MOLECULAR IMPRINTING OF A HYDROPHYLIC BETA-BLOCKER, ATENOLOL, FOR CHIRAL SENSING AND SEPARATION: BETWEEN FAILURE AND SUCCESS

Even though over the last few decades molecularly imprinted polymers (MIPs) became well-established analytical tools for the selective recognition of small molecules, there is still some knowledge gaps to fill in the molecular imprinting of highly polar compounds and biomacromolecules. One of the great potential and in the meantime considerable challenge of these engineered polymeric materials lays in the differentiation between chiral forms of a target molecule, as the supreme form of molecular recognition.

In our studies, atenolol, the most hydrophilic representative of the beta-blockers, was chosen as model template, searching for the most efficient molecular imprinting strategy for the fabrication of MIP-based chiral electrochemical sensing platforms, as well as, of cost-effective enantioselective stationary phases.

As a first approach, the development of a MIP-based chiral electrochemical sensor has been considered given the electroactive nature of beta-blockers due to the alcoholic moiety bound directly to the asymmetric carbon. Different non-covalent imprinting protocols adapted to the electrodeposition of ultra-thin, conductive (2,2’-bithiophene) and non-conductive (methacrylic acid) MIP-based recognition layers for the fabrication of chiral electrochemical sensors were investigated. Particularities of the surface conditioning and available electrochemical detection modes (direct and indirect) on the molecular recognition mechanism have been pointed out, demonstrating a simultaneous selectivity of the sensor towards the R-antipodes of four β-blocker representatives.

As for the elaboration of chiral MIP-based stationary phases for liquid chromatography and capillary electrochromatography, apart from the conventional non-covalent approach, additional strategies such as metal ion-mediated imprinting both as a bulk or monolith were tested. The influence of various experimental parameters (functional monomer, metal ion, crosslinker, molar ratio of constituents, porogen, ionic liquids, type of radical initiation, etc.) able to influence the formation of a stable and soluble ternary metal complex involving both the polar chiral template and the functional monomer, as well as the imprinting efficiency and polymer porosity were critically assessed. Optical and electron spectroscopic techniques were used for monitoring the influence of different variables before and after the polymerization process.

Aknowledgements: Work supported by “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca through internal grants no. 4944/11/08.03.2016 and 4945/19/08.03.2016.