Halogen bonding relay and mobile anion transporters with kinetically controlled chloride selectivity

Abstract

Selective transmembrane transport of chloride over competing proton or hydroxide transport is key for the therapeutic applications of anionophores, but remains a significant challenge. Current approaches rely on enhancing chloride...

Molecular Machines For The Control Of Transmembrane Transport

“…114,115 Langton and co-workers subsequently reported a relay transporter with a bis-iodotriazole halogen bonding (XB) anion receptor. 112 The relay transporter 22 XB showed enhanced transport activity with an EC 50 value of 0.18 mol % with respect to lipid in POPC LUVs, compared to ∼ 2 mol % in POPC/ cholesterol (7:3) for Smith's urea derivative 21a. 111 In the presence of the protonophore FCCP, the activity of the halogenbonding relay transporter 22 XB was significantly enhanced (EC 50 = 0.036 mol %), as a result of appreciable Cl − > H + /OH − selectivity.…”

“…Anion carriers operate via consecutive ion binding, membrane translocation, and ion release steps, and are typically characterized by anion binding-limited transport activity, , although some rare examples of translocation-limited mobile carriers have been reported. , For the development of stimuli-responsive mobile carriers, including those based on molecular machines, it is therefore important to consider the impact of changing receptor interactions on the ion binding step as well as carrier geometry and lipophilicity, in order to influence the translocation rate of the ion–mobile carrier complex. Recently, the interplay of binding and translocation kinetics have also been highlighted to be essential to the selectivity of mobile carriers …”

“…Relay transporters. A. Smith’s urea relay transporter 21 , Langton’s bis-iodotriazole hydrogen ( 22 HB ), and halogen bonding ( 22 XB ) relay transporters . B. Schematic of the relay transport mechanism.…”

“…Langton and co-workers subsequently reported a relay transporter with a bis-iodotriazole halogen bonding (XB) anion receptor . The relay transporter 22 XB showed enhanced transport activity with an EC 50 value of 0.18 mol % with respect to lipid in POPC LUVs, compared to ∼ 2 mol % in POPC/cholesterol (7:3) for Smith’s urea derivative 21a .…”

“…Recently, the interplay of binding and translocation kinetics have also been highlighted to be essential to the selectivity of mobile carriers. 58 Mechanically Interlocked Mobile Carriers. Mechanically interlocked structures, both naturally derived and synthetically obtained, are beginning to gain greater traction in biomedical applications.…”