2.B.53.  The Thiourea Anionophore (TUAP) Family

Compounds containing cyanoguanidine and 3-amino-1,2,4-benzothiadiazine-1,1-dioxide have been studied as anion receptors and transporters. Significant affinity for oxo-anions was observed in organic solution, and the receptors were found to function as transmembrane chloride/nitrate antiporters with transport rates enhanced in the presence of a valinomycin-K+ complex (Wenzel et al. 2011). The transmembrane transport of bicarbonate and other anions has been reviewed with emphasis on synthetic anion transporters (Martínez-Crespo and Valkenier 2022).

Gale and co-workers synthesized an extended series of 1-hexyl-3-phenylthioureas with variety of substituents on the 4-position of the phenyl ring (compounds 53–74 described in Fig 13 of Gale et al. 2017). Increases in lipophilicity resulted in increased anion transport, but transport was also related to the diffusion rate by which the carrier passed from one side to the other of the membrane as well as the anion binding capacity.  Anions transported with different compounds included Cl- and other halogen anions as well as NO3-.  See figure 16 in Gale et al. 2017 for the generalized structure of these thioureas (R1-φ-NH-CS-NH-R2) and Table 1 for the various compounds synthesized. Lipophilic thiourea derivatives that catalyze Cl-/NO3- and Cl-/HCO3- exchange reactions have also been described (Busschaert et al. 2010).

The generalized reaction catalyzed by these compounds is: 

Anions (in) ⇌ Anions (out)

This family belongs to the Thiourea Artificial Ion Transporter.



Busschaert, N., P.A. Gale, C.J. Haynes, M.E. Light, S.J. Moore, C.C. Tong, J.T. Davis, and W.A. Harrell, Jr. (2010). Tripodal transmembrane transporters for bicarbonate. Chem Commun (Camb) 46: 6252-6254.

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

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

Wenzel, M., M.E. Light, A.P. Davis, and P.A. Gale. (2011). Thiourea isosteres as anion receptors and transmembrane transporters. Chem Commun (Camb) 47: 7641-7643.