Catching chloride : searching for non-Hofmeister selectivity behavior in systematically varied polyamide macrocyclic receptors

The binding selectivity of structurally simple anion receptors is governed by the Hofmeister series (SO42- > HPO42- > carboxylates ∼ H2PO4- > HCO3- > Cl-), and exceptions to this rule are rare and require utilization of structurally sophisticated receptors. In this paper we examined a set of 48 structurally diverse anion receptors, barely one fourth of which exhibit selectivity for chloride over more basic dihydrogen phosphate (H2PO4-) or carboxylates (MeCO2- and PhCO2-). Searching for regularities in the properties of these mainly macrocyclic-derived receptors across quite systematic changes in structure, combined with analysis of multiple crystal structures, allowed us to identify the crucial structural features that are likely required for the occurrence of the phenomenon of selective chloride binding. Examination of a subset of other 'case study' receptors reported in the literature as being particularly chloride-selective served as a confirmation of our hypotheses. As such, our findings are valid for all artificial receptors with exceptional selectivity for chloride, as well as for natural chloride channel proteins (ClC).


Binding data analysis
Table S1.Binding data for the studied receptors gathered from the literature [a] Solvent mixture K a. anion (M -1 ) K rel = log (K a. Cl -/ K anion ) Entry Host Ringsize Linker Titration method [b] #
[a] All titration experiments were conducted at 298K, if not otherwise stated; [b] A: 1 H NMR, B: UV-Vis, C: ITC; [c] temperature was not reported; [d] complex binding mode; [e] T = 303 K.

Diffractometer and data collection
The x-ray measurements of Uc1•H 2 O and Uc1•TBACl were performed at 100(2) K on a KM4CCD -axis diffractometer with graphite-monochromated MoK  .The corresponding crystal was positioned at 62 mm from the CCD camera.1200 (Uc1) or 750 (Uc1•TBACl) frames were measured at 1 o intervals with a counting time of 11 or 9 sec for Uc1 and Uc1•TBACl, respectively.The data were corrected for Lorentz and polarization effects.Empirical correction for absorption was applied. 36Data reduction and analysis were carried out with the Oxford Diffraction programs. 36-37

Structure refinement
The structure was solved by direct methods 38 and refined using WinGX 39 and SHELXL Software Package. 40he refinement was based on F 2 for all reflections except those with very negative F 2 .Weighted R factors wR and all goodness-of-fit S values are based on F 2 .Conventional R factors are based on F with F set to zero for negative F 2 .The F o 2 >2σ(F o 2 ) criterion was used only for calculating R factors and is not relevant to the choice of reflections for the refinement.The R factors based on F 2 are about twice as large as those based on F. All hydrogen atoms were located geometrically and their position and temperature factors were not refined except those engaged in hydrogen bonds.Scattering factors were taken from Tables 6.1.1.4and 4.2.4.2 in Ref. 41 .The H-bonds in crystal structure were determined according to IUPAC recommendation. 42he crystal structure of Uc1 contains disordered p-nitrophenyl substituent and partially occupied solvent molecules such as disordered n-pentan, water, and methanol molecules.All of the oxygen-containing solvent molecules, except the water molecule located within macrocyclic cavity, were refinement without the hydrogen atoms.It is noteworthy that, the exact dimensions and cell volume should be probably doubled (i.e.: a = 8.214 Å, b = 19.363Å, c = 23.930Å,  = 109.07°, = 97.28°, = 93.34°,V = 3547.71Å 3 ) as compared to the data mentioned in the cif file.However, since the reflections proving this assumption were weak, the final structure was refinement as the average from two smaller elemental cells.The crystal structure of Uc1•TBACl contains water molecule which is dislocated between two adjacent macrocycles.This results in incomplete hydrogen bond saturation of the water molecule which is engaged in just two, albeit strong, hydrogen bonds with the oxygen carbonyl atoms of the adjacent macrocyclic molecules.
Crystal data and structure refinement details for solvate (left) and TBACl complex (right) of Uc1.