S-oxygenation of thiocarbamides. 3. Nonlinear kinetics in the oxidation of trimethylthiourea by acidic bromate

The oxidation of trimethylthiourea (TMTU) by acidic bromate has been studied. The reaction mimics the dynamics observed in the oxidation of unsubstituted thiourea by bromate with an induction period before formation of bromine. The stoichiometry of the reaction was determined to be 4:3, thus 4BrO(3)- + 3R(1)R(2)C=S+ 3H(2)O --> 4Br- + 3R(1)R(2)C=O + 3SO(4)(2-) + 6H+. This substituted thiourea is oxidized at a much faster rate than the unsubstituted thiourea. The oxidation mechanism of TMTU involves initial oxidations through sulfenic and sulfinic acids. At the sulfinic acid stage, the major oxidation pathway is through the cleavage of the C-S bond to form a reducing sulfur leaving group, which is easily oxidized to sulfate. The minor pathway through the sulfonic acid produces a very stable intermediate that is oxidized only very slowly to urea and sulfate. The direct reaction of aqueous bromine with TMTU was faster than reactions that form bromine, with a bimolecular rate constant of (1.50 +/- 0.04) x 10(2) M(-1) s(-1). This rapid reaction ensured that no oligooscillatory bromine formation was observed. The oxidation of TMTU was modeled by a simple reaction scheme containing 20 reactions.     

Oxyhalogen-sulfur chemistry: kinetics and mechanism of oxidation of N-acetylthiourea by chlorite and chlorine dioxide

The oxidation reactions of N-acetylthiourea (ACTU) by chlorite and chlorine dioxide were studied in slightly acidic media. The ACTU-ClO(2)(-) reaction has a complex dependence on acid with acid catalysis in pH > 2 followed by acid retardation in higher acid conditions. In excess chlorite conditions the reaction is characterized by a very short induction period followed by a sudden and rapid formation of chlorine dioxide and sulfate. In some ratios of oxidant to reductant mixtures, oligo-oscillatory formation of chlorine dioxide is observed. The stoichiometry of the reaction is 2:1, with a complete desulfurization of the ACTU thiocarbamide to produce the corresponding urea product: 2ClO(2)(-) + CH(3)CONH(NH(2))C=S + H(2)O --> CH(3)CONH(NH(2))C=O + SO(4)(2-) + 2Cl(-) + 2H(+) (A). The reaction of chlorine dioxide and ACTU is extremely rapid and autocatalytic. The stoichiometry of this reaction is 8ClO(2)(aq) + 5CH(3)CONH(NH(2))C=S + 9H(2)O --> 5CH(3)CONH(NH(2))C=O + 5SO(4)(2-) + 8Cl(-) + 18H(+) (B). The ACTU-ClO(2)(-) reaction shows a much stronger HOCl autocatalysis than that which has been observed with other oxychlorine-thiocarbamide reactions. The reaction of chlorine dioxide with ACTU involves the initial formation of an adduct which hydrolyses to eliminate an unstable oxychlorine intermediate HClO(2)(-) which then combines with another ClO(2) molecule to produce and accumulate ClO(2)(-). The oxidation of ACTU involves the successive oxidation of the sulfur center through the sulfenic and sulfinic acids. Oxidation of the sulfinic acid by chlorine dioxide proceeds directly to sulfate bypassing the sulfonic acid. Sulfonic acids are inert to further oxidation and are only oxidized to sulfate via an initial hydrolysis reaction to yield bisulfite, which is then rapidly oxidized. Chlorine dioxide production after the induction period is due to the reaction of the intermediate HOCl species with ClO(2)(-). Oligo-oscillatory behavior arises from the fact that reactions that form ClO(2) are comparable in magnitude to those that consume ClO(2), and hence the assertion of each set of reactions is based on availability of reagents that fuel them. A computer simulation study involving 30 elementary and composite reactions gave a good fit to the induction period observed in the formation of chlorine dioxide and in the autocatalytic consumption of ACTU in its oxidation by ClO(2).     

Kinetic study on hydrolysis and oxidation of formamidine disulfide in acidic solutions

Hydrolysis and oxidation of formamidine disulfide in acidic medium were investigated using high-performance liquid chromatography(HPLC) and mass spectrometry(MS) at 25 °C.By controlling the slow reaction rate and choosing appropriate mobile phase,HPLC provides the unique advantages over other methods(UV-Vis,chemical separation) in species tracking and kinetic study.In addition to thiourea and formamidine sulfinic acid,two unreported products were also detected in the hydrolysis reaction.Mass spectrometry measurement indicates these two products to be formamidine sulfenic acid and thiocyanogen with mass weights of 92.28 and 116.36,respectively.In the oxidation of formamidine disulfide by hydrogen peroxide,besides thiourea,formamidine sulfenic acid,formamidine sulfinic acid,thiocyanogen and urea,formamidine sulfonic acid and sulfate could be detected.The oxidation reaction was found to be first order in both formamidine disulfide and hydrogen peroxide.The rate constants of hydrolysis and oxidation reactions were determined in the pH range of 1.5-3.0.It was found both rate constants are increased with the increasing of pH.Experimental curves of different species can be effectively simulated via a mechanism scheme for formamidine disulfide oxidation,including hydrolysis equilibrium of formamidine disulfide and irreversible hydrolysis of formamidine sulfenic acid.     

S-oxygenation of thiocarbamides I: Oxidation of phenylthiourea by chlorite in acidic media

The oxidation of 1-phenyl-2-thiourea (PTU) by chlorite was studied in aqueous acidic media. The reaction is extremely complex with reaction dynamics strongly influenced by the pH of reaction medium. In excess chlorite concentrations the reaction stoichiometry involves the complete desulfurization of PTU to yield a urea residue and sulfate: 2ClO2- + PhN(H)CSNH2 + H2O --> SO4(2-) + PhN(H)CONH2 + 2Cl- + 2H+. In excess PTU, mixtures of sulfinic and sulfonic acids are formed. The reaction was followed spectrophotometrically by observing the formation of chlorine dioxide which is formed from the reaction of the reactive intermediate HOCl and chlorite: 2ClO2- + HOCl + H+ --> 2ClO2(aq) + Cl- + H2O. The complexity of the ClO2- - PTU reaction arises from the fact that the reaction of ClO2 with PTU is slow enough to allow the accumulation of ClO2 in the presence of PTU. Hence the formation of ClO2 was observed to be oligooscillatory with transient formation of ClO2 even in conditions of excess oxidant. The reaction showed complex acid dependence with acid catalysis in pH conditions higher than pKa of HClO2 and acid retardation in pH conditions of less than 2.0. The rate of oxidation of PTU was given by -d[PTU]/dt = k1[ClO2-][PTU] + k2[HClO2][PTU] with the rate law: -d[PTU]/dt = [Cl(III)](T)[PTU]0/K(a1) + [H+] [k1K(a1) + k2[H+]]; where [Cl(III)]T is the sum of chlorite and chlorous acid and K(a1) is the acid dissociation constant for chlorous acid. The following bimolecular rate constants were evaluated; k1 = 31.5+/-2.3 M(-1) s(-1) and k2 = 114+/-7 M(-1) s(-1). The direct reaction of ClO2 with PTU was autocatalytic in low acid concentrations with a stoichiometric ratio of 8:5; 8ClO2 + 5PhN(H)CSNH2 + 9H2O --> 5SO4(2-) + 5PhN(H)CONH2 + 8Cl- + 18H+. The proposed mechanism implicates HOCl as a major intermediate whose autocatalytic production determined the observed global dynamics of the reaction. A comprehensive 29-reaction scheme is evoked to describe the complex reaction dynamics.     

Kinetics and mechanism of the oxidation of thiourea by chlorine dioxide

The stoichiometry and kinetics of the oxidation of thiourea (SC(NH₂)₂) by chlorine dioxide (ClO₂) have been studied by uv-vis spectrophotometry using conventional and stopped-flow mixing techniques at 25.0 ± 0.1°C, pH 0.3–4.8. In high acid and initial 10:1 molar ratio of thiourea to chlorine dioxide, thiourea is oxidized relatively rapidly to dithiobisformamidine ion ((NH₂)₂CSSC(NH₂)₂²⁺), which slowly decomposes to thiourea, sulfur, and cyanamide (NCNH₂). In high acid and excess ClO₂, thiourea is oxidized to relatively stable formamidine sulfinic acid ((NH) (NH₂)CSO₂H). In high acid and molar ratios of ClO₂ to thiourea of 5:1 and higher, some oxidation to formamidine sulfonic acid ((NH) (NH₂)CSO₃H) occurs. At lower acidity, along with Cl^?, the major ClO₂ reduction product, byproduct sulfate is detected and, at pH < 3, ClO₂^?, also, appears. Kinetics data were collected for high excess thiourea with varying pH. The [ClO₂]-time curves are straight lines with negative slopes that increase in magnitude with increasing [thiourea]. The dependence on [thiourea] is first-order; the dependence on [ClO₂] is zero-order for 90% of reaction. With decreasing pH, the rate increases and the disappearance of ClO₂ becomes autocatalytic. Studies of the effects of reaction products on the rate of reaction lead to the conclusion that autocatalysis at low pH is due to the greater reactivity of HClO₂ compared with ClO₂^?. A 10-step mechanism incorporating a slow one-electron transfer from thiourea to ClO₂ to generate the (NH) (NH₂)CS · radical and subsequent more rapid reactions has been constructed and implemented in a computer simulation which provides a reasonably accurate fit to the observed kinetics curves. © 1993 John Wiley & Sons, Inc.     

Kinetics and mechanisms of chlorine dioxide and chlorite oxidations of cysteine and glutathione

Chlorine dioxide oxidation of cysteine (CSH) is investigated under pseudo-first-order conditions (with excess CSH) in buffered aqueous solutions, p[H+] 2.7-9.5 at 25.0 degrees C. The rates of chlorine dioxide decay are first order in both ClO2 and CSH concentrations and increase rapidly as the pH increases. The proposed mechanism is an electron transfer from CS- to ClO2 (1.03 x 10(8) M(-1) s(-1)) with a subsequent rapid reaction of the CS* radical and a second ClO2 to form a cysteinyl-ClO2 adduct (CSOClO). This highly reactive adduct decays via two pathways. In acidic solutions, it hydrolyzes to give CSO(2)H (sulfinic acid) and HOCl, which in turn rapidly react to form CSO3H (cysteic acid) and Cl-. As the pH increases, the (CSOClO) adduct reacts with CS- by a second pathway to form cystine (CSSC) and chlorite ion (ClO2-). The reaction stoichiometry changes from 6 ClO2:5 CSH at low pH to 2 ClO2:10 CSH at high pH. The ClO2 oxidation of glutathione anion (GS-) is also rapid with a second-order rate constant of 1.40 x 10(8) M(-1) s(-1). The reaction of ClO2 with CSSC is 7 orders of magnitude slower than the corresponding reaction with cysteinyl anion (CS-) at pH 6.7. Chlorite ion reacts with CSH; however, at p[H+] 6.7, the observed rate of this reaction is slower than the ClO2/CSH reaction by 6 orders of magnitude. Chlorite ion oxidizes CSH while being reduced to HOCl, which in turn reacts rapidly with CSH to form Cl-. The reaction products are CSSC and CSO3H with a pH-dependent distribution similar to the ClO2/CSH system.     

Travelling wave in the chlorite-thiourea reaction

The oxidation of thiourea by chlorite within the pH range of 2 to 5.5 has been found to produce a single wave of chlorine dioxide in unstirred solutions. The wave has been studied in narrow tubes of varying diameters and in petri dishes. The wave appears after an induction period that depends on the acid concentration, the [ClO₂^?]/[CS(NH₂)₂] ratio, the temperature, and the diameter of the tube. The wave starts from the surface in a tube and from the edges in a petri dish. The rate of wave movement is proportional to the ratio and the acid concentration. Barium chloride and starch were used as indicators. The wave could be initiated electrochemically and by addition of a drop of solution containing chlorine dioxide. The chlorine dioxide is produced by the oxidation of chlorite by hypochlorous acid.     

S-oxygenation of thiocarbamides IV: Kinetics of oxidation of tetramethylthiourea by aqueous bromine and acidic bromate

The kinetics and mechanism of oxidation of tetramethylthiourea (TTTU) by bromine and acidic bromate has been studied in aqueous media. The kinetics of reaction of bromate with TTTU was characterized by an induction period followed by formation of bromine. The reaction stoichiometry was determined to be 4BrO(3)(-) + 3(R)(2)C═S + 3H(2)O → 4Br(-) + 3(R)(2)C═O + 3SO(4)(2-) + 6H(+). For the reaction of TTTU with bromine, a 4:1 stoichiometric ratio of bromine to TTTU was obtained with 4Br(2) + (R)(2)C═S + 5H(2)O → 8Br(-) + SO(4)(2-) + (R)(2)C═O + 10H(+). The oxidation pathway went through the formation of tetramethythiourea sulfenic acid as evidenced by the electrospray ionization mass spectrum of the dynamic reaction solution. This S-oxide was then oxidized to produce tetramethylurea and sulfate as final products of reaction. There was no evidence for the formation of the sulfinic and sulfonic acids in the oxidation pathway. This implicates the sulfoxylate anion as a precursor to formation of sulfate. In aerobic conditions, this anion can unleash a series of genotoxic reactive oxygen species which can explain TTTU's observed toxicity. A bimolecular rate constant of 5.33 ± 0.32 M(-1) s(-1) for the direct reaction of TTTU with bromine was obtained.     

Glutathione oxidation in real time by thermospray liquid chromatography-mass spectrometry

The oxidation and reduction of glutathione and oxidized glutathione were studied in real time by liquid chromatography-mass spectrometry during exposure to hydrogen peroxide and mercaptoethanol. By mass spectrometry mixed disulfides and both reversible and irreversible oxidations of sulfur to higher states (sulfinic and sulfonic acids) were directly observed during exposure to hydrogen peroxide. The irreversible oxidation of glutathione to glutathione sulfonic acid could be detected after 30 min exposure of glutathione to 40 mM H2O2 at 20 degrees C. A peak consistent with glutathione-sulfinic acid was transiently present, suggesting this compound behaved as an oxygen consuming antioxidant. Liquid chromatography-mass spectrometry appears to be an excellent method to study oxidation and reductions of sulfur containing peptides and amino acids.     

Three autocatalysts and self-inhibition in a single reaction: a detailed mechanism of the chlorite-tetrathionate reaction

The chlorite-tetrathionate reaction has been studied spectrophotometrically in the pH range of 4.65-5.35 at T = 25.0 +/- 0.2 degrees C with an ionic strength of 0.5 M, adjusted with sodium acetate as a buffer component. The reaction is unique in that it demonstrates autocatalysis with respect to the hydrogen and chloride ion products and the key intermediate, HOCl. The thermodynamically most-favorable stoichiometry, 2S(4)O(6)2- + 7ClO2- + 6H2O --> 8SO(4)2- + 7Cl- + 12H+, is not found. Under our experimental conditions, chlorine dioxide, the chlorate ion, or both are detected in appreciable amounts among the products. Initial rate studies reveal that the formation of chlorine dioxide varies in an unusual way, with the chlorite ion acting as a self-inhibitor. The reaction is supercatalytic (i.e., second order with respect to autocatalyst H+). The autocatalytic behavior with respect to Cl- comes from chloride catalysis of the chlorite-hypochlorous acid and hypochlorous acid-tetrathionate subsystems. A detailed kinetic study and a model that explains this unusual kinetic behavior are presented.     

亚氯酸盐-硫脲反应体系的非线性动力学

The reaction between chlorite and thiourea could display batch oligooscillation and CSTR oscillation of pH.Batch pH peak has the same character with pH oscillation in a CSTR.The oxidation of thiourea produced intermediates such as HOSC(NH)NH2,HO2SC(NH)NH2,HO3S(NH)NH2 and bisulfite.The valence change of sulfur has close relation with pH dynamics.Through the mechanistic analysis,a general model of sulfur(－ II) oxidation,which consists of negative hydrogen ion feedback(S(－ II) to S(0)),a transition process of S(0) to S(IV) and positive proton feedback from S(IV) to S(VI),could simulate batch oligooscillation and CSTR oscillation.This result is setting up a new channel to uncover the reaction mechanism and simulate the nonlinear phenomena in the reactions between chlorite and Sulfur(－ II).     

Application of an amperometric sensor to in-line monitoring of pulp bleaching with chlorine dioxide

Chlorine dioxide is replacing chlorine as the active compound in pulp bleaching in order to reduce the amount of chlorine used in the process and hence also in the waste waters. In bleaching with chlorine dioxide part of the effective bleaching chemical is usually chlorite. The electrochemistry of chlorine dioxide and chlorite at solid electrodes was studied by cyclic voltammetry at different pH values. The observed voltammograms indicated that reduction of chlorine dioxide gives chlorite and oxidation of chlorite gives chlorine dioxide. Both voltammograms were well developed, indicating a reversible process. Both platinum and glassy carbon were used as the working electrode. The dependence of the limiting current of chlorine dioxide and chlorite on pH was studied at both electrodes. The method was tested in the chlorine dioxide bleaching stage D1 in a typical bleaching process. A good correlation was found between the concentrations of chlorine dioxide and chlorite measured by the in-line amperometric method and a standard titrimetric method.     

Photoredox‐Catalyzed Functionalization of Alkenes with Thiourea Dioxide: Construction of Alkyl Sulfones or Sulfonamides

Sulfonylation of alkenes through photoredox‐catalyzed functionalization of alkenes with thiourea dioxide under visible‐light irradiation is achieved. The reaction of alkenes, thiourea dioxide and electrophiles provides a green and efficient access to alkyl sulfones and sulfonamides. A broad reaction scope is presented with good functional group compatibility and excellent regioselectivity. A plausible mechanism involving a radical addition process with sulfur dioxide radical anion (SO₂^‐) derived from the oxidation of sulfur dioxide anion (SO₂^2–) is proposed, which is supported by fluorescence quenching experiments.     

Characterization by tandem mass spectrometry of stable cysteine sulfenic acid in a cysteine switch peptide of matrix metalloproteinases

Cysteine sulfenic acid (Cys-SOH) is an elusive intermediate in reactive oxygen species-induced oxidation reactions of many proteins such as peroxiredoxins and tyrosine phosphatases. Cys-SOH is proposed to play a vital role in catalytic and signaling functions. The formation of cysteine sulfinic acid (Cys-SO(2)H) and cysteine sulfonic acid (Cys-SO(3)H) has been implicated in the activation of matrix metalloproteinase-7 (MMP-7) and oxidation of thiol to cysteine sulfinic acid has been associated with the autolytic cleavage of MMP-7. We have examined the formation of cysteine sulfenic acid in a synthetic peptide PRCGVPDVA, which is a cysteine switch domain of MMP-7 and other matrix metalloproteases. We have prepared the cysteine sulfenic acid containing peptide, PRC(SOH)GVPDVA, by reaction with hydroxyl radicals generated by the Fenton reaction (Fe(+2)/H(2)O(2)). We characterized this modified peptide by tandem mass spectrometry and accurate mass measurement experiments. In addition, we used 7-chloro-4-nitrobenzo-2-oxa-1,3-diazol (NBD-Cl) reagent to form an adduct with PRC(SOH)GVPDVA to provide additional evidence for the viability of PRC(SOH)GVPDVA in solution. We also characterized an intramolecular cysteine sulfinamide cross-link product PRC[S(O)N]GVPDVA based on tandem mass spectrometry and accurate mass measurement experiments. These results contribute to the understanding of a proteolytic cleavage mechanism that is traditionally associated with MMP activation.     

Untersuchungen an Stickstoff-Chlor-Verbindungen. VIII. Tieftemperatur-Umsetzungen von Aminen mit Chlordioxid in wasserfreien Medien – Darstellung von Chlorsäureamiden und Amin-Chlordioxid-Addukten

Studies on Nitrogen-Chlorine Compounds. VIII. Low Temperature Reactions between Amines and Chlorine Dioxide in Non-Aqeous Solutions – Preparation of Chloric Acid Amides and Adducts between Amines and Chlorine Dioxide The radicalic redox reaction between amines and chlorine dioxide leads to different reaction products dependent on the kind of amine: reactive protons in α position to nitrogen are abstracted, and azomethinium chlorite is formed besides the chlorite or chlorate of the protonated base. In case of absence of reactive protons in α position to nitrogen these are abstracted from nitrogen if possible; amidochlorates are formed – which are described here for the first time – besides the salt of the protonated base. In case of absence of reactive protons at nitrogen the reaction stops after formation of an adduct between amine and chlorine dioxide. For this several new examples are reported.     

Direct potentiometric titration of chlorite in presence of chlorate, chlorine dioxide and chloride

A direct potentiometric titration of chlorite in the presence of chlorate, chlorine dioxide and chloride is described. Chlorite is determined in 0.01-0.0005 M sodium chlorite at pH 2.0-3.5 using hypochlorite solution. The course of the reaction is followed potentiometrically using saturated calomel and platinum electrodes; the end-point is indicated by a potential jump of about 230 mV. Under these conditions no reaction takes place with chlorate, chlorine dioxide or chloride. Previously, the determination of chlorite in such mixtures was only possible by difference from several oxidimetric titrations.     

Fragmentation of protonated ions of peptides containing cysteine,cysteine sulfinic acid,and cysteine sulfonic acid

The oxidation of the sulfhydryl group in cysteine to sulfenic acid, sulfinic acid, and sulfonic acid in proteins is important in a number of enzymatic processes. In this study we examined the fragmentation of four peptides containing cysteine, cysteine sulfinic acid (Cys-SO(2)H), and cysteine sulfonic acid (Cys-SO(3)H) in an ion-trap mass spectrometer. Our results show that the presence of a Cys-SO(2)H in a peptide leads to preferential cleavage of the amide bond at the C-terminal side of the oxidized cysteine residue. The results are important for the determination of the site of the cysteine oxidation and might be useful for the sequencing of cysteine-containing peptides.     

Dissection of the mechanism of manganese porphyrin-catalyzed chlorine dioxide generation

Chlorine dioxide, an industrially important biocide and bleach, is produced rapidly and efficiently from chlorite ion in the presence of water-soluble, manganese porphyrins and porphyrazines at neutral pH under mild conditions. The electron-deficient manganese(III) tetra-(N,N-dimethyl)imidazolium porphyrin (MnTDMImP), tetra-(N,N-dimethyl)benzimidazolium (MnTDMBImP) porphyrin, and manganese(III) tetra-N-methyl-2,3-pyridinoporphyrazine (MnTM23PyPz) were found to be the most efficient catalysts for this process. The more typical manganese tetra-4-N-methylpyridiumporphyrin (Mn-4-TMPyP) was much less effective. Rates for the best catalysts were in the range of 0.24-32 TO/s with MnTM23PyPz being the fastest. The kinetics of reactions of the various ClO(x) species (e.g., chlorite ion, hypochlorous acid, and chlorine dioxide) with authentic oxomanganese(IV) and dioxomanganese(V)MnTDMImP intermediates were studied by stopped-flow spectroscopy. Rate-limiting oxidation of the manganese(III) catalyst by chlorite ion via oxygen atom transfer is proposed to afford a trans-dioxomanganese(V) intermediate. Both trans-dioxomanganese(V)TDMImP and oxoaqua-manganese(IV)TDMImP oxidize chlorite ion by 1-electron, generating the product chlorine dioxide with bimolecular rate constants of 6.30 × 10(3) M(-1) s(-1) and 3.13 × 10(3) M(-1) s(-1), respectively, at pH 6.8. Chlorine dioxide was able to oxidize manganese(III)TDMImP to oxomanganese(IV) at a similar rate, establishing a redox steady-state equilibrium under turnover conditions. Hypochlorous acid (HOCl) produced during turnover was found to rapidly and reversibly react with manganese(III)TDMImP to give dioxoMn(V)TDMImP and chloride ion. The measured equilibrium constant for this reaction (K(eq) = 2.2 at pH 5.1) afforded a value for the oxoMn(V)/Mn(III) redox couple under catalytic conditions (E' = 1.35 V vs NHE). In subsequent processes, chlorine dioxide reacts with both oxomanganese(V) and oxomanganese(IV)TDMImP to afford chlorate ion. Kinetic simulations of the proposed mechanism using experimentally measured rate constants were in agreement with observed chlorine dioxide growth and decay curves, measured chlorate yields, and the oxoMn(IV)/Mn(III) redox potential (1.03 V vs NHE). This acid-free catalysis could form the basis for a new process to make ClO(2).     

Catalytic reactions of chlorite with a polypyridylruthenium(II) complex: disproportionation, chlorine dioxide formation and alcohol oxidation

cis-[Ru(2,9-Me(2)phen)(2)(OH(2))(2)](2+) reacts readily with chlorite at room temperature at pH 4.9 and 6.8. The ruthenium(II) complex can catalyze the disproportionation of chlorite to chlorate and chloride, the oxidation of chlorite to chlorine dioxide, as well as the oxidation of alcohols by chlorite.     

Exploiting soft and hard X-ray absorption spectroscopy to characterize metallodrug/protein interactions: the binding of [trans-RuCl4(Im)(dimethylsulfoxide)][ImH] (Im = imidazole) to bovine serum albumin

The reaction of bovine serum albumin (BSA) with [ trans-RuCl 4(Im)(dimethylsulfoxide)][ImH] (Im = imidazole) (NAMI-A), an experimental ruthenium(III) anticancer drug, and the formation of the respective NAMI-A/BSA adduct were investigated by X-ray absorption spectroscopy (XAS) at the sulfur and chlorine K-edges and at the ruthenium K- and L 3-edges. Ruthenium K and L 3-edge spectra proved unambiguously that the ruthenium center remains in the oxidation state +3 after protein binding. Comparative analysis of the chlorine K-edge XAS spectra of NAMI-A and NAMI-A/BSA, revealed that the chlorine environment is greatly perturbed upon protein binding. Only modest changes were observed in the sulfur K-edge spectra that are dominated by several protein sulfur groups. Overall, valuable information on the nature of this metallodrug/protein adduct and on the mechanism of its formation was gained; XAS spectroscopy turns out to be a very suitable method for the characterization of this kind of systems.