Higher Order Constitutional Dynamic Networks: [2x3] and [3x3] Networks Displaying Multiple, Synergistic and Competitive Hierarchical Adaptation

The present study investigates the constitutional dynamic networks (CDNs) underlying dynamic covalent libraries (DCLs) that extend beyond the [2x2] case toward higher orders, namely [2x3] and [3x3] CDNs involving respectively six and nine constituents generated from the recombination of five and six components linked through reversible chemical reactions. It explores the behavior of such systems under the action of one or two effectors. More specifically and for the sake of proof of principle, it makes use of DCLs involving dynamic organic ligands and analyzes their single and double adaptive response under the action of one and two metal cation effectors. Thus, interconversions within [2x3] DCLs of six constituents (hydrazone, anylhydrazone, and imine ligands) give access to the generation of [2x3] CDNs of 3D trigonal prismatic type consisting of three [2x2] subnetworks and presenting specific responses to the application of Cu+ and Zn2+ metal cation effectors, in particular double agonistic amplification. More complex [3x3] CDNs based on nine ligand constituents of imine, hydrazone, and acylhydrazone types were also designed and subjected to the application of one Or two effectors, e.g., Cu+ and Fe2+ metal cations, revealing novel types of adaptive behavior: (i) agonistic amplification between a single constituent and a full [2x2] sub-network, and (ii) agonistic amplification along a single diagonal connecting three constituents. Of special interest is also the dependence of the response of the system to hierarchical sequence of effector application, whereby initial interaction with Cu+ ions results in the destruction of the network, whereas the sequence Fe2+ followed by Cu+ yields a clean three-constituent DCL. Finally and strikingly, the present results also demonstrate that the increase in complexity of the system by introduction of an additional entity leads to a simpler output through dynamic competition between components.