The use of organophosphorus chemical warfare agents still remains an ongoing global threat. Here we investigate the binding of small-molecule organic guests including phosphate esters, sulfonate esters, carbonate esters and a sulfite ester – some of which act as simulants for organophosphorus chemical warfare agents – in the cavity of a water-soluble coordination cage. For several of these guest species, binding constants in the range 10² to 10³ M⁻¹ were determined in water/DMSO (98 : 2 v/v) solution, through a combination of fluorescence and ¹H NMR spectroscopy, and subsequent fitting of titration data to a 1 : 1 binding isotherm model. For three cage/guest complexes crystallographic structure determinations were possible: in two cases (with guests phenyl methanesulfonate and phenyl propyl carbonate) the guest lies inside the cavity, forming a range of CH⋯O hydrogen-bonding interactions with the cage interior surface involving CH groups on the cationic cage surface that act as H-bond donors and O atoms on the guests that act as H-bond acceptors. In a third case, with the guest 4-nitrophenyl-methanesulfonate, the guest lies in the spaces outside a cage cavity between cages and forms weak CH⋯O interactions with the cage exterior surface: the cavity is occupied by a network of H-bonded water molecules, though this guest does show cavity binding in solution. For the isomeric guests 4-nitrophenyl-methanesulfonate and 4-nitrophenyl methyl sulfite, hydrolysis in water/DMSO (98 : 2 v/v) could be monitored colorimetrically via appearance of the 4-nitrophenolate anion; both showed accelerated hydrolysis rates in the presence of the host cage with second-order rate constants for the catalysed reactions in the range 10⁻³ to 10⁻² M⁻¹ s⁻¹ at pH 9. The typical rate dependence on external pH and the increased reaction rates when chloride ions are present (which can bind inside the cavity and displace other cavity-bound guests) imply that the catalysed reaction actually occurs at the external surface of the cage rather than inside the cavity.