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Sphingosine-1-phosphate (S1P) is a bioactive sphingo-lipid with a broad range of activities coupled to its role in G-protein coupled receptor signalling. Monitoring of both intra and extra cellular levels of this lipid is challenging due to its low abundance and lack of robust affinity assays or sensors. We here report on fluorescent sensory core-shell molecularly imprinted polymer (MIP) particles responsive to near physiologically relevant levels of S1P and the S1P receptor modulator fingolimod phosphate (FP) in spiked human serum samples. Imprinting was achieved using the tetrabutylammonium (TBA) salt of FP or phosphatidic acid (DPPA·Na) as templates in combination with a polymerizable nitrobenzoxadiazole (NBD)-urea monomer with the dual role of capturing the phospho-anion and signalling its presence. The monomers were grafted from ca 300 nm RAFT-modified silica core particles using ethyleneglycol dimethacrylate (EGDMA) as crosslinker resulting in 10–20 nm thick shells displaying selective fluorescence response to the targeted lipids S1P and DPPA in aqueous buffered media. Potential use of the sensory particles for monitoring S1P in serum was demonstrated on spiked serum samples, proving a linear range of 18–60 µM and a detection limit of 5.6 µM, a value in the same range as the plasma concentration of the biomarker. [ABSTRACT FROM AUTHOR]

A 2,3-diaminophenazine bis-urea fluorescent probe monomer ( 1) was developed. It responds to phenylphosphate and phosphorylated amino acids in a ratiometric fashion with enhanced fluorescence accompanied by the development of a redshifted emission band arising from an excited-state proton transfer (ESPT) process in the hydrogen-bonded probe/analyte complex. The two urea groups of 1 form a cleft-like binding pocket ( Kb>1010 L2 mol−2 for 1:2 complex). Imprinting of 1 in presence of ethyl ester- and fluorenylmethyloxycarbonyl (Fmoc)-protected phosphorylated tyrosine (Fmoc-pTyr-OEt) as the template, methacrylamide as co-monomer, and ethyleneglycol dimethacrylate as cross-linker gave few-nanometer-thick molecularly imprinted polymer (MIP) shells on silica core microparticles with excellent selectivity for the template in a buffered biphasic assay. The supramolecular recognition features were established by spectroscopic and NMR studies. Rational screening of co-monomers and cross-linkers allowed to single out the best performing MIP components, giving significant imprinting factors (IF>3.5) while retaining ESPT emission and the ratiometric response in the thin polymer shell. Combination of the bead-based detection scheme with the phase-transfer assay dramatically improved the IF to 15.9, allowing sensitive determination of the analyte directly in aqueous media. [ABSTRACT FROM AUTHOR]

The article offers information on a study concerning fluorescent sensory microparticles which consist of molecularly imprinted polymer (MIP) and silica core. It says that the N-carbobenzyloxy-l-phenylalanine(Cbz-l-Phe or Z-l-Phe, Scheme 1) was used a template and the fluorescent monomer was developed using nitrobenzoxadiazole (NBD) fluorophore. The integration of the MIP on silica microparticles makes the assay response times and the handling of the sensor particles straightforward.

Optically responsive receptors toward imides based on 6-substituted 2,4-bis(acrylamido)pyrimidines are presented. The monomers were readily prepared in good yield. Solution binding to 1-benzyluracil (RU) monitored by ¹H NMR appeared lower than a previously reported pyridine-based monomer. However, as indicated by ¹H NMR and JR spectral investigations, the association strength was demonstrated to be "masked" by dimerization of the pyrimidine-based monomer units. Thus, from dilution experiments, a dimerization constant of 731 M-1 was estimated for the pyrimidine-based monomer 2,4-bis(acrylamido)-6-piperidinopyrimicline whereas for the pyridine-based monomer 2,6- bis(acrylamido)pyridine, no self-association was observed. This precluded an accurate determination of the binding constant for RU to the former monomer whereas for the latter a binding constant of 757 M-1 was measured. Despite the strong self-association, the novel monomer was shown to lead to enhanced imprinting effects when compared to imprinted polymers prepared analogously, but using the pyridine-based monomer as the recognition element. This was attributed to a higher intrinsic binding affinity exhibited by the pyrimidine based host monomer vis a vis the guest and the existence in the former of more than one interaction site for the guest. The monomers exhibited fluorescence emission informative of the mode of monomer incorporation in the polymer and the presence of guest species. Thus, the fluorescence was rapidly and selectively quenched upon template addition, with the degree of quenching correlating with binding affinity and the amount of template bound to the polymer. [ABSTRACT FROM AUTHOR]

Highlights: [•] Imidazolium cationic monomers used for imprinting of naproxen. [•] Methacrylic and xerogel formats were comprehensively compared. [•] Both formats yielded successful imprinting performance. [•] Xerogel achieved a higher selectivity against an analogue, ibuprofen. [•] Overall, however, methacrylic polymer, exhibited superior features. [ABSTRACT FROM AUTHOR]

In this study, computational methodswere employed in efforts toelucidate physical mechanisms underlying the ligand selectivity ofpolymeric sorbents produced through the molecular imprinting of 17-β-estradiol.Previous computational and experimental studies had identified candidatesystems applicable to the development of synthetic polymeric receptorsfor the detection and possible removal of pollutants with endocrine-disruptingproperties. Here we present a series of comprehensive molecular dynamicsstudies of candidate molecular imprinting prepolymerization systems.The results from the studies highlight the role of the cross-linkerand the importance of the interplay between functionalities of thevarious monomers employed in template complexation. The significanceof these results for future studies is discussed. [ABSTRACT FROM AUTHOR]

A naphthalimide-based fluorescent indicator monomer 1 for the integration into chromo- and fluorogenic molecularly imprinted polymers (MIPs) was synthesized and characterized. The monomer was equipped with a urea binding site to respond to carboxylate-containing guests with absorption and fluorescence changes, namely a bathochromic shift in absorption and fluorescence quenching. Detailed spectroscopic analyses of the title compound and various models revealed the signaling mechanism. Titration studies employing benzoate and Z-L-phenylalanine (Z-L-Phe) suggest that indicator monomers such as the title compound undergo a mixture of deprotonation and complex formation in the presence of benzoate but yield hydrogen-bonded complexes, which are desirable for the molecular imprinting process, with weakly basic guests like Z-L-Phe. Compound 1 could be successfully employed in the synthesis of monolithic and thin-film MIPs against Z-L-Phe, Z-L-glutamic acid, and penicillin G. Chromatographic assessment of the selectivity features of the monoliths revealed enantioselective discrimination and clear imprinting effects. Immobilized on glass coverslips, the thin-film MIPs of 1 displayed a clear signaling behavior with a pronounced enantioselective fluorescence quenching dependence and a promising discrimination against cross-analytes. [ABSTRACT FROM AUTHOR]

A series of urea-based vinyl monomers was synthesized and investigated for their ability to function as polymerizable hosts for the molecular imprinting of N-Z-D- or L-glutamic acid in polar media (DMSO or DMF). The monomers were synthesized in one step from a polymerizable isocyanate and a nonpolymerizable amine or vice versa, with yields typically over 70%. Prior to polymerization their solution binding properties vis-à-vis tetrabutylammonium benzoate in DMSO were investigated by ¹H NMR, UV-vis and fluorescence monitored titrations. The affinities of the urea monomers for benzoate depended upon the substitution pattern of the urea, with all diaryl ureas exhibiting high affinity. EDMA-based imprinted polymers prepared in DMF or DMSO against Z-D-(or L)glutamic acid using 2 equiv of the urea monomer and 2 equiv of base were able to recognize the imprinted dianion as well as larger molecules containing the glutamic acid substructure. The affinity, reflected in liquid chromatography retention data, correlated with the solution binding properties of the corresponding monomers. [ABSTRACT FROM AUTHOR]