Synthesis of Novel Benzo-15-Crown-5-Tethered β-Cyclodextrins and Their Enhanced Molecular Binding Abilities by Alkali Metal Cation Coordination

Two novel benzo-15-crown-5 tethered β-cyclodextrins 1 and 2have been synthesized by coupling substituted benzo-15-crown-5 with correspondingβ-cyclodextrin derivatives. Their inclusion complexation behavior withrepresentative guests, such as cyclohexanol, cyclohexane carboxylic acid, cyclohexaneacetic acid, sodium cyclohexane carboxylate, and potassium cyclohexane carboxylate,was investigated in aqueous solution by means of fluorescence spectrometry. As compared with parent β-cyclodextrin, benzo-15-crown-5 tethered β-cyclodextrins 1–2 display significantly enhanced molecular binding abilities and selectivities towards model substrates, especially towards substrates containing alkali-metal cations. These results indicate that, bearing two recognition sites in a single molecule, these supramolecular architectures can strongly enhance the molecular binding ability of parent β-cyclodextrin by the cooperative binding of the β-cyclodextrin cavity and the crown ether moiety. Possessing a shorter linker, crown ether-β-cyclodextrin 2 shows much higher binding affinity with guest molecules than crown ether-β-cyclodextrin 1, which may be attributed to the binding size and molecular multiple recognition behavior between host and guest.     

Investigating the hydrogen-bond acceptor site of the nicotinic pharmacophore model: a computational and experimental study using epibatidine-related molecular probes

The binding mode of nicotinic agonists has been thoroughly investigated in the last decades. It is now accepted that the charged amino group is bound by a cation-π interaction to a conserved tryptophan residue, and that the aromatic moiety is projected into a hydrophobic pocket deeply located inside the binding cleft. A hydrogen bond donor/acceptor, maybe a water molecule solvating this receptor subsite, contributes to further stabilize the nicotinic ligands. The position of this water molecule has been established by several X-ray structures of the acetylcholine-binding protein. In this study, we computationally analyzed the role of this water molecule as a putative hydrogen bond donor/acceptor moiety in the agonist binding site of the three most relevant heteromeric (α4β2, α3β4) and homomeric (α7) neuronal nicotinic acetylcholine receptor (nAChR) subtypes. Our theoretical investigation made use of epibatidine 1 and deschloroepibatidine 2 as molecular probes, and was then extended to their analogues 3 and 4, which were subsequently synthesized and tested at the three target receptor subtypes. Although the pharmacological data for the new ligands 3 and 4 indicated a reduction of the affinity at the studied nAChRs with respect to reference agonists, a variation of the selectivity profile was clearly evidenced.     

New tetracyclic heteroaromatic compounds based on dehydroamino acids: photophysical and electrochemical studies of interaction with DNA

A benzothienoindole (BTIN) and a benzofuroindole (BFIN) were synthesized in high yields, as potential new DNA target compounds, using a metal-assisted intramolecular C-N cyclization of the methyl esters of N-(tert-butoxycarbonyl)-β,β-bis(dibenzothien-4-yl or dibenzofur-4-yl)dehydroalanines. The latter were obtained by a bis-Suzuki coupling of a β,β-dibromodehydroalanine with the corresponding heteroarylboronic acids. The absorption and fluorescence properties of the new tetracyclic compounds were studied in different solvents and in the presence of salmon sperm DNA. The results in several solvents show that either BTIN or BFIN can be used as fluorescence solvent sensitive probes. Spectroscopic studies of their interaction with dsDNA allowed to determine binding constant (K_i) values and binding site sizes (n). Fluorescence quenching experiments using iodide ion showed that intercalation is the preferred mode of binding to DNA. From the results obtained, BTIN is the more intercalative compound and has a higher affinity to DNA. The interaction of BTIN with DNA was also studied electrochemically, by using differential pulse voltammetry (DPV) in connection with disposable pencil graphite electrode (PGE). After the interaction of BTIN with DNA, the oxidation signals of BTIN and adenine strongly decreased. The latter result was attributed to the binding of BTIN to DNA and the former points to a possible damage of the oxidizable groups of BTIN after intercalation into DNA. The results of spectroscopic and electrochemical studies of BTIN interaction with DNA are in good agreement.     

Carbohydrate recognition of symmetrical tripodal receptor type tris(2-aminoethyl)amine derivatives

Carbohydrate recognition of some bioactive symmetrical tripodal receptor type tris(2-aminoethyl)amine (TAEA) derivatives was investigated. In calorimetric experiments, the highest binding constant (Ka) of compound C (C₃₅H₄₉N₅O₄S) with methyl α-d-mannopyranoside was Ka = 858 M^?1 with 1:1 stoichiometry. Formation of hydrogen bonds in binding between symmetrical tripodal receptor type compound C and sugars was suggested by the large negative values of ?H° (=?34 to ?511 kJ mol^?1). In a comparison of each set of α- and β-anomers of some monosaccharides (methyl α/β-d-galactopyranoside, methyl α/β-d-glucopyranoside, and methyl α/β-l-fucopyranoside), compound C showed that the binding constant of β-anomer was larger than that of the corresponding α-anomer, indicating higher β-anomer selectivity. The calculated energy-minimized structure of the complex of compound C with guest methyl α-d-mannopyranoside is also presented. The experimental results obtained from this work indicated that symmetrical tripodal receptor type TAEA derivative C has a lectin-like carbohydrate recognition property.     

Dipyrrolylquinoxaline-bridged hydrazones: a new class of chemosensors for copper(II)

Novel 2,3-bis(1H-pyrrol-2-yl)quinoxaline-functionalized hydrazones were prepared and characterized as new chemosensors for copper(II) ion. The binding properties of the compounds 4, 5, 6 and 7 for cations were examined by UV–vis, fluorescence spectroscopy, and linear sweep voltammetric experiments (LSV). The results indicate that a 1:1 stoichiometric complex is formed between compound 4 (or 5, 6, 7) and copper(II) ion, and the association constant is 1.3?×?10⁵ M^?1 for 4, 2.1?×?10⁶ M^?1 for 5, 4.1?×?10⁵ M^?1 for 6 and 8.0?×?10⁵ M^?1 for 7, respectively. The recognition mechanism between compound 4 (or 5, 6, 7) and metal ion was discussed based on their electrochemical properties, absorbance changes, and the fluorescence quenching effect when they interact with each other. Control experiments revealed that compound 4 (or 5, 6, 7) has a highly selective response to copper (II) ion.     

Cyclic voltammetry of phenol

The possibility of phenol determination by cyclic voltammetry (CVA) on electrochemically modified glassy-carbon electrodes (GCE) was studied. The effect of the rate of linear potential sweep on the sensitivity of phenol determination was investigated. The adsorption nature of the analytical signal of phenol was revealed. The formation of the hydroquinone-quinone couple by the electrochemical oxidation of phenol was proved by CVA.     

Investigation of the electro-oxidation and oxidation of catechol in the presence of sulfanilic acid

The electrochemical oxidation of catechol (1) in the presence of sulfanilic acid (2) was investigated. Some electrochemical (EC) techniques such as cyclic voltammetry and controlledpotential coulometry were used. The oxidation reaction of catechol (1) with periodate in the presence of sulfanilic acid (2) was also investigated spectrophotometrically. The results indicate that the o-quinone derived from catechol participate in Michael addition reaction with sulfanilic acid (2). In addition, according to the ECE mechanism, the observed homogeneous rate constant (k _obs) for the reaction ofo-quinone derived from catechol (1) with sulfanilic acid (2) has been estimated by digital simulation of cyclic voltammograms.     

Molecular Recognition and Cooperative Binding Ability of Fluorescent Dyes by Bridged Bisβ-cyclodextrin)s Tethered with Aromatic Diamine

A novel bridged bis(β-cyclodextrin),m-phenylenediimino-bridged bis(6-imino-6-deoxy-β-cyclodextrin) (2), was synthesized by the reaction of m-phenylenediamine and 6-deoxy-6-formyl-β-cyclodextrin. The inclusion complexation behavior of the novel bridged bis(β-cyclodextrin) 2,as well as native β-cyclodextrin (1),p-phenylenediamino-bridged bis(6-amino-6-deoxy-β-cyclodextrin) (3) and 4,4'-bianilino-bridged bis(6-amino-6-deoxy-β-cyclodextrin) (4) with representative fluorescent dye molecules, i.e., acridine red (AR), neutral red (NR), Rhodamine B (RhB), ammonium 8-anilino-1-naphthalenesulfonate (ANS) and sodium 6-toluidino-2-naphthalenesulfonate (TNS), was investigated at 25 °C in aqueous phosphate buffer solution (pH 7.20) by means of fluorescence, and circular dichroism, as well as 2D NMR spectrometry. The spectrofluorometric titrations have been performed to calculate the complex stability constants (K_S) and Gibbs free energy changes (Δ G°) for the stoichiometric 1 : 1 inclusion complexation of 1–4 with fluorescent dye molecules. The results obtained demonstrated that bis(β-cyclodextrin)s 2–4 showed much higher affinities toward these guest dyesthan native β-cyclodextrin 1. Typically, dimer 2 displayed the highest binding ability upon inclusion complexation with ANS, affording 35 times higher K_S value than native β-cyclodextrin. The significantlyenhanced binding abilities of these bis(β-cyclodextrin)s are discussed from thebinding mode and viewpoints of size/shape-fit concept and multiple recognition mechanism.     

Combined Theoretical and Experimental Study of the Complexation of a Hexaarylbenzene-Based Receptor with the Potassium Cation

In this study, non-covalent binding interactions of the hexaarylbenzene-based receptor (R) with the potassium cation have been investigated. Employing quantum mechanical density functional theory calculations, the most probable structure of the KR ⁺ complex species was predicted. In this complex, the K⁺ cation synergistically interacts with the polar ethereal oxygen fence and with the central hydrophobic benzene bottom via cation?C?? interaction. The strength of the KR ⁺ complex was evaluated experimentally by affinity capillary electrophoresis. From the dependence of the effective electrophoretic mobility of the receptor R on the concentration of the potassium ion in the background electrolyte, the thermodynamic binding (stability, association) constant (K _KR) of the KR ⁺ complex in methanol was evaluated as log₁₀?K _KR?=?3.20?±?0.22.     

A theoretical investigation of intermolecular interaction of a phthalimide based “on–off” sensor with different halide ions: tuning its efficiency and electro-optical properties

The interaction between chemosensor, N-(2-methyl-1,3-dioxo-indan-5-yl)-benzamide (1) and different halide ions (F ^? , Cl^? and Br^?) has been investigated using density functional theory (DFT). A clear insight of the sensor anion binding process has been presented. Our calculations revealed that the observed colorimetric and fluorescent signals are induced due to the ground state deprotonation of the sensor molecule caused by F^? which has two times higher binding affinity than other halide ions (Cl^? and Br^?). Derivatives of system 1 have been made to find a better sensor with higher binding affinity and longer wavelength of absorption. All the derivatives are better sensors than the parent 1 except 4-methyl-N-(2-methyl-1,3-dioxo-indan-5-yl)-benzamide (2). Among these derivatives, trimethyl-[4-(2-methyl-1,3-dioxo-indan-5-ylcarbamoyl)-phenyl]-ammonium (8) and (5-benzoylamino-1,3-dioxo-indan-2-yl)-trimethyl-ammonium (9) showed a change to higher binding energies of about 58 Kcal/mol and longer absorption wavelengths of 53 nm after deprotonation process than the parent system 1 which is highly demanded in selective chemical sensing. Systems 8, 9 and their deprotonated zwitterionic forms (8z and 9z) have also been studied for their nonlinear optical responses. Systems 8, 9 showed significantly good first hyperpolarizability (β) of 84 × 10^?30 and 40 × 10^?30 esu, respectively. These β values increase in zwitterionic states up to 216 × 10^?30 and 109 × 10^?30 esu, respectively after deprotonation with F^?, representing a new signal of deprotonation.     

Bi-directional Inclusion Complexation of Methylalkyl Viologens with β-Cyclodextrin and Naphthyl group-Tethered β-Cyclodextrins

Inclusion complexation of methylalkyl viologens(C₁C_nV²⁺; n = 7–10, 12) withmono-6-O-(2-sulfonato-6-naphthyl)-β-CD (1)and mono-6-O-(2-naphthyl)-β-CD (2) werestudied by steady-state and time-resolved fluorescencespectroscopies and compared with the binding of theviologens with native β-CD investigated by induced circulardichroism. The viologens form bimodal complexes with1 and 2, in which the bipyridinium group of theviologens is placed on the primary side (type I complex) andsecondary side (type II complex) of β-CD cavity, while thegroup is predominantly on the secondary side in complexeswith native β-CD. The microscopic binding constantsK_I and K _II were calculated from theanalysis of fluorescence data. The formation of the type Icomplexes with 1 and 2 appears to be largely dueto the charge–transfer interaction between the bipyridinium andnaphthyl groups in the complexes. This work shows thatthe location of the bipyridinium group in β-CDcomplexes and in the type II complexes of the viologens with1 and 2 depends little on the length of alkyl chainof the viologens.     

Electrochemical oxidation of catechol and 4-tert-butylcatechol in the presence of 1-Methyl-1H-imidazole-2-thiol: Synthesis and kinetic study

Electrochemical oxidation of catechol 1a and 4-tert-butylcatechol 1b has been studied in the presence of 1-methyl-1Himidazole- 2-thiol 3 as nucleophile in aqueous solution, using cyclic voltammetry and controlled-potential coulometry. The results indicate the participation of catechol 1a and 4-tert-butylcatechol 1b in Michael reaction with 3 to form the corresponding catechol thioethers 6a and 4b. Based on the observed EC mechanism, the homogeneous rate constants were estimated by comparing the experimental cyclic voltammetric responses with digital simulated results.     

Electrochemical determination of acetaminophen in the presence of propranolol using an electrode modified with a Schiff base from 2-hydroxy-1-naphthaldehyde and ethylenediamine and multi-walled carbon nanotubes

A carbon paste electrode, modified with N,N′-bis-(2-hydroxy-1-naphthalidene)ethylenediamine and multi-walled carbon nanotubes (HNED-MWCNPE), was used for the determination of acetaminophen (ACOP) and propranolol (PP). Cyclic voltammetry (CV), chronocoulometry, chronoamperometry and differential pulse voltammetry (DPV) techniques were employed to study electro-oxidation of ACOP. The results revealed that the modified electrode showed an electrocatalytic activity toward the anodic oxidation of acetaminophen by a marked enhancement in the current response in buffered solution at pH 8.0. Some kinetic parameters such as the electron transfer coefficient (α) were also determined for the ACOP oxidation. The linear concentration range of 1 × 10^?3?1 × 10^?6 M with a detection limit of 4.6 × 10^?8 M (n = 16) for ACOP was obtained using DPV (pH 8.0). The modified electrode shows good sensitivity, selectivity and stability. The prepared electrode was also applied for the determination of ACOP in human blood serum.     

Synthesis of two new p-tert-butylcalix[4]arene β-ketoimin derivatives for extraction of dichromate anion

In this study the selective derivatization of p-tert-butylcalix[4]arene was carried out and two new p-tert-butylcalix[4]arene β-ketoimin, 5,11,17,23-tetra-tert-butyl-25,27-bis-3-methyl-[(β-ketoimine)-ethoxy]-26,28-dihydroxycalix[4]arene (4), and 5,11,17,23-tetra-tert-butyl-25,27-bis-3-chloro-[(β-ketoimine)-ethoxy]-26,28-dihydroxycalix[4]arene (5) have been synthesized. In the synthesis, the lower rim of p-tert-butylcalix[4]arene was modified in order to acquire binding site for the recognition of dichromate anion. It was observed that these ionophores 4 and 5 showed high affinity towards dichromate anion. The protonated Schiff-base forms of the receptors were effective for transferring the HCr₂O₇ ^? anion from aqueous phase to a dichloromethane phase.     

Reaktionen mit phosphororganischen Verbindungen, 38. Mitt.: Zur Reaktivität von β-Cyanovinyl-triphenylphosphoniumbromid

β-Cyanovinyl-triphenylphosphonium bromide (1) rearranges to (2-cyano-1-phenylethyl)diphenylphosphine oxide (2) on treatment with alkali.1 reacts with NaN₃ to 5-triphenyl-phosphonium-1.2.3-triazole-ylide (3) and with cyclopentadiene to (5-cyano-bicyclo[2.2.1]hepten-2-yl-6)triphenylphosphonium bromide (4). Reaction of1 with thioamides leads to (α-cyano-β-amino-β-alkyl)-allyl-triphenylphosphonium hromides (6) together with [(2-alkyl-4-aminothiazolyl)-5-methyl]triphenylphosphonium bromides (5). (2-amino-3-imidazo[1.2—α]pyridinyl) methyl]triphenylphosphonium bromide (7) results from reaction of1 with 2-aminopyridine, [(2-amino-3-imidazo[1.2—α]pyrimidinyl)methyl]triphenylphosphonium bromides (8 and9) from 2-aminopyrimidine and 2-amino-4-6-dimethylpyrimidine resp.     

Nanostructure-based electrochemical sensor for determination of glutathione in hemolysed erythrocytes and urine

A sensitive and selective electrochemical method was developed for the determination of glutathione (GSH) in hemolysed erythrocyte using vinylferocene modified carbon nanotubes paste electrode (VFMCNTPE). The results indicate that the electrode is efficient in terms of its electrocatalytic activity for the oxidation of GSH, leading to a reduced overpotential by more than 470 mV. Also, the values of catalytic rate constant (k), and diffusion coefficient (D) for GSH were calculated. The electrocatalytic oxidation peak current of GSH showed two linear dynamic ranges with a detection limit of 0.09 μM GSH. The linear calibration ranges were obtained between 0.2–4.0 and 4.0–250.0 μM GSH using square wave voltammetry (SWV) method. The proposed method was also examined as a selective, simple and precise electrochemical sensor for the determination of GSH in real samples such as urine and hemolysed erythrocyte.     

Anion binding properties of indolylmethanes

The anion binding properties of the indolylmethanes (1) were investigated by ¹H-NMR spectroscopy in CDCl₃. Tris(3-methylindol-2-yl)methane (1a) selectively bound a chloride anion the over other tested anions (Br^?, I^?, HSO ₄ ^? , and NO ₃ ^? ). In contrast, analogous compounds, phenyl bis(3-methylindol-2-yl)methane (1b), 2-hydroxyphenyl bis(3-methylindol-2-yl)methane (1c), tri(indol-3-yl)methane (1d), and phenyl di(indol-2-yl)methane (1e), showed a low anion binding ability and selectivity. These results indicate that the number and a position of the binding sites (indole NH protons) of the indolylmethanes are important factors for the formation of the complex with an anion. The high binding ability and selectivity of 1a toward a chloride anion is attributed to the proper size of the binding pocket for a chloride anion and the formation of multiple hydrogen bonds between the three indole NH protons and a chloride anion. The anion affinity of 1a was significantly affected by the cation component of quaternary ammonium salts, indicating that it is ion pair binding and not solely anion binding.     

DFT studies on inclusion complexes of 1-phenyl-1-propanol enantiomers with modified cyclic decapeptides

The inclusion complexes of two modified cyclic decapeptides with 1-phenyl-1-propanol (PP) enantiomers were first studied using the density functional theory B3LYP method. Our calculated results indicated that modified cyclic decapeptide (CM-CDP and DA-CDP) could form stable inclusion complexes. Significantly, based on the structural characteristics and hydrogen bond analyses, we found that the primary driving force of inclusion complex formation is a cooperative work of hydrogen bonds, steric effect, and electronic interactions, which facilitates the enhancement of binding affinity of the PP enantiomers with CM-CDP and DA-CDP. The current study shows that modified cyclic decapeptide is a desirable host molecule for chiral and molecular recognition.     

Biaryl-based anion receptors bearing thiourea groups: fluoride anion receptor

The synthesis, characterization and binding studies with anions for biaryl-based anion receptors bearing thiourea groups have been described. The results revealed that receptors (1 and 2) showed good selectivity and binding affinity for F^?, and among them binaphthyl-based receptor (1a) showed the best binding affinity for F^? in comparison to other tested anions (Cl^?, Br^?, I^?, $ {\text{NO}}_{3}^{ - } ,\;{\text{HSO}}_{4}^{ - } , $ AcO^? and $ {\text{H}}_{2} {\text{PO}}_{4}^{ - } $ ). This is probably due to the fact that the moderate rigidity of binaphthyl skeleton in 1a is able to provide the better geometry of two thiourea groups for incorporating F^? into the binding pocket. The higher basicity of F^? also participated in this selectivity.     

Voltammetric determination of cadmium (II) based on a composite film of a thiol-functionalized mesoporous molecular sieve and an ionic liquid

A composite film made from a thiol-functionalized mesoporous molecular sieve and an ionic liquid is introduced for use in a voltammetric sensor for Cd(II). The electrode exhibits excellent sensitivity towards Cd(II) in showing a markedly increased stripping peak current. Following the optimization of the experimental parameters, a linear response is obtained in the concentration range from 29?nM to 0.87?mM of Cd(II). The detection limit is as low as 1.0?nM (at S/N?=?3) after an accumulation at ?1.1?V for 4?min. The method was successfully applied to determine Cd(II) in water samples. Features such as large electroactive area, fast electron transfer and low background current make this electrode a promising platform for fabricating reliable electrochemical sensors for various species, such as heavy metals and environmental pollutants.