA)₂SO₄, (i) 2 + excess TBAH₂PO₄, and (g) 2 + excess (TBA)₃HP₂O₇ in CD₂Cl₂.

Fig. 5. (Top) Putative binding mode for the chloride anion complex of receptor 2. (Bottom) Partial ¹H NMR spectra recorded during the titration of receptor 2 (3 mM) with tetrabutylammonium chloride (TBACl) in CD₂Cl₂.

Fig. 6. Partial ¹H NMR spectra recorded during the titration of receptor 2 (3 mM) with tetrabutylammonium iodide (TBAI) in CD₂Cl₂.

Fig. 7. (Top) Proposed interaction modes between receptor 2 and the fluoride anion. (Bottom) Partial ¹H NMR spectra recorded during the titration of receptor 2 (3 mM) with tetrabutylammonium fluoride (TBAF) in CD₂Cl₂.

Fig. 8. X-ray crystal structure of the deprotonated form of receptor 2 ([2–2H]²⁻). The data crystal was twinned. Most hydrogen atoms, solvent molecules, and two tetrabutylammonium cations positioned above and below the dianionic macrocycle have been removed for clarity. Displacement ellipsoids are scaled to the 50% probability level.

Fig. 9. (Top) Photographs showing the fluorescence changes of CH₂Cl₂ solutions of receptor 2 (10 μM) in the presence of the indicated anions (as their respective TBA⁺ salts for all anions but the bicarbonate anion, which was used in its TEA⁺ salt form). (Bottom) Corresponding fluorescence spectra of receptor 2 (10 μM) upon excitation at 301 nm.

Fig. 10. Fluorescence spectra of receptor 2 (10 μM) recorded during titrations with TBAF (left) and TBAH₂PO₄ (right), respectively, in CH₂Cl₂. The excitation wavelength (λ_ex) was = 301 nm.

Fig. 11. Lowest energy structures of receptor 2 and its two possible limiting complexes with fluoride, chloride, and hydrogen sulfate, respectively, as computed in the gas phase and the corresponding calculated binding energies (ΔE) for the interaction of receptor 2 with the anions in question.

Fig. 12. Two lowest energy structures (left and middle) of receptor 1 and the corresponding computed energies. The optimized structure of the complex 1·Cl⁻ (right) and its corresponding computed energy and anion binding energy.

Fig. 13. Three structural states of receptor 1 used to define its strain energies and the corresponding computed energy values.

Fig. 14. Three structural states of receptor 2 used to define its strain energies and the corresponding computed energy values.