Tracking the chemical surface properties of racemic thalidomide and its enantiomers using a biomimetic functional surface on a quartz crystal microbalance

We present details of the chemical surface properties of the molecularly imprinted polymer (MIP) on quartz crystal microbalance (QCM) for the tracking of the chiral recognition of racemic thalidomide and its (R)‐enantiomer. We investigate the assembly and specific patterns of enantiomer and racemate of thalidomide on the poly(urethane) coating consisted of the synthetic‐estrogen bisphenol A (BPA) on a QCM electrode by infrared spectroscopy and atomic force microscopy (AFM), which confirmed the surface properties of these materials. The BPA present on the surface of the coating layer revealed a positive frequency response for the racemic thalidomide that eventually appeared. This involved a negative shift of 80 Hz for a 200 µg mL^?1 racemic thalidomide, and in all cases, a negative shift of 200 Hz for a 100 µg mL^?1 (R)‐thalidomide. The affinity constants (K_a) for the racemate adsorbed onto the polymer layer imprinted with (R)‐thalidomide were lower than those for the (R)‐thalidomide. Also, the binding energy involved a different binding process of the chiral forms and indicated that the two enantiomers had a twofold difference in their binding energies. Thus, the advantage of the use of BPA is proven that will function as hydrogen‐bond donors in the enantioselective recognition site of the MIP. The data of functional analysis demonstrated that the biomimetic detection using molecular imprinting turn out to a study of the pharmaceutical effects of a pharmaceutically chiral compound on natural receptor functions. This approach is highly useful that highlight an enhanced understanding of the mechanism of stereochemistry required for biological controls. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42309.     

Recognition Properties and Competitive Assays of a Dual Dopamine/Serotonin Selective Molecularly Imprinted Polymer

A molecularly imprinted polymer (MIP) with dual dopamine/serotonin-like binding sites (DS-MIP) was synthesized for use as a receptor model of study the drug-interaction of biological mixed receptors at a molecular level. The polymer material was produced using methacrylic acid (MAA) and acrylamide (ACM) as functional monomers, N,N′-methylene bisacrylamide (MBAA) as cross-linker, methanol/water mixture (4:1, v/v) as porogen and a mixture of dopamine (D) and serotonin (S) as templates. The prepared DS-MIP exhibited the greatest rebinding of the template(s) in aqueous methanol solution with decreased recognition in acetonitrile, water and methanol solvent. The binding affinity and binding capacity of DS-MIP with S were found to be higher than those of DS-MIP with D. The selectivity profiles of DS-MIP suggest that the D binding site of DS-MIP has sufficient integrity to discriminate between species of non-optimal functional group orientation, whilst the S binding site of DS-MIP is less selective toward species having structural features and functional group orientations different from S. The ligand binding activities of a series of ergot derivatives (ergocryptine, ergocornine, ergocristine, ergonovine, agroclavine, pergolide and terguride) have been studied with the DS-MIP using a competitive ligand binding assay protocol. The binding affinities of DS-MIP were demonstrated in the micro- or submicro-molar range for a series of ergot derivatives, whereas the binding affinities were considerably greater to natural receptors derived from the rat hypothalamus. The DS-MIP afforded the same pattern of differentiation as the natural receptors, i.e. affinity for the clavines > lysergic acid derivatives > ergopeptines. The results suggest that the discrimination for the ergot derivatives by the dopamine and serotonin sites of DS-MIP is due to the structural features and functional orientation of the phenylethylamine and indolylethylamine entities at the binding sites, and the fidelity of the dopamine and serotonin imprinted cavities.     

The composite nanomaterials containing (R)‐thalidomide‐molecularly imprinted polymers as a recognition system for enantioselective‐controlled release and targeted drug delivery

A molecularly imprinted polymer (MIP) enantioselective receptor for the (R)‐thalidomide enantiomer was synthesized and evaluated for its ability to deliver the drug to cancer cells. Polymer networks with precisely engineered binding sites were built into the assembled nanoparticles by a self‐organizing template in the prepolymerized mixture using methacrylic acid, a fluorescently active 2,6‐bis(acrylamido)pyridine and N,N′ methylene‐bis‐acrylamide, via both a covalent approach and a physical approach. The fine‐tuning of particle diameters was carried out by changes to the polymerizing synthesis method, the type of solvent and the amount of the poloxamer that led to an optimal formulation of the nanoparticles with sizes as small as 100 nm. Data from the ¹H‐nuclear magnetic resonance spectroscopy revealed the important structural motifs of an (R)‐thalidomide‐selective cavity for two different polymerization processes. We have investigated their ability for enantiomer recognition and the potential ability to protect the chiral MIP with a self‐assembled poloxamer structure. Moreover, the effect of the smaller molecular size can not only enable favorable imaging properties but also facilitate enhanced green fluorescence intensity for the deposited MIP and the (R)‐thalidomide in the poloxamer nanoparticles in a cell‐line in which the grafted MIP being higher than the deposited one. It was also demonstrated that the deposited MIP nanoparticles had the potential to make the drug effective for attacking multidrug ‐ resistant cells. Thus, the poloxamer nanoparticles containing a thermoresponsive MIP could maximize the release of the nontoxic (R)‐thalidomide at the tumor tissue, with the help of a proper temperature shift at the site. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41930.