Centro de Química e Bioquímica, Centro de Química Estrutural, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade de Lisboa, Campo Grande, 1749-016, Lisboa, Portugal.
Department of Chemistry, CICECO - Aveiro Institute of Materials, University of Aveiro, 3810-193, Aveiro, Portugal.
Chemistry. 2020 Jan 16;26(4):888-899. doi: 10.1002/chem.201904255. Epub 2019 Dec 27.
The anion-binding and transport properties of an extensive library of thiophene-based molecules are reported. Seventeen bis-urea positional isomers, with different binding conformations and lipophilicities, have been synthesized by appending α- or β-thiophene or α-, β-, or γ-benzo[b]thiophene moieties to an ortho-phenylenediamine central core, yielding six subsets of positional isomers. Through H NMR, X-ray crystallography, molecular modelling, and anion efflux studies, it is demonstrated that the most active transporters adopt a pre-organized binding conformation capable of promoting the recognition of chloride, using urea and C-H binding groups in a cooperative fashion. Additional large unilamellar vesicle-based assays, carried out under electroneutral and electrogenic conditions, together with N-methyl-d-glucamine chloride assays, have indicated that anion efflux occurs mainly through an H /Cl symport mechanism. On the other hand, the most efficient anion transporter displays cytotoxicity against tumor cell lines, while having no effects on a cystic fibrosis cell line.
本文报道了一系列噻吩类分子的阴离子结合和传输性质。通过在间苯二胺的中心核上连接α-或β-噻吩或α-、β-或γ-苯并[b]噻吩部分，合成了十七个双脲位异构体，它们具有不同的结合构象和亲脂性，生成了六个位异构体子集。通过 1 H NMR、X 射线晶体学、分子建模和阴离子外排研究，证明最活跃的转运体采用预组织的结合构象，能够以协同方式利用脲和 C-H 结合基团促进氯化物的识别。在电中性和生电条件下进行的额外的大单室囊泡基础测定以及 N-甲基-D-葡糖胺氯化物测定表明，阴离子外排主要通过 H / Cl 协同转运机制发生。另一方面，最有效的阴离子转运体对肿瘤细胞系表现出细胞毒性，而对囊性纤维化细胞系没有影响。
