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2.B.86.  The Phosphazane Anion Carrier (PAC) Family 

 Plajer et al. 2020 explored the anion binding and transport properties of a wide range of compounds (including the selenium analogue 36c) (see the top figure below) and also compounds 37a–c (see the second figure below). These researchers determined the stability constant of 36c with chloride by UV/vis titration techniques in acetonitrile. They found that this compound binds chloride with a log K of 5.74 ± 0.05. For phosphazanes 37a–c, 1H NMR titration techniques were used in acetonitrile-d3. In this case the stability constants were found to be 37c (235 ± 7 M−1) > 37b (155 ± 3 M−1) > 37a (18 ± 2 M−1).

Coordination of chloride by 36a–c.

Phosphazanes 37a–c.

The anion transport properties of these compounds were studied using both lucigenin (to study chloride transport and anion exchange) and HPTS based assays (to study selectivity) in POPC LUVs. The results of the lucigenin assay with 36c and 37c showed that compound 36c is the better anion transporter of the two systems. This was rationalized by its higher affinity for chloride and the presence of the CF3 functionalized aromatic groups. The HPTS assay showed that the compounds function as anion antiport agents. The anion transport properties of phosphazane 36c were compared to organic analogues containing 3,5-bis(trifluoromethyl) phenyl groups from a previous study with 36c EC50 = 8.56 nM as compared to the analogous thiourea EC50 = 8.02 nM and squaramide EC50 = 0.35 nM. The researchers also compared the anion transport ability of the series 37a–c and found an increase in membrane transport activity on moving to the heavier chalcogens (i.e., transport activity followed the trend 37c > 37b > 37a). The authors attributed this to both the affinity of the transporters for chloride (Se > S > O) and the matching trend in their hydrophobicity. Plajer et al. 2020 have also introduced metal-coordinating groups into this scaffold to pre-organize the anion binding site and enhance anion transport activity.

References associated with 2.B.86 family:

Plajer, A.J., J. Zhu, P. Pröhm, F.J. Rizzuto, U.F. Keyser, and D.S. Wright. (2020). Conformational Control in Main Group Phosphazane Anion Receptors and Transporters. J. Am. Chem. Soc. 142: 1029-1037. 31877039