Polymerisation mechanisms as the missing link in rational design of imprinted polymer networks

Molecularly imprinted polymers (MIPs) are synthetic polymer networks formed around template molecules to create selective molecular recognition sites. While decades of research have advanced our understanding of pre-polymerisation complexation and the properties of finished MIP materials, the polymerisation step itself remains a conceptual black box in imprinting design. This Perspective argues that polymerisation—the dynamic process by which monomers are covalently linked and cross-linked around a template—is the decisive yet under-explored stage governing the fidelity, selectivity, and function of imprinted polymer networks. We adopt a design-first, mechanism-centric viewpoint to examine how polymerisation encodes molecular recognition and catalytic function in MIPs, molecularly imprinted catalysts (MICs), and enantiopure molecularly imprinted catalysts (EMICs). We explain why conventional fixed-topology molecular simulations, such as classical molecular dynamics, are intrinsically unable to capture imprinting fidelity, and we highlight how reactive molecular dynamics approaches open new avenues for resolving cavity formation, network growth, and the emergence of functional sites. Polymerisation is reframed as a dynamic encoding process in which the trajectory of network formation—the sequence of radical initiation, propagation, and cross-linking events—critically determines the architecture and performance of binding sites. We propose mechanistic descriptors of polymer growth, including growth-front propagation patterns, cross-linking motifs, and kinetic trapping phenomena, as new design variables for imprinting that move beyond static pre-assembly metrics. Insights from MIPs are generalised to MICs and EMICs, in which polymerisation locks in transition-state-stabilising functional-group arrangements, and implications for other porous polymer and molecular-recognition materials are briefly discussed. By elucidating polymerisation mechanisms, this Perspective establishes a broadly applicable, predictive, mechanism-driven framework for the rational design of imprinted polymer networks and calls for polymerisation to be treated not as an uncontrollable curing step but as a tunable, information-rich process central to the next generation of molecularly imprinted materials.