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

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 alpha-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. H-1 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.

Automated summary

A cyclo[2]carbazole[2]pyrrole (2), composed of two carbazoles and two pyrroles, was synthesized by directly linking the carbazole 1- and 8-carbon atoms to the pyrrole alpha-carbon atoms. The resulting macrocycle 2 has an extensively conjugated 16-membered macrocyclic ring and a preorganized anion binding site consisting of two pyrrole subunits. H-1 NMR spectroscopic analysis revealed that only the diagonally opposed pyrrole NH protons are involved in anion binding, and cyclo[2]carbazole[2]pyrrole 2 binds anions with higher affinity than calix[4]pyrrole (1). Computational studies suggest that the higher anion affinity of receptor 2 is due to its larger binding energy and lower host strain energy associated with anion complexation. In the presence of excess fluoride or bicarbonate anions, compound 2 loses two pyrrolic NH protons and forms a stable dianionic macrocycle [2-2H](2-) with quenched fluorescence.