Chemistry Research Laboratory, Mansfield Road, Oxford, OX1 3TA, UK.
Nanoscale. 2024 Nov 28;16(46):21545-21553. doi: 10.1039/d4nr03220a.
Ion transport across biological membranes, facilitated by naturally occurring ion channels and pumps, plays a crucial role in biological processes. Gating is an important aspect of these systems, whereby transport is regulated by a range of external stimuli such as light, ligands and membrane potential. While synthetic ion transport systems, especially those with gating mechanisms, are rare, they have garnered significant attention due to their potential applications in targeted therapeutics as anticancer agents or to treat channelopathies. In this work, we report stimuli-responsive anion transporters based on dynamic hydrogen bonding interactions of hydroxyl-functionalised hydrazone anionophores. Caging of the hydroxyl groups with moities that are responsive to light and HS locks the hydrazone protons through intramolecular hydrogen bonding, rendering them unavailable for anion binding and transport. Upon decaging with light or HS, the hydrogen bonding pattern is reversed, rendering the hydrazone protons available for anion binding, and leading to efficient switch-on of ion transport across the lipid bilayer membrane.
离子通过生物膜的运输，由天然存在的离子通道和泵来介导，在生物过程中起着至关重要的作用。门控是这些系统的一个重要方面，通过这种方式，运输受到各种外部刺激的调节，如光、配体和膜电位。虽然合成离子传输系统，特别是那些具有门控机制的系统，非常罕见，但由于它们在靶向治疗中的潜在应用，如作为抗癌剂或治疗通道病，它们引起了人们的极大关注。在这项工作中，我们报告了基于羟基功能化腙阴离子载体的动态氢键相互作用的对刺激响应的阴离子载体。通过用光或 HS 封闭羟基基团，可以通过分子内氢键锁定腙质子，使其无法与阴离子结合和运输。用光或 HS 去封闭后，氢键模式发生反转，使腙质子可与阴离子结合，并导致离子在脂质双层膜中有效开启运输。
