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Anion Recognition by a Bioactive Diureidodecalin Anionophore: Solid‐State, Solution, and Computational Studies
Author(s) -
Jurček Ondřej,
Valkenier Hennie,
Puttreddy Rakesh,
Novák Martin,
Sparkes Hazel A.,
Marek Radek,
Rissanen Kari,
Davis Anthony P.
Publication year - 2018
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201800537
Subject(s) - chemistry , binding affinities , selectivity , acceptor , binding site , chloride , affinities , crystal structure , transporter , ion , crystallography , stereochemistry , receptor , biochemistry , organic chemistry , physics , gene , condensed matter physics , catalysis
Recent work has identified a bis‐( p ‐nitrophenyl)ureidodecalin anion carrier as a promising candidate for biomedical applications, showing good activity for chloride transport in cells yet almost no cytotoxicity. To underpin further development of this and related compounds, a detailed structural and binding investigation is reported. Crystal structures of the transporter as five solvates confirm the diaxial positioning of urea groups while revealing a degree of conformational flexibility. Structures of complexes with Cl − , Br − , NO 3 − , SO 4 2− and AcO − , supported by computational studies, show how the binding site can adapt to accommodate these anions. 1 H NMR binding studies revealed exceptionally high affinities for anions in DMSO, decreasing in the order SO 4 2− >H 2 PO 4 − ≈HCO 3 − ≈AcO − ≫HSO 4 − >Cl − >Br − >NO 3 − >I − . Analysis of the binding results suggests that selectivity is determined mainly by the H‐bond acceptor strength of different anions, but is also modulated by receptor geometry.