Off-On Photo- and Redox-Triggered Anion Transport Using an Indole-Based Hydrogen Bond Switch

Abstract

A stimulus-responsive indole-based hydrogen bonding switch is reported, which enables off-on activation of transmembrane ion transport in response to photo- and redox triggers. This is achieved by alkylation of an indole-based anionophore, preorganized through intramolecular hydrogen bonding, with o-nitrobenzyl and azobenzene cages. This renders the anionophore inactive through formation of a six-membered intramolecular hydrogen bonding interaction and locking of the anion binding protons. Decaging with biologically relevant light and redox stimuli leads to efficient activation of anion transport across lipid bilayer membranes by unlocking the hydrogen bond donors, such that they are now available for anion binding and transport.

Figure 1

(A) Schematic representation of stimulus-responsive anion transport. Chemical structures of (B) active transporters 1–3 and (C) caged protransporters 1a and 1b. (D) Illustration of redox-triggered anionophore activation.

Figure 2

(A) General chemical structure representing transporters 1–3. (B) Table showing clogP values (calculated using MarvinSketch) and chloride association constant (K_a) values of transporters 1–3. (C) Plot of chemical shift (d) of H₁ proton vs concentration of TBACl added, fitted to a 1:1 binding model, for the active transporters 1–3.

Figure 3

(A) Activity comparison of 1–3 (3.5 mol %) across POPC–LUVs⊃HPTS. (B) Ion transport activity of 1 (2.5 mol %) across DPPC-based vesicles at 25 and 45 °C, respectively. (C) Schematic representation of lucigenin-based chloride efflux using either extravesicular SO₄^2– or NO₃^– ions. (D) Ion transport activity of 1 (20 mol %) in the presence of external SO₄^2– and NO₃^– ions.

Scheme 1. Chemical Synthesis of Active Transporters 1–3

Scheme 2. Chemical Synthesis of Inactive Protransporters 1a and 1b

Figure 4

(A) Transport activity of 1a upon photoirradiation at 405 nm of light using an LED (1 W) across POPC–LUVs⊃HPTS. (B) Transport activity of 1b upon treating with zinc (10 equiv) and ammonium formate (25–200 equiv) across POPC–LUVs⊃lucigenin.