2.B.13 The Tetrapyrrolic Macrocyclic Anion Antiporter, Anion/Cation Symporter (TPMC) Family 

Meso-octamethyloctafluorocalixpyrrole, a simple tetrapyrrolic macrocycle, and other pyrroles function as chloride/nitrate and chloride/bicarbonate antiporters for lipid bilayer transmembrane anion transport (Gale et al. 2010). They are examples of synthetic macrocyclic pyrrole-based systems capable of transmembrane anion transport (Gale 2011).  A variety of such compounds can transport different ions such as nitrate, bicarbonate and chloride, and anion transport is influenced by the presence of cations (Adriaenssens et al. 2013).  These versatile molecules function as receptors, transporters and molecular switches (Kim and Sessler 2015). Due to their anion transport capacities, they can induce appoptosis in animal cells (Ko et al. 2014). The transmembrane transport of bicarbonate and other anions has been reviewed with emphasis on synthetic anion transporters (Martínez-Crespo and Valkenier 2022).

Calix[4]pyrrole macrocycles exhibit versatility in the development of transmembrane ion transporters. These cyclic compounds are capable of binding both anions and large, polarizable cations through the pyrrolic N–H groups and the aromatic cup, respectively (Gale et al. 2017). Meso-octamethylcalix[4]pyrrole promotes CsCl transmembrane co-transport (symport). Fluorination of the pyrrole rings enhances the acidity of the NH hydrogen bond donor groups, leading to stronger NH-Cl- interactions and dramatically changing the transmembrane transport activity of the molecule. For example, compound 2 is an efficient anion exchanger, promoting nitrate/chloride and bicarbonate/chloride exchange (Gale et al. 2017). Compound 2 is capable of chloride uniport in the absence of caesium cations. Strapped calix[4]pyrroles 3–6, bearing triazole groups that enhance the chloride binding affinity enhanced chloride/nitrate exchange.  An oligoether-strapped calix[4]pyrrole 7 formed stable 1:1 ion-pair complexes with LiCl and NaCl and functioned both as a chloride/nitrate exchanger as well as an M+/Cl- co-transporter.

This family is related to the family with TC# 2.B.19.

The generalized reactions catalyzed by tetrapyrrolic compounds are:

Anion-1 (in) + Anion-2 (out) → Anion-1 (out) + Anion-2 (in)

Anion (in) + Cation (in) → Anion (out) + Cation (out)



Adriaenssens, L., C. Estarellas, A. Vargas Jentzsch, M. Martinez Belmonte, S. Matile, and P. Ballester. (2013). Quantification of nitrate-π interactions and selective transport of nitrate using calix[4]pyrroles with two aromatic walls. J. Am. Chem. Soc. 135: 8324-8330.

Gale, P.A. (2011). From anion receptors to transporters. Acc Chem Res 44: 216-226.

Gale, P.A., C.C. Tong, C.J. Haynes, O. Adeosun, D.E. Gross, E. Karnas, E.M. Sedenberg, R. Quesada, and J.L. Sessler. (2010). Octafluorocalix[4]pyrrole: a chloride/bicarbonate antiport agent. J. Am. Chem. Soc. 132: 3240-3241.

Gale, P.A., J.T. Davis, and R. Quesada. (2017). Anion transport and supramolecular medicinal chemistry. Chem Soc Rev 46: 2497-2519.

Kim, D.S. and J.L. Sessler. (2015). Calix[4]pyrroles: versatile molecular containers with ion transport, recognition, and molecular switching functions. Chem Soc Rev 44: 532-546.

Ko, S.K., S.K. Kim, A. Share, V.M. Lynch, J. Park, W. Namkung, W. Van Rossom, N. Busschaert, P.A. Gale, J.L. Sessler, and I. Shin. (2014). Synthetic ion transporters can induce apoptosis by facilitating chloride anion transport into cells. Nat Chem 6: 885-892.

Martínez-Crespo, L. and H. Valkenier. (2022). Transmembrane Transport of Bicarbonate by Anion Receptors. Chempluschem 87: e202200266.