Picking on Carbonate: Kinetic Selectivity in the Encapsulation of Anions

Abstract

Supramolecular hosts bind to inorganic anions at a fast rate and select them in proportion with thermodynamic stability of the corresponding [anion�host] complexes, forming in a reversible manner. In this study, we describe the action of hexapodal capsule 1 and its remarkable ability to select anions based on a large span of rates by which they enter this host. The thermodynamic affinity of 1 toward eighteen anions extends over eight orders of magnitude (0 < K a < 10 8 M À 1 ; 1 H NMR spectroscopy). The capsule would retain CO 3 2À (K a = 10 7 M À 1 ) for hours in the presence of eleven competing anions, including stronger binding SO 4 2À , HAsO 4 2À and HPO 4 2À (K a = 10 7 -10 8 M À 1 ). The observed selection resulted from 1 possessing narrow apertures (ca. 3 × 6 Å) comparable in size to anions (d = 3.5-7.1 Å) slowing down the encapsulation to last from seconds to days. The unorthodox mode of action of 1 sets the stage for creating hosts that pick anions by their ability to access the host.

A double-decker cage for allosteric encapsulation of ATP

“…This suggestion is also supported with recent studies 19,21 in which we used templating anions to bias the conformation of hexakis aldehyde 2 for trapping a hexakis amine ligand giving a hexapodal capsule capable of binding anions in the kinetic fashion. 21 An energy-minimized conformer of [1-H 6 ] 6+ (MMFFs, Fig. 1D) includes two adjoining pockets each with three ammonium and three amide sites.…”

Measuring anion binding at biomembrane interfaces

“…Thus, in DMSO the anion binding affinities of 1 are dominated by the strength of electrostatic interactions leading to favourable binding of charge-dense anions. Interestingly, for a recently reported hexapodal cage that binds anions via less acidic alkyl amide NH and imine CH sites 19 , a weaker SO 4 2– /I – selectivity of ~30 and a I – > Cl – selectivity were found in DMSO- d 6 contrasting the behaviour of macrocycle 1 that binds anion via highly acidic aromatic urea and carbazole NH sites. This suggests that the extent of preference for charge-dense anions is influenced by the acidity of anion binding sites.…”

“…2a ) and H 2 PO 4 – (Supplementary Fig. 14 ) lead to slow exchange 1 H NMR responses, which were rarely observed 19 in the relatively competitive organic solvent DMSO highlighting the anion binding potency of 1 . By contrast, the complexes of 1 with Cl – , Br – , NO 3 – and I – show fast exchange with the free macrocycle (Supplementary Figs.…”

Benchmarking Adaptive Steered Molecular Dynamics (ASMD) on CHARMM Force Fields

“…[12,17] The approach has also been adopted by several other groups to, for example, reveal mutagenesis effects of calcium binding affinity in cardic troponin c, [18] and kinetic selectivity in anion encapsulation. [19] The quality and reliability of these simulations are largely dependent upon the accuracy of the underlying empirical force field (FF) of choice. There are many available choices for the allatom, additive potential functions, such as the CHARMM, [20][21][22][23] AMBER, [24,25] and OPLS-AA FFs.…”

“…We have previously demonstrated the accuracy of this approach for the mechanical unhinging of Neuropeptide Y, [10] for the mechanical unfolding of the hydrophobic‐homopolymer , [14–16] and the unfolding of two small β ‐hairpin peptides [12,17] . The approach has also been adopted by several other groups to, for example, reveal mutagenesis effects of calcium binding affinity in cardic troponin c, [18] and kinetic selectivity in anion encapsulation [19] …”