Chemistry - A European Journal
Journal Article
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 1H 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. © 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
P.a Vieira
M.Q.b Miranda
I.b Marques
L.-J.c Chen
E.N.W.c Howe
C.c Zhen
C.Y.c Leung
M.J.d Spooner
B.e Morgado
O.A.B.e da Cruz e Silva
C.a Moiteiro
P.A.c Gale
V.b Félix
Publication
Year of publication: 2020
Identifiers
ISSN: 09476539
Locators
DOI: 10.1002/chem.201904255