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Highlights • Chiral derivatization with (+)-FLEC was employed for all proteinogenic amino acids. • The selectivity of two phenyl stationary phases was compared. • Phenyl-based stationary phases are suitable for achieving diastereoselectivity. • Mobile phase pH has a tremendous influence on resolution. Abstract D-amino acids (AA) analysis is becoming more and more relevant for metabolomics, therefore new analytical tools need to be developed. A common approach to achieve AA enantioseparation is chiral derivatization. Among the chiral derivatization reagents, (+) or (-)-1-(9-fluorenyl) ethyl chloroformate ((+) or (-)-FLEC) has proved to be one of the most versatile. Suitable chiral selectivity for FLEC derivatives of amino acids could be obtained in reversed-phase HPLC using nonpolar stationary phases (C4, C8 and C18) and tetrahydrofuran (THF) based mobile phases. This study is meant to provide alternatives to the use of THF as organic modifier by evaluating the selectivity obtained on two phenyl based stationary phases for 19 FLEC-DL-AA pairs of diastereomers using UHPLC-MS. Several mobile phases consisting of ammonium acetate and different common organic solvents (acetonitrile (ACN), methanol (MeOH), 2-propanol (IPA)) were tested using gradient elution. Experimental design was employed for the optimization of the separation conditions. In the optimized conditions, complete chiral separation can be achieved for 18 out of 19 FLEC-DL-AAs in less than 30 min. [ABSTRACT FROM AUTHOR]

A targeted CE-MS approach was developed for the chiral analysis of biologically relevant amino acids in artificial cerebrospinal fluid (aCSF). In order to achieve chiral resolution, the five amino acids (Ser, Asn, Asp, Gln and Glu) were derivatized with (+)-1-(9-fluorenyl)ethyl chloroformate ((+)-FLEC). The diastereoselectivity was found to be highly dependent on pH for all analytes and the optimized background electrolyte (BGE) consisted of 150 mM acetic acid, adjusted to pH 3.7 with NH 4 OH. Furthermore, a reversal of the migration order of Asp derivatives was observed. This phenomenon seems to be caused by intra-molecular interactions affecting the pK a of the second ionizable group (the side chain carboxyl). The applicability of this method was evaluated using aCSF. A solid phase extraction (SPE) protocol was developed for the selective extraction of the FLEC derivatives. A full evaluation of the matrix effect and extraction yield was performed concluding that the matrix effect is marginal and the recoveries are between 46 and 92%. The method offers adequate sensitivity (limits of detection below 1 μM). [ABSTRACT FROM AUTHOR]

Over the last 30 years, (±)-1-(9-fluorenyl)ethyl chloroformate ((±)-FLEC) was used as a chiral derivatizing agent in various analytical applications involving a wide range of endogenous, pharmaceutical and environmentally relevant molecules. This comprehensive review aims to present all the significant aspects related to the state of the art in FLEC labeling and subsequent chiral separation of the resulting diastereomers using LC, SFC and CE techniques. [ABSTRACT FROM AUTHOR]

This study is focused on the molecular recognition mechanism of a methacrylate-based R (+)-atenolol molecularly imprinted polymer (MIP), employed as a chiral sensing interface in the construction of a novel electrochemical sensor. The MIP was electrogenerated as an ultrathin-film onto the surface of a carbon paste working electrode under potentiodynamic conditions in a non-aqueous media. Differential pulse voltammetry served as signal transduction method for the direct and indirect (by means of two redox probes, [Fe(CN) 6 ] 3−/4− and 1,1′-ferrocene dimethanol, respectively) detection of the underlying molecular recognition process. The rebinding of the template enantiomer led to changes in solute permeability of the MIP-layer, indicating the presence of a “gate effect” as part of the molecular recognition process. [ABSTRACT FROM AUTHOR]

In the context of bioanalytical method development, process automatization is nowadays a necessity in order to save time, improve method reliability and reduce costs. For the first time, a fully automatized micellar electrokinetic chromatography–mass spectrometry (MEKC-MS) method with in-capillary derivatization was developed for the chiral analysis of d - and l -amino acids using (−)-1-(9-fluorenyl) ethyl chloroformate (FLEC) as labeling reagent. The derivatization procedure was optimized using an experimental design approach leading to the following conditions: sample and FLEC plugs in a 2:1 ratio (15 s, 30 mbar: 7.5 s, 30 mbar) followed by 15 min of mixing using a voltage of 0.1 kV. The formed diastereomers were then separated using a background electrolyte (BGE) consisting of 150 mM ammonium perfluorooctanoate (APFO) (pH = 9.5) and detected by mass spectrometry (MS). Complete chiral resolution was obtained for 8 amino acids, while partial separation was achieved for 6 other amino acid pairs. The method showed good reproducibility and linearity in the low micromolar concentration range. The applicability of the method to biological samples was tested by analyzing artificial cerebrospinal fluid (aCSF) samples. [ABSTRACT FROM AUTHOR]

Background and aim. Beta-adrenergic antagonists have been established as first line treatment in the medical management of hypertension, acute coronary syndrome and other cardiovascular diseases, as well as for the prevention of initial episodes of gastrointestinal bleeding in patients with cirrhosis and esophageal varices, glaucoma, and have recently become the main form of treatment of infantile hemangiomas. The aim of the present study is to calculate for 14 beta-blockers several quantum chemical descriptors in order to interpret various molecular properties such as electronic structure, conformation, reactivity, in the interest of determining how such descriptors could have an impact on our understanding of the experimental observations and describing various aspects of chemical binding of beta-blockers in terms of these descriptors. Methods. The 2D chemical structures of the beta-blockers (14 molecules with one stereogenic center) were cleaned in 3D, their geometry was preoptimized using the software MOPAC2012, by PM6 method, and then further refined using standard settings in MOE; HOMO and LUMO descriptors were calculated using semi-empirical molecular orbital methods AM1, MNDO and PM3, for the lowest energy conformers and the quantum chemical descriptors (HLG, electronegativity, chemical potential, hardness and softness, electrophilicity) were then calculated. Results. According to HOMO-LUMO gap and the chemical hardness the most stable compounds are alprenolol, bisoprolol and esmolol. The softness values calculated for the study molecules revolve around 0.100. Propranolol, sotalol and timolol have among the highest electrophilicity index of the studied beta-blocker molecules. Results obtained from calculations showed that acebutolol, atenolol, timolol and sotalol have the highest values for the electronegativity index. Conclusions. The future aim is to determine whether it is possible to find a valid correlation between these descriptors and the physicochemical behavior of the molecules from this class. The HLG could be correlated to the experimentally recorded electrochemical properties of the molecules. HOMO could be correlated to the observed oxidation potential, since the required voltage is related to the energy of the HOMO, because only the electron from this orbital is involved in the oxidation process. [ABSTRACT FROM AUTHOR]

Colchicine, as one of the most ancient drugs of human kind, is still in the focal point of the current research due to its multimodal mechanism of action. The elucidation of colchicine’s still unknown redox properties may play an important role in deciphering its beneficial and harmful implications over the human body. Therefore, a systematic mechanistic study of colchicine’s oxidation has been undertaken by electrochemistry coupled to mass spectrometry using two different types of electrolytic cells, in order to clarify the existing inconsistencies with respect to this topic. At around 1 V vs. Pd/H 2 , initiated by a one-electron transfer, the oxidation of colchicine sets off leading to a cation radical, whose further oxidation may evolve on several different pathways. The main product of the anodic electrochemical reaction, regardless of the carrier solution’s pH is represented by a 7-hydroxy derivative of colchicine. At more anodic potentials (above 1.4 V vs. Pd/H 2 ) compounds arising from epoxidation and/or multiple hydroxylation occur. No di- or tridemethylated quinone structures, as previously suggested in the literature for the electrolytic oxidation of colchicine, has been detected in the mass spectra. [ABSTRACT FROM AUTHOR]

Electrochemistry/mass spectrometry (EC/MS) using two different types of electrolytic cells was employed for the systematic mechanistic study of colchicine's reduction, both in aqueous and non-aqueous media. In aqueous media, at around − 1 V vs. Ag/AgCl, colchicine suffers a single-electron reduction to a transient anion radical, which after a follow-up protonation leads to a neutral free radical (E r C i mechanism). Depending on the experimental conditions, the latter undergoes some dimerization. At more negative potentials (− 1.4 V vs. Ag/AgCl) and pH < 7, the free radical is undergoing another single-electron reduction and a subsequent protonation. In the absence of protons (aprotic media), the one-electron reduction gives the anion radical. This process becomes fully reversible at high scan rates (≥ 10 V/s). [ABSTRACT FROM AUTHOR]

The development of a chiral electrochemical sensor using an electrogenerated molecularly imprinted polymer (MIP)-based ultrathin film using R(+)-atenolol (ATNL) as a template was reported. The proposed sensor exhibited distinctive enantiospecific oxidation peaks toward the R-antipodes of four β-blocker representatives and additional oxidation peaks common to both enantiomers of each studied β-blocker, allowing thus the simultaneous analysis of all of their enantiomers in a single analysis. The specific preconditioning of the polymer by alternative exposure to aqueous and nonaqueous medium was proven to be essential for the chiral recognition ability of the obtained sensor. The rebinding property of the MIP film was studied by using a well-known redox probe, a change in the morphology and diffusive permeability of the thin polymeric layer in the presence of its template being observed. The applicability of the optimized analytical procedure was demonstrated by the analysis of ATNL's enantiomers in the range of 1.88 × 10-7-1.88 × 10-5 mol/L. The developed polymeric interface is the first reported transductor of a chiral electrochemical sensor able to exhibit simultaneous enantiospecificity toward several β-blocker representatives extensively used in the pharmaceutical and biomedical fields, offering good prospects in the simple, cost-effective, and fast assessment of their enantiomeric ratio and total concentration. [ABSTRACT FROM AUTHOR]

Abstract: A simple, fast and accurate method of chiral recognition and quantification of propranolol enantiomers by surface enhanced Raman scattering (SERS) and multivariate regression analysis through supramolecular interaction with β-cyclodextrin is reported. Computational chemistry served as a tool of elucidating the underlying mechanism of molecular interactions responsible for chiral discrimination. The influence of several factors (nature and concentration of chiral auxiliary, selector-selectand ratio, pH, interaction time, etc.) over the obtained SERS spectra was assessed, followed by the construction of the chemometric model with the optimized operational conditions. The performance of the obtained semi-empirical model was established using a validation set of pure enantiomers and its intended use was demonstrated by the assessment of the enantiomeric excess of propranolol in pharmaceutical formulations (tablets) without the need of tedious and expensive chiral separation. The obtained results were also confirmed by chiral high-performance liquid chromatography. [Copyright &y& Elsevier]

The separation and UV absorbance detection of colchicine by three different capillary electrophoretic methods is described. Colchicine is known as a neutral compound, being able to be determined by electrokinetic chromatography. For the first time, a non-aqueous capillary electrophoretic method is described, based on the electromigration of ionized colchicine induced by 10 mM HClO4 in a mixture of methanol:acetonitrile (1:2, v/v) containing 60 mM ammonium formiate, opening up new perspectives in the trace analysis of the highly toxic drug from clinical and food samples using online coupling of the CE system to a mass spectrometer. For the quantitative assessment of colchicine content from meadow saffron (Colchicum autumnale L.) seeds and 1 mg colchicine tablets, a simple, quick and sensitive micellar electrokinetic chromatographic method was developed and fully validated according to ICH guidelines in terms of selectivity, linearity, accuracy, intermediate precision and limits of detection and quantification (95.2 ng mL-1). In order to further improve the detection limits, allowing the analysis of trace levels of colchicine in biosamples and food products, an on-column preconcentration using sweeping-MEKC was investigated. Linearity of response was observed on 10-160 ng mL-1 colchicine, with an estimated detection limit of around 3 ng mL-1 colchicine. By further improving the affinity of the separation vector towards colchicine this limit could be further decreased. Preliminary application of the method for the detection of trace amounts of colchicine spiked in non-fat milk and human urine (10 ng mL-1 ) shows encouraging results. [ABSTRACT FROM AUTHOR]

Antioxidant therapies are of interest in the prevention and management of ocular disorders such as cataracts. Although an active area of interest, topical therapy with antioxidants for the treatment of cataracts is complicated by multiple ocular anatomical barriers, product stability, and solubility. Entrapment and delivery of antioxidants with poly(lactic-co-glycolic acid) nanoparticles is a possible solution to these challenges, however, little is known regarding their effects in vitro or in vivo. Our first aim was to investigate the impact of blank and lutein loaded PLGA nanoparticles on viability and development of reactive oxygen species in lens epithelial cells in vitro. Photo-oxidative stress was induced by ultraviolet light exposure with cell viability and reactive oxygen species monitored. Next, an in vivo, selenite model was utilized to induce cataract formation in rodents. Eyes were treated topically with both free lutein and lutein loaded nanoparticles (LNP) at varying concentrations. Eyes were monitored for the development of anterior segment changes and cataract formation. The ability of nanodelivered lutein to reach the anterior segment of the eye was evaluated by liquid chromatography coupled to mass spectrometry of aqueous humor samples and liquid chromatography coupled to tandem mass spectrometry (targeted LC-MS/MS) of lenses. LNP had a minimal impact on the viability of lens epithelial cells during the short exposure timeframe (24 h) and at concentrations < 0.2 μg LNP/μl. A significant reduction in the development of reactive oxygen species was also noted. Animals treated with LNPs at an equivalent lutein concentration of 1,278 μg /mL showed the greatest reduction in cataract scores. Lutein delivery to the anterior segment was confirmed through evaluation of aqueous humor and lens sample evaluation. Topical treatment was not associated with the development of secondary keratitis or anterior uveitis when applied once daily for one week. LNPs may be an effective in the treatment of cataracts. [ABSTRACT FROM AUTHOR]

Molecularly imprinted polymers (MIPs) are established artificial molecular recognition platforms with tailored selectivity towards a target molecule, whose synthesis and functionality are highly influenced by the nature of the solvent employed in their synthesis. Steps towards the "greenification" of molecular imprinting technology (MIT) has already been initiated by the elaboration of green MIT principles; developing MIPs in a solvent-free environment may not only offer an eco-friendly alternative, but could also significantly influence the affinity and expected selectivity of the resulting binding sites. In the current study the first solvent-free mechanochemical synthesis of MIPs via liquid-assisted grinding (LAG) is reported. The successful synthesis of the imprinted polymer was functionally demonstrated by measuring its template rebinding capacity and the selectivity of the molecular recognition process in comparison with the ones obtained by the conventional, non-covalent molecular imprinting process in liquid media. The results demonstrated similar binding capacities towards the template molecule and superior chemoselectivity compared to the solution-based MIP synthesis method. The adoption of green chemistry principles with all their inherent advantages in the synthesis of MIPs may not only be able to alleviate the potential environmental and health concerns associated with their analytical (e.g., selective adsorbents) and biomedical (e.g., drug carriers or reservoirs) applications, but might also offer a conceptual change in molecular imprinting technology. [ABSTRACT FROM AUTHOR]

Synthetic cathinones (SCs) are a group of new psychoactive substances often referred to as "legal highs" or "bath salts", being characterized by a dynamic change, new compounds continuously emerging on the market. This creates a lack of fast screening tests, making SCs a constant concern for law enforcement agencies. Herein, we present a fast and simple method for the detection of four SCs (alpha-pyrrolidinovalerophenone, N-ethylhexedrone, 4-chloroethcathinone, and 3-chloromethcathinone) based on their electrochemical profiles in a decentralized manner. In this regard, the voltametric characterization of the SCs was performed by cyclic and square wave voltammetry. The elucidation of the SCs redox pathways was successfully achieved using liquid chromatography coupled to (tandem) mass spectrometry. For the rational identification of the ideal experimental conditions, chemometric data processing was employed, considering two critical qualitative and quantitative variables: the type of the electrochemical platform and the pH of the electrolyte. The analytical figures of merit were determined on standard working solutions using the optimized method, which exhibited wide linear ranges and LODs suitable for confiscated sample screening. Finally, the performance of the method was evaluated on real confiscated samples, the resulting validation parameters being similar to those obtained with another portable device (i.e., Raman spectrometer). [ABSTRACT FROM AUTHOR]

In the interest of developing and characterizing a polymeric nanoparticle pesticide delivery vehicle to soybeans, zein nanoparticle (ZNP) uptake by the roots and biodistribution to the leaves of soybean plants was measured. Zein was tagged with fluorescein isothiocyanate (FITC) and made into nanoparticles (135 ± 3 nm diameter. 0.202 ± 0.034 PDI and 81 ± 4 mV zeta-potential at pH 6) using an emulsion-diffusion method. After 10 days of hydroponic exposure, association between particles and roots of plants was found to vary based on bulk nanoparticle concentration. While 0.37 mg NP/mg dry weight were detected in roots immersed in 0.88 mg NP/mL nanoparticle suspension, 0.58 mg NP/mg dry weight associated with roots immersed in a high dose nanoparticle suspension of 1.75 mg NP/mL at 10 days. Nanoparticle root uptake followed second order kinetics. A small amount of increased fluorescence was detected in the hydroponically exposed plant's leaves, suggesting that either small amounts of particles or other fluorescent contaminants of zein were up taken by the roots and biodistributed within the plant. To the authors' knowledge, this is the first study in which the uptake and time-dependent association between polymeric nanoparticles and soybeans are quantified. [ABSTRACT FROM AUTHOR]

The topical administration of medicines is the preferred route in ocular therapy, at least for the anterior segment of the eye. However, the eye's inherent functional and biological barriers all work against the active pharmaceutical ingredient (API) to efficiently reach the targeted retinal structures. The main objective of this article is to offer a systematic review of the scientific literature in recent years, focusing on the latest developments of topical treatment intended for retinal degenerative diseases. Database search returned 102 clinical studies, focused on topical treatment for age macular degeneration, macular edemas (in diabetic retinopathy, surgery related or in retinal dystrophies) or glaucoma. After the exclusion of low-powered studies and those combining vitreo-retinal surgery, 35 articles remained for analysis. Currently, the topical treatment of retinal degenerative diseases is limited by the difficulty to deliver effective drug concentrations to the posterior eye structures. However, in the case of drug classes like NSAIDs, the presence of certain molecular and metabolic features for specific representatives makes the topical administration currently feasible in several clinical contexts. For other drug classes, either a fine-tuning of the API's pharmacokinetic profile or the use of more advanced formulation strategies, such as rationally designed nanostructured drugs and vehicles, crystalline polymorphs or supramolecular complexes, could bring the much awaited breakthrough for a more predictable and controlled delivery towards the retinal structures and could eventually be employed in the future for the development of more effective ways of delivering drugs to the posterior eye, with the ultimate goal of improving their clinical efficacy. [ABSTRACT FROM AUTHOR]

(1) Background: The current limitations of glioblastoma (GBM) chemotherapy were addressed by developing a molecularly imprinted polymer (MIP)-based drug reservoir designed for the localized and sustained release of ruxolitinib (RUX) within the tumor post-resection cavity, targeting residual infiltrative cancerous cells, with minimum toxic effects toward normal tissue. (2) Methods: MIP reservoirs were synthesized by precipitation polymerization using acrylamide, trifluoromethacrylic acid, methacrylic acid, and styrene as monomers. Drug release profiles were evaluated by real-time and accelerated release studies in phosphate-buffered solution as a release medium. The cytotoxicity of polymers and free monomers was evaluated in vitro on GBM C6 cells using the Alamar Blue assay, optical microscopy, and CCK8 cell viability assay. (3) Results: Among the four synthesized MIPs, trifluoromethacrylic acid-based polymer (MIP 2) was superior in terms of loading capacity (69.9 μg RUX/mg MIP), drug release, and efficacy on GBM cells. Accelerated drug release studies showed that, after 96 h, MIP 2 released 42% of the loaded drug at pH = 7.4, with its kinetics fitted to the Korsmeyer–Peppas model. The cell viability assay proved that all studied imprinted polymers provided high efficacy on GBM cells. (4) Conclusions: Four different drug-loaded MIPs were developed and characterized within this study, with the purpose of obtaining a drug delivery system (DDS) embedded in a fibrin-based hydrogel for the local, post-surgical administration of RUX in GBM in animal models. MIP 2 emerged as superior to the others, making it more suitable and promising for further in vivo testing. [ABSTRACT FROM AUTHOR]

The high affinity and/or selectivity of oligonucleotide-mediated binding offers a myriad of therapeutical and analytical applications, whose rational design implies an accurate knowledge of the involved molecular mechanisms, concurring equilibrium processes and key affinity parameters. Oligonucleotide-functionalized gold surfaces or nanostructures are regularly employed analytical platforms for the development of label-free optical or electrochemical biosensors, and recently, novel detection platform designs have been increasingly considering the synergistic effect of polyvalent binding, involving the simultaneous interaction of two or several oligonucleotide strands. Considering the general lack of studies involving ternary single-stranded DNA (ssDNA) interactions, a complementary analytical workflow involving capillary gel electrophoretic (CGE) mobility shift assay, microcalorimetry and computational modeling has been deployed for the characterization of a series of free and surface-bound binary and ternary oligonucleotide interactions. As a proof of concept, the DNA analogue of MicroRNA 21 (miR21), a well-known oncogenic short MicroRNA (miRNA) sequence, has been chosen as a target molecule, simulating limiting-case scenarios involved in dual molecular recognition models exploited in affinity (bio)sensing. Novel data for the characterization of oligonucleotide interacting modules is revealed, offering a fast and complete mapping of the specific or non-specific, often competing, binary and ternary order interactions in dynamic equilibria, occurring between various free and metal surface-bound oligonucleotides. [ABSTRACT FROM AUTHOR]

Molecularly imprinted polymers (MIPs) have been proven to be a promising candidate for drug delivery systems (DDS) due to their ability to provide a sustained and controlled drug release, making them useful for treating a wide range of medical conditions. MIP-based DDS offer many advantages, including the administration of a smaller drug doses, due to the higher drug payload or targeted delivery, resulting in fewer side effects, as well as the possibility of attaining high concentrations of the drug in the targeted tissues. Whether designed as drug reservoirs or targeted DDS, MIPs are of great value to drug delivery as conventional drug formulations can be redesigned as DDS to overcome the active pharmaceutical ingredient's (APIs) poor bioavailability, toxic effects, or other shortcomings that previously made them less efficient or unsuitable for therapy. Therefore, MIP design could be a promising alternative to the challenging research and development of new lead compounds. Research on MIPs is primarily conducted from a material science perspective, which often overlooks some of their key pharmaceutical requirements. In this review, we emphasize the specific features that make MIPs suitable for clinical use, from both a material science and a biopharmaceutical perspective. [ABSTRACT FROM AUTHOR]

Simultaneous electrophoretic separation of inorganic anions and cations from ground waters by dual opposite end injection and their capacitively coupled contactless conductometric detection is described. The chemometry assisted method development revealed that using this type of detection, apart from many advantages, implies a careful fine tuning of experimental variables. Proper choice of buffer components is the most critical aspect of the recorded signal's quality and the obtained resolution, where minor changes could lead to major changes in the recorded electropherograms. From a big variety of acidic and basic electrolytes, a pyromellitic acid/citric acid based buffer (pH = 3.70) was chosen for the baseline separation of 11 cations and anions in a single, less than 3 min run, using a PVA coated fused silica capillary. The estimated limits of detection (0.07–2 ppm) and defined limits of quantification (0.3–7 ppm) were comparable or better than those described for indirect UV detection, allowing much broader linear ranges (up to 120 ppm) for most of the studied ions. Following method validation the method was successfully applied for the assessment of inorganic ion content of 51 geotagged drinking water (domestic well) samples collected from the rural area of Cluj County, Romania, and correlations between sample composition and their geographical origin were identified by multivariate data analysis. [ABSTRACT FROM AUTHOR]

• Both enantiomers of cysteine tested as surface bound diastereoisomeric selectors in chiral electrochemical sensing. • Unexpected change in electrochemical enantioselectivity upon the exchange of the surface-bound chiral selector's antipode is recorded. • Dual chiral systems are not a straightforward solution for enantioselectivity enhancement. • Normalized peak current ratios showed better enantiodiscrimination of propranolol compared to the raw peak potential/current changes. • Important differences in the heterogeneous electron transfer rate constant on the l-cysteine modified electrode were observed after the adsorption of propranolol enantiomers. The present study aims to explore the interaction mechanisms between propranolol (PRNL) enantiomers and bare and L/D-Cysteine modified gold nanoparticles (L/D-Cys−AuNPs) surfaces, using electrochemical (cyclic voltammetry, differential pulse voltammetry, electrochemical impedance spectroscopy) and microcalorimetric (isothermal titration calorimetry) techniques. In the absence of a chiral environment, PRNL enantiomers are strongly physisorbed on the AuNPs modified surface, yet no significant difference was recorded in the oxidation peak potential (+0.778 V R(+)-PRNL versus +0.78 V for S(-)-PRNL). Upon decorating AuNPs with l-Cys, an ∼40 mV anodic shift is recorded for S(-)-PRNL due to a more favored orientation of its diastereoisomer on the electrode's surface towards electron transfer. Interestingly, by altering the conformation of the diastereoisomeric chiral selector (replacing l-Cys with d-Cys), the enantioselective nature of the recorded electrochemical signals fades out. Additionally, the potential synergistic effects of a dual chiral system, based on the covalently bound l-/D-Cys−AuNPs and β-cyclodextrin (β-CD), a free, host-guest type chiral selector, added to the electrolyte, has also been studied. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract: Magnetised silica-based microparticles (MMPs) (5μm) with a high density of nanopores were used for horseradish peroxidase (HRP) immobilization and amperometric biosensor development in batch conditions. The resulting biosensor was applied to study the peroxidation of clozapine (CLZ) which is a dibenzoazepine drug often used in the treatment of neurological disorders. The amperometric response corresponded to the electroreduction of CLZ-oxidized products namely a nitrenium cation and quinoneimine derivative of CLZ. Despite a relatively low amount of immobilized HRP (0.3μmol/g), clozapine quantification in the micromolar concentration range was achieved by the use of a magnetized solid paraffin carbon paste electrode for microparticles attraction. Diffusion of substrate and products of the enzyme reaction within the nanopores were identified as limiting factors in the biosensor response. This amperometric biosensor configuration has number of interesting advantages such as ease and reproducible microparticle layer renewing, low enzyme consumption, controlled surface immobilization, protective enzyme microenvironment etc. [Copyright &y& Elsevier]

This study presents a novel electrochemical (EC) methodology for activating the SERS features of disposable silver screen-printed electrodes (AgSPEs) using a pseudohalide as a precipitating agent to guide the assembly of a nano-filamentous silver network responsible for a strong SERS enhancement. To the best of our knowledge, the use of thiocyanate for SPEs activation for quantitative purposes has not been reported before. In order to better study this complex system, time-resolved (TR) operando spectroelectrochemistry (SEC) measurements were performed by SERS and UV-Vis and correlated with SEM imaging of the electrode surface at different steps. Moreover, to significantly increase the reproducibility of the assays, a rapid EC protocol was proposed for the first time to obtain a reliable Ag/AgSCN reference electrode (RE) and a comprehensive optimization process was conducted to determine the critical parameters. Additionally, propranolol, as an emerging pharmaceutical pollutant has been selected as a model molecule to demonstrate the applicability of the method for rapid (3 min) quantitative analysis in the nM range from real river and tap water samples. [Display omitted] • KSCN as precipitating agent and critical control factor. • Insights provided by operando Raman and UV-Vis measurements. • Improved reproducibility with Ag/AgSCN reference electrode. • New methodology for AgSPEs activation for quantitative purposes. • In situ EC-assisted SERS nM detection of propranolol in tap and river water. [ABSTRACT FROM AUTHOR]

Despite the considerable effort made in the past decades, multiple aspects of cancer management remain a challenge for the scientific community. The severe toxicity and poor bioavailability of conventional chemotherapeutics, and the multidrug resistance have turned the attention of researchers towards the quest of drug carriers engineered to offer an efficient, localized, temporized, and doze-controlled delivery of antitumor agents of proven clinical value. Molecular imprinting of chemotherapeutics is very appealing in the design of drug delivery systems since the specific and selective binding sites created within the polymeric matrix turn these complex structures into value-added carriers with tunable features, notably high loading capacity, and a good control of payload release. Our work aims to summarize the present state-of-the art of molecularly imprinted polymer-based drug delivery systems developed for anticancer therapy, with emphasis on the particularities of the chemotherapeutics' release and with a critical assessment of the current challenges and future perspectives of these unique drug carriers. [ABSTRACT FROM AUTHOR]

Unfortunately the name of Jean Jacques Vanden Eynde was missing as co-author of this contribution. The correct list of authors is: Ioan O. Neaga, Stephanie Hambye, Ede Bodoki, Claudio Palmieri, Jean Jacques Vanden Eynde, Eugénie Ansseau, Alexandra Belayew, Radu Oprean, Bertrand Blankert. [ABSTRACT FROM AUTHOR]

Abstract Design of nanostructured systems for pesticide delivery allows the implementation of a rational and sustainable use of these chemicals. Zein nanoparticles (ZNPs) enable extended foliar adhesion, as well as prolonged and controlled release of the entrapped agrochemical. The present study aimed to investigate degradation of ZNPs with various surface properties under environmentally relevant conditions. Accelerated degradation studies were performed on freeze-dried ZNPs synthesized with different cationic and non-ionic surfactants. These polymeric particles dispersed in alkaline media (pH = 9) revealed hydrodynamic diameters ranging between 210.6 and 297.3 nm and negative surface charges from −44.3 mV to −34.56 mV. Degradation profiles of the studied particles were assessed within the pH limits of soils under agricultural exploitation (pH 4 and 9). The time-dependent decrease of the parent protein fractions was monitored by capillary gel electrophoresis, where the rate constants of the hydrolytic degradation allows the estimation of ZNPs' persistence at any temperature of interest. Results showed that in alkaline media promotes a faster chemical degradation of ZNPs (total at 20 °C in ∼3918 days at pH = 4 vs. 205 days at pH = 9), however the nature of the used surfactant may completely reverse the observed trend. Identifying the technological variables that impact their surface chemistry and susceptibility towards hydrolytic degradation, opens new perspectives in the programmed degradation of ZNPs, which may ensure a safer and more sustainable use of these nanodelivery systems. Although chemometric models were able to assess quantitative correlations between recorded physical properties of the ZNPs and the estimated time necessary for their full degradation, further studies are needed to elucidate the causality between the nature of used surfactants and estimated degradation times in aqueous media. Highlights • Up to date no data on the fate and environmental impact of zein nanoparticles (ZNPs) was available. • A better insight on the wear down of the ZNPs under environmentally relevant conditions is provided. • In general, alkaline media promotes a faster hydrolytic degradation of ZNPs. • The nature of surfactant has a strong influence on the estimated persistence time of ZNPs. • Correlations between the ZNPs with various surface chemistries and their estimated environmental persistence was assessed. [ABSTRACT FROM AUTHOR]

Myotonic dystrophy type 1 (DM1) is an autosomal dominantly inherited degenerative disease with a slow progression. At the present, there is no commercially available treatment, but sustained effort is currently undertaken for the development of a promising lead compound. In the present paper we report the development of a fast, versatile, and cost-effective affinity capillary electrophoresis (ACE) method for the screening and identification of potential drug candidates targeting pathological ARN probes relevant for DM1. The affinity studies were conducted in physiologically relevant conditions using 50 mM HEPES buffer (pH 7.4) in a fused silica capillary dynamically coated with poly(ethylene oxide), by testing a library of potential ligands against (CUG)50 RNA as target probe with a total run time of 4-5 h/ligand. For the most promising ligands, their affinity parameters were assessed and some results formerly reported on the affinity of pentamidine (PTMD) and neomycin against CUG repeats were confirmed. To the best of the authors’ knowledge, the estimated binding stoichiometry for some of the tested compounds (i.e., ~ 121:1 for PTMD against the tested RNA probe) is reported for the first time. Additionally, the potential of a novel pentamidine like compound, namely 1,2-ethane bis-1-amino-4-benzamidine (EBAB) with much lower in vivo toxicity than its parent compound has also been confirmed studying its effect on a live cell model by fluorescence microscopy. Further tests, such as the evaluation of the rescue in the mis-splicing of the involved genes, can be performed to corroborate the potential therapeutic value of EBAB in DM1 treatment.ᅟ [ABSTRACT FROM AUTHOR]

• Electrochemically roughened AuSPEs are good candidates for SERS substrates. • EC-SERS brings many advantages for analytical applications. • An electric potential of −0.8 V vs Ag/AgCl enhances the SERS signal of TBZ. • TBZ was detected and quantified fast and directly in supplemented juice samples. • EC-SERS sensors can be integrated in microfluidic chips for real-time analyses. Thiabendazole (TBZ), a benzimidazole fungicide used for post-harvest treatment, may be a trace contaminant of food matrices. In this work, we report the first EC-SERS (electrochemical-surface enhanced Raman spectroscopy) detection of TBZ in spiked apple juice using electrochemically (EC) roughened, gold-based screen-printed electrodes (AuSPEs) and portable instrumentation. Polarizing the substrate (−0.8 V vs Ag/AgCl) improves the recorded SERS signal of TBZ, allowing to reach a limit of detection (LOD) in juice of 0.061 ppm with a relatively wide linear range (0.5–10 μM) and good intermediate precision (%RSD < 10). The recovery of TBZ from unprocessed juice was found to be more than 82 %. Furthermore, a proof-of-concept integration of AuSPEs with a miniaturized flow cell for the preconcentration of TBZ and the controlled delivery of sample and reagents has been demonstrated. This approach paves the way for integrated, portable analytical systems applicable for on-site sample collection, processing, and analysis. [ABSTRACT FROM AUTHOR]

The discovery of surface enhanced Raman scattering (SERS) from an electrochemical (EC)-SERS experiment is known as a historic breakthrough. Five decades have passed and Raman spectroelectrochemistry (SEC) has developed into a common characterization tool that provides information about the electrode–electrolyte interface. Recently, this technique has been successfully explored for analytical purposes. EC was found to highly improve the performances of SERS sensors, providing, among others, controlled adsorption of analytes and increased reproducibility. In this review, we highlight the potential of EC-SERS sensors to be implemented for point-of-need (PON) analyses as miniaturized devices, and their ability to revolutionize fields like quality control, diagnosis or environmental and food safety. Important developments have been achieved in Raman spectroelectrochemistry, which now represents a promising alternative to conventional analytical methods and interests more and more researchers. The studies included in this review open endless possibilities for real-life EC-SERS analytical applications. [Display omitted] • SERS provides valuable information at the electrode/electrolyte interface. • Control of surface charge brings numerous advantages in SERS quantitative analysis. • Dual EC-SERS sensors are prone to miniaturization. • EC-SERS is promising for point-of-need analytical applications. [ABSTRACT FROM AUTHOR]

Abstract: In the present work we report an experimental and theoretical study on propranolol a widely used beta-blocking drug. Raman and Surface Enhanced Raman Spectroscopies (SERSs) have been employed for the detection of the molecular vibrations, while quantum chemical calculations based on density functional theory (DFT) have been used to determine the geometrical, energetic and vibrational characteristics of propranolol. Using a 785nm laser line, the SERS spectra of the two propranolol enantiomers adsorbed on hydroxylamine reduced silver colloids have been measured in the 3–11 pH range. Based on DFT calculations performed at the B3LYP level of theory the FT-IR, Raman and SERS spectra of propranolol enantiomers were assigned. The adsorption geometry of both enantiomers onto the silver surface was predicted using the calculated molecular electrostatic potential (MEP) in association with data obtained from SERS. [Copyright &y& Elsevier]

Abstract: The enantioseparation of 10 basic drugs was evaluated in NACE systems using heptakis(2-O-methyl-3-O-acetyl-6-O-sulfo)-β-CD (HMAS-β-CD). For this purpose, a D-optimal design with 21 experimental points was applied. Four antifungal agents (econazole, isoconazole, miconazole, sulconazole), three local anesthetics (bupivacaine, mepivacaine and prilocaine), two sympathomimetics (salbutamol and terbutaline) and one β-blocker (carvedilol) were selected as basic model analytes. The influence on the enantiomeric resolution of anionic CD and BGE anion concentrations as well as the BGE anion nature was investigated. For all studied analytes, the enantiomeric resolution was shown to be significantly influenced by the CD concentration. Based on the observed results, a generic NACE system was recommended, namely 20mM HMAS-β-CD and 10mM ammonium camphorSO3 − in methanol acidified with 0.75M formic acid. Moreover, this NACE system was compared to previous conditions with heptakis(2,3-di-O-methyl-6-O-sulfo)-β-CD (HDMS-β-CD) or heptakis(2,3-di-O-acetyl-6-O-sulfo)-β-CD (HDAS-β-CD). Finally, two generic systems using either HDAS-β-CD or HMAS-β-CD were proposed and evaluated for the enantioseparation of ketamine and norketamine after incubation of ketamine in phenobarbital-induced male rat liver microsomes systems. [ABSTRACT FROM AUTHOR]

The current study is focused on the preparation of Mo-10 vol%La 2 O 3 and Mo-10 vol% La 2 Zr 2 O 7 composite powders via low- and high-energy ball milling approaches as potential candidates for near-future high-temperature structural applications. The mechanical milling parameters play a critical role on the final powder's microstructure. When using the high-energy milling mode (using 800 rpm, ball-to-powder ratio (BPR) 100: 6), the homogeneous powder agglomerates are formed with refined laminated microstructure and more uniform ceramic phase distribution in both Mo-La 2 O 3 and Mo-La 2 Zr 2 O 7 systems compared to the powders produced by means of the low-energy milling mode (using 350 rpm, BPR 100: 6), where inhomogeneous powder mixture with less embedding of ceramic phases into Mo agglomerates was obtained. This study also focuses on the evaluation of high-temperature phase and microstructural stability of the produced composite powders treated at the temperature of 1300 °C under the different gaseous environments, including ambient, inert and reducing atmospheres. The Mo-10 vol% La 2 Zr 2 O 7 composite powder exhibited better thermal stability during the high-temperature exposure in all tested atmospheres in comparison with the Mo-La 2 O 3 composite powder, since it revealed less intensive formation of the intermediate phases, such as lanthanum oxymolybdates. Therefore, the Mo-10 vol% La 2 Zr 2 O 7 composite powder was used further for consolidation by means of spark plasma sintering at 1600 °C. The successful production of Mo-La 2 Zr 2 O 7 composite with homogeneous distribution of ceramic phase, the grain size about of 5 μm, and hardness of 3.4 GPa was not reported so far. • Composite Mo-La 2 O 3 and Mo-La 2 Zr 2 O 7 powders were prepared via high-energy milling. • Mo-La 2 Zr 2 O 7 composite powder shows better thermal stability than Mo-La 2 O 3 at 1300 °C. • Formation of lanthanum oxymolybdates occurs during annealing in inert atmospheres. • Mo-10vol.%La 2 Zr 2 O 7 composite was successfully produced for the first time using SPS. [ABSTRACT FROM AUTHOR]

Extensive effort and research are currently channeled towards the implementation of SERS (Surface Enhanced Raman Spectroscopy) as a standard analytical tool as it has undisputedly demonstrated a great potential for trace detection of various analytes. Novel and improved substrates are continuously reported in this regard. It is generally believed that plasmonic nanostructures with plasmon resonances close to the excitation wavelength (on-resonance) generate stronger SERS enhancements, but this finding is still under debate. In the current paper, we compared off-resonance gold nanobones (GNBs) with on-resonance GNBs and gold nanorods (GNRs) in both colloidal dispersion and as close-packed films self-assembled at liquid-liquid interface. Rhodamine 6G (R6G) was used as a Raman reporter in order to evaluate SERS performances. A 17-, 18-, and 55-fold increase in the Raman signal was observed for nanostructures (off-resonance GNBs, on-resonance GNBs, and on-resonance GNRs, respectively) assembled at liquid-liquid interface compared to the same nanostructures in colloidal dispersion. SERS performances of off-resonance GNBs were superior to on-resonance nanostructures in both cases. Furthermore, when off-resonance GNBs were assembled at the liquid interface, a relative standard deviation of 4.56% of the recorded signal intensity and a limit of detection (LOD) of 5 × 10−9 M could be obtained for R6G, rendering this substrate suitable for analytical applications. [ABSTRACT FROM AUTHOR]

Although the human eye is an easily accessible sensory organ, it remains a challenge for drug administration due to the presence of several anatomical and physiological barriers which limit the access of drugs to its internal structures. Molecular imprinting technology may be considered the avant-garde approach in advanced drug delivery applications and, in particular, in ocular therapy. In fact, molecularly imprinted polymers hold the promise to compensate for the current shortcomings of the available arsenal of drug delivery systems intended for ocular therapy. The present manuscript aims to review the recent advances, the current challenges and most importantly to raise awareness on the underexplored potential and future perspectives of molecularly imprinted polymer-based drug delivery systems intended for the treatment of eye diseases. [ABSTRACT FROM AUTHOR]

A new simple and convenient strategy for boosting the enantioselectivity of cyclodextrins (CDs) as highly available homochiral macrocyclic hosts using the co-assembly of physisorbed propranolol (PRNL) enantiomers on gold nanoparticles (AuNPs) and different CDs was reported, exploiting the gainful effects of surface-confined supramolecular associations. All the experiments were conducted both in bulk enantiomer solution (unrestricted, homogenous system) and on the antipodes physisorbed at the gold-liquid interface (surface confined, heterogenous system), employing various electroanalytical techniques (differential pulse voltammetry, cyclic voltammetry and electrochemical impedance spectroscopy), isothermal titration calorimetry and computational modeling. In the unrestricted system, where the freedom of movement of PRNL molecules is not hampered, unassailable enantioselectivity may not be allocated to either of the tested CDs. However, by limiting the degrees of freedom of PRNL antipodes upon their adsorption to a non-chiral surface of electrochemically-generated AuNPs, a particular amplification of the conformational differences between the resulting supramolecular complexes with native CDs may arise. Molecular dynamics simulations of the supramolecular interactions on both homogenous and heterogenous system revealed important differences compared to the previously reported quantum chemical calculations performed in vacuo. Besides the advances of fundamental knowledge, this proof-of-concept data may offer an alternative strategy for the fast chiral probing of various analytes by interfacial supramolecular electrochemistry. [ABSTRACT FROM AUTHOR]

Organochlorine pesticides (OCPs) embody highly lipophilic hazardous chemicals that are being phased out globally. Due to their persistent nature, they are still contaminating the environment, being classified as persistent organic pollutants (POPs). They bioaccumulate through bioconcentration and biomagnification, leading to elevated concentrations at higher trophic levels. Studies show that human long-term exposure to OCPs is correlated with a large panel of common chronic diseases. Due to toxicity concerns, most OCPs are listed as persistent organic pollutants (POPs). Conventionally, separation techniques such as gas chromatography are used to analyze OCPs (e.g., gas chromatography coupled with mass spectrometry (GC/MS)) or electron capture detection (GC/ECD). These are accurate, but expensive and time-consuming methods, which can only be performed in centralized lab environments after extensive pretreatment of the collected samples. Thus, researchers are continuously fueling the need to pursue new faster and less expensive alternatives for their detection and quantification that can be used in the field, possibly in miniaturized lab-on-a-chip systems. In this context, surface enhanced Raman spectroscopy (SERS) represents an exceptional analytical tool for the trace detection of pollutants, offering molecular fingerprint-type data and high sensitivity. For maximum signal amplification, two conditions are imposed: an efficient substrate and a high affinity toward the analyte. Unfortunately, due to the highly hydrophobic nature of these pollutants (OCPs,) they usually have a low affinity toward SERS substrates, increasing the challenge in their SERS detection. In order to overcome this limitation and take advantage of on-site Raman analysis of pollutants, researchers are devising ingenious strategies that are synthetically discussed in this review paper. Aiming to maximize the weak Raman signal of organochlorine pesticides, current practices of increasing the substrate's performance, along with efforts in improving the selectivity by SERS substrate functionalization meant to adsorb the OCPs in close proximity (via covalent, electrostatic or hydrophobic bonds), are both discussed. Moreover, the prospects of multiplex analysis are also approached. Finally, other perspectives for capturing such hydrophobic molecules (MIPs—molecularly imprinted polymers, immunoassays) and SERS coupled techniques (microfluidics—SERS, electrochemistry—SERS) to overcome some of the restraints are presented. [ABSTRACT FROM AUTHOR]

An innovative sandwich MIP-based electrochemical sensor was fabricated for the fast and selective detection of adenosine. The covalent-imprinted biomimetic recognition element relies on two overlapping polymeric films, an underlaying composite boronate-affinity and poly(bithiophene)-structural layer and an overlaying poly(3-indolacetic acid) coating bearing carboxyl groups, intended to further shape the selectivity of the sensor towards adenosine. The sensor's behavior and analytical performance was characterized by cyclic voltammetry (CV), differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy (EIS). The recorded DPVs showed a linear response to increasing concentration of adenosine in the range of 0.37 μM–37.4 μM with a limit of detection of 0.21 μM. The selectivity of the MIP sensor towards adenosine was demonstrated against more than 10 structurally related interferents. The developed sensor was applied for the fast and quantitative assessment of adenosine in spiked urine samples with good recoveries (102.98%–106.34%), proving at least comparable bioanalytical performances in terms of sensitivity, yet greatly improved in terms of selectivity and analysis time to previously reported sensors. • First study reporting MIP-based electrochemical sensor for adenosine determination. • Biomimetic sandwich-structured sensing interface for the detection of adenosine. • Dual imprinting process by spatially-oriented covalent and non-covalent interactions. • Facile manufacturing of multi-use electrochemical sensor offering short analysis times. • Very good selectivity demonstrated on many analytically relevant interferents. [ABSTRACT FROM AUTHOR]

A highly selective and sensitive molecularly imprinted polymer (MIP)-based electrochemical sensor was fabricated for the determination of azithromycin, a broad-spectrum macrolide antibiotic, from various biological samples (urine, tears, plasma). The reversible boronate ester bond-mediated, thin (~75 nm) MIP-based biomimetic recognition layer was electrodeposited in non-aqueous media onto the surface of a glassy carbon electrode (GCE). The surface morphology and the analytical performances of the developed sensor were assessed by scanning electron (SEM) and atomic force microscopy (AFM), electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). By employing an indirect electrochemical detection in the presence of 10 mM ferro/ferricyanide as redox probe, the sensor exhibited a very wide dynamic range (13.33 nM–66.67 μM), with an estimated detection limit in the subnanomolar range (0.85 nM azithromycin). The simple to construct sensor demonstrates reusability and good shelf-life, exhibiting remarkable selectivity over a wide number of structurally related and non-related antibiotics, commonly associated drugs and endogenous compounds. • Biomimetic recognition layer using cyclic boronate ester-based imprinted polymer. • Subnanomolar sensitivity, excellent selectivity due to covalent imprinting approach. • Facile manufacturing of multi-use electrochemical sensor with good shelf-life. • Very good recoveries of AZI from various spiked biological fluids. • The first study reporting AZI assessment from tears using an electrochemical sensor. [ABSTRACT FROM AUTHOR]

Enantioselective electrochemical sensors seem to hold the promise for a fast and easy alternative for the chiral probing of bioactive molecules. However, the underlying mechanism responsible for the chiral recognition is rarely known, and suitable investigational tools are dearly missed. Therefore, as a proof-of-concept, our study is focused on investigating the interaction mechanism of the enantiomers of a chiral drug molecule, namely propranolol (PRNL) with the surface of bare and l -cysteine (l -Cys) modified gold nanoparticles employing various electrochemical techniques (differential pulse voltammetry and electrochemical impedance spectroscopy) and computational modeling (molecular dynamics simulations). If the strong surface adsorption of PRNL antipodes on bare gold nanoparticles may not be exploited for enantioselective recognition, upon the functionalization of the nanostructures with l -Cys, the almost two fold increase in the oxidation current is also accompanied by a cathodic shift (∼40 mV) of the peak potential for the S(−)-enantiomer. This peak potential shift seems to be the consequence of a favored orientation of the surface adsorbed S(−)-enantiomer towards electron transfer and/or a weaker interaction with the chiral selector and thus a higher free energy of the transient diastereoisomeric complex, in comparison with its R(+)-antipode. Computational modeling highlighted the H-bond donor and acceptor atoms of both the chiral selector (l -Cys) and adsorbates (PRNL enantiomers) responsible for the recorded enantioselective electrochemical signal. Correlations between the observed electrochemical signal and enantioselective molecular interactions occurring at the surface of the electrode may lead the way towards a more rational design of future chiral electrochemical sensing platforms. Image 10619 • Insights of PRNL enantiodiscrimination at the surface of L-Cys@AuNPs provided. • Molecular interactions were correlated with the chiral electrochemical signal. • The main force modulating the recorded enantioselectivity is hydrogen bonding. • A significantly higher number of H-bonds is developed by the adsorbed R(+)-PRNL. • Computational modeling a valuable tool for the investigation of chiral interactions. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]