Optimization of Cortisol-Selective Molecularly Imprinted Polymers Enabled by Molecular Dynamics Simulations
Optimization of Cortisol-Selective Molecularly Imprinted Polymers Enabled by Molecular Dynamics Simulations
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DOI：
10.1021/acsabm.1c00774
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发表时间：
2021-08-19
影响因子：
4.7
通讯作者：
Leese, Hannah S.
中科院分区：
文献类型：
--
作者：
Daniels, Emma;Mustafa, Yasemin L.;Leese, Hannah S.
如今，我们严重依赖技术，并越来越多地利用它来监测自身健康。识别灵敏、准确且能够进行实时皮质醇分析的生物传感器，是这些技术帮助我们维持身心健康的一个重要潜在特征。皮质醇是一种存在于汗液中的著名应激生物标志物，对其进行检测和定量，为监测焦虑提供了一种非侵入性且可能实时的方法。分子印迹聚合物是此类设备中皮质醇识别元件的有吸引力的候选材料，因为它们能够选择性地重新结合目标模板分子。然而，印迹机制以及随后的重新结合取决于预聚合混合物的选择和组成，而模板、功能单体、交联剂和溶剂分子之间的分子相互作用尚未完全被理解。在此，我们报道了一种对皮质醇检测具有选择性的分子印迹聚合物的合成与评估。分子动力学模拟被用于研究所合成的分子印迹聚合物的预聚合混合物中所有成分之间的相互作用。改变预聚合混合物的成分比例表明，交联剂分子相对于模板的数量会影响印迹质量。经确定，皮质醇、甲基丙烯酸和乙二醇二甲基丙烯酸酯的成分比例分别为1∶6∶30时，在所研究的聚合物体系中产生皮质醇的最佳理论络合。实验合成和重新结合结果表明印迹因子高达6.45。通过对那些模拟的分子印迹组成进行实验分析，也证实了预聚合混合物分子动力学模拟所预测的皮质醇亲和力趋势，展示了这些模拟的预测能力。
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.