Stable Peptides Instead of Stapled Peptides: Highly Potent αvβ6‐Selective Integrin Ligands

The αvβ6 integrin binds the RGD‐containing peptide of the foot and mouth disease virus with high selectivity. In this study, the long binding helix of this ligand was downsized to an enzymatically stable cyclic peptide endowed with sub‐nanomolar binding affinity toward the αvβ6 receptor and remarkable selectivity against other integrins. Computational studies were performed to disclose the molecular bases underlying the high binding affinity and receptor subtype selectivity of this peptide. Finally, the utility of the ligand for use in biomedical studies was also demonstrated here.     

Closo-alanes (Al4H4, AlnHn+2, 4 <or= n <or= 8): a new chapter in aluminum hydride chemistry

Anion photoelectron spectroscopy and density functional theory were employed to study aluminum hydride clusters, AlnHm- (4 相似文献   

Novel solid-phase extraction and preconcentration technique coupled with ICP-AES for the determination of Cr(III), Ni(II), and Zn(II) in various water samples

Newly synthesized 2-propylpiperidine-1-carbodithioate (2-PPC) was used for the extraction of Cr(III), Ni(II), and Zn(II) from various water samples. In the present investigation, the use of a syringe loaded with sorbent for the separation and enrichment of Cr(III), Ni(II), and Zn(II) prior to their determination by inductively coupled plasma-atomic emission spectrometry (ICP-AES) was proposed to substitute the batch and column techniques. The described method was compared with the column technique with respect to fastness, simplicity, recovery, and risk of contamination. The syringe was loaded with 1.0 g of sorbent in order to retain the analyte elements. Next, 7.0 mL of sample solution (pH 5.0 ± 0.2) was drawn into the syringe in 15 s and discharged over 15 s. Then, an eluent (3.0 M HCl) was drawn into the syringe and ejected back to desorb the analyte elements. At the optimum conditions, the percentage recoveries of Cr(III), Ni(II), and Zn(II) were in the range of 94.50 to 99.62% with a standard deviation (S.D.) of 0.03%. The elements could be concentrated by drawing and discharging several portions of sample successively and eluting only one time. The detailed study of various interferences proved the method to be highly selective. The risk of contamination is less than that with the column technique. The method was successfully applied to the determination of Cr(III), Ni(II), and Zn(II) in spiked and natural water samples. The results obtained are in good agreement with those obtained by the reported methods at the 95% confidence level. The text was submitted by the authors in English.     

Oxidation of L-lysine by diperiodatocuprate (III) in aqueous alkaline medium by the stopped flow technique

The kinetics of oxidation of L-lysine by diperiodatocuprate (III) (DPC) in alkaline medium at a constant ionic strength of 0.15 mol/dm³ was studied spectrophotometrically. The reaction between DPC and L-lysine in an alkaline medium had a 1: 2 stoichiometry (L-lysine: DPC). The reaction was first order in [DPC] and less than first order in [L-lysine] and [alkali]. The addition of periodate had no effect on the rate of the reaction. The intervention of free radicals was observed in the reaction. The oxidation reaction in alkaline medium was shown to proceed via a DPC-L-lysine complex. The main products were identified by spot test and spectral studies. The reaction constants involved in different steps of the mechanism were calculated. The activation parameters with respect to the slow step of the mechanism were computed and discussed, and thermodynamic values were also determined. The article is published in the original.     

Determination of rhodium in water samples using cloud point extraction (CPE) coupled with flame atomic absorption spectrometry (FAAS)

Cloud point extraction was applied as a method for preconcentration of rhodium after formation of a complex with 2-propylpiperidine-1-carbodithioate (2-PPC), and later determined by flame atomic absorption spectrometry using TritonX-114 as surfactant. Rhodium was complexed with 2-PPC in an aqueous phase and kept for 15 min in a thermostatted bath at 40 °C. Separation of the two phases was accomplished by centrifugation for 15 min at 4000 rpm. The chemical variables affecting the cloud point extraction were optimized and successfully applied to rhodium determination in various water samples. Under optimized conditions, the preconcentration system (100 mL sample) permitted an enhancement factor of 50. The detection limits obtained under optimal conditions was 0.052 ng mL⁻¹. The extraction efficiency was investigated at different rhodium concentrations (7.0–42.0 μg mL⁻¹), and good recoveries (96.42–99.14%) were obtained using this method. It has been applied to the determination of rhodium in water and was compared with reported methods in terms of Student’s ‘t’-test and variance ratio ‘f’-test.     

Thermodynamic Parameters for the Association of Fluorinated Benzenesulfonamides with Bovine Carbonic Anhydrase II

This paper describes a calorimetric study of the association of a series of seven fluorinated benzenesulfonamide ligands (C₆H_nF_5?nSO₂NH₂) with bovine carbonic anhydrase II (BCA). Quantitative structure–activity relationships between the free energy, enthalpy, and entropy of binding and pK_a and log P of the ligands allowed the evaluation of the thermodynamic parameters in terms of the two independent effects of fluorination on the ligand: its electrostatic potential and its hydrophobicity. The parameters were partitioned to the three different structural interactions between the ligand and BCA: the Zn^II cofactor–sulfonamide bond (≈65 % of the free energy of binding), the hydrogen bonds between the ligand and BCA (≈10 %), and the contacts between the phenyl ring of the ligand and BCA (≈25 %). Calorimetry revealed that all of the ligands studied bind in a 1:1 stoichiometry with BCA; this result was confirmed by ¹⁹F NMR spectroscopy and X‐ray crystallography (for complexes with human carbonic anhydrase II).     

Structure and solution dynamics of a “P–N–P” ligand attached to calix[4]arene scaffold and its palladium dichloride complex

A new diphosphazane ligand, Ph₂PN(CHMe₂)P(Ph){1,3-dimethoxycalix[4]arene} (2), in which the P–N–P unit is appended to calix[4]arene backbone, and its PdCl₂ complex (3) have been synthesized. The structures of the conformers of both the compounds in solution have been elucidated with the help of two-dimensional NMR experiments. Single crystal X-ray diffraction studies reveal the partial cone and cone conformations of the calixarene unit in the ligand (2) and the Pd-complex (3), respectively.     

Oxidative transformation of ciprofloxacin by alkaline permanganate – A kinetic and mechanistic study

This spectroscopic study presents the kinetics and degradation pathways of oxidation of ciprofloxacin by permanganate in alkaline medium at constant ionic strength of 0.04 mol⁻³. Orders with respect to substrate, oxidant and alkali concentrations were determined. Effect of ionic strength and solvent polarity of the medium on the rate of the reaction was studied. The oxidation products were identified by LC-ESI-MS technique. Product characterization of ciprofloxacin reaction mixtures indicates the formation of three major products corresponding to m/z 263, 306, and 348 (corresponding to full or partial dealkylation of the piperazine ring). The piperazine moiety of ciprofloxacin is the predominant oxidative site to KMnO₄. Product analyses showed that oxidation by permanganate results in dealkylation at the piperazine moiety of ciprofloxacin, with the quinolone ring essentially intact. The reaction kinetics and product characterization point to a reaction mechanism that likely begins with formation of a complex between ciprofloxacin and the KMnO₄, followed by oxidation at the aromatic N1 atom of piperazine moiety to generate an anilinyl radical intermediate. The radical intermediates subsequently undergo N-dealkylation. Investigations of the reaction at different temperatures allowed the determination of the activation parameters with respect to the slow step of proposed mechanism. The proposed mechanism and the derived rate laws are consistent with the observed kinetics.     

Physicochemical Investigation of Engineered Nanosuspensions Containing Model Drug,Lansoprazole

Lansoprazole is a proton-pump inhibitor used in treatment of gastric ulcers, gastroesophageal reflux disease (GERD), and Zollinger–Ellison syndrome. The objective of the study was physicochemical investigation and comparative characterization of nanosuspensions of lansoprazole by complexing with β-cyclodextrin and β-cyclodextrin-based nanosponges to enhance its solubility and stability. Inclusion complexes of lansoprazole with β-cyclodextrin and nanosponges were prepared by physical method and polymer condensation method, respectively. Particle size, zeta potential, encapsulation efficiency, in vitro release, FTIR, and Differential Scanning Calorimeter (DSC) studies were used as characterization parameters. The average particle size of lansoprazole nanoparticles was found to be in the range of 178.7 ± 6.39 nm to 204.9 ± 2.91 nm. The high zeta potential values were attained to ensure a high-energy barrier and favor a good stability of nanosuspensions. In vitro release study showed the controlled release of lansoprazole, which was more satisfactory than individual drug. FTIR spectroscopy showed that there was interaction of cyclodextrin and its nanosponges with drug. DSC study revealed that drug was involved in complexion with cyclodextrin and nanosponges. Solubility and stability of lansoprazole were remarkably improved by inclusion complexation. Based on these findings, it can be concluded that engineered nanosuspension of lansoprazole is a promising carrier for nanoparticulate drug delivery in gastric ulcer.     

Synthesis and Characterization of Novel 1‐Methyl‐3‐(4‐phenyl‐4H‐1,2,4‐triazol‐3‐yl)‐1H‐indazole Derivatives

A series of novel 1‐methyl‐3‐(4‐phenyl‐4H‐1,2,4‐triazol‐3‐yl)‐1H‐indazoles was synthesized in three steps from 5‐(1‐methyl‐1H‐indazol‐3‐yl)‐4‐phenyl‐2H‐1,2,4‐triazole‐3(4H)‐thiones. 5‐(1‐Methyl‐1H‐indazol‐3‐yl)‐4‐phenyl‐2H‐1,2,4‐triazole‐3(4H)‐thiones were converted into 1‐methyl‐3‐(5‐(methylsulfonyl)‐4‐phenyl‐4H‐1,2,4‐triazol‐3‐yl)‐1H‐indazoles upon methylation followed by treatment with aq. KMnO₄. The reaction of 1‐methyl‐3‐(5‐(methylsulfonyl)‐4‐phenyl‐4H‐1,2,4‐triazol‐3‐yl)‐1H‐indazoles with Raney nickel resulted in desulphonylation to afford corresponding 1‐methyl‐3‐(4‐phenyl‐4H‐1,2,4‐triazol‐3‐yl)‐1H‐indazoles. All the new synthesized compounds were characterized by spectral techniques.