Dynamics of organophosphate guest encapsulation in heteroleptic coordination cages†

Heteroleptic coordination cages allow the design of different host structures that can bind guest molecules within their cavities. In a previous work, the energetics of organophosphate encapsulation in palladium(II)-based heteroleptic coordination cages that differ in terms of their ability to form hydrogen bonds have been investigated [Platzek et al., Endohedrally Functionalized Heteroleptic Coordination Cages for Phosphate Ester Binding, Angew. Chem., Int. Ed. 2022, 61, e2022093]. The present work focuses on the dynamics of this system. Dynamic information is obtained through the application of a Markov state model (MSM) to unbiased multi-microsecond atomistic molecular dynamics simulations of guest binding and release. The MSM reveals that both the bound state and the binding/unbinding pathways are highly dynamic, with different types of interactions mediating the binding of the diphenylphosphate guest. Thus, the simulations highlight the dynamic nature of the nanoconfinement in the host–guest systems, with possible implications for the use of such coordination cages as catalysts.