Aromatic Interaction‐Driven Adaptive Transformation of Macrocyclic Unimolecular Chloride Channels Into Nanopores
Abstract
ABSTRACT Biological ion channels and pores frequently exhibit dynamic, concentration‐dependent adaptive assembly, yet synthetic systems that faithfully replicate this intriguing behavior remain rare. In this study, we present a novel class of tripeptide‐appended macrocyclic ion channels that undergo aromatic interaction‐driven adaptive transformation from unimolecular chloride channels into higher‐order nanopores. At low concentrations, analogues with aromatic tripeptide‐functionalized macrocycles ( MC‐F and MC‐W ) function as discrete and efficient chloride channels. Upon increasing the concentration, cooperative aromatic interactions among the tripeptide side chains promote their lateral self‐assembly into stable nanopores, enabling efficient transmembrane transport of small molecules, including carboxyfluorescein and glucose. In contrast, the aliphatic analogues ( MC‐A , MC‐L , and MC‐I ) remain restricted to unimolecular chloride channels. Single‐channel measurements combined with theoretical calculations further substantiate the structural stability and energetic preference of tetrameric and pentameric assemblies within lipid bilayers. Collectively, this work establishes cooperative aromatic interactions as a versatile and robust design principle for engineering adaptive artificial channels, thereby narrowing the functional gap between synthetic systems and the dynamic regulatory behavior of natural channels.
Article Details
Authors (14)
Xiaopan Xie
State Key Laboratory of Vaccines for Infectious Diseases Xiang An Biomedicine Laboratory Fujian Provincial Key Laboratory of Innovative Drug Target Research MOE Key Laboratory of Spectrochemical Analysis and Instrumentation School of Pharmaceutical Sciences Xiamen University Xiamen Fujian China
Juncheng Wan
State Key Laboratory of Vaccines for Infectious Diseases Xiang An Biomedicine Laboratory Fujian Provincial Key Laboratory of Innovative Drug Target Research MOE Key Laboratory of Spectrochemical Analysis and Instrumentation School of Pharmaceutical Sciences Xiamen University Xiamen Fujian China
Jin Zhou
Department of Oncology Sichuan Cancer Hospital Chengdu China
Zeli Yu
State Key Laboratory of Vaccines for Infectious Diseases Xiang An Biomedicine Laboratory Fujian Provincial Key Laboratory of Innovative Drug Target Research MOE Key Laboratory of Spectrochemical Analysis and Instrumentation School of Pharmaceutical Sciences Xiamen University Xiamen Fujian China
Guanyi Chen
Chuchu Li
State Key Laboratory of Vaccines for Infectious Diseases Xiang An Biomedicine Laboratory Fujian Provincial Key Laboratory of Innovative Drug Target Research MOE Key Laboratory of Spectrochemical Analysis and Instrumentation School of Pharmaceutical Sciences Xiamen University Xiamen Fujian China
Congrui Ren
School of Physics Shandong University Jinan Shandong China
Pengzhe Li
State Key Laboratory of Vaccines for Infectious Diseases Xiang An Biomedicine Laboratory Fujian Provincial Key Laboratory of Innovative Drug Target Research MOE Key Laboratory of Spectrochemical Analysis and Instrumentation School of Pharmaceutical Sciences Xiamen University Xiamen Fujian China
Meng Yang
Zhiping Zeng
Fei Zeng
Department of Gastric and Hernia Surgery, Nanjing Drum Tower Hospital, College of Engineering and Applied Sciences, State Key Laboratory of Analytical Chemistry for Life Science
Weifeng Li
Yuguang Mu
Changliang Ren
State Key Laboratory of Vaccines for Infectious Diseases Xiang An Biomedicine Laboratory Fujian Provincial Key Laboratory of Innovative Drug Target Research MOE Key Laboratory of Spectrochemical Analysis and Instrumentation School of Pharmaceutical Sciences Xiamen University Xiamen Fujian China