authors |
Marques, I; Costa, PMR; Miranda, MQ; Busschaert, N; Howe, ENW; Clarke, HJ; Haynes, CJE; Kirby, IL; Rodilla, AM; Perez-Tomas, R; Gale, PA; Felix, V |
nationality |
International |
journal |
PHYSICAL CHEMISTRY CHEMICAL PHYSICS |
keywords |
MOLECULAR-DYNAMICS SIMULATIONS; RECEPTOR CHEMISTRY HIGHLIGHTS; PI SLIDES; MEDICINAL CHEMISTRY; TAMBJAMINE-ANALOGS; CHLORIDE TRANSPORT; LIPID-BILAYERS; FORCE-FIELD; BIS-UREAS; RECOGNITION |
abstract |
A comprehensive experimental and theoretical investigation of the transmembrane chloride transport promoted by four series of squaramide derivatives, with different degrees of fluorination, number of convergent N-H binding units and conformational shapes, is reported. The experimental chloride binding and transport abilities of these small synthetic molecules in liposomes were rationalised with quantum descriptors and molecular dynamics simulations in POPC bilayers. The tripodal tren-based compounds, with three squaramide binding motifs, have high chloride affinity, isolating the anion from water molecules within the membrane model and preventing its release to the aqueous phase, in agreement with the absence of experimental transport activity. In contrast, the symmetrical mono-squaramides, with moderate chloride binding affinity, are able to bind and release chloride either in the aqueous phase or at the membrane interface level, in line with experimentally observed high transport activity. The PMF profiles associated with the diffusion of these free transporters and their chloride complexes across phospholipid bilayers show that the assisted chloride translocation is thermodynamically favoured. |
publisher |
ROYAL SOC CHEMISTRY |
issn |
1463-9076 |
year published |
2018 |
volume |
20 |
issue |
32 |
beginning page |
20796 |
ending page |
20811 |
digital object identifier (doi) |
10.1039/c8cp02576b |
web of science category |
Chemistry, Physical; Physics, Atomic, Molecular & Chemical |
subject category |
Chemistry; Physics |
unique article identifier |
WOS:000447367900006
|
ciceco authors
impact metrics
journal analysis (jcr 2019):
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journal impact factor |
3.43 |
5 year journal impact factor |
3.735 |
category normalized journal impact factor percentile |
69.267 |
dimensions (citation analysis):
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altmetrics (social interaction):
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