Oxidation Of Hydroxyurea Research Articles

Spectrophotometric Determination of Hydroxyurea in Pharmaceutical Preparations

A simple spectrophotometric method for the determination of hydroxyurea has been developed. The method is based on the oxidation of hydroxyurea with iron(III) in acidic medium, and the liberated iron(II) reacts with 1,10-phenanthroline to form the orange-red chelate which has a maximum absorption at 510 nm. Beer's law is obeyed over the concentration range 5-160 μg of hydroxyurea in a final volume of 25 ml, with a molar absorptivity of 2.36×104 l.mol-1.cm-1 and Sandell's sensitivity index of 0.0032 μg.cm-2, a relative error of -2.4 to +1.6% and a relative standard deviation of ±0.32 to ±1.5%, depending on the concentration level. Interferences due to excipients have been examined. The proposed method has been applied successfully to the determination of hydroxyurea in pharmaceutical formulations (capsules). ).

Hydroxyurea electrooxidation at gold electrodes. In situ infrared spectroelectrochemical and DFT characterization of adsorbed intermediates

The oxidation of hydroxyurea (H2NCONHOH, HU) at Au(100), Au(111) and Au(111)–25nm thin film electrodes is studied spectroelectrochemically in perchloric acid solutions. HU, which in agreement with DFT results interacts weakly with the gold surfaces, oxidizes irreversibly at gold electrodes irrespective of the surface orientation. The in situ infrared external reflection spectra prove the formation of dissolved carbon dioxide and adsorbed cyanate as products of the HU electrooxidation reaction. A band at ca. 2230cm−1 can be related both to dissolved isocyanic acid coming from the protonation of adsorbed cyanate or to nitrous oxide coming from the oxidation of hydroxylamine, which is formed (together with adsorbed cyanate) upon the chemical decomposition of hydroxyurea. ATR-SEIRAS experiments allow the observation of other adsorbate bands that can be tentatively ascribed to reaction intermediates that conserve the NCN skeleton and are bonded to the metal by the nitrogen atoms at near on-top positions. Bonding to the surface can be either unidentate or bidentate, involving covalent-type bonds or dative bonding through the lone pairs of the N atoms. Some of the signals of the experimental spectra, in particular those appearing around 1800cm−1, can be assigned to the CO stretch of adsorbed intermediates having a nitrosyl group formed by oxidation of the NOH moiety (namely, adsorbed nitrosoformamide or its deprotonated form). The bands observed around 1650cm−1 can correspond either to the NO stretching mode of the former species or to the CO stretching modes of adspecies conserving the NOH group.

Voltammetric and in situ infrared spectroscopy studies of hydroxyurea electrooxidation at Au(111) electrodes in HClO4 solutions

The oxidation of hydroxyurea (H2NCONHOH, HU) at Au(111) single crystal and Au(111)-25nm thin film electrodes is studied spectroelectrochemically in HClO4 solutions using external reflection infrared and Surface Enhanced Infrared Reflection Absorption Spectroscopy under Attenuated Total Reflection conditions (ATR-SEIRAS). The in situ external reflection spectra prove the formation of dissolved carbon dioxide and adsorbed cyanate during the electrooxidation of HU. The enhanced surface sensitivity of the ATR-SEIRAS experiments facilitates the detection of adsorbed cyanate and allows the observation of other adsorbate bands tentatively ascribed to reaction intermediates involving partial oxidation of the HU molecules, some of them corresponding to nitrosyl groups.

Anodic voltammetric behavior of hydroxyurea and its electroanalytical determination in pharmaceutical dosage form and urine

A simple and a novel electroanalysis of hydroxyurea (HU) drug at pencil graphite electrode (PGE) has been investigated by using cyclic, linear sweep and differential pulse voltammetric techniques. The oxidation of HU was irreversible and exhibits a diffusion controlled process and is of pH dependence. The oxidation mechanism was proposed. The dependence of the current on pH, the concentration, nature of buffer, and scan rate was investigated to optimize the experimental conditions for the determination of HU. It was found that the optimum buffer for the determination of HU was pH of 8.0. In the range of 0.01 to 1.0mM, the current measured by differential pulse voltammetry presents a good linear property as a function of the concentration of HU with a limit of detection of 7.89μM. The developed method was successfully applied to HU determination in pharmaceutical formulation and human urine.

Novel electroanalysis of hydroxyurea at glassy carbon and gold electrode surfaces

A simple and a novel electroanalysis of hydroxyurea (HU) drug at glassy carbon and gold electrode was investigated for the first time using cyclic, linear sweep and differential pulse voltammetric techniques. The oxidation of HU was irreversible and exhibited a diffusion controlled process on both electrodes. The oxidation mechanism was proposed. The dependence of the current on pH, the concentration, nature of buffer, and scan rate was investigated to optimize the experimental conditions for the determination of HU. It was found that the optimum buffer pH was 7.0, a physiological pH. In the range of 0.01 to 1.0 mM, the current measured by differential pulse voltammetry showed a linear relationship with HU concentration with limit of detection of 0.46 µM for glassy carbon electrode and 0.92 µM for gold electrode. In addition, reproducibility, precision and accuracy of the method were checked as well. The developed method was successfully applied to HU determination in pharmaceutical formulation and human biological fluids. The method finds its applications in quality control laboratories and pharmacokinetics.

Electrochemical response of hydroxyurea by different voltammetric techniques at carbon paste electrode

A simple and novel electroanalysis of hydroxyurea (HU) drug at carbon paste electrode has been investigated for the first time using cyclic, linear sweep and differential pulse voltammetric techniques. The oxidation of HU is irreversible and exhibits a diffusion controlled process and is pH dependent. The oxidation mechanism is proposed. The dependence of the current on pH, the concentration, nature of buffer, and scan rate is investigated to optimize the experimental conditions for the determination of HU. It was found that the optimum buffer for the determination of HU was pH 7.0, a physiological pH. In the range of 0.2 to 1.0 mM, the current measured by differential pulse voltammetry presents a good linear property as a function of the concentration of HU with a limit of detection of 6.52 μM. In addition, reproducibility, precision and accuracy of the method were checked as well. The developed method was successfully applied to HU determination in pharmaceutical formulation and human urine. The method finds its applications in quality control laboratories and pharmacokinetics.

Kinetics of the oxidation of hydroxyurea with vanadium(V) ions in acidic aqueous solution

Hydroxyurea (HU) effectively reduces vanadate (VO2+) into vanadyl (VO2+) species in acidic aqueous solution acting as a two-electron donor. The reaction starts by the formation of a transient complex followed by an electron transfer process that includes the formation and subsequent fading out of a free radical, U• (U•≡H2N–C(=O)N(H)O•). The rate determining step of the redox reaction is the formation of a free radical either by the inner-sphere one-electron transfer within the formed VO2+-complexes, or by an outer sphere one-electron transfer from VO2+-complex to the second VO2+ ion. Assuming a rapid pre-equilibrium for the proton-transfer and complexation reactions, an inner-sphere electron transfer pathway has been proposed (VO2-U2+\({\mathop{\longrightarrow}\limits^{k_{1}}}\) VO2+-U•2+, k1 = 1.4 s−1) when HU is in excess. When VO2+ in excess, an additional reaction possibly proceeds through two outer-sphere electron-transfer pathways: VO2-U2+ + VO2+ + 2H2O \({\mathop{\longrightarrow}\limits^{k_{4}}}\) VO2+ + VO2+ + U•, and VO2-U2+ + VO(OH)2+ + 2H2O \({\mathop{\longrightarrow}\limits^{k_{5}}}\) VO(OH)2+ + VO2+ + U•, characterized by k4 = 22 s−1 mol−1 dm3, and k5 = 3.8 × 103 s−1 mol−1 dm3.

Oxidation of hydroxyurea with oxovanadium(V) ions in acidic aqueous solution

Hydroxyurea (HU) effectively reduces vanadium(V) into vanadium(IV) species (hereafter V V and V IV species, respectively) in acidic aqueous solution via the formation of a transient complex followed by an electron transfer process that includes the formation and subsequent fading out of a free radical, U (U ≡ H 2N–C(=O)N(H)O ). The electron paramagnetic resonance (EPR) spectra of U in H 2O/D 2O solutions suggest that the unpaired electron is located predominantly on the hydroxamate hydroxyl-oxygen atom. Visible and V IV–EPR spectroscopic data reveal HU as a two-electron donor, whereas formation of U , which reduces a second V V, indicates that electron transfer occurs in two successive one-electron steps. At the molarity ratio [V V]/[HU] = 2, the studied reaction can be formulated as: 2 V V + HU → 2 V IV + 0.98 CO 2 + 0.44 N 2O + 1.1 NH 3 + 0.1 NH 2OH. Lack of evidence for the formation of NO is suggested to be a consequence of the slow oxidation of HNO due to the too low reduction potential of the V V/V IV couple under the experimental conditions used. The nuclear magnetic resonance ( 51V-NMR) spectral data indicate protonation of ( H 2 O ) 4 V V O 2 + , and the protonation equilibrium constant was determined to be K = 0.7 M −1. Spectrophotometric titration data for the V V–HU system reveal formation of (H 2O) 2V VO(OH)U + and (H 2O) 3V VOU 2+. Their stability constants were calculated as K 110 = 5 M −1 and K 111 = 22 M −2, where the subscript digits refer to ( H 2 O ) 4 V V O 2 + , HU and H +, respectively.

C-nitrosoformamides, a new class of transient dienophiles formed by oxidation of N-hydroxyureas

Oxidation of hydroxyurea with sodium or tetraethylammonium periodate in the presence of cyclopentadiene gave a cycloadduct (3a) formed, apparently, by capture of the transient dienophile, C-nitrosoformamide. N-Methyl-, N-phenyl-, N,N-dimethyl-, and N,N-diphenyl-C-nitrosoformamide were likewise trapped as their cycloadducts with cyclopentadiene. Cycloadducts of 2,3-dimethylbuta-1,3-diene, thebaine, ergosteryl acetate, and 9,10-dimethylanthracene (DMA) were prepared similarly. The cyclopentadiene adducts (3) dissociated at 80 °C in the presence of 2,3-dimethylbuta-1,3-diene to give the corresponding adducts (4) of the nitrosoformamides and dimethylbutadiene. Unexpectedly, the 1,4-adducts (4) were accompanied by substantial amounts of hydroxamic acids (5) arising from ‘ene’ reactions of the nitrosoformamides and dimethylbutadiene. The cyclopentadiene adducts of N,N-dimethyl- and N,N-diphenyl-C-nitrosoformamide, when heated alone, decomposed to give the corresponding carbamic anhydrides. The cycloadduct (15) of DMA and C-nitrosoformamide dissociated at 40 °C in the presence of thebaine (11) to give the thebaine adduct (12; R = H) and DMA.