The conformational and binding properties of ethylbipyridinio-modifiedβ-Cyclodextrin using induced circular dichroism

The conformational and binding properties of mono-6-deoxy-6[4-(1-ethyl-4-pyridinio)-1-pyridinio]--cyclodextrin (1) in complex formation with some guest compounds were examined by induced circular dichroism (ICD) spectra in aqueous solution. Compound 1 showed much stronger binding ability for some guest compounds (1: 1 complexes), compared with-cyclodextrin (-CDx) and a positively charged -CDx [C-6-mono-pyridino--CDx (2)]. Marked conformational changes of1 (the spatial position of the ethyl viologen (C₂V²⁺) group relative to the cavity in 1) were observed upon complex formation with some guests like 1-adamantanecarboxylic acid (ACA) and sodium cholate (SC).     

Validation of the AmpC β-lactamase binding site and identification of inhibitors with novel scaffolds

AmpC β-lactamase confers resistance to β-lactam antibiotics in multiple Gram-negative bacteria. Therefore, identification of non-β-lactam compounds that inhibit the enzyme is considered crucial to the development of novel antibacterial therapies. Given the highly solvent-exposed active site, it is important to study the induced-fit movements and water-mediated interactions to improve docking accuracy and virtual screening enrichments in structure-based design of new AmpC inhibitors. Here, we tested multiple models of the AmpC binding site to investigate the importance of conserved water molecules and binding site plasticity on molecular docking. The results indicate that at least one conserved water molecule greatly improves the binding pose predictions and virtual screening enrichments of known noncovalent AmpC inhibitors. The best model was tested prospectively in the virtual screening of about 6 million commercially available compounds. Sixty-one chemically diverse top-scoring compounds were experimentally tested, which led to the identification of seven previously unknown inhibitors. These findings validate the essential features of the AmpC binding site for molecular recognition and are useful for further optimization of identified inhibitors.     

Synthesis and characterization of a novel amphiphilic copolymer containing β-cyclodextrin

In this article, maleic anhydride was used to attain the modified β-cyclodextrin (MAH-β-CD), and the MAH-β-CD was copolymerized with acrylamide (AM), acrylic acid (AA), and 2-acrylamido-2-methyl propane sulfonic acid (AMPS) via free radical copolymerization. The polymerization conditions were optimized through single-variable method. Subsequently, the copolymer structure was characterized through Fourier transform infrared (FTIR) spectroscopy, proton nuclear magnetic resonance (¹HNMR) spectroscopy, and scanning electron microscopy (SEM). The three-dimensional network structure formed in aqueous solutions was observed via experimental results of SEM. Subsequently, several aspects of the properties of the copolymer, such as temperature tolerance, shear tolerance, salt resistance, and oil displacement ability, were investigated by comparing with hydrolyzed polyacrylamide (HPAM). Results indicate that the copolymer showed better performances than HPAM; thus, it could be concluded that the introduction of β-cyclodextrin in the polymer chain was helpful in enhancing the oil displacement efficiency in high-temperature and high-salinity oil field.     

A novel method for simultaneous analysis of three β2-agonists in foods with the use of a gold-nanoparticle modified glassy carbon electrode and chemometrics

An electrochemical method involving a gold nanoparticle modified glassy carbon electrode (AuNPs/GCE) was researched and developed for the simultaneous analysis of three β(2)-agonists, ractopamine (RAC), salbutamol (SAL) and clenbuterol (CLB). The three analytes were electrocatalytically oxidized at the AuNP/GCE, which enhanced the oxidation peak current and influenced the shift of the oxidation potentials to lower values in comparison with the analysis involving only the GCE. The differential pulse stripping voltammetry (DPSV) voltammograms from the drug mixture produced complex, overlapping profiles, and chemometrics methods were applied for calibration modeling. The peak currents associated with RAC, SAL and CLB measurements were linear as a function of their concentrations (ranges within 0.005-0.150 μg mL(-1)); the detection limits for RAC, SAL and CLB were 2.4, 5.8 and 2.6 ng mL(-1), respectively. It was shown that satisfactory quantitative results were obtained with the use of the MVC1 package of chemometrics methods e.g. the PLS1 calibration model produced a relative prediction error (RPE(T)) of 7.0% and an average recovery of 97.6%. The above AuNP/GCE was successfully employed for the simultaneous analysis of RAC, SAL and CLB in pork meat, liver and pig feed samples.     

Investigation of the inclusion complex of tolfenamic acid with β-cyclodextrin: Geometry and NBO analysis

Quantum chemical calculations were carried out to investigate geometry and driving forces for inclusion complexes of tolfenamic acid (TA) into β-CD (at 1:1 stoichiometry). Two possible orientations of TA in the β-CD cavity were considered. Both PM3MM and ONIOM2 method evidence that TA is encapsulated in the β-CD cavity for A and B orientation. Finally, charge transfer between the donor and acceptor orbitals of each TA and β-CD play an important role to stabilize the inclusion complex.     

The structural analysis of the inclusion complex of β-cyclodextrin with m-nitrophenoxyacetic acid

The inclusion complex of β-cyclodextrin with m-nitrophenoxyacetic acid was studied by single crystal X-ray diffraction,2D NMR spectroscopy and semi-empirical methods AMI.The crystallographic study shows that two β-cyclodextrins are held together by hydrogen bonds to form head-to-head dimers.The disordered guest molecule adjusts itself to attain the most stable accommodation into the cavity in which the nitro group is located at the dimer interface while the carboxyl group is buried in the primary hydroxyl groups of β-cyclodextrin.The guest inside the cavity is disordered over two sites and exhibits mobility.Moreover,2D NMR spectroscopy and theoretical study show the same inclusion behavior.In comparison to the inclusion complex of β-cyclodextrin with p-nitrophenoxyacetic acid,the host-guest stoichiometries are different,i.e.,2:1 for m-nitrophenoxyacetic acid and 1:1 for p-nitrophenoxyacetic acid,while the inclusion orientation and the packing pattern of the host are similar in both complexes.     

Rapid formation of β-allyl substituted isotetronic acid derivatives via Claisen rearrangement using a microfludic device

The thermal Claisen rearrangement of O-allyl substituted isotetronic acids 1 was successfully carried out within a glass microreactor operated with temperature at 150℃and a flow rate of 1 mL/h.The strategy provides an efficient alternative way toβ-allyl substituted isotetronic acid derivatives 2 in high yields with much accelerated reaction speed.     

Synthesis of a novel β-cyclodextrin derivative with high solubility and the electrochemical properties of ferrocene-carbonyl-β-cyclodextrin inclusion complex as an electron transfer mediator

A facile strategy for preparing water-soluble β-cyclodextrin derivative, carbonyl-β-cyclodextrin, was developed by partial oxidation of β-cyclodextrin. The solubility of carbonyl-β-cyclodextrin was greatly enhanced due to the breaking of intramolecular hydrogen bond network of β-cyclodextrin. Ferrocene was included into the cavity of carbonyl-β-cyclodextrin to form Fc-carbonyl-β-cyclodextrin inclusion complex. The electrochemical properties of Fc-carbonyl-β-cyclodextrin were studied. The Fc-carbonyl-β-cyclodextrin complex exhibited high solubility and was shown to be good electrochemical probe and efficient mediator for bioelectrocatalysis of glucose oxidase. The bioelectrocatalytic efficacy of Fc-carbonyl-β-cyclodextrin complex opened up homogeneous applications of ferrocene in amperometric biosensor systems.     

Electrochemical chiral recognition of tryptophan using a glassy carbon electrode modified with β-cyclodextrin and graphene

We report on a method for electrochemical enantioselective recognition of tryptophan (Trp) enantiomers. It is based on competitive host-guest interaction between a deoxy-(2-aminoethylamino)-β-cyclodextrin (CD) bound to graphene nanosheets and the Cu(II) complexes of the Trp enantiomers via a ligand exchange mechanism. Chiral recognition was investigated via cyclic voltammetry and electrochemical impedance spectroscopy. The results reveal that the CD bound to graphene displays a stronger interaction with the Cu(II) complex of L-Trp than to that of D-Trp. The method was applied to the determination of the ratio of Trp enantiomers in mixtures.

The optical activity of β,γ-enones in ground and excited states using circular dichroism and circularly polarized luminescence

The circularly polarized luminescence (CPL) and electronic circular dichroism (CD) spectroscopic parameters corresponding to the n←π* and n→π* transitions, respectively, have been calculated for selected β,γ-enones using density functional theory. For the smallest β,γ-enone, (1R,4R)-bicyclo[2.2.1]hept-5-en-2-one (norbornenone), coupled-cluster calculations have also been carried out. The excited-state potential energy surface for three of the five enones studied reveals two minima with different C[double bond, length as m-dash]OC[double bond, length as m-dash]C dihedral angles, and with rotatory strengths of opposite sign. The relative energies of the minima determine the sign of the CPL intensity, which may be the same or opposite as in the CD spectrum, in agreement with experimental data. The results obtained in this first computational study of CPL demonstrate its usefulness as an indicator of excited-state structures of chiral species.     

C-hexylpyrogallol[4]arene and β-cyclodextrin as directors of the mode of binding of Coumarin 153 with DNA

The supramolecular interaction between calf thymus DNA (ctDNA) and Coumarin 153 in the presence of β-cyclodextrin (β-CD) or C-hexylpyrogallol[4]arene (C-HPA) was studied. Inclusion complexes of Coumarin 153 with β-CD and C-HPA were characterised by infrared spectroscopy, proton nuclear magnetic resonance spectroscopy and two-dimensional rotating-frame nuclear overhauser effect spectroscopy. The inclusion complexation was further followed by steady-state and time-resolved fluorescence measurements. The influence of β-CD or C-HPA in the binding strength and binding model of C153 with ctDNA was studied by UV–visible, fluorescence and molecular modelling technique. The possible group of interaction of Coumarin 153 with DNA, β-CD and C-HPA was shown by molecular modelling technique.     

Rapid hydrolysis of phosphate ester promoted by Ce(IV) conjugating with a β-cyclodextrin monomer and dimer

Two N-donor ligands (L(1) and L(2)) derived from a β-cyclodextrin (βCD) monomer and dimer were employed to mediate the hydrolytic activity and stability of the Ce(IV) ion in aqueous solution. Complexes Ce(IV)-L(1) and Ce(IV)-L(2) were prepared in situ and characterized by means of UV-vis and NMR measurements. Ce(IV)-L(1) catalyzed the hydrolysis of a DNA model, bis(4-nitrophenyl)phosphate (BNPP) with k(cat) = 5.2 × 10(-3) s(-1) (half-life t(1/2) ≈ 2 minutes) under mild conditions, which represented an approximate 130 million-fold acceleration with respect to the spontaneous hydrolysis of BNPP. The dinuclear species, [Ce(2)L(1)(2)(OH)(5)](3+), contributed splendidly to the catalytic efficiency which echoed the active species postulation of [Ce(2)(OH)(7)](+) in the literature. Ce(IV)-L(2) exhibited efficient binding with BNPP giving 1/K(M) = 2.1 × 10(5) M(-1) which exceeded other Ce(IV) species, e.g. [Ce(4)(OH)(15)](+), by 2 orders of magnitude, which highlighted the hydrophobicity effect of βCDs. Such a highly binding affinity leads to the second-order rate constant, k(cat)/K(M) = 2.3 × 10(2) M(-1) s(-1), which probably ranks as the highest in the non-enzymatic cleavage of BNPP under similar conditions. Additionally, Ce(IV)-L(2) showed favorable tolerance to basic aqua owing to the bulky protection of double βCD pendants.     

Pharmacology and structures of the free base of the anaesthetic kazcaine and its complex with β-cyclodextrin

The base form of the local anaesthetic kazcaine (BFK, [1-(2-ethoxyethyl)-4-ethynyl-4-benzoyloxypiperidine, C₁₈H₂₃NO₃]) and β-cyclodextrin (β-CD) co-crystallized as BFK:β-CD inclusion complex in 1:2 M ratio from a mixture of water and ethanol while the filtered mother liquor yielded crystals of free BFK. X-ray diffraction showed that the crystals of BFK and its inclusion complex with β-CD belong to monoclinic (P2₁/c) and triclinic (P1) space groups, respectively. The crystals of free BFK are stabilized by pairs of C–H?O, C–H?π and ≡C–H?O type interactions and van der Waals contacts. In the 1:2 BFK:β-CD complex the two β-CD molecules are in hydrogen-bonding contact with their primary hydroxyl groups, the 1-(2-ethoxyethyl)-4-ethynyl-piperidine moiety being located in one and the benzoyloxy group of BFK in the other β-CD. This crystal structure is of the channel-type, the β-CD molecules of the 1:2 BFK:β-CD complex interacting with their secondary hydroxyl groups. The pharmacological activities of the 1:2 BFK/β-CD inclusion complex have been determined in mice, rats, porpoises and rabbits and compare favourably with those of kazcaine, procaine, dicaine, lidocaine and trimecaine. The methods used include terminal (superficial), infiltration, conduction anaesthesia, and acute toxicity.     

Properties and separation method of enantiomers of the mono- and bis-substituted derivatives of 3,3′,4,4′-tetramethyl-1,1′-diphosphaferrocene: structural analysis using X-ray diffraction and circular dichroism

This work expands on the recent separation of the enantiomers of the C₂-symmetrical bis-substituted derivatives of 1,1′-diphosphaferrocene. The effective separation of mono-substituted 1,1′-diphosphaferrocenes by the proposed method is demonstrated. The absolute configuration of the three separated components was established using X-ray diffraction. Circular dichroism spectra were collected for all of the separated compounds. The spectrum of each compound shows a characteristic curve, and the curves for the enantiomers are symmetrical. We also show that the correct absolute configuration for similar species can be assigned on the basis of the obtained data. We propose an explanation for the abnormal ¹H NMR spectra of phospholyl protons in some derivatives of 1,1′-diphosphaferrocene. A density functional theory (DFT) study of the conformation, as well as circular dichroism and NMR spectra of the chosen species, is also presented.     

Adamantane-bearing benzylamines and benzylamides: novel building blocks for supramolecular systems with finely tuned binding properties towards β-cyclodextrin

Novel building blocks for the synthesis of supramolecular components based on adamantane-bearing benzylamines were prepared. The binding properties of these amines and the corresponding acetamides towards β-cyclodextrin (β-CD) were studied using mass spectrometry, NMR spectrometry, isothermal titration calorimetry and semi-empirical calculations. It was found that all of the examined guests predominantly formed 1:1 inclusion complexes in an enthalpy-driven manner with association constants of the order of 10²–10³ M^? 1. Stronger binding to the β-CD cavity was observed for guests with a longer spacer between the adamantane and benzene moieties and/or a 1,4-disubstituted benzene ring.     

Synthesis and characterization of inclusion complex of the vasodilator drug minoxidil with β-cyclodextrin

The inclusion complex of β-cyclodextrin and minoxidil (2,4-diamino-6-piperidinopyrimidine 3-oxide) was synthesized using two methods—kneading and freeze-drying—and characterized by UV-Vis spectroscopy, infrared spectroscopy, powder X-ray diffractometry, differential scanning calorimetry, thermal gravimetric analysis, and nuclear magnetic resonance spectroscopy. These techniques have demonstrated the existence of inclusion compound formation between the host and guest with a molar ratio of 1:1. The studies of solubility and the data obtained by nuclear magnetic resonance spectroscopy showed a weak interaction between the guest and the cyclodextrin molecules in solution.