Water-soluble Receptor Research Articles

Selective and sensitive investigation of aluminium contamination from cookware based on novel water-soluble fluorescence turn-on chemosensor

The ubiquitous use of aluminium cookware raises serious concerns about the introduction of aluminium by leaching upon prolonged cooking, especially in acidic foods. To mimic a consumer-relevant exposure scenario, an experimental model design was conceptualized for the estimation of leaching from aluminium sheets in acidic additives under variable cooking conditions. A novel water-soluble receptor (Z)-2-((2-hydroxy-3-methoxybenzylidene)amino)-2-(hydroxymethyl)propane-1,3-diol (VT) was synthesized, which gave a selective and sensitive fluorescence turn-on response towards aluminium ions. The 1:1 binding stoichiometry between VT and Al3+ has been confirmed by Job's plot, which is further supported by 1H NMR, 27Al NMR, HRMS, and DFT studies. Test strips were fabricated for quick semi-quantitative estimation of aluminium ions under UV irradiation. Leaching studies show that on increasing the acidity of solution of acidic additives results in an increased aluminium leaching ranging from 4.95 to 11.43 mg/h. Surface morphology by SEM and AFM shows the pitting corrosion of Al sheets.

Aqueous recognition of purine and pyrimidine bases by an anthracene-based macrocyclic receptor.

A water-soluble bis-anthracenyl tetralactam binds biogenic heterocycles with high affinities in aqueous solution, rising to 107 M-1 for the purine hypoxanthine. Recognition occurs through a combination of hydrogen bonding and hydrophobic interactions, and results in fluorescence changes which suggest applications in sensing.

Copper ion luminescence on/off sensing by a quinoline-appended ruthenium(II)-polypyridyl complex in aqueous media

Abstract An efficient chemosensor RuL based on a quinoline tethered Ru (bpy)22+ derivative is developed for Cu2+ ion detection in pure aqueous medium. Receptor RuL has been characterized using standard spectral studies including UV–visible, fluorescence, ESI-MS and 1H NMR techniques. The crystal structure of RuL is determined by X-ray diffraction studies which revealed that Ru(II) is coordinated to nitrogen atoms of phenanthroline moiety. However N atoms of quinoline and imidazole units are uncoordinated and freely accessible for further functionalization. Changes in photochemical properties of RuL, high selectivity, reversibility by EDTA, excellent detection limit (50.67 nM) and high binding parameters displayed excellent sensing ability for Cu2+ ion. This work illustrates application of a water-soluble receptor in excellent sensing of cupric ion.

Characterization of an engineered water-soluble variant of the full-length human mu opioid receptor

A water-soluble variant of the transmembrane domain of the human mu opioid receptor (wsMOR-TM) was previously characterized. This study explored whether the full-length version of the engineered water-soluble receptor, (wsMOR-FL), could be overexpressed in Escherichia coli and if it would retain water solubility, binding capability and thermostability. wsMOR was over-expressed and purified in E. coli BL21(DE3) cells (EMD/Novagen) as we reported previously for the wsMOR-TM. Both native N and C termini were added back to the highly engineered wsMOR-TM. Six His-tag was added in the N terminus for purification purposes. The wsMOR-FL was characterized using atomic force microscope for its monomeric state, circular dichroism for its secondary structure and thermostability. Its binding with naltrexone is also determined. Compared to the native human MOR, wsMOR-FL displays similar helical secondary structure content and comparable affinity (nM) for the antagonist naltrexone. The secondary structure of the receptor remains stable within a wide range of pH (6–9). In contrast to the transmembrane portion, the secondary structure of full-length receptor tolerated a wide range of temperature (10–90 °C). The receptor remains predominantly as a monomer in solution, as directly imaged using atomic force microscopy. This study demonstrated that functional full-length water-soluble variant of human mu receptor can be over-expressed and purified using an E. coli over-expression system. This provides a novel tool for the investigation of structural and functional properties of the human MOR. N- and C-termini strengthened the thermostability of the protein in this specific water soluble variant. Communicated by Ramaswamy H. Sarma

Water Soluble G-protein Coupled Receptor Enabled Biosensors.

This article will briefly overview our efforts in the engineering of water soluble variants of a G-protein coupled receptor (GPCR) and its novel applications to develop biosensors using such water soluble variants of GPCR. While the technologies using water soluble GPCR are still under development, they offer new tools and strategies to study the function of GPCR, explore potential new compounds for potential clinical usage, and monitor endogenous peptides in various physiological and pathological conditions.

A fluoride selective water-soluble anion receptor based on a 1,2-phenylenediacetic acid and calcium ion dimer

The dimeric receptor 1 from 1,2-phenylenediacetic acid and calcium ions recognized fluoride ions almost exclusively in 100% water.

A glycoluril dimer-triptycene hybrid receptor: synthesis and molecular recognition properties.

The strategic combination of the methylene bridged glycoluril dimer and triptycene skeletons delivers acyclic water soluble hybrid receptor 1 which is analogous to cucurbit[6]uril. The molecular recognition properties of host 1 toward hydrophobic cationic guests are investigated in detail by a combination of 1H NMR spectroscopy and isothermal titration calorimetry (ITC) studies. The fluorescence emission of 1 can be selectively and efficiently quenched upon the formation of 1·26 and 1·28 complexes.

Para-Sulfonatocalix[4]arene stabilized gold nanoparticles multilayers interfaced to electrodes through host-guest interaction for sensitive ErbB2 detection

Nanoparticle (NP) structure, compositing and the nature of the NP-functionalized electrode interface have a strong influence upon electrochemical properties that are critical in applications such as sensing, photocatalysis and electrocatalysis. Existing methods to fabricate NP-functionalized electrodes do not allow or precise control over all these variables, especially the NP-electrode interface, making it difficult to understand and predict how structural changes influence electrode activity and consequently limit the application. To conquer this problem, in this study, we fabricated a stepwise construction of a novel supramolecular stabilized gold nanoparticles (AuNPs) multilayer mediated by guest molecules, yielding 3D AuNPs assembly at the electrode interface. para-Sulfonatocalix[4]arene (pSC4), a water soluble macrocyclic synthetic receptor, has been served as a stabilizing ligand for preparation and gaining new insights into pSC4 stabilized gold nanoparticles (pSC4-AuNPs) tethered on the electrode interface through host-guest interaction. We investigated the electrochemical properties of multilayer pSC4-AuNPs modified gold electrode using different core size of AuNPs with varying layer number. The electron transfer ability was characterized by electrochemical impedance spectroscopy (EIS). Electrochemical signals are significantly enhanced through the layer-by-layer assembly of pSC4-AuNPs due to its high conductivity and high effective area. With this innovative method, by taking the assay of a tumor marker as an example, human epidermal growth factor receptor 2 (ErbB2) was successfully measured with a detection limit of 0.5ng/mL. Taking the advantage of the pSC4-AuNPs multilayer's good biocompatibility, high effective area and high electronic transmission, 3D AuNPs multilayer produced on the electrode interface suggests a portable synthetic pathway for the application into sensitive electrochemical biosensor.

Water soluble and efficient amino acid Schiff base receptor for reversible fluorescence turn-on detection of Zn2+ ions: Quantum chemical calculations and detection of bacteria

An amino acid Schiff base (R) capable of recognizing Zn2+ ions selectively and sensitively in an aqueous medium was prepared and characterized. Upon addition of Zn2+ ions, the receptor exhibits fluorescence intensity enhancements (~40 fold) at 460nm (quantum yield, Φ=0.05 for R and Φ=0.18 for R–Zn2+) and can be detected by naked eye under UV light. The receptor can recognize the Zn2+ (1.04×10−8M) selectively for other metal ions in the pH range of 7.5–11. The Zn2+ chelation with R decreases the loss of energy through non-radiative transition and leads to fluorescence enhancement. The binding mode of the receptor with Zn2+ was investigated by 1H NMR titration and further validated by ESI-MS. The elemental color mapping and SEM/EDS analysis were also used to study the binding of R with Zn2+. Density functional theory calculations were carried out to understand the binding mechanism. The receptor was applied as a microbial sensor for Escherichia coli and Staphylococcus aureus.

The interaction of La3+ complexes of DOTA/DTPA glycoconjugates with the RCA120 lectin: a saturation transfer difference NMR spectroscopic study

The study of ligand-receptor interactions using high-resolution NMR techniques, namely the saturation transfer difference (STD), is presented for the recognition process between La(III) complexes of 1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane monoamide and diethylenetriaminepentaacetic acid bisamide glycoconjugates and the galactose-specific lectin Ricinus communis agglutinin (RCA(120)). This new class of Gd(III)-based potential targeted MRI contrast agents (CAs), bearing one or two terminal sugar (galactosyl or lactosyl) moieties, has been designed for in vivo binding to the asialoglycoprotein receptor, which is specifically expressed at the surface of liver hepatocytes, with the aim of leading to a new possible diagnosis of liver diseases. The in vitro affinity constants for the affinity of the divalent La(III)-glycoconjugate complexes for RCA(120), used as a simple, water-soluble receptor model, were higher than those of the monovalent analogues. The combination of the experimental data obtained from the STD NMR experiments with molecular modelling protocols (Autodock 4.1) allowed us to predict the mode of binding of monovalent and divalent forms of these CAs to the galactose 1α binding sites of RCA(120). The atomic details of the molecular interactions allowed us to corroborate and supported the interaction of both sugar moieties and the linkers with the surface of the protein and, thus, their contribution to the observed interaction stabilities.

Pd(II) Metal Coordination-driven Isomerically Preorganized Receptors with the Enhanced Affinity for Aromatic Carboxylates in Water

Preorganization of synthetic receptor has recently received much attention in the molecular recognition research fields. As a model system for mimicry of biological events in relation to specific substrate recognition, various synthetic receptors based on calix[4]arene, resorcin[4]arene and foldamer structures have been extensively employed for the research of molecular recognition, presenting strong complex formation for specific guests including anionic species and biomolecules. In particular, water-soluble receptor attracts much attention in the molecular recognition, since significant biological events are mediated or triggered by specific substrate-receptor recognition in the aqueous media and it is very important to develop a preorganized structure of proteins for understanding the selective protein-substrate binding behaviors at the molecular level. The concept of preorganization is very crucial in the design and synthesis of artificial receptor, stabilizing substrate-receptor complex as well as the structure of receptor. Preorganization of artificial receptors has been produced via covalent synthetic methods and noncovalent interactions including hydrogen bonding and metal coordination. Previously, we have reported the preparation of water soluble receptor based on resorcin[4]arene, which was preorganized through intramolecular Pd complexation in water and thus showed more than ten times enhanced affinities for proper anionic guests in H NMR titrations. Herein we present molecular recognition of the isomerically preorganized receptors in aqueous media, which are inspired

Formation of a Unique 1:2 Calcium-Calixquinone Complex in Aqueous Media

Department of Chemistry, Chung-Ang University, Seoul 156-756, Korea Received December 3, 2010, Accepted December 26, 2010We report the complexation behavior of calix[4]arenemonoquinone-triacid (CTAQ), which is an electroactiveand water-soluble receptor for calcium ion. UV-visible and NMR spectroscopic studies revealed that CTAQ inaqueous media forms 1:2 as well as 1:1 (metal ion:CTAQ) stoichiometric complexes with Ca

Selective detection of zwitterionic arginine with a new Zn(ii)-terpyridine complex: potential application in protein labeling and determination

A new water-soluble receptor 1 has been synthesized and it showed selective recognition of zwitterionic arginine in aqueous media. Moreover, the receptor 1 could be regard as a facile tool for protein labeling and quantitative determination (LOD = 15 nM).

A fluorescence turn-on Hg<sup>2+</sup> probe based on rhodamine with excellent sensitivity and selectivity in living cells

A highly sensitive and selective Hg2+ probe 4 based on rhodamine-b was developed and characterized. In consideration of environmental and biological application, we connected a water soluble receptor group (sulfonated β-naphtol) and rhodamine-b together through hydrazine hydrate in high yield. The result turns out that this compound not only exhibits excellent sensitivity and selectivity toward Hg2+, but also shows well cell permeability and compatibility in vitro.

A fluorescein-containing, small-molecule, water-soluble receptor for cytosine free bases

In this study, we synthesized small-molecule, water-soluble, fluorescein-containing ureido compounds 6 and 8 as target receptors for cytosine free bases and then investigated the binding of cytosine free bases with the receptors using 15N NMR spectroscopy and partially labeled cytosine-2,4- 13C-1,3,4- 15N-cytosine. Binding with the receptor 6a (the disodium form of 6) caused the chemical shift of the nitrogen atom of the amino group of cytosine to move downfield; binding of the receptor 8a (the disodium form of 8), which is possessing no corresponding aryl nitrogen atom, had no effect on this signal. Fluorescence spectroscopy revealed that binding of cytosine and its derivatives led to quenching of the fluorescence of receptor 6a; in contrast, the quenching of receptor 8a was only slightly affected by cytosine. Because the fluorescence of 6a was not quenched by either deoxycytidine or uracil, it appears that this receptor is a specific for cytosine among the DNA bases. We used the fluorescence of 6a to measure the apparent binding constants for various cytosine derivatives, including the anticancer prodrug 5-fluorocytosine. Receptor 6a is the first small-molecule, water-soluble fluorescent receptor for the specific binding of cytosine free bases in aqueous solution.

Design, synthesis, and structure–activity relationships of indole-3-carboxamides as novel water soluble cannabinoid CB1 receptor agonists

A novel CB1 receptor agonist lead series was identified using a high-throughput screening approach. The initial screen afforded a single confirmed hit with poor water solubility. Structural variations were explored with the aim of introducing water solubility and improving potency. This led to the discovery of Org 28611, a potent, water soluble CB1 receptor agonist, which was selected for clinical evaluation as a potential intravenous analgesic agent.

A water soluble, anion-binding zwitterionic capsule based on electrostatic interactions between self-complementary hemispheres

A water soluble anion receptor is reported that binds bromide in aqueous solution via CH...Br(-) interactions in a dimeric capsule.

Selective Recognition of Uracil and Its Derivatives Using a DNA Repair Enzyme Structural Mimic

During DNA repair, uracil DNA glycosylase (UDG) pulls unwanted uracil into its active site through hydrogen bonding and pi-pi stacking interactions. The reason why UDG binds only uracil tightly--and not its derivatives, such as thymine--remains unclear. In this study, we synthesized the stable, water-soluble receptor 1a as a structural mimic of the active site in UDG. Compound 1a contains a 2,6-bis(glycylamino)pyridine group, which mimics the amino acid residues of UDG that interact with uracil through a hydrogen-bonding network; it also possesses a pyrene moiety as a pi-pi stacking interaction element and fluorescent probe that mimics the aromatic groups (phenyl and fluorescent indolyl units) found in the active site of UDG. Receptor 1a binds selectively to uracil and derivatives (including thymine, 5-formyluracil, 5-fluorouracil, and 5-nitrouracil) and some DNA and RNA nucleosides (including thymidine and uridine) through hydrogen bonding and pi-pi stacking interactions. Interestingly, a plot of log K(b) with respect to the values of pK(a) of the N(3)H units of uracil and its derivatives was linear, with a negative slope (beta) of -0.24 +/- 0.03. Thus, compounds featuring lower values of pK(a) for their N(3)H units provided greater apparent binding constants for their complexes with receptor 1a, suggesting acidity-dependent binding of uracil and its derivatives to this receptor; notably, uracil bound more tightly than did thymine. Our study provides some insight into how uracil and its derivatives in DNA are bound by DNA repair enzymes through hydrogen bonding and pi-pi stacking interactions.

Effect of protein-modifying reagents on water-soluble and membrane bound ovarian LH/hCG receptor.

Preincubation of corpora lutea membrane and follicular fluid water-soluble receptor with protein-modifying reagents suggests that sulfhydryl, histidyl and tyrosyl groups are involved in the interaction of hCG with the receptor.

Effect of phospholipase C induced hydrolysis of phospholipids on membrane-bound and water-soluble LH/hCG receptors in porcine corpora lutea.

The role of phospholipids in the function of LH/hCG receptors was studied in two receptor preparations: the membrane fraction of porcine corpora lutea (CL) and the water-soluble receptor in follicular fluid (LFF) which was characterized. Digestion of CL membranes with phospholipase C (PL-C) abolished, in a dose responsive manner, specific binding of [125I]hCG and decreased phospholipid concentrations in the membranes. This loss of LH/hCG receptors was prevented by o-phenanthroline, an inhibitor of PL-C. A similar effect on membrane-bound receptors was observed when lipids were extracted with ethanol-diethylether. On the other hand, treatment of water-soluble receptors with PL-C or delipidation of LFF with Amberlit IRA 400 had no effect on [125I]hCG specific binding. These data suggest that phospholipids play an important role in the accessibility of membrane-bound receptors but are not involved in direct interaction of gonadotropin with binding sites.