Optimization of Cortisol-Selective Molecularly Imprinted Polymers Enabled by Molecular Dynamics Simulations

Abstract

Today, we heavily rely on technology and increasingly utilize it to monitor our own health. The identification of sensitive, accurate biosensors that are capable of real-time cortisol analysis is one important potential feature for these technologies to aid us in the maintenance of our physical and mental wellbeing. Detection and quantification of cortisol, a well-known stress biomarker present in sweat, offers a noninvasive and potentially real-time method for monitoring anxiety. Molecularly imprinted polymers are attractive candidates for cortisol recognition elements in such devices as they can selectively rebind a targeted template molecule. However, mechanisms of imprinting and subsequent rebinding depend on the choice and composition of the prepolymerization mixture where the molecular interactions between the template, functional monomer, cross-linker, and solvent molecules are not fully understood. Here, we report the synthesis and evaluation of a molecularly imprinted polymer selective for cortisol detection. Molecular dynamics simulations were used to investigate the interactions between all components in the prepolymerization mixture of the as-synthesized molecularly imprinted polymer. Varying the component ratio of the prepolymerization mixture indicates that the number of cross-linker molecules relative to the template impacts the quality of imprinting. It was determined that a component ratio of 1:6:30 of cortisol, methacrylic acid, and ethylene glycol dimethacrylate, respectively, yields the optimal theoretical complexation of cortisol for the polymeric systems investigated. Experimental synthesis and rebinding results demonstrate an imprinting factor of up to 6.45. The trends in cortisol affinity predicted by molecular dynamics simulations of the prepolymerization mixture were also corroborated through experimental analysis of those modeled molecularly imprinted compositions, demonstrating the predictive capabilities of these simulations.

Molecularly imprinted polymers in diagnostics: accessing analytes in biofluids

“…65 Regardless of the limited control over the physical form of the obtained imprinted species, many MIP publications still employ the bulk polymerisation approach, possibly due to reproducibility and simplicity with respect to the preparation and formulation of this polymerisation process. 60,61,63,66 Bulk polymerisation limitations have led to the development of alternative approaches, including in situ prepared monoliths, molecularly imprinted monoliths, MIP membranes, and MIP beads. 22,[67][68][69][70][71] Precipitation polymerisation (Figure 2b) is credited to the processes improved heat control and direct preparation of large-scale production.…”

Remediation of pharmaceuticals from wastewater via computationally selected molecularly imprinted polymers

“…Capitalising on our previous work on modelling MIP systems, 36–39 in this work, the pre-polymerisation mixture for a FLX-MIP is simulated using MD. Methacrylic acid (MAA), itaconic acid (IA), 2 (hydroxyethyl)methacrylate (HEMA), acrylamide (ACA) and acrylonitrile (ACN) were selected as FM candidates.…”

Molecularly Imprinted Polymer-Based Sensor for Electrochemical Detection of Cortisol

“…Klangphukhiew et al carried out the polymerization process by placing the pre-polymerization solution into a nitrogen furnace at a temperature of 70 °C for 24 h [ 55 ]. Incorporating nitrogen gas into the pre-polymerization process [ 9 , 48 , 56 , 57 , 58 ], or during the polymerization process [ 55 , 59 , 60 ], has been applied to the bulk imprinting method. It works as a degassing or purging agent to remove dissolved oxygen and eliminate compounds with low molecular weights that can potentially cause the constructed polymer to return to the monomer form [ 61 , 62 ].…”

“…By manipulating the non-covalent interactions between monomers, molecular templates, cross-linkers, and solvents, MIPs can produce a polymer chain with pockets or cavities with shapes and functional groups corresponding to the template molecule. In this case, cortisol is used as the template molecule [ 9 ]. The MIP that has been formed will undergo a molecular template removal process to eliminate all the remaining cortisol for the rebinding process with cortisol in the actual sample [ 3 ].…”