Coordination‐Cage‐Catalysed Hydrolysis of Organophosphates: Cavity‐ or Surface‐Based?

Abstract

The hydrophobic central cavity of a water‐soluble M8L12 cubic coordination cage can accommodate a range of phospho‐diester and phospho‐triester guests such as the insecticide “dichlorvos” (2,2‐dichlorovinyl dimethyl phosphate) and the chemical warfare agent analogue di(isopropyl) chlorophosphate. The accumulation of hydroxide ions around the cationic cage surface due to ion‐pairing in solution generates a high local pH around the cage, resulting in catalysed hydrolysis of the phospho‐triester guests. A series of control experiments unexpectedly demonstrates that—in marked contrast to previous cases—it is not necessary for the phospho‐triester substrates to be bound inside the cavity for catalysed hydrolysis to occur. This suggests that catalysis can occur on the exterior surface of the cage as well as the interior surface, with the exterior‐binding catalysis pathway dominating here because of the small binding constants for these phospho‐triester substrates in the cage cavity. These observations suggest that cationic but hydrophobic surfaces could act as quite general catalysts in water by bringing substrates into contact with the surface (via the hydrophobic effect) where there is also a high local concentration of anions (due to ion pairing/electrostatic effects).

Catalysis of an Aldol Condensation Using a Coordination Cage

“…Control experiments suggested that the reaction does not actually occur inside the cage cavity, but at the external surface, which is a possibility that has very recently emerged from related studies on catalysis with this cage system [57]. In the confined space of the cavity, any successful reaction would require an ideal configuration of the cavity-bound and surface-bound reacting partners, and when this happens, it can lead to very large rate enhancements [10,29].…”

“…This binds strongly in the cage cavity (>10 6 M −1 ) [32] and therefore prevents the substrate ID from binding, however, it has no effect on the rate at which bindone is formed. This clearly indicates that cavity-based binding of ID is not necessary for the catalysis to occur, therefore it follows that the catalysed reaction occurs at the external surface of the cage where enolate anions of ID accumulate [57].…”

“…In the confined space of the cavity, any successful reaction would require an ideal configuration of the cavity-bound and surface-bound reacting partners, and when this happens, it can lead to very large rate enhancements [10,29]. However, hydrophobic substrates that do not bind in the cavity, or that cannot react for geometric reasons whilst inside the cavity, can also interact with the cage exterior surface, which is just as hydrophobic as the interior surface and has a greater area: these substrates can thereby be brought into the region around the cationic surface where anions have accumulated because of ion-pairing effects [57]. The key control experiment here is to perform the reaction in the presence of an excess of cycloundecanone.…”

Metal‐Organic Frameworks and Metal‐Organic Cages – A Perspective

“…The hydrolysis of phosphate esters, such as the insecticide dichlorvos, was promoted on the exterior surface of a cubic cobalt(II) M 8 L 12 MOC (Figure 7c). [147] In such cases, MOC assembly provides the necessary cationic but hydrophobic surface to bind both substrate and basic anion required for the reaction. The same MOCs could also catalyze the Kemp elimination of benzisoxazole to 2-cyanophenolate in its cavity, through both interior and exterior binding processes.…”

“…Initially more chloride bound than hydroxide, inhibiting the reaction, but as the cyanophenolate product (which had the highest binding affinity for the MOC exterior) built up, it preferentially bound to the outside instead and accelerated further reactions inside (Figure 7d and Figure 7e). Exploiting the finite nature of MOCs for catalysis: (a) Octahedral M 6 L 4 MOC, illustrating the U-shaped conformation of the bound diterpenoid guest observed in the crystal structure (with exposed prenyl group highlighted in orange); [145] (b) Regioselective electrophilic substitution reactions performed on the host-guest complex where central alkenes (highlighted in purple) do not react; (c) Crystal structure of an M 8 L 12 cubic MOC with the insecticide dichlorvos bound on the edge; [147] (d) Rate of Kemp elimination in the M 8 L 12 cubic MOC compared to background rate; [39] (e) Inhibition of Kemp elimination by chloride early in reaction and autocatalysis of Kemp elimination by phenolate later in reaction.…”