Abstract
The Kemp elimination (reaction of benzisoxazole with base to give 2-cyanophenolate) is catalyzed in the cavity of a cubic M8L12 coordination cage because of a combination of (i) benzisoxazole binding in the cage cavity driven by the hydrophobic effect, and (ii) accumulation of hydroxide ions around the 16+ cage surface driven by ion-pairing. Here we show how reaction of the cavity-bound guest is modified by the presence of other anions which can also accumulate around the cage surface and displace hydroxide, inhibiting catalysis of the cage-based reaction. Addition of chloride or fluoride inhibits the reaction with hydroxide to the extent that a new autocatalytic pathway becomes apparent, resulting in a sigmoidal reaction profile. In this pathway the product 2-cyanophenolate itself accumulates around the cationic cage surface, acting as the base for the next reaction cycle. The affinity of different anions for the cage surface is therefore 2-cyanophenolate (generating autocatalysis) > chloride > fluoride (which both inhibit the reaction with hydroxide but cannot deprotonate the benzisoxazole guest) > hydroxide (default reaction pathway). The presence of this autocatalytic pathway demonstrates that a reaction of a cavity-bound guest can be induced with different anions around the cage surface in a controllable way; this was confirmed by adding different phenolates to the reaction, which accelerate the Kemp elimination to different extents depending on their basicity. This represents a significant step toward the goal of using the cage as a catalyst for bimolecular reactions between a cavity-bound guest and anions accumulated around the surface.
Highlights
The ability of hollow container molecules to bind small molecules or ions as guests in their central cavity[1−5] has led to a wide range of possible applications[2] from drug uptake/release[3] to photocatalysis.[4]
The effect is sufficiently strong that when the bulk solution was at pD 8.5, the bound guest underwent the Kemp elimination at the same rate as when it was free in solution at pD 13.8.11 The ability of our cationic cage to accumulate anions around its surface was shown by a control experiment using competing anions:[11] in the presence of an excess of chloride ions, the catalysis was switched off and the benzisoxazole reacted at only the background rate, even though (i) it remained bound in the cage cavity and (ii) chloride does not itself directly interfere with the Kemp elimination.[12]
This observation is important as it suggests that a wide range of different types of anion might accumulate around the cage in water, especially “soft” anions that are weakly solvated: this, in turn, could provide a mechanism to surround any of a wide range of guests3d,14 with a high local concentration of a selected anion, using two orthogonal interactions
Summary
The ability of hollow container molecules to bind small molecules or ions as guests in their central cavity[1−5] has led to a wide range of possible applications[2] from drug uptake/release[3] to photocatalysis.[4]. The effect is sufficiently strong that when the bulk solution was at pD 8.5, the bound guest underwent the Kemp elimination at the same rate as when it was free in solution at pD 13.8.11 The ability of our cationic cage to accumulate anions around its surface was shown by a control experiment using competing anions:[11] in the presence of an excess of chloride ions, the catalysis was switched off and the benzisoxazole reacted at only the background rate, even though (i) it remained bound in the cage cavity and (ii) chloride does not itself directly interfere with the Kemp elimination.[12] This effect was ascribed to the fact that chloride ions, being more desolvated than hydroxide ions,[13] would preferentially bind to the cage surface and thereby displace the hydroxide ions from their proximity to the substrate This observation is important as it suggests that a wide range of different types of anion might accumulate around the cage in water, especially “soft” anions that are weakly solvated: this, in turn, could provide a mechanism to surround any of a wide range of guests3d,14 with a high local concentration of a selected anion, using two orthogonal interactions. We note that strong binding of anions in the central cavities of two-dimensional metal/ligand arrays such as cyclic helicates[21,22] have been known since Lehn first reported the templation of a pentanuclear cyclic helicate by a chloride ion, giving a structure containing a strongly bound chloride that could not be removed with Ag(I) salts.[21]
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