Acetohydroxamic Acid Research Articles

ChemInform Abstract: Nitrosylation of Hexafluoridotechnetate(IV).

Abstract[Tc(NO)(NH3)4F]4[TcF6] [HF2]2 is obtained in almost quantitative yield by reaction of K2[TcF6] with acetohydroxamic acid (Ac‐NH‐OH) in aqueous HF solution.

Fluorimetric urease inhibition assay on a multilayer microfluidic chip with immunoaffinity immobilized enzyme reactors

We fabricated a three-layer polydimethylsiloxane (PDMS)-based microfluidic chip for realizing urease inhibition assay with sensitive fluorescence detection. Procedures such as sample prehandling, enzyme reaction, reagent mixing, fluorescence derivatization, and detection can be readily carried out. Urease reactors were prepared by adsorption of rabbit immunoglobulin G (IgG) and immunoreaction with urease-conjugated goat anti-rabbit IgG. Acetohydroxamic acid (AHA) as a competitive inhibitor of urease was tested on the chip. Microfluidically generated gradient concentrations of AHA with substrate (urea) were loaded into urease reactors. After incubation, the produced ammonia was transported out of reactors and then reacted with o-phthalaldehyde (OPA) to generate fluorescent products. Urease inhibition was indicated by a decrease in fluorescence signal detected by microplate reader. The IC50 value of AHA was determined and showed good agreement with that obtained in microplate. The presented device combines several steps of the analytical process with advantages of low reagent consumption, reduced analysis time, and ease of manipulation. This microfluidic approach can be extended to the screening of inhibitory compounds in drug discovery.

Hydroxamic Acids as a Reductometric Titrants: Determination of Cerium in Alloys

Hydroxamic acids like acetohydroxamic acid (AHA) and oxalohydroxamic acid (OHA) have been employed as a reductometric titrant for the determination of cerium in 2 N sulphuric acid. Stoichiometry of the reaction is established. One mole of AHA and OHA were found to consume 6.0 and 12.0 equivalents of the oxidant respectively in these reactions. The titre values are obtained by second derivative plots of potentiometric titrations.

ChemInform Abstract: One‐Step Synthesis of 5‐Substituted 1H‐Tetrazoles from an Aldehyde by Reaction with Acetohydroxamic Acid and Sodium Azide under Bi(OTf)3 Catalysis.

AbstractA simple direct conversion of aromatic and aliphatic aldehydes is achieved under conditions A) to give the tetrazoles in good yields.

Structure based virtual screening-driven identification of monastrol as a potent urease inhibitor

Virtual screening uses computer based methods to discover new ligands on the basis of biological structures. Among all virtual screening methods structure based docking has received considerable attention. In an attempt to identify new ligands as urease inhibitors, structure-based virtual screening (SBVS) of an in-house database of 10,000 organic compounds was carried out. The X-ray crystallographic structure of Bacillus pasteurii (BP) in complex with acetohydroxamic acid (PDB Code 4UBP) was used as a protein structure. As a starting point, ~10,000 compounds of our in-house database were analyzed to check redundancy and the compounds found repeated were removed from the database. Finally 6993 compounds were docked into the active site of BP urease using GOLD and MOE-Dock software. A remarkable feature of this study was the identification of monastrol, a well-known KSP inhibitor already in clinical trials, as a novel urease inhibitor. The hits identified were further evaluated by molecular docking and on examination of the affinity predictions, twenty-seven analogs of monastrol were synthesized by a multicomponent Biginelli reaction followed by their in vitro screening as urease inhibitors. Finally twelve compounds were identified as new urease inhibitors. The excellent in vitro activity suggested that these compounds may serve as viable lead compounds for the treatment of urease related problems.

Syntheses, urease inhibition activities, and fluorescent properties of transition metal complexes

Four transition metal complexes with Schiff base and 1,10-phenanthroline, [Cu(L)(phen)]2·C2H5OH (1), [Zn(L)(phen)]2·C2H5OH (2), [Ni(L)(phen)]2·C2H5OH (3), and [Co(L)(phen)]2·C2H5OH (4) (H2L = 1-((2-hydroxynaphthalen-1-yl)methylene)thiosemicarbazide; phen = 1,10-phenanthroline) were synthesized and characterized by physico-chemical methods. The crystal structure of 1 was determined by X-ray single-crystal diffraction analysis. 1 crystallizes in the orthorhombic space group Pbca with a = 15.008(9), b = 16.100(10), c = 37.54(2) Å, V = 9070(10) Å3, Z = 8, GOOF = 1.002, R 1 = 0.0626, and wR 2 = 0.0912. The fluorescence and urease inhibitory activities of the compounds were tested. The enzymatic activity study indicated that 3 possessed potent inhibition against jack bean urease, with IC50 = 1.2 ± 0.1 μM, and about 35 times more than 42.1 ± 0.4 acetohydroxamic acid as positive reference. This suggests that inhibitory efficiency of these complexes can be strongly influenced by different transition metal ions.

Nitrosylation of Hexafluoridotechnetate(IV)

AbstractPotassium hexafluoridotechnetate(IV), K2[TcF6], slowly reacts in aqueous solution with acetohydroxamic acid with formation of the ammine nitrosyltechnetium(I) complex [Tc(NO)(NH3)4F]+. The product crystallizes as mixed TcF62–/HF2– salt of the composition [Tc(NO)(NH3)4F]4[TcF6][HF2]2. [Tc(NO)(NH3)4F]+ represents the first nitrosyltechnetium complex with a fluorido ligand in its coordination sphere. The Tc–F bonds in two crystallographically independent species are 1.987(2) and 2.034(2) Å, respectively. This is slightly longer than in the [TcF6]2– counterion.

Synthesis, structure–activity relationship analysis and kinetics study of reductive derivatives of flavonoids as Helicobacter pylori urease inhibitors

In a continuing study for discovering urease inhibitors based on flavonoids, nineteen reductive derivatives of flavonoids were synthesized and evaluated against Helicobacter pylori urease. Analysis of structure–activity relationship disclosed that 4-deoxy analogues are more potent than other reductive products. Out of them, 4′,7,8-trihydroxyl-2-isoflavene (13) was found to be the most active with IC50 of 0.85 μM, being over 20-fold more potent than the commercial available urease inhibitor, acetohydroxamic acid (AHA). Kinetics study revealed that 13 is a competitive inhibitor of H. pylori urease with a Ki value of 0.641 μM, which is well matched with the results of molecular docking. Biological evaluation and mechanism study of 13 suggest that it is a good candidate for discovering novel anti-gastritis and anti-gastric ulcer agent.

Novel inhibitors of urease from Corydalis govaniana Wall.

A new compound govaniadine (1), along with three known tetrahydroprotoberberine-type alkaloids caseadine (2), caseamine (3), and protopine (4), were isolated from the plant Corydalis govaniana Wall. All alkaloids 1–4 exhibited a good urease enzyme inhibition with IC50±S.E.M. values of 20.2±3.6, 38.9±2.8, 66.7±1.2, and 54.1±1.2μM, respectively, which are comparable to the standard inhibitor, acetohydroxamic acid (IC50=42.0μM). None of these compounds showed inhibition against α-chymotrypsin. This is the first report of urease inhibiting tetrahydroprotoberberine-type alkaloids.

Synthesis, structure, and activity evaluation of two silver(I) complexes as Helicobacter pylori urease inhibitors

Two silver(I) compounds, [Ag(R,R-hxn)](C7H4BrO2) · 2H2O (I) (Chxn = 1,2-diaminocyclohexane) and [Ag(C5H6N2)2]2(C8H4O4) · 10H2O (II), were synthesized and complex I was structurally characterized by X-ray crystallography. Compound I contains a catena-(trans-1,2-diaminocyclohexane) silver polycation ([Ag(Chxn)]∞) in a roughly linear fashion, while II possesses a linear-type silver monocation. Compounds I and II were evaluated for their inhibitory activities against Helicobacter pylori urease in vitro. Both were found to have strong inhibitory activities against H. pylori urease comparable to that of acetohydroxamic acid.

One-Step Synthesis of 5-Substituted 1H-Tetrazoles from an Aldehyde by Reaction with Acetohydroxamic Acid and Sodium Azide under Bi(OTf)3 Catalysis

Correction to: One-Step Synthesis of 5-Substituted 1H-Tetrazoles from an Aldehyde by Reaction with Acetohydroxamic Acid and Sodium Azide under Bi(OTf)3 CatalysisSynthesis 2013; 45(04): 507-510DOI: 10.1055/s-0032-1318108

One-Step Synthesis of 5-Substituted 1H-Tetrazoles from an Aldehyde by Reaction with Acetohydroxamic Acid and Sodium Azide under Bi(OTf)3 Catalysis

An efficient one-step method for the synthesis of 5-substituted 1<i>H</i>-tetrazoles from aldehydes by reaction with aceto­hydroxamic acid and sodium azide using bismuth(III) triflate as the catalyst is described.

Conformational analysis of a secondary hydroxamic acid in aqueous solution by NOE spectroscopy

Hydroxamic acids are metal-binding compounds used by micro-organisms and possess applications in medicine and industry. Hydroxamic acids favor two conformations, E and Z; metal binding is limited to the Z conformation. The Z conformation may be identifiable by NOE spectroscopy, but analysis is complicated by the potential for long-range coupling as well as for relayed NOEs due to conformational switching. In this report, we re-examine the reported conformational preference of N-methyl acetohydroxamic acid (NMHA) in D(2)O using NOE spectroscopy. We find that the favored conformation of NMHA in aqueous solution is the E conformation, contrary to an earlier report. NOE build-up curves are proposed as a valuable tool to probe conformational behavior in similar systems.

Voltammetric determination of ethyl acetate in ethanol fuel using a Fe3+/Nafion®-coated glassy carbon electrode

A voltammetric method for the determination of ethyl acetate in ethanol fuel using a Fe3+/Nafion®-coated glassy carbon electrode (GCE) is proposed. The ethyl acetate present in the ethanol fuel was previously converted to acetohydroxamic acid via pretreatment with hydroxylamine chloride. The acetohydroxamic acid promptly reacted with the iron (III) present in the film, producing iron (III) acetohydroxamate, which presents a well-defined voltammetric peak current at −0.02V. Optimization of the voltammetric parameters for the cyclic, linear sweep, square wave, and differential pulse modalities was carried out for this chemically-modified electrode. Square wave voltammetry afforded the best response for acetohydroxamic acid detection. The analytical curve for this species was linear from 9 to 100μmolL−1 according to the following equation: ip (μA)=0.27+2.55Cacetohydroxamic acid (μmolL−1), with linear correlation coefficient equal to 0.993. The technique presented limit of detection equal to 5.3μmolL−1 and quantification limit of 17.6μmolL−1. The proposed method was compared to the official method of ethyl acetate analysis (Gas Chromatography), and a satisfactory correlation was found between these techniques.

The use of cyclic nitroxide radicals as HNO scavengers

Reduction of cyclic stable nitroxides (RNO) by HNO to the respective hydroxylamines (RNO-H) has been demonstrated using EPR spectrometry. HNO shows low reactivity toward piperidine, pyrrolidine and nitronyl nitroxides with rate constants below 1.4×105M−1s−1 at pH 7.0, despite the high driving force for these reactions. The rate constants can be predicted assuming that the reactions take place via a concerted proton–electron transfer pathway and significantly low self-exchange rate constants for HNO/NO and RNO-H/RNO. NO does not react with piperidine and pyrrolidine nitroxides, but does add to HNO forming the highly oxidizing and moderately reducing hyponitrite radicals. In this work, the radicals are produced by pulse radiolysis and the rate constants of their reactions with 2,2,6,6,-tetramethylpiperidine-1-oxyl (TEMPO), 4-hydroxy-2,2,6,6-tetramethyl piperidine-1-oxyl (TEMPOL) and 3-carbamoyl-PROXYL have been determined at pH 6.8 to be (2.4±0.2)×106, (9.8±0.2)×105, (5.9±0.5)×105M−1s−1, respectively. This low reactivity implies that NO competes efficiently with these nitroxides for the hyponitrite radical. The ability of TEMPOL and 2-(4-carboxyphenyl)-4,4,5,5,-tetramethyl-imidazoline-1-oxyl-3-oxide (C-PTIO) to oxidize HNO and their different reactivity toward NO are used to quantify HNO formed via acetohydroxamic acid oxidation. The extent of TEMPOL or C-PTIO reduction was similar to the yield of HNO formed upon oxidation by OH under anoxia, but not by the metmyoglobin and H2O2 reaction system where both nitroxides catalytically facilitate H2O2 depletion and nitrite accumulation. In this system the conversion of C-PTIO into 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl (C-PTI) is a minor reaction, which does not provide any mechanistic insight.

Neptunium Extraction and Stability in the GANEX Solvent: 0.2 M TODGA/0.5 M DMDOHEMA/Kerosene

Batch distribution studies show that above ~1 M HNO3 Np(IV) and Np(VI) are well extracted into a solvent of 0.2 M TODGA/0.5 M DMDOHEMA in kerosene that has been formulated for the extraction of transuranic actinides in the GANEX (grouped actinide extraction) process. Np(IV) and Np(VI) are quite stable in the solvent phase, although Np(VI) is slowly reduced to Np(IV) on standing. Stripping of Np(IV,VI) ions from the GANEX solvent has been shown to be quite efficient using acetohydroxamic acid providing aqueous HNO3 concentrations are below ~0.3 M. In contrast, Np(V) shows much lower distribution ratios and is unstable in the GANEX solvent phase with quite rapid formation of Np(IV) observed. Closer analysis shows this to be due to Np(V) disproportionation, which is enhanced at higher organic phase acidities. Disproportionation of Np(V) is also shown to occur in separate TODGA and DMDOHEMA kerosene solutions. These observations thus enable conditions for neptunium extraction to be optimized during the design of a GANEX flowsheet.

Oxidation of N-hydroxy-l-arginine by hypochlorous acid to form nitroxyl (HNO)

Recent research has shown that nitroxyl (HNO) has important and unique biological activity, especially as a potential alternative to current treatments of cardiac failure. HNO is a reactive molecule that undergoes efficient dimerization and subsequent dehydration to form nitrous oxide (N2O), making its detection in solution or biologically relevant preparations difficult. Due to this limitation, HNO has not yet been observed in vivo, though several pathways for its endogenous generation have been postulated. Here, we investigate the oxidation of N-hydroxy-l-arginine (NOHA) by hypochlorous acid (HOCl), which is generated in vivo from hydrogen peroxide and chloride by the heme enzyme, myeloperoxidase. NOHA is an intermediate in the enzymatic production of nitric oxide (NO) by NO synthases, and has been shown previously to be chemically oxidized to either HNO or NO, depending on the oxidant employed. Using membrane inlet mass spectrometry and standard N2O analysis by gas chromatography, we find that NOHA is oxidized by excess HOCl to form HNO-derived N2O. In addition, we also observe the analogous production of HNO from the HOCl oxidation of hydroxylamine, hydroxyurea, and (to a lesser extent) acetohydroxamic acid.

Synthesis, structures and urease inhibition studies of Schiff base metal complexes derived from 3,5-dibromosalicylaldehyde

Eleven mononuclear copper(II), nickel(II), zinc(II) and cobalt(II) complexes of Schiff base ligands derived from 3,5-dibromosalicylaldehyde/3,5-dichlorosalicylaldehyde were synthesized and determined by single crystal X-ray analysis. The crystal structures of complexes 1, 2, 4, 5, 6, 8 and 11 present the square-planar coordination geometry at the metal center and complexes 7, 9 and 10 show the distorted tetrahedral geometry. While one copper center in 3 has a square-planar geometry, the other copper is slightly distorted square-planar. The inhibitory activities of all the obtained complexes were tested in vitro against jack bean urease. It was found that Schiff base copper(II) complexes 1, 3, 5, 8 and 11 showed strong urease inhibitory activities (IC50 = 1.51–3.52 μM) compared with acetohydroxamic acid (IC50 = 62.52 μM), which was a positive reference. Their structure–activity relationships were further discussed.

ChemInform Abstract: Acetohydroxamic Acid: A New Reagent for Efficient Synthesis of Nitriles Directly from Aldehydes Using Bi(O‐Tf)3 as the Catalyst.

AbstractTreatment of aldehydes according to A) results in formation of nitriles via an aldoxime intermediate.

Growth-Inhibiting, Bactericidal, and Urease Inhibitory Effects of Paeonia lactiflora Root Constituents and Related Compounds on Antibiotic-Susceptible and -Resistant Strains of Helicobacter pylori

An assessment was made of the growth-inhibiting, bactericidal, and urease inhibitory activities of paeonol (PA), benzoic acid (BA), methyl gallate (MG), and 1,2,3,4,6-penta-O-galloyl-β-d-glucopyranose (PGG) identified in Paeonia lactiflora root, structurally related compounds, and four antibiotics toward three reference strains and four clinical isolates of Helicobacter pylori using broth dilution bioassay and Western blot. BA and PA showed strong bactericidal effect at pH 4, while MG and PGG were effective at pH 7. These constituents exhibited strong growth-inhibiting and bactericidal activity toward the five strains resistant to amoxicillin (minimal inhibitory concentration (MIC) 12.5 mg/L), clarithromycin (64 mg/L), metronidazole (64 mg/L), or tetracycline (15 mg/L), indicating that these constituents and the antibiotics do not share a common mode of action. Structural characteristics, such as types of functional groups and carbon skeleton, and hydrophobicity appear to play a role in determining the anti- H. pylori activity. H. pylori urease inhibitory activity of PGG was comparable to that of acetohydroxamic acid, while MG was less potent at inhibiting urease than thiourea. The UreB band disappeared at 250 mg/L PGG on Western blot, while the UreA bands were faintly visible at 1000 mg/L PGG. These constituents showed no significant cytotoxicity. Global efforts to reduce the level of antibiotics justify further studies on P. lactiflora root-derived materials containing MG, PA, and PGG as potential antibacterial products or lead molecules for the prevention or eradication from humans from diseases caused by H. pylori .