A Light‐Driven Molecular Machine Controls K⁺ Channel Transport and Induces Cancer Cell Apoptosis

Abstract

The design of artificial ion channels with high activity, selectivity and gating function is challenging. Herein, we designed the light‐driven motor molecule MC2, which provides new design criteria to overcome these challenges. MC2 forms a selective K+ channel through a single molecular transmembrane mechanism, and the light‐driven rotary motion significantly accelerates ion transport, which endows the irradiated motor molecule with excellent cytotoxicity and cancer cell selectivity. Mechanistic studies reveal that the rotary motion of MC2 promotes K+ efflux, generates reactive oxygen species and eventually activates caspase‐3‐dependent apoptosis in cancer cells. Combined with the spatiotemporally controllable advantages of light, we believe this strategy can be exploited in the structural design and application of next‐generation synthetic cation transporters for the treatment of cancer and other diseases.

Crown Ether‐Based Ion Transporters in Bilayer Membranes

“…Taking advantage of the characteristic of double‐bond as a light‐promoted rotatable group, variable practical molecular motors have been achieved so far. Recently, Bao and coworkers [48] reported an artificial light‐gated molecular motor 62 (Figure 4i). Consisting of a rotor and stator, a motor subject that connected with the flexible alkyl chains of two crown ethers by a renowned click reaction was synthesized, which was capable of forming a channel with selectivity for K + over Na + and the ion transport could also be accelerated under UV light.…”

Assessment of a host–guest interaction in a bilayer membrane model

“… 2 More recently, numerous studies have focused on transport of ions through bilayer membranes by using amphiphilic molecules that show ion conduction by dint of channel function or pore formation. 3 In some cases, these synthetic channels are designed to function as unimolecular conductors 4 while other pore-formers self-assemble. As part of our effort in this area, we found that crown ethers having alkyl side arms can form assemblies that exhibit evidence of ion conduction rather than function as simple carriers.…”

A K+-selective channel with a record-high K+/Na+selectivity of 20.1

“…1 n ,2 f,g Another inspiring direction is the development of synthetic transporters that do not follow the traditional channel or carrier mechanisms. 3…”