Improved Enantioselectivity for Atenolol Employing Pivot Based Molecular Imprinting

Abstract

In the last few decades, molecular imprinting technology went through a spectacular evolution becoming a well-established tool for the synthesis of highly selective biomimetic molecular recognition platforms. Nevertheless, there is still room for advancement in the molecular imprinting of highly polar chiral compounds. The aim of the present work was to investigate the favorable kosmotropic effect of a ternary complex involving a polar chiral template (eutomer of atenolol) and a functional monomer, bridged by a central metal ion through well-defined, spatially directional coordinate bonds. The efficiency of the chiral molecular recognition was systematically assessed on polymers obtained both by non-covalent and metal-mediated molecular imprinting. The influence on the chromatographic retention and enantioselectivity of different experimental variables (functional monomers, cross-linkers, chaotropic agents, metal ions, porogenic systems, etc.) were studied on both slurry packed and monolithic HPLC columns. Deliberate changes in the imprinting and rebinding (chromatographic) processes, along with additional thermodynamic studies shed light on the particularities of the molecular recognition mechanism. The best performing polymer in terms of enantioselectivity (α = 1.60) was achieved using 4-vinyl pyridine as functional monomer and secondary ligand for the Co(II)-mediated imprinting of S-atenolol in the presence of EDMA as cross-linker in a porogenic mixture of [BMIM][BF4]:DMF:DMSO = 10:1:5, v/v/v.

Perspectives of Molecularly Imprinted Polymer-Based Drug Delivery Systems in Ocular Therapy

“…In developing ocular drug delivery systems various aspects of the conventional molecular imprinting process need to be carefully adapted for the intended application field and preferred therapeutic strategy, but also aligned to the pharmaceutical requirements and regulations. MIPs have been initially developed for and employed mainly in analytical applications, as stationary phases/selective sorbents in separations sciences [29] and more recently as interfaces in the development of (bio)chemical sensors. The main feature which differentiated them from the traditional stationary phases/interfaces was their predetermined ligand selectivity, induced during the synthesis process.…”

“…Alternative molecular imprinting strategies, such as metal-ion mediated imprinting, are able to increase the degree of order throughout the polymerization step by welldefined, spatially-directional coordinate bonds [29]. This kosmotropic effect leads to imprinted cavities of higher fidelity, and even to mimic the active sites of enzymes.…”

Synthesis of Atenolol-Imprinted Polymers with Methyl Methacrylate as Functional Monomer in Propanol Using Bulk and Precipitation Polymerization Method

“…Methyl methacrylate is a functional monomer that can act as a hydrogen bond acceptor to its template [4]. Other researchers have done research on MI-SPE for atenolol [5–7], but none of them used precipitation polymerization as we used in this study, and the recoveries are below 80%. The porogen chosen in this study is propanol because it has low polarity that can reduce interference during the polymerization process and increase the number of MIP-binding sites [8].…”

Enantioselective Synthesis, Enantiomeric Separations and Chiral Recognition

“…This Special Issue is aimed at offering an opportunity to all the contributors to make their results and techniques more visible, and to present the most recent findings. This Special Issue has received remarkably positive feedback, with many contributions submitted by numerous geographically diverse scientists, resulting in a collection of 19 publications, including six exhaustive review articles [2][3][4][5][6][7], and thirteen original articles [8][9][10][11][12][13][14][15][16][17][18][19][20]. Among the contributing authors, we can find countries of origin such as Algeria, Australia, Brazil, Canada, China, Croatia, Czech Republic, Egypt, India, Italy, Japan, Portugal, Romania, Russia, and Taiwan.…”

“…Molecular imprinting technology is a well-established tool for the synthesis of highly selective biomimetic molecular recognition platforms. One article reports the improvement in chiral selectivity of the important β-blocker atenolol by the addition of a metal pivot versus the traditional molecular imprinted polymer formulation [12].…”