Full elucidation of the transmembrane anion transport mechanism of squaramides using in silico investigations.

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.

Highly effective yet simple transmembrane anion transporters based upon ortho-phenylenediamine bis-ureas.

Simple, highly fluorinated receptors are shown to function as highly effective transmembrane anion antiporters with the most active transporters rivalling the transport efficacy of natural anion transporter prodigiosin for bicarbonate.

Systematic experimental charge density analysis of anion receptor complexes.

The first systematic electronic resolution study of a series of urea-based anion receptor complexes is presented. The hydrogen bonding in these multi-component systems was fully characterised using Bader's Quantum Theory of Atoms In Molecules (QTAIM) with the strength of the various N-H···anion hydrogen bonds quantified and the individual contributions of different intermolecular forces to the overall receptor: anion interaction derived by comparison of the charge densities in the related complexes. The strength of the N-Hanion hydrogen bonds was correlated to the basicity of the anion and related to the structure of the receptors.

Acylthioureas as anion transporters: the effect of intramolecular hydrogen bonding.

Small molecule synthetic anion transporters may have potential application as therapeutic agents for the treatment of diseases including cystic fibrosis and cancer. Understanding the factors that can dictate the anion transport activity of such transporters is a crucial step towards their application in biological systems. In this study a series of acylthiourea anion transporters were synthesised and their anion binding and transport properties in POPC bilayers have been investigated.

Accurate method to quantify binding in supramolecular chemistry.

An approach for accurate and comparable measurement of host-guest binding affinities is introduced whereby differences in binding strength (ΔlogKass values) are measured between two host molecules toward a particular guest under identical solvent conditions. Measuring differences instead of absolute values enables obtaining highly accurate results, because many of the uncertainty sources (the solvation/association state of the guest in solution, deviations in solvent composition, etc.) cancel out.