Toward Rational Design of Electrogenerated Molecularly Imprinted Polymers (eMIPs): Maximizing Monomer/Template Affinity

Molecularly imprinted polymers (MIPs) may be used to confer specific recognition properties to a variety of practical sensors and sorbents. However, the synthetic parameters (monomer species, template/monomer ratio, etc.) used to generate MIPs significantly impact their sensitivity and selectivity, generally requiring arduous empirical optimization to obtain materials with maximal target affinity. We present a MIP synthesis strategy that prioritizes the optimization of the pre-polymerization complex as a predictive model for the final polymer properties and demonstrate how greater target affinity may be obtained without iterative analysis of the polymer film. 2,4-Dichlorophenoxyacetic acid (2,4-D), a prevalent herbicide, was chosen for detection using electrogenerated molecularly imprinted polymers (eMIPs). eMIPs were rationally designed using molecular simulations to down-select an ideal functional monomer with a maximal affinity for 2,4-D. Following monomer selection, proton-based nuclear magnetic resonance (1H NMR) titrations were used to verify the simulation results and optimize the monomer/2,4-D ratio by tracking the chemical shift associated with monomer/target binding. Following optimization, eMIPs were synthesized by the anodic electropolymerization of the selected monomer, o-phenylenediamine, onto gold substrates in the presence of 2,4-D, which was subsequently stripped away via solvent washing to reveal 2,4-D-specific binding sites. Surface sites were blocked upon 2,4-D association with the eMIP when placed in contaminated water, which was tracked electrochemically. The ability of molecular simulations and 1H NMR titrations to predict optimal monomer/2,4-D ratios was evaluated by fitting the experimental data to a Langmuir–Freundlich isotherm, revealing a significant increase in target affinity (Ka) and binding site homogeneity (m) related to the chemical shifts exhibited by the pre-polymerization complex for o-phenylenediamine (o-PD). The two techniques, when evaluated on o-PD, predicted ideal monomer/template ratios with remarkable agreement. Thus, the synthetic strategy outlined herein represents a streamlined approach for the rapid prototyping and design of eMIP-based sensing elements essential for the realization of next-generation polymeric sensors and sorbents.