Fabrication of Cortisol- and Sodium Lactate-Selective Molecularly Imprinted Polymers for Biomaterial Sensors Informed by Molecular Dynamics Simulations

The progressive development of biosensors aims to simultaneously provide a high degree of sensitivity in addition to instantaneous detection of specific biomarkers for accurate health surveillance purposes. These self-monitoring health technologies serve to aid in the maintenance of both the physical and mental wellbeing of humankind. The detection and quantification of cortisol and sodium lactate, biomarkers associated with stress, hypoxemia and bacterial infections (e.g., sepsis) can be achieved via molecularly imprinted polymers performing as synthetic recognition elements. Mechanisms of imprinting and subsequent rebinding depend on the choice and composition of the pre-polymerisation mixture, where molecular interactions between the template, functional monomer, crosslinker and solvent molecules are not fully understood. Here, the synthesis and evaluation of two individual chemically polymerised molecularly imprinted cortisol- and sodium lactate-selective polymers are reported. Initially, molecular dynamics simulations were utilised to investigate the interactions between all components in the pre-polymerisation mixture of the cortisol-sensitive biomaterial. Varying the component ratio of the pre-polymerisation mixture indicates that the number of crosslinker molecules relative to the template impacts the quality of imprinting. It was experimentally determined that a component ratio of 1:6:30 of cortisol (template), methacrylic acid (functional monomer), and ethylene glycol dimethacrylate (crosslinker), respectively, yields the optimal theoretical complexation of cortisol for this polymeric system.¹ The optimisation of this imprinted species was informed by molecular dynamics, which was used as a tool to investigate the mechanisms within the imprinting process. The trends in cortisol affinity predicted by these simulations were reflected via experimental analysis of the modelled molecularly imprinted compositions. Furthermore, the simulated data enabled this procedure to be adapted, substituting the cortisol template for sodium lactate (component ratio of 1:6:30). Experimentally recaptured cortisol and sodium lactate demonstrated an imprinting factor of up to 6.45 and 0.36 with a high degree of reusability. Moreover, a competitive species in the form of hippuric acid demonstrated the selective capabilities of both templated polymers. Thus, the predictive proficiency of the simulations carried out for the cortisol-selective species have highlighted their ability to inform the synthesis of an optimal polymer system for efficient cortisol- and sodium lactate-selective molecularly imprinted polymers.<br/><br/>1. Daniels, E; Mustafa, Y. L.; Herdes, C.; Leese, H.S. Optimization of Cortisol-Selective Molecularly Imprinted Polymers Enabled by Molecular Dynamics Simulations. <i>ACS Appl. Bio Mater.</i> <b>2021,</b> <i>4</i> (9), 7243-7253.