Theoretical Studies of Cortisol-Imprinted Prepolymerization Mixtures: Structural Insights into Improving the Selectivity of Affinity Sensors

Abstract

The binding affinity of molecularly imprinted polymers (MIPs) relies on the mechanisms and the extent of the functional monomertemplate interactions present in the prepolymerization mixture. Thus, a clear understanding and optimizing the physiochemical parameters governing these interactions is key in designing and modeling MIPs with good selectivity. Quantum chemical method was applied here for the theoretical investigation into the interaction between cortisol and pyrrole in a molecularly imprinted prepolymerization mixtures. Since polypyrrole (PPy) is one of the most extensively used conducting polymers in design of bioanalytical sensors, pyrrole is chosen as a functional monomer. The pre-assembly system of possible conformations of cortisol/pyrrole monomer systems have been optimized with the use of density functional theory (DFT) at B3LYP/6-311G (d) level using Gaussian 09 software. The binding energy calculations of a range of structurally related steroids (cortisol, progesterone, prednisolone, 21-deoxycortisol and 6-methyprednisolone) with functional monomer have been analyzed through computational modelling. The most stable configurations of cortisol/functional monomer complexes have been optimized and selected. Based on the conformational analysis and the calculated binding energies of steroid/pyrrole molecular imprinted systems, we have concluded that the interactions between cortisol and pyrrole are more specific and stronger in comparison to the interactions between other steroid hormones (progesterone, prednisolone, 21-deoxycortisol and 6-methyprednisolone) and pyrrole. In the recent years, molecularly imprinted polymers (MIPs) have become one of the most useful materials for designing new analytical methodologies as they are selective molecular recognition phases. 1They are similar to immunosorbents in that MIPs can be tailored for different target analysis.2-4 During the molecular imprinting process highly cross-linked co-polymers are formed around analyte molecules acting as cavity-creating templates. After extractive removal of the template, the remaining molecularly imprinted polymer matrix contains 3-dimensional binding cavities facilitating rebinding due to complementary shape and functionality for the template molecule (Figure 1). Depending upon the nature of chemical bonds involved, MIPs synthesis techniques can be classified into two common approaches: (i) covalent imprinting and (ii) non-covalent imprinting. Non-covalent imprinting has been most widely adopted in many laboratories due its flexibility in choice of functional monomers and template molecules. The main non-covalent interactions responsible for molecular recognition in biomimetic systems are hydrogen bonding, ion-pairing, and π-π interactions. Hydrogen-bonding interactions is a strong interaction that plays a crucial role in biological recognition systems and in determining the structures of proteins and nucleic acids. The combination of utilizing strong hydrogen-bonding interactions with MIPs will create imprinted polymers wi...

Electropolymerized Molecularly Imprinted Polymer Synthesis Guided by an Integrated Data-Driven Framework for Cortisol Detection

“…The mainstay of this framework is a surrogate model, upon which tailored data analytics methods can be further employed to quantify the relationship between synthesis parameters of e-MIPs and resulting sensing performances, thereby providing guidelines for e-MIPs synthesis. As a proof-of-concept, cortisol (template)–pyrrole (monomer) system is selected in this research due to the following reasons: (1) cortisol, popularly called “stress hormone”, is a highly valuable biomarker to be measured for stress management and personalized health monitoring, (2) pyrrole is a widely used monomer for electropolymerization, and computational studies show that pyrrole can form more specific and stronger interaction with cortisol than other interfering steroid hormones (e.g., progesterone, prednisolone), (3) overoxidation of imprinted polypyrrole (PPy) can be used to extract cortisol from the polymer matrix, , which is more controllable and repeatable than other chemical removal methods. While there are various surrogate models available for elucidating the causative relation of input and output in the experimental data set, in this research, we used the Gaussian process (GP) because it is intrinsically probabilistic that it is capable of accounting for the effects of inevitable measurement variations and synthesis uncertainties when performing model training and prediction. , This tightly aligns with the stochastic nature of real-world problems.…”

Development of a Redox-Label-Doped Molecularly Imprinted Polymer on β-Cyclodextrin/Reduced Graphene Oxide for Electrochemical Detection of a Stress Biomarker

“…In contrast, electrochemical polymerization techniques offer a simple, one-step process of directly depositing an MIP on the electrode surface with a greater degree of control over polymer morphology . Computational studies have suggested that pyrrole-based polymers are suitable for fabricating cortisol-specific electrochemical MIP sensors. , The oxygen-containing electronegative functional groups present on the cortisol can interact with electropositive hydrogen attached to the nitrogen of pyrrole via hydrogen bonding, which helps in encapsulating cortisol in the polypyrrole (PPy) network during electropolymerization. Pyrrole can be electrochemically polymerized under ambient conditions, and the resulting PPy is stable and conductive in neutral pH, making it an excellent candidate for physiological MIPs and other sensing applications. , …”

Investigating the behaviors of corticosterone hormone in different solvents by using DFT calculations and experimental data

“…Reasonable correlations were found among the predicted IR, Raman and UV spectra with the corresponding experimental ones [56]. The calculations of gap values [54] and some descriptors were performed, as suggested by Parr and Pearson [59][60][61][62][63][64][65][66][67][68], because the prediction of reactivities and behaviours in the three media are of interest for this hormone with anti-inflammatory and immunosuppressive properties [20,21,23,27,[30][31][32][35][36][37][39][40][41][42][43][44].…”

“…The IUPAC name of corticosterone is (11β)-11,21-dihydroxypregn-4-ene-3,20-dione although it is also known as 11β,21-dihydroxyprogesterone or simply as 17-deoxycortisol . The adrenal gland produces this hormone with antiinflammatory and immunosuppressive properties [20,21,23,27,[30][31][32][35][36][37][39][40][41][42][43][44]. So far, there are a lot of articles related to structural, chemical and biological studies on glucocorticoids, from experimental studies by using spectroscopic and electrochemical techniques up to different theoretical studies because these species present dual regulation effects on the immune function which are strongly dependent on the concentration.…”

“…So far, there are a lot of articles related to structural, chemical and biological studies on glucocorticoids, from experimental studies by using spectroscopic and electrochemical techniques up to different theoretical studies because these species present dual regulation effects on the immune function which are strongly dependent on the concentration. Thus, experimental structures of corticosterone .and their derivatives were already reported [19,24,25,29] together with other theoretical studies on structure, descriptors and reactivity [22,26,37]. Additional studies on temperature effects in low-frequency Raman spectra and terahertz adsorption and Raman scattering were also reported for corticosteroid and mineralocorticoid hormones [33,34], respectively but, the complete vibrational assignments of corticosterone in the different media by using SQMFF methodology were no reported yet.…”