N-phenylbenzohydroxamic Acid Research Articles

Unusual Two-Step Claisen-type Rearrangement Reaction under Physiological Conditions.

N-aryl hydroxamic acids, which are best known for their metal-chelating properties in chemical and biomedical research, have been found to markedly detoxify carcinogenic halogenated quinones. However, the exact chemical mechanism underlying such detoxication remains unclear. Here, we show that a very fast reaction took place between N-phenylbenzohydroxamic acid (N-PhBHA) and 2,5-dichloro-1,4-benzoquinone (DCBQ), forming an unexpected new carbon-carbon bonding phenyl-quinone product with high yield. In contrast, no reaction was observed with O-benzoyl N-PhBHA. Analogous results were observed for other N-aryl hydroxamic acids and halogenated quinones, which have an ortho-hydrogen adjacent to the reaction site (DCBQ-type). Interestingly, no free radical intermediates could be detected by both ESR spin-trapping and radical-scavenging methods during the reaction process. Taken together, we proposed that nucleophilic substitution followed by an unusual two-step Claisen-type rearrangement reaction was responsible for the formation of a new C-C bonding compound and the detoxication reaction. This represents the first report of an unusually mild and facile two-step Claisen-type rearrangement, which could take place under normal physiological conditions.

Oxovanadium complex as potential nucleic acid binder

ABSTRACTDNA binding study of a vanadium(V) complex, Oxo-chloro-bis-N-phenylbenzohydroxamto-vanadium(V), derived from N-phenylbenzohydroxamic acid(PBHA) form a violet color complex with vanadium (V) in presence of hydrochloric acid is performed using absorption, fluorescence and viscometric techniques. The binding parameters of the PBHA-V(V) complex using calf thymus DNA (ct-DNA) and torula yeast RNA (t-RNA) have been determined. The complex shows the ability of cooperatively minor groove binding with ct-DNA as indicated by remarkable hyperchromicity and a blue shift of the absorption spectra. Quenching of metal complex calculation was carried out with Stern-Volmer equation and Ksv was found to be 2.32 ± 0.18 × 104 M−1, while in the case of t-RNA, enhancement is observed and that means the compound was not able to displace the Ethidium Bromide(EB)-t-RNA complex. Molecular docking was also applied to predict the mode of interaction of the hydroxamic acid with ct-DNA and t-RNA. DNA binding results of the complex are compared with those of the parent ligand.

Pd(en)(H2O)2]2+ and [Pd(pic)(H2O)2]2+ complexation by monohydroxamic acids: A solution equilibrium and solid state approach

Complex formation between [Pd(en/pic)(H2O)2]2+ (en=ethylenediamine, pic=pyridine-2-methylamine) and primary hydroxamic acids (ahaH=acetohydroxamic, bhaH=benzohydroxamic acid) or secondary hydroxamic acids (meahaH=N-methyl-acetohydroxamic, pheahaH=N-phenylacetohydroxamic and phebhaH=N-phenylbenzohydroxamic acid) was studied in aqueous solution by pH-potentiometry, 1H NMR and ESI-TOF-MS. Secondary hydroxamates form 1:1 species with the [Pd(N,N)(H2O)2]2+ ions via the [O,O] chelating sets. Unexpectedly, in the primary ligands deprotonation and coordination of the hydroxamate-NH starts as low as pH <2, where the RCC(O)N−O− ion is capable of linking two [Pd(diamine)]2+ units via the coordination through the [O,O] chelate to one unit and through the monodentate hydroxymato-N− atom to the another one. As a consequence, primary ligands can bind an excess of metal ion too. A trinuclear complex predominates in a wide pH-range (5–10 for en, 3–10 for pic) and the hydroxide ion starts to compete with the hydroxymato ligand only above pH 10. In the trinuclear species two [O,O] chelated Pd(II) units are bridged via a third palladium core that binds to the hydroximato-N donors of the two ligands. This binding mode was also proved by MS studies in solution and by revealing the molecular structure of [(Pd(en))3(bhaH−1)2](BF4)2·2H2O (2), the first reported structure with a Pd(II)-hydroxymate-N− monodentate coordination, characterized with single crystal X-ray diffraction in the solid state.

RNA-Binding Efficacy of N-Phenylbenzohydroxamic Acid: An Invitro and Insilico Approach

RNA has attracted recent attention for its key role in gene expression and hence targeting by small molecules for therapeutic intervention. This study is aimed to elucidate the specificity of RNA binding affinity of parent compound of N-arylhydroxamic acids series, N-phenylbenzohydroxamic acid trivially named as PBHA,C6H5NOH.C6H5C ˭ O. The binding behavior was examined by various biophysical methods such as absorption, fluorescence, and viscosity measurements. Molecular docking was also done. The value of affinity constant and overall binding constant was calculated 5.79 ± 0.03 × 104 M−1 and K’ = 1.09 ± 0.03 × 105 M−1, respectively. The Stern-Volmer constant Ksv obtained was 2.28 ± 0.04 × 104 M−1. The compound (PBHA) shows a concentration-based enhancement of fluorescence intensity with increasing RNA concentration. Fluorescence quenching of PBHA–RNA complex in presence of K4 [Fe(CN)6] was also observed. Viscometric studies complimented the UV results where a continuous increase in relative viscosity of the RNA solution was observed with added optimal PBHA concentration. All the experimental evidences indicate that PBHA can strongly bind to RNA through an intercalative mode.

Determination of Arsenic in Environment by Spectrophotometric Technique using Hydroxamic Acids

A simple, rapid, stable and sensitive direct visible spectrophotometric method has been developed for the determination of trace amount of arsenic in environmental samples of Bhopal city using N-PBHA, N-p- ClPBHA and N-p-ClPCHA, Arsenic (III) reacts with different hydroxamic acids and forms light pink to violet colored complex in acidic medium which were extracted in n- hexane. The calibration graph was linear over the concentrationrange of 0.0003786-0.004164, 0.003786-0.06057 and 0.003786-0.04921µgml -1 for N-Phenyl- benzo-hydroxamic acid (N-PBHA), N-p- Chloro-phenyl- benzo-hydroxamic acid (N-p-ClPBHA) and N-p- Chloro-phenyl-cinnamohydroxamic acid (N-p-ClPCHA), respectively. The molar absorptivities were found to be 2.892x10 5 , 1.5973x10 4 and 2.0238x10 4 L mol -1 cm -1 for the three hydroxamic acids. The optimum reaction

A reliable determination of zinc levels in beverages with and without alcohol by flame atomic absorption spectrometry after cloud point extraction

Cloud point extraction (CPE) has been used for the preconcentration and quantification of zinc after the formation of a stable complex with N-phenylbenzohydroxamic acid (PBHA) at pH 9.0 and analysis by flame atomic absorption spectrometry (FAAS) using polyethylene glycol tert-octylphenyl ether (Triton X-114) as the extracting surfactant. The chemical variables affecting the phase separation and the viscosity affecting the detection process were optimized. A preconcentration of only 50 mL of sample in the presence of 0.02% (w/v) Triton X-114 and 2.0 × 10−4 mol L−1 PBHA permitted the detection and quantification of 0.42 and 1.41 μg L−1 zinc, respectively. The improvement and preconcentration factors were 74.2 and 50 for zinc, respectively. The accuracy was controlled by analysis of the certified reference materials, SRM 1515 and SRM 1573a. The obtained results were in good agreement with the certified values. The proposed method was successfully applied to the determination of trace levels of zinc in beverage samples with satisfactory results. The results of zinc determination in the digested samples with HNO3/H2O2 (3 : 1, v/v) are in agreement with that in the digested samples with HNO3/HClO4 (5 : 1, v/v). Zinc levels are in the range of 44.40–110.15 μg L−1 with standard deviation values ranging from 1.35 to 2.65 μg L−1 for the canned beverages without alcohol and 35.65–135.80 μg L−1 with standard deviation values ranging from 1.10 to 3.50 μg L−1 for the beverages with alcohol.

Synthesis, crystal structure, and bioactivity of two triphenylantimony derivatives with benzohydroxamic acid and N-phenylbenzohydroxamic acid

Reaction of triphenylantimony dichloride with benzohydroxamic acid or N-phenylbenzohydroxamic acid in 1 : 1 stoichiometry yielded two new triphenylantimony derivatives formulated as [Ph3SbL1L2] (L1 = benzohydroxamato, L2 = methoxide, 1; L1 = N-phenylbenzohydroxamato, L2 = Cl, 2), which have been characterized by FT-IR, NMR spectroscopy, elemental analysis, and melting point. Single-crystal X-ray diffraction analyses for 1 and 2 reveal that the antimony is six-coordinate adopting distorted octahedral geometry with one phenyl and methoxide or chloride in axial positions. In the supramolecular structure, a double-chain is shown for 2 constructed by C–H ··· X (X = O, C or π) weak interactions, while 1 exhibits a 1-D-chain structure connected by O–H ··· O and N–H ··· N hydrogen bonds. In vitro antitumor study reveals that 1 and 2 display activities against two human tumor cell lines – A549 and HCT-8. To explore the antitumor activity mechanism, DNA binding properties of 1 and 2 with calf thymus DNA (ct-DNA) have been investigated by fluorescence spectra, indicating that 1 and 2 bind to ct-DNA via intercalation, which could induce the death of cancer cells.

Solvent-dependent conformational and fluorescence change of an N-phenylbenzohydroxamic acid derivative bearing two pyrene moieties

The conformation of N-phenylbenzohydroxamic acid has been reported to change depending on the solvent properties. Here, we newly synthesized N-phenylbenzohydroxamic acid derivative, which contains two pyrene moieties separated from the phenyl rings by ethylene linkers. It showed solvent-dependent conformational change, and its fluorescence was also solvent-dependent, that is, only monomer fluorescence of pyrene was observed in DMSO or DMF, whereas the excimer fluorescence was observed in CH2Cl2 or CHCl3. Thus, the structural characteristics could be converted to fluorescence change as output, which would be a good candidate as a fluorescent sensor.

Cloud-Point Extraction for On-Line Trace Determination of Copper(II) by Flame Atomic Absorption Spectrometry

A cloud point extraction-flow injection procedure is proposed for on-line determination of trace amounts of copper(II) by flame atomic absorption spectrometry. Copper(II) was extracted using the non-ionic surfactant, Triton X-114 after complex formation with N-phenyl benzohydroxamic acid at pH 5 in the presence of sodium sulfate as a salting-out agent at 25 °C. After the cloud point having been obtained in the reaction coil at room temperature, the surfactant-rich phase containing the complex was collected in a mini-column packed with cotton. Then, the complex was eluted into the nebulizer of flame atomic absorption spectrometer by passing ethanol containing 1% (v/v) nitric acid. The chemical and flow variables including pH, reagent and surfactant concentrations, sample and eluent flow rates affecting the extraction and determination were optimized and the enhancement factor was estimated to be 45. The sample throughput (15 h-1) was greater than batch technique. The calibration graph was linear in the range of 5–220 μg l−1. A good precision for 50 μg l−1 copper(II) (1.9% RSD, n = 8) and detection limit (3Sb m−1) 1.00 μg l−1 were obtained. The accuracy was assessed by the analysis of a standard reference material (NBS-364) and the obtained results were in good agreement with certified amounts of copper. The proposed method was applied to the determination of copper(II) in water and hair samples.

Acid-catalyzed hydrolysis of N-phenylbenzohydroxamic acid

The kinetics of hydrolysis of N-phenylbenzohydroxamic acid have been studied from 0.9 to 10.8 mol dm -3 H 2 SO 4 in 10/90 (v/v) n-propanol-water medium at 55 °C. The rate of reaction increases initially with increasing acidity, reaches a maximum and then decreases. After that at high acidities there is steep increase in reaction rate. The effect of temperature on the rate of hydrolysis has been studied. Activation parameters have been calculated. Bimolecular nature has been supported by Hammett, Zucker-Hammett, Bunnett, Bunnett-Olsen and Arrhenius activation parameters etc.

Solution Equilibria of Ternary Systems Involving Transition Metal Ions, Hydroxamic Acids, and Bioligands

The formation of ternary complexes of the Cu(II), Co(II), Ni(II), and Zn(II) metal ions with some hydroxamic acids (acetohydroxamic acid, Aha; benzohydroxamic acid, Bha; salicylhydroxamic acid, Sham; and N-phenylbenzohydroxamic acid, N-PhBha) and some bioligands (α-alanine, α-ala; l-valine, l-val; norvaline, norval; aspartic acid, aspart; glutamic acid, glut; asparagines, asperg; histamine, Him; and imidazole, imid) was investigated using the potentiometric technique at 25 °C and I = 0.10 mol·dm−3 NaNO3. The stability constants of these ternary systems were calculated. The order of stability of the ternary complexes in terms of the nature of metal ions, hydroxamic acids, and bioligands was investigated and discussed as well as the values of Δ log K and log X for the ternary systems. The concentration distribution curves of the various binary and ternary complex species in solution were evaluated. The effect of temperature of the medium on both the ionization process of Aha, Sham, aspart, and glut and the ...

Kinetics of hydrolysis of N-phenylbenzohydroxamic acid in acetone-water medium

The kinetics of hydrolysis of N-phenylbenzohydroxamic acid have been studied in 1.8 to 8.1 mol dm -3 H 2 SO 4 at 55 °C. The rate of reaction increases with increasing concentration of H 2 SO 4 , nearly linearly up to 7.2 mol dm -3 and then increased sharply. The rate maximum was not observed. The effect of temperature on the rate of hydrolysis has been studied. Activation parameters have been calculated. Bimolecular nature of hydrolysis has been supported by Arrhenius parameters, Bunnett-Olsen, Zucker-Hammett hypothesis etc.

The pK&lt;sub&gt;a&lt;/sub&gt; values of ligands and stability constants of the complexes of Fe(III), Cu(II) and Ni(II) with some hydroxamic acids: a comparative study of three different potentiometric methods

The determination of ionization constants and the chelating properties exhibited by a series of derivatives of N-phenylbenzohydroxamic acid, N-phenyllaurohydroxamic acid and 1-naphthalenemethylimminodiacetohydroxamic acid type ligands toward Fe(III), Cu(II) and Ni(II) ions were studied by pH-metric method. The data obtained by pH-metric method were analyzed by three standard methods namely, Bjerrum's method, Irving and Rossotti method, and Sarkar and Kruck method. The ionization constants of hydroxamic acids and the stability constants of metal-ligand complexes were calculated using the above three methods and it was found that the values obtained closely agreed with each other. The evaluation of the calculated stability constants shows that the substituent effect on the N-phenyl ring leads to more basic character at the carbonyl oxygen and it influences significantly the stability of the complex species formed by the hydroxamate moieties. The stability constant and the species distribution of Fe(III) - 1-naphthalenemethylimminodiacetohydroxamic acid system at physiological pH range (6.8 - 7.2) suggest that 1-naphthalenemethylimminodiacetohydroxamic acid is an effective source for the iron overload. Keywords: Bjerrum method, hydroxamic acid, Irving and Rossotti method, Sarkar and Kruck method, stability constant doi:10.4038/jnsfsr.v36i3.154 Journal of the National Science Foundation of Sri Lanka 36 (3) 191-198

Fluorescence quenching and bonding properties of some hydroxamic acid derivatives by iron(III) and manganese(II)

Spectrophotometric investigations of highly fluorescent metal chelating molecules are of relevance due to their potential application in novel, selective fluorescence-based sensors. Benzene and naphthalene chromophores are highly fluorescent while hydroxamic acids are widely used as ligands for complexation of transition metals. In order to develop fluorescence probes, several phenyl derivatives of N-phenylbenzohydroxamic acid and an aminodihydroxamic acid linked with a naphthalene chromophore were synthesized and their selective ionophoric properties towards iron(III) and manganese(II) ions were investigated using fluorescence and absorption spectroscopy. Both methods confirm the formation of 1:1 and 1:2 complexes for iron(III) and a 1:1 complex for manganese(II). The complex that is formed depends on the concentration of the ligand and pH of the medium. The amino dihydroxamic acid exhibits a prominent selectivity towards iron(III) with a two-step 1:1 and 1:2 quenching mechanism at pH 3 and towards manganese(II) with a 1:1 quenching mechanism at a probe concentration of 1 x 10(-5) mol dm(-3) at pH 9.5 The logarithm of overall formation constants of 1:1 and 1:2 complexes of iron(III) were estimated as 3.30 and 9.05, respectively.

Partial Molar Volumes and Viscosity B-Coefficient of N-Phenylbenzohydroxamic Acid in Dimethylsulfoxide at Different Temperatures

The densities and viscosities of N-phenylbenzohydroxamic acid (PBHA) have been determined as a function of concentration in dimethylsulfoxide (DMSO) at various temperatures, (298.15, 303.15, 308.15, 313.15, and 318.15) K. The density data have been analyzed using Masson’s equation, and partial molar volume (Vϕ0) at infinite dilution and the slope Sv* of Masson’s equation are computed. The limited partial molar expansibilities (ϕE0) have also been calculated from the temperature dependence of limiting partial molar volume (Vϕ0). The viscosity data have been analyzed using the Jones−Dole equation, and the viscosity B-coefficients are calculated. The results have been discussed in terms of solute−solvent interaction, and it was found that PBHA acts as a structure maker in the present system.

Solvent-Dependent Conformational Switching of N-Phenylhydroxamic Acid and Its Application in Crystal Engineering

N-Phenylbenzohydroxamic acid (3) showed solvent-dependent conformational alteration. Thus, compound 3 exists predominantly in cis form (> 98%) in CD2Cl2, whereas the percentage of the cis isomer decreased to 49% in methanol-d4, and the trans conformer was major (77%) in acetone-d6. Solvent-dependent alteration of the amide conformation was observed only in the hydroxamic acids, and the ratio of the cis conformer (98% in CD2Cl2) of N-phenylbenzhydrazide (6) was little affected by the solvent. Two unique crystal structures were obtained depending on the recrystallization solvent, and each crystal corresponded in structure to the major conformer in the solvent. These two crystals of 3 were distinguished by IR spectroscopy and DSC analysis. Although the origin of the solvent-dependent conformational switching of 3 is unclear, the results could be applied to design and development of solvent- or external-stimuli-responsive molecular machines.

Absolute pK a determination for N-phenylbenzohydroxamic acid derivatives

Ab initio calculations on isomers of N-phenylbenzohydroxamic acid derivatives and their deprotonation process have been performed. Gas phase geometries were optimised using complete basis set method, CBS-QB3 as implemented in gaussian 98 suite. It was observed that in the gas phase, the Z-isomer of the molecule and the E-isomer of the anion are stable. Acid dissociation constants obtained using CBS-QB3 gas phase energies and HF/6−31+G(d)/CPCM hydration energies closely agree with the experimental values determined in 50% ethanol in water or 50% methanol in water media, provided that the most stable isomer for the molecule and the anion in water is taken as the Z–isomer. The following pK a values were obtained for the compounds listed in the order (experimental-ethanol; experimental-methanol; theoretical); N-phenylbenzohydroxamic acid—[9.81,9.81,10.13]; N-( o-chloro)phenylbenzohydroxamic acid—[9.64,9.61,10.34]; N-( o-bromo)phenylbenzohydroxamic acid—[9.72,9.66,9.94] and N-( o-methoxy)phenylbenzohydroxamic acid—[9.97, 9.97, 9.59].

Theoretical investigation of the conformational behaviour ofN-phenylbenzohydroxamic acid in solution

Using ab initio theoretical approaches, we investigated the relative stability of two of the possible isomers of N-phenylbenzohydroxamic acid, PhCONOHPh. In particular, within the framework of density functional theory (DFT), we studied the cis and trans conformational isomers of PhCONOHPh, both in the gas phase and in solution. A polarizable continuum model (C-PCM) and a cluster approach were used to simulate the solute-solvent interactions and their effect on the relative stabilities of the isomers. The possible formation of dimers, experimentally postulated, was also taken into account. Finally, (13)C and (1)H NMR spectra were computed and analysed in order to compare them with available experimental data.

NMR studies of phenylbenzohydroxamic acid and kinetics of complex formation with nickel(II).

The behavior of N-phenylbenzohydroxamic acid (PBHA) in organic solvents has been investigated by (1)H and (13)C NMR spectroscopy. Measurements in acetone at different temperatures and concentrations enable one to individualized two signals, in a 20/80 area ratio, which were ascribed to partition of PBHA between two isomers, HZ (cis) and HE (trans). The dependence of the low-intensity peak on concentration and temperature strongly suggests dimer formation. Since only the HZ form can give dimers, it may be concluded that in acetone PBHA is present mainly in the HE form. (13)C NMR measurements in methanol yielded a 50/50 [HZ]/[HE] ratio. The equilibria and kinetics of complex formation in aqueous solutions between Ni(II) and PBHA were investigated by spectrophotometric and stopped-flow techniques at 25 degrees C and 0.2 M ionic strength. Two reaction paths, involving the binding of Ni(2+) to the neutral PBHA and to its anion, were observed. The rate constants of the forward and reverse steps are k(1) = (7.1 +/- 0.3) x 10(2) M(-)(1) s(-)(1) and k(-1) = (4.9 +/- 0.6) s(-)(1) for the step involving the undissociated PBHA and k(2) = (5.5 +/- 0.7) x 10(4) M(-)(1) s(-)(1) and k(-2) = (1.2 +/- 0.1) s(-)(1) for the step involving the anion. The k(2) value indicates that the PBHA anion reacts with Ni(2+) according to Eigen's mechanism and that in water the cis form prevails. The k(1) value is lower by a factor of 13 compared to the value estimated on the basis of Eigen's mechanism, suggesting that at least 90% of the neutral ligand is present in a nonreactive conformation.

Monooxovanadium(V) complexes with bidentateN-phenylbenzohydroxamate

Two complexes of oxovanadium(V) with VO(ONO)-(OO)-type coordination were synthesized and analysed by X-ray diffraction. These compounds are (acetylacetone benzoylhydrazonato-O,N,O')(N-hydroxy-N-phenylbenzamido-O,O')oxovanadium(V), [VO(C 12 H 12 N 2 O 2 )(C 13 H 10 NO 2 )], and (N-hydroxy-N-phenylbenzamido-O,O')oxo(N-salicylidene-L-alaninato-O,N,O')vanadium(V), [VO(C 10 H 9 NO 3 )(C 13 H 10 NO 2 )]; N-hydroxy-N-phenylbenzamide is also known as N-phenylbenzohydroxamic acid. The distorted octahedral coordination at vanadium is similar in both complexes; the equatorial plane is defined by one N and two O atoms of the tridentate hydrazone ligand and the oxime O atom of the hydroxamate ligand, while the axial oxo group is trans to the carbonyl O atom of the hydroxamate ligand.