Thermodynamics of Halide Binding to a Neutral Bambusuril in Water and Organic Solvents

Abstract

Driving forces of anion binding in water in contrast to nonpolar environments are of high interest because of their relevance to biology and medicine. Here we report a neutral bambusuril macrocycle (1), soluble in both water and nonpolar solvents due to decoration with 12 polyethylene glycol-based substituents. The new bambusuril has the highest affinity for I in pure water ever reported for a synthetic macrocycle relying on hydrogen bonding interactions rather than metal coordination or Coulombic forces. Isothermal titration calorimetry (ITC) experiments in nine different solvents, ranging from polar water to nonpolar carbon tetrachloride, provided insight into the forces responsible for halide binding by bambusurils. The different importance of anion solvation and solvent expulsion from the cavity of the macrocycle in various solvents is illustrated by the fact that halide binding in water and chloroform is exclusively driven by favorable enthalpy with an entropic penalty, while in alcohols and nonpolar solvents, both favorable enthalpy and entropy contribute to anion encapsulation. DFT calculations and correlation of thermodynamic data with the solvent Swain acity parameter further underscore the importance of solvent effects on anion binding by bambusurils.

Functionalization of Bambusurils by a Thiol–Ene Click Reaction and a Facile Method for the Preparation of Anion‐Free Bambus[6]urils

“…It was reported that carboxyalkyl bambusurils complexes of HSO 4 − can be converted to their corresponding anion‐free BU[6] by a treatment with basic water . More recently (trioxadecyl) 12 BU[6], bearing polyethylene glycol substituents and TBABF 4 , was obtained as its NaBF 4 complex after purification by silicagel chromatography, and was obtained free of BF 4 − anion by water continuous extraction over one week . All these reported methods are burdensome and time consuming.…”

“…Nitrobenzyl BU[4] derivatives have been successfully reduced into water‐soluble aminobenzyl BU[4] that were further transformed into the corresponding urea bambus[4]urils . Bambus[6]urils containing 12 (ethylene glycol) functions were recently reported to be as soluble in water as in nonpolar solvents . Although thiobambusurils are still unknown, some heterobambusurils called semithiobambus[4]urils and semithiobambus[6]urils have been prepared from semi‐thioglycoluril derivatives, and used as precursors for semi‐aza‐bambusurils bearing guanidines, which can act as anion channels .…”

“…These microwave conditions have also been successfully used by the groups of Keinan and Sindelar A templating anion is always required either using reflux or microwaves to promote the formation of the hexameric BU[6], in preference to the tetrameric BU[4]. Although this methodology has been well established, BU[6] derivatives are generally isolated with an anion present inside their cavity and time‐consuming steps are necessary to obtain anion‐free BU[6] …”

“…BU [6] are able to bind anionsw ithin their cavity with high affinity and selectivity, making them very attractive supramolecular receptors. [1] Since the discoveryo f the first BU [6] by the group of Sindelar, [2] the BUs family has expandedboth in size and substitution.B U [4] and BU [6] can be substituted on the nitrogen atoms of their glycoluril unit by methyl, benzyl, propyl, or allyl groups and they are named Me 12 BU [6], [2] Bn 12 BU [6], [3] Bn 8 BU [4], [3] Pr 12 BU [6], [3] allyl 8 BU[4], and allyl 12 BU [6],r espectively. [4] They are generallys oluble in organic solvents.…”

Thermodynamics of Anion Binding by Chalcogen Bonding Receptors

“…Upon binding between I − and 1.Te , the released CD 3 CN molecules undergo a greater extent of re‐ordering compared with [D 6 ]acetone, giving rise to a greater entropic penalty. A similar reasoning has been invoked to account for the exothermic, but entropically disfavoured anion binding in solvents exhibiting a degree of structural ordering such as water and chloroform …”