Voltammetric Study of Nitro Radical Anion Generated from Some Nitrofuran Compounds of Pharmacological Significance

The electrochemical behavior of 2‐(5‐amino‐ 1,3,4‐oxadiazolyl)‐5‐nitrofuran (NF359) and its comparison with well‐known drugs such as nifurtimox (NFX) and nitrofurazone (NFZ) in protic, mixed and aprotic media by cyclic voltammetry, tast and differential pulse polarography was studied. All the compounds were electrochemically reducible in all media being the reduction of the nitrofuran group the main voltammetric signal. The one‐electron reduction couple due to the nitro radical anion formation was visualized in mixed (for NF359 and NFZ) and aprotic media (for all compounds). By applying a cyclic voltammetric methodology we have calculated the decay constants (k₂) of the corresponding nitro radical anions in mixed and aprotic media. In mixed medium data fit well with a disproportionation reaction of the nitro radical anion but in aprotic medium fit better with a dimerization reaction. Also, considering cyclic voltammetric measurements in aprotic media we have estimated the reduction potential of the RNO₂/RNO₂^.? couple in aqueous medium, pH 7 (E¹₇ values) finding very good correlation with E¹₇ values obtained by pulse radiolysis. Furthermore we have calculated the equilibrium constants from the electron transfer from nitro radical anion to oxygen (k_O2) finding that nitro radical anion from NF359 is thermodynamically favored to react with oxygen in respect to both NFZ and NFX.     

Electrochemical Study of 4‐Substituted Analogues of Megazol

The electrochemical behavior of three different megazol analogues substituted at position 4 and their comparison with the parent compound megazol in protic and aprotic media by cyclic voltammetry, Tast and differential pulse polarography was studied. All the compounds were electrochemically reducible in both media with the reduction of the nitroimidazole group the main voltammetric signal. The one‐electron reduction couple due to the nitro radical anion formation was visualized only in aprotic media for all these compounds. By applying cyclic voltammetric methodology we have calculated the dimerization reaction decay constants (k₂) of the corresponding nitro radical anions in aprotic media. The nitro radical anion obtained from the synthesized nitroimidazole compound having a bromine substituent in 4‐position (GC‐141) was significantly more stable than the corresponding radical formed from the compound lacking of the substituent in 4‐position, megazol.     

Nitroradical Anion Formation from some Iodo‐Substituted Nitroimidazoles

The electrochemical behavior of iodo nitroimidazole derivatives such as 1‐methyl‐4‐iodo‐5‐nitroimidazole (M‐I‐NIm) and 1‐methyl‐2,4‐diiodo‐5‐nitroimidazole (M‐I₂‐NIm) and the parent compound 1‐methyl‐5‐nitroimidazole (M‐NIm), was studied in protic, mixed and non‐aqueous media. The electrochemical study was carried out using Differential Pulse Polarography (DPP), Cyclic Voltammetry (CV), Differential Pulse Voltammetry (DPV) and coulometry and as working electrodes mercury and glassy carbon were used. As can be expected, in all media, the effect of introduce iodo as substituent in the nitroimidazole ring produced a decrease of the energy requirements of the nitro group reduction. Certainly, this fact can be explained by the electron withdrawing character of the iodo substituent that acts diminishing the electronic density on the nitro group thus facilitating their reduction. In all the studied media the reduction of M‐NIm produced a detectable signal for a nitro radical anion derivative. In the case of M‐I‐NIm the nitro radical anion was only detectable in both mixed and non‐aqueous media. On the other hand the nitro radical anion for the M‐I₂‐NIm was detected only in non‐aqueous medium. When glassy carbon electrode was used as the working electrode in a mixed medium a detectable nitro radical anion derivative appeared for all compounds, thus permitting an adequate comparison between them. The obtained values of k₂ for M‐NIm, M‐I‐NIm and M‐I₂‐NIm in non‐aqueous medium were 5.81×10², 132×10² and 1100×10² M^?1 s^?1, respectively. From the obtained k₂ and t_1/2 values in this medium, it is concluded that there is a direct dependence between the presence of iodo substitution in the nitroimidazole ring with the stability of the nitro radical anion.     

Polarographic behaviour of 2,4-dinitrodiphenylamine in amphiprotic media

Two six-electron diffusion-controlled irreversible waves are obtained for the polarographic reduction of 2,4-dinitrodiphenylamine (DPA) in buffered and unbuffered media in all compositions of methanol-water mixtures. Based on the polarographic and coulometric data, it is suggested that each of the nitro groups is reduced to the corresponding amine in a single stepvia the diimine intermediate to give 2,4-diamino DPA as the final product. The influence of various factors such as structure of the depolariser, pH and composition of methanol on the reduction of the compound is also discussed.     

Influence of Methyl Substituent Position on Redox Properties of Nitroaromatics Related to 2,4,6‐Trinitrotoluene

The environmental remediation of military installation sites is very important due to frequently large presence of carcinogenic derivatives of explosives in the ground and in ground waters. These nitroaromatic explosives and their derivatives are assessed by sensing devices. It is highly important to have insight on the reasons affecting the reduction potentials of these compounds. The redox properties of mono‐, di‐ and tri‐nitroaromatic compounds are studied with cyclic voltammetry at a glassy carbon electrode for comparison. We show that the presence of a methyl group in the aromatic system leads into more negative reduction potentials. The ease of nitro group reduction vary from meta>para>ortho positions relative to a methyl group. The redox properties were also studied at various pH ranging from 2 to 10. Acidic environments facilitated the reduction processes at lower potentials. These findings will have a profound influence upon understanding the processes during reductive decontaminations of the polluted sites as well as for construction of highly sensitive sensors for their determination.     

Oxygen reduction at the surface of glassy carbon electrodes modified with anthraquinone derivatives and dyes

The preparation, electrochemical and catalytic behaviour of glassy carbon electrodes modified by anthra-9,10-quinone, its amino derivatives and dyes were investigated. The stability of the modified electrodes was studied by cyclic voltammetry in acidic and neutral media. The electrocatalytic ability of the modified electrodes for the reduction of dioxygen to hydrogen peroxide was examined by cyclic voltammetry, chronoamperometry and chronocoulometry techniques. The influence of pH on the electrochemical and catalytic behaviour was studied and pH 5.0–8.0 was chosen as the optimum working pH by comparing the shift in oxygen reduction potential. The anthraquinone-adsorbed glassy carbon electrodes possess excellent electrocatalytic abilities for dioxygen reduction with overpotential ranging from 280 to 560 mV lower than that at a plain glassy carbon electrode. Hydrodynamic voltammetric studies were performed to determine the heterogeneous rate constants for the reduction of O₂ at the surface of the modified electrodes, mass specific activity of the anthraquinones used and the apparent diffusion coefficient of O₂ in buffered aqueous O₂-saturated solutions. Studies showed the involvement of two electrons in dioxygen reduction.     

Selective Reduction of Nitroarenes with Molybdenum Disulfide

Commercial MoS₂ was found to be a highly selective catalyst for the reduction of nitrobenzenes to the corresponding anilines with hydrazine under mild conditions. MoS₂ is not only much cheaper, but also more selective than noble metal catalysts for the reduction of functional nitrobenzenes to the corresponding anilines. Nitrobenzenes with halides (F, Cl, Br and I) were reduced selectively, and the corresponding anilines were obtained in excellent yields, and no dehalogenation was detected. Functional groups such as NH₂, OH, alkene groups were tolerated during the reduction of the nitro compounds. The reduction of p‐chloronitrobenzene was studied over MoS₂ and Pd/C respectively with hydrazine. The yield of p‐chloroaniline was much higher with MoS₂ than that with Pd/C at full conversion.     

Probing the Role of Surface Energetics of Electrons and their Accumulation in Photoreduction Processes on TiO2

We address the role of the energetics of photogenerated electrons in the reduction of 4‐nitrobenzaldehyde on TiO₂. This model molecule bears two functional groups featuring different reducibilities. Electrochemistry shows that reduction to 4‐aminobenzyl alcohol occurs in entirely distinct potential ranges. Partial reduction of the ?NO₂ group, affording 4‐aminobenzaldehyde, takes place through surface states at potentials positive of the flatband potential (E_fb). Dark currents caused by reduction of the aldehyde group are observed only at potentials more negative than E_fb, and the process requires an electron accumulation regime. Photocatalysis with TiO₂ suspensions agrees with the electrochemical data. In particular, reduction of the nitro group is a relatively fast process (k=0.059 s^?1), whereas that of the aldehyde group is slower (k=0.001 s^?1) and requires electron photoaccumulation. Control of the photogenerated charge is a prospective means for achieving chemoselective reductions.     

偶氮染料在酸性介质中的电还原性质

研究了4个偶氮染料在酸性介质中的电还原性质。偶氮基在酸性介质中的还原均为不可逆四电子一步全还原。邻、对位上有吸电子基(如—CO_2Bu-n)的偶氮基较间位有吸电子基时更易被还原。分子中同时含有偶氮基和硝基时,偶氮基先被还原。     

Determination of secnidazole in tablets and human serum by cathodic adsorptive stripping voltammetry

The electrochemical reduction of secnidazole was carried out in BR buffer solutions in the pH range 2.0–11.8 by dc polarography. The polarograms exhibited two irreversible reduction waves in acidic media and one wave in alkaline media, corresponding to the reduction of nitro group in the drug. The cathodic adsorptive voltammetric behavior was studied on glassy carbon electrode to optimize an analytical method for determination of secnidazole. The drug was determined in the range between 4.0 × 10^?6 and 1.2 × 10^?4 mol L^?1. The proposed method was successfully applied to the determination of the drug content in tablets with mean recovery and relative standard deviation of 100.91% and 1.82%, respectively. It was also applied to human serum with a good precision and accuracy.     

Electrochemical preparation of orthophenylenediamine on different cathodes in sulfuric acid

The electrochemical reduction of nitro group of orthonitroaniline (ONA) is carried out on Pb, Cu, and Sn electrodes. The effect of current density, temperature, and acid concentration on product yield is studied. The polarization curve for ONA in acidic condition is recorded. Under preparative electrolysis, ONA gives a mixture of hydroxylamine and phenylenediamine, the proportion of phenylenediamine increasing with the electrolysis time. The product formation is confirmed by thin-layer chromatography, melting-point test, UV-visible, IR, and NMR methods. The operating conditions are optimized for a good yield of orthophenylenediamine. The catalytic activity of different metals for the reduction of nitro group is discussed. The percent yield of orthophenylenediamine is found to be high on the lead electrode. Published in Russian in Elektrokhimiya, 2007, Vol. 43, No. 2, pp. 215–221. The text was submitted by the authors in English.     

Selective reduction of the nitro group in the presence of the azoxy group. Synthesis of 2-(alkyl-NNO-azoxy)anilines

Tin(ii) chloride selectively reduces the aromatic nitro group to the amino group, the azoxy group remaining intact. This allows the preparation of 2-(R-NNO-azoxy)anilines from 2-(R-NNO-azoxy)nitrobenzenes bearing electron-donating or weak electron-withdrawing substituents (Me or Br) in the benzene ring and alkyl substituents at the distal N atom of the azoxy group. The presence of electron-withdrawing substituents at the azoxy group (for example, CO₂Et) leads to a change in the direction of the reaction resulting in selective reduction of the azoxy group to the hydrazo group.     

甲酸铵催化转移氢化还原肽链中的芳香硝基——对氨基苯丙氨酸的间接引入

研究了用甲酸铵催化转移氢化法(AF-CTH)对不同类型肽中的芳香硝基的还原行为, 这些肽类化合物包括促黑激素(MSH: 四肽)、促黄体素释放激素(LHRH: 十肽)和强腓肽(十七肽)的类似物. 用HPLC对还原过程进行了跟踪监测, 结果显示, 除含对氯苯丙氨酸残基的LHRH类似物因发生脱氯副反应不适合用AF-CTH还原外, 其余序列还原过程中均无明显副反应发生, 硝基几乎定量地转化成为相应的氨基, 实现了对氨基苯丙氨酸向肽链的间接引入. 另外发现, 硝基还原所需的时间与肽链长度有关, 肽链越长, 还原所需时间越长, 但与其在序列中的位置关系不明显.     

Low‐Valent Titanium Induced Simultaneous Reduction of Nitro Group and S?S Bond in Nitrodisulfides: A Facile Synthesis of 2H‐1,4‐Benzothiazines

The simultaneous reduction of nitro group and S? S bond in nitrodisulfides by TiCl₄/Sm system led to the active intermediates 2, which were “living” double‐anions in situ and reacted smoothly with ω‐bromoketones to afford the desired 2/7–1,4‐benzothiazines in good yields under mild and neutral conditions.     

Effect of pH on the Reduction of Graphene Oxide on its Structure and Oxygen Reduction Capabilities in the Alkaline Media

The reduction of many catalysts in aqueous media is usually carried out in a basic environment using most reducing agents. Graphene oxide (GO) was synthesized and reduced by sodium borohydride in an aqueous solution over a wide spectrum of pH values ranging from 1 to 13. X‐ray diffraction (XRD) and infrared spectroscopy (FTIR) confirmed the reduction of the graphene oxide at each respective pH value. Raman and X‐Ray photoelectron spectroscopy (XPS) spectra displayed an increased repair in the graphitic sp² domain of the catalysts as the pH value of the solution was increased. Half‐cell electrochemical testing in basic media showed higher oxygen reduction capabilities in the catalysts that were reduced at higher pH values. The onset potential of the oxygen reduction reaction (ORR) also increased as the pH of the solution increased overall due to the increased repair in the graphitic domain of the catalysts reduced at higher pH values.     

Electroreduction and polarographic determination of nitrazepam in serum

The electroreduction of nitrazepam has been investigated by polarography, cyclic voltammetry, chronopotentiometry and controlled potential coulometry. The drug is decomposed in acidic and alkaline solutions but is fairly stable in neutral media. In phosphate buffer pH 6.9 the reduction occurs in two steps. The first step is a 4-electron reduction of the nitro group to the hydroxylamine and the second step is a 2-elcctron reduction of the azomethine (>C=N-) group. The first polarographic wave probably involves a rate-determining 2-electron reduction of the nitro group. This wave is well defined and suitable for determination of the drug in the range 10 ⁻⁶- 5·10⁻⁴M. The half-wave potential is -0.38 V vs. Ag/AgCl, and the current is diffusion-controlled. The oxidized form of nitrazepam is strongly adsorbed at the electrode surface, hence the drug can be determined in the presence of surface-active substances like proteins. A procedure has been developed for the direct polarographic determination of microgram quantities of the drug in serum. The proposed method is very rapid and accurate and permits determination of 0.5 -80 μg per ml of the drug in serum.     

Routes to N‐vinyl‐nitroimidazoles and N‐vinyl‐deazapurines

The preparations of 4‐ and 5‐nitro‐1‐vinylimidazole ( 2 and 7 ) are described. Selective reduction of the nitro group using Fe/dil.HCl is achieved for the 4‐nitro derivative but this is not effective when ethoxymethylenemalononitrile is used to trap the amine. For 5‐nitroimidazole studies the N‐vinyl substituent is kept masked as a 2‐chloroethyl group, which remains unchanged during catalytic reduction of the nitro function (Pd/C), and is revealed by HCl elimination at a later stage. In this way, the 1‐deazapurine 13 and the tricyclic derivative 14 have been prepared.     

An efficient in situ reduction and cyclization reaction for synthesis of spiro compound derivatives in Fe–H2O–AcOH medium from nitro compounds

An efficient in situ reduction and cyclization reaction for the synthesis of nitrogen‐containing spiro compounds directly form 5‐nitro‐1H‐indazole, 6‐nitro‐1H‐indazole and 5‐nitroindole in Fe–H₂O–AcOH medium is reported. 5‐Nitro‐1H‐indazole, 6‐nitro‐1H‐indazole and 5‐nitroindole were first used to synthesize spiro compounds, and this is a novel method for the synthesis of spiro compounds from nitro compounds. The advantages of this reaction are stable reagents, easily available raw materials, wide range of substrates and high yields.     

Limitation of ferrozine method for Fe(II) detection: reduction kinetics of micromolar concentration of Fe(III) by ferrozine in the dark

The dark reduction kinetics of micromolar concentrations of Fe(III) in aqueous solution were studied in the presence of millimolar concentrations of ferrozine (FZ) over the pH range 4.0–7.0. A pseudo-first-order kinetics model was used to describe Fe(III) reduction at pH 4.0 and 5.0, and the reduction rate decreased with increasing pH or initial Fe(III) concentration. A more molecular-based kinetics model was developed to describe Fe(III) reduction at pH 6.0 and 7.0. From this model, the intrinsic rate constants (k₁) of Fe(III) reduction by FZ in the dark were obtained as 0.133 ± 0.004 M^?1 s^?1 at pH 6.0 and 0.101 ± 0.009 M^?1 s^?1 at pH 7.0. It was also found in this model that a higher pH, a higher concentration of Fe(III), a lower concentration of FZ and less incubation time led to a lower fraction of Fe(III) reduction by FZ in the dark.