In silico analysis of the histaprodifen induced activation pathway of the guinea-pig histamine H<Subscript>1</Subscript>-receptor

The binding of (partial) agonists in the binding pocket of biogenic amine receptors induces a conformational change from the inactive to the active state of the receptors. There is only little knowledge about the binding pathways of ligands into binding pocket on molecular level. So far, it was not possible with molecular dynamic simulations to observe the ligand binding and receptor activation. Furthermore, there is nearly nothing known, in which state of ligand binding, the receptor gets activated. The aim of this study was to get more detailed insight into the process of ligand binding and receptor activation. With the recently developed LigPath algorithm, we scanned the potential energy surface of the binding process of dimeric histaprodifen, a partial agonist at the histamine H₁-receptor, into the guinea pig histamine H₁-receptor, taking also into account the receptor activation. The calculations exhibited large conformational changes of Trp^6.48 and Phe^6.55 during ligand binding and receptor activation. Additionally, conformational changes were also observed for Phe^6.52, Tyr^6.51 and Phe^6.44. Conformational changes of Trp^6.48 and Phe^6.52 are discussed in literature as rotamer toggle switch in context with receptor activation. Additionally, the calculations indicate that the binding of dimeric histaprodifen, accompanied by receptor activation is energetically preferred. In general, this study gives new, theoretical insights onto ligand binding and receptor activation on molecular level.     

Benzimidazole-based ratiometric fluorescent receptor exhibiting molecular logic gate for Cu and Fe

We synthesized a novel fluorescent receptor based upon a benzimidazole moiety in a dipodal framework. The receptor exhibited a dual fluorescence emission which is quenched upon addition of Cu²⁺ or Fe³⁺. Interestingly, the receptor offers a ratiometric property and an ‘OR’ logic gate property to Cu²⁺ and Fe³⁺.     

A chemosensor showing discriminating fluorescent response for highly selective and nanomolar detection of Cu and Zn and its application in molecular logic gate

A fluorescent based receptor (4Z)-4-(4-diethylamino)-2-hydroxybenzylidene amino)-1,2dihydro-1,5-dimethyl-2-phenylpyrazol-3-one (receptor 3) was developed for the highly selective and sensitive detection of Cu²⁺ and Zn²⁺ in semi-aqueous system. The fluorescence of receptor 3 was enhanced and quenched, respectively, with the addition of Zn²⁺ and Cu²⁺ ions over other surveyed cations. The receptor formed host-guest complexes in 1:1 stoichiometry with the detection limit of 5 nM and 15 nM for Cu²⁺ and Zn²⁺ ions, respectively. Further, we have effectively utilized the two metal ions (Cu²⁺ and Zn²⁺) as chemical inputs for the manufacture of INHIBIT type logic gate at molecular level using the fluorescence responses of receptor 3 at 450 nm.     

A Selective Colorimetric and Fluorescent Chemodosimeter for Fe(III) Ion Based on Hydrolysis of Schiff Base

An efficient colorimetric and fluorescent chemodosimeter for Fe³⁺ ions has been developed. The visual and fluorescent behaviors of the receptor toward various metal ions were investigated. The receptor shows exclusive response toward Fe³⁺ ions and also distinguishes Fe³⁺ from other cations by color change and unusual fluorescence enhancement in aqueous solution (DMSO/H₂O = 4/1, v/v). Thus, the receptor can be used as a colorimetric and fluorescent sensor for the determination of Fe³⁺ ion. The visual color detection limit and the fluorescence detection limit of the receptor towards Fe³⁺ are (1.42 ± 0.01) × 10^‐6 M and (7.57 ± 0.04) × 10^‐8 M, respectively. The fluorescence microscopy experiments showed that the receptor is efficient for detection of Fe³⁺ in vitro, developing a good image of the biological organelles. The sensing mechanism is proven to be a hydrolysis process     

A benzimidazole-based fluorescent sensor for Cu2+ and its complex with a phosphate anion formed through a Cu2+ displacement approach

A benzimidazole-based imine linked receptor was synthesized for fluorescent recognition of Cu²⁺ in a CH₃CN/H₂O (8:2, v/v) solvent system. The receptor offers an opportunity for the selective estimation of Cu²⁺ in the presence of another metal ion at equimolar concentration. The Cu²⁺ complex with the receptor acted as a sensor for a phosphate anion, and the phosphate recognition event restored the fluorescence intensity of the receptor.     

Single sensor for multiple analytes: fluorogenic detection of Al3+ in aqueous media and AcO− in organic media

A simple novel receptor, designed to have a combination of both oxygen and nitrogen-binding sites for metal ion and hydrogen bond donor sites for anion, was synthesised. The receptor has been explored for the selective detection of cation Al³⁺ over the other interfering metal ions and anion AcO^?  against a range of physiologically relevant anions in the fluorescence spectroscopy. The receptor shows a different response to aluminium and acetate in the emission spectra. The binding isotherm and detection limit demonstrate that the receptor is an excellent fluorometric probe for Al³⁺ and AcO^? .     

Colorimetric anion chemosensor based on 2-aminobenzimidazole: naked-eye detection of biologically important anions

We synthesized a novel colorimetric anion chemosensor bearing benzimidazole motifs as recognition sites in the pods of the receptor. The addition of tetrabutylammonium salts of F⁻ or AcO⁻ to the solution of receptor caused dramatic color changes from colorless to yellow, which was clearly visible to the naked eye. The receptor showed no significant changes on addition of other anions such as Cl⁻, Br⁻, I⁻, NO₃⁻, and H₂PO₄⁻.     

Highly Fe selective ratiometric fluorescent probe based on imine-linked benzimidazole

We synthesized a novel benzimidazole-based fluorescent receptor bearing imine linkages with two sets of sp² nitrogens, and investigated its binding properties toward various metal ions. The receptor exhibited a shift in emission band upon binding with Fe³⁺ ions, and no such significant response was noticed in other metal ions. The receptor shows a property of selective ratiometric fluorescent probe of Fe³⁺ ions without interferences of the background metal ions.     

The agonistic binding site at the histamine H2 receptor. II. Theoretical investigations of histamine binding to receptor models of the seven α-helical transmembrane domain

Summary In the first part (pp. 461–478 in this issue) of this study regarding the histamine H₂ receptor agonistic binding site, the best possible interactions of histamine with an -helical oligopeptide, mimicking a part of the fifth transmembrane -helical domain (TM5) of the histamine H₂ receptor, were considered. It was established that histamine can only bind via two H-bonds with a pure -helical TM5, when the binding site consists of Tyr¹⁸²/Asp¹⁸⁶ and not of the Asp¹⁸⁶/Thr¹⁹⁰ couple. In this second part, two particular three-dimensional models of G-protein-coupled receptors previously reported in the literature are compared in relation to agonist binding at the histamine H₂ receptor. The differences between these two receptor models are discussed in relation to the general benefits and limitations of such receptor models. Also the pros and cons of simplifying receptor models to a relatively easy-to-deal-with oligopeptide for mimicking agonistic binding to an agonistic binding site are addressed. Within complete receptor models, the simultaneous interaction of histamine with both TM3 and TM5 can be analysed. The earlier suggested three-point interaction of histamine with the histamine H₂ receptor can be explored. Our results demonstrate that a three-point interaction cannot be established for the Asp⁹⁸/Asp¹⁸⁶/Thr¹⁹⁰ binding site in either of the investigated receptor models, whereas histamine can form three H-bonds in case the agonistic binding site is constituted by the Asp⁹⁸/Tyr¹⁸²/Asp¹⁸⁶ triplet. Furthermore this latter triplet is seen to be able to accommodate a series of substituted histamine analogues with known histamine H₂ agonistic activity as well.     

Ratiometric fluorescent determination of Zn(II): a new class of tripodal receptor using mixed imine and amide linkages

We synthesized a novel receptor with a unique combination of sp² nitrogen (-CHN-) and carbonyl groups from amide linkages. These two moieties are judiciously incorporated into the receptor design such that these sites simultaneous binding a metal ion may generate a stable five-member ring. The receptor has been used to selectively detect Zn²⁺ through changes in the fluorescence spectra. Upon Zn²⁺ binding with the receptor, the fluorescence band shifted to enhance fluorescence intensity, allowing ratiometric determination of Zn²⁺ concentration.     

Dipodal fluorescent chemosensor for Cu and resultant complex as a chemosensor for iodide

A dipodal receptor was synthesized by condensation of isophthalaldehyde and p-toluenesulfonylhydrazide. The receptor was found to be selective for Cu²⁺ recognition in CH₃CN. The resultant Cu²⁺ receptor complex selectively recognized iodide through cation displacement assay in a CH₃CN/H₂O (8:2, v/v) solvent system.     

A new tripodal anion receptor with selective binding for H2PO4 and F ions

The anions binding properties of the pyrrole-based tripodal anion receptor 1 were studied by X-ray crystallography, ¹H NMR, and ESI-MS. It revealed that this new tripodal receptor has a preference for binding H₂PO₄⁻ and F⁻ ions.     

Benzimidazole-based chromogenic chemosensor for the recognition of oxalic acid via counter ion displacement assay in semi-aqueous medium

An azo dye-coupled benzimidazole-based receptor 1 was synthesized and investigated as a receptor for metal ions in semi-aqueous medium. The receptor recognizes Cu²⁺ with high selectivity over other metal ions. The resultant complex 1·Cu²⁺ was found to selectively bind oxalic acid via counter ion displacement.     

A theoretical study on the importance of steric effects,electronic properties,interaction and solvation energies in the ‘host–guest’ chemistry of protonated azacryptands and halide anions

It is well known that the selectivity of a receptor for an anion depends on the compatibility of the cavity size of the receptor and the size of the anion. In this work the macrobicyclic [H₆L(X)]⁵⁺ (X⁻=F, Cl, Br); are studied theoretically and compared with [H₆L′(F)]⁵⁺ having a smaller cavity size. It was shown that the ideal match between the sizes of the protonated azacryptand and the fluoride ion exists in the [H₆L′(F)]⁵⁺ complex but the [H₆L]⁶⁺ is a better receptor than [H₆L′]⁶⁺ in solution. Thus the results clearly indicate that in some special cases a better receptor is not one whose cavity size has better compatibility with the anion size.     

Synthesis and electrochemical sensing behaviour of a new ferrocene functionalized tet ‘a’ macrocyclic receptor towards transition metal ions

A new ferrocene functionalized macrocyclic receptor 1,8‐bis(ferrocenylmethyl)‐5,5,7,12,12,14‐hexamethyl‐1,4,8,11‐tetraazacyclotetradecane (R) has been designed and synthesized to study its potential application as chemosensor. The receptor has been characterized by spectral techniques and X‐ray diffraction. The compound crystallizes in the orthorhombic space group Pcab with four molecules in a unit cell (half‐a‐molecule in the asymmetric unit). The electrochemical studies of the receptor in dioxane–water (7:3 v/v, 25 °C) indicate that the receptor is pH‐dependent with a displacement of E_1/2 to more anodic potentials with a decrease in the pH from 12 to 5. The electrochemical behaviour of R was also studied in the presence of Mn²⁺, Co²⁺, Ni²⁺, Cu²⁺ and Zn²⁺ in dioxane–water (7:3 v/v, 25 °C, [Buⁿ₄N][ClO₄]), showing that upon complexation the ferrocene–ferrocenium half‐wave potential shifts anodically in relation to that of the free receptor. The maximum electrochemical shift (ΔE_1/2) of 46 mV was found in the presence of Cu²⁺, followed by Co²⁺ (20 mV), Mn²⁺ (15 mV), Ni²⁺ (13 mV) and Zn²⁺ (9 mV). Moreover, the receptor R is able to electrochemically and selectively sense Cu²⁺ in the presence of the other transition metal cations studied. Copyright © 2007 John Wiley & Sons, Ltd.     

Synthesis of Schiff Base Bearing Phenolic Hydroxy Group and Its Anion Recognition

A new anion receptor bearing phenolic hydroxy group based on 3,5-ditertbutylsalicylaldehyde-p-nitrophenylhydrazone (1) was designed and synthesized. Upon addition of AcO^- and F^-, the receptor exhibited visible color changes from deep yellow to purple. However, no obvious color changes were observed on addition of the other anions tested (H₂PO₄^-, Cl^-, Br^-, I^-). The binding properties of the receptor with anions such as AcO^- and F^- were investigated by UV-Vis and fluorescent titrations. The result indicated that the receptor 1 had a higher affinity to AcO^- and F^- and a 1:1 host-guest complex was formed through H-bond interactions between 1 and anions.     

Recognition of anions and monocarboxylic acids by a fluorescent guanidine-based receptor

A guanidine-based fluorescent receptor has been synthesised to study its binding behaviour towards anions (F^? , Cl^? , Br^? , I^?  and AcO^? ). The two donor N–H bonds of the receptor do not point in the same direction; rather, one N–H bond is intramolecularly hydrogen-bonded with the carbonyl oxygen atom. The nature of the donor–acceptor (DA) arrangement induces moderate binding properties. The binding behaviour towards monocarboxylic acids (benzoic acid and phenylacetic acid) is also compared. The binding behaviour of receptor 1 towards the F^?  anion is higher among the anions studied, whereas in the case of monocarboxylic acid, the binding constant with phenylacetic acid is higher than benzoic acid.     

Selective detection of F− by chromogenic tetrazole receptor

A chromogenic anion host 4, containing two amide functionalities linked to azo dye and tetrazole rings, was synthesised and its complexes with various anions were investigated. The results show that receptor 4 can recognise selectively biologically important F^?  ion. The binding affinity for F^?  was investigated by naked-eye colour change, UV–vis and ¹H NMR spectroscopy. Addition of F^?  ion in CH₃CN and Dimethyl sulfoxide to receptor 4 causes a change in colour of the solution from colourless to yellow. The stoichiometry for host:anion is 1:1. Furthermore, receptor 4 was used as an ion carrier in ion-selective membrane electrodes. Selectivity of this membrane was studied towards various anions in water solution. Binding behaviour of receptor 4 towards several anions (Cl^? , F^? , Br^? , I^? ) has been investigated using density functional theory calculations.     

Enhanced fluorescence detection of metal ions using light-harvesting mesoporous organosilica

Enhanced fluorescence detection of metal ions was realized in a system consisting of a fluorescent 2,2′‐bipyridine (BPy) receptor and light‐harvesting periodic mesoporous organosilica (PMO). The fluorescent BPy receptor with two silyl groups was synthesized and covalently attached to the pore walls of biphenyl (Bp)‐bridged PMO powder. The fluorescence intensity from the BPy receptor was significantly enhanced by the light‐harvesting property of Bp‐PMO, that is, the energy funneling into the BPy receptor from a large number of Bp groups in the PMO framework which absorbed UV light effectively. The enhanced emission of the BPy receptor was quenched upon the addition of a low concentration of Cu²⁺ (0.15–1.2×10^?6 M ), resulting in the sensitive detection of Cu²⁺. Upon titration of Zn²⁺ (0.3–6.0×10^?6 M ), the fluorescence excitation spectrum was systematically changed with an isosbestic point at 375 nm through 1:1 complexation of BPy and Zn²⁺ similar to that observed in BPy‐based solutions, indicating almost complete preservation of the binding property of the BPy receptor despite covalent fixing on the solid surface. These results demonstrate that light‐harvesting PMOs have great potential as supporting materials for enhanced fluorescence chemosensors.     

Highly sensitive and selective determination of Hg2+ by using 3-((2-(1H-benzo[d]imidazol-2-yl)phenylimino)methyl)benzene-1,2-diol as fluorescent chemosensor and its application in real water sample

A new receptor 3-((2-(1H-benzo[d]imidazol-2-yl)phenylimino)methyl)benzene-1,2-diol (1) was synthesised and developed as a highly selective fluorescent chemosensor for the detection of Hg²⁺ in semi-aqueous media. The fluorescence of receptor 1 was dramatically and selectively quenched on complexation with Hg²⁺ ion with the detection limit down to 0.20 μM. The developed sensor was successfully applied for the determination of Hg²⁺ content in water samples. Density Functional Theory (DFT) calculations were performed to study the mechanistic behaviour behind the binding of Hg²⁺ with receptor 1.