Electro-polymerized poly-methyldopa as a novel synthetic mussel-inspired molecularly imprinted polymeric sensor for darifenacin: Computational and experimental study

The massive progress in molecularly imprinted polymers has encouraged the inclusion of new molecules as functional monomers to attain more selective recognition. Herein and for the first time, methyldopa which is a promising dopamine synthetic analogue with multiple phenolic, carboxylic and aminic functional groups, was adopted for fabricating a highly selective molecularly imprinted polymer via a facile electro-polymerization approach. Firstly, a validated computational simulation was conducted based on density functional theory and Mulliken charges for screening binding affinity between the template drug, Darifenacin (DAR), and different monomers, namely; o-phenylenediamine, dopamine and methyldopa. Theoretically, the most stable complex with a binding energy of -170.29 kJ/mol was formed with methyldopa. Simulation analysis was also exploited to predict the optimum stoichiometric ratio between DAR and methyldopa where 1:4 was suggested as the appropriate one for polymer preparation. Such observations were then experimentally verified through UV-spectrophotometry and Job`s method in addition to 1H-NMR spectroscopy for identifying possible molecular interactions and binding sites. Poly-methyldopa (PMD) polymer was generated in presence of DAR, followed by electro-deposition of gold nanoparticles on a pencil graphite electrode substrate (AuNP@PMD/PGE). The fabricated electrode was thoroughly characterized by means of atomic force microscope, field-emission scanning electron microscope, X-ray photoelectron spectroscopy and cyclic voltammetry. Using differential pulse voltammetry, the sensor yielded a reproducible voltammetric response over a dynamic linearity range of 3.0 × 10−6 M - 5.0 × 10−5 M of DAR with a detection limit of 9.4 × 10−7 M. The high selectivity and sensitivity of the sensor towards the target analyte over various interfering components promoted its straightforward applicability in dosage form and spiked human plasma.