Chlorine Dioxide Is a Size-Selective Antimicrobial Agent

Background / Aims: ClO2, the so-called "ideal biocide", could also be applied as an antiseptic if it was understood why the solution killing microbes rapidly does not cause any harm to humans or to animals. Our aim was to find the source of that selectivity by studying its reaction-diffusion mechanism both theoretically and experimentally. Methods: ClO2 permeation measurements through protein membranes were performed and the time delay of ClO2 transport due to reaction and diffusion was determined. To calculate ClO2 penetration depths and estimate bacterial killing times, approximate solutions of the reaction-diffusion equation were derived. In these calculations evaporation rates of ClO2 were also measured and taken into account. Results: The rate law of the reaction-diffusion model predicts that the killing time is proportional to the square of the characteristic size (e. g. diameter) of a body, thus, small ones will be killed extremely fast. For example, the killing time for a bacterium is on the order of milliseconds in a 300 ppm ClO2 solution. Thus, a few minutes of contact time (limited by the volatility of ClO2) is quite enough to kill all bacteria, but short enough to keep ClO2 penetration into the living tissues of a greater organism safely below 0.1 mm, minimizing cytotoxic effects when applying it as an antiseptic. Additional properties of ClO2, advantageous for an antiseptic, are also discussed. Most importantly, that bacteria are not able to develop resistance against ClO2 as it reacts with biological thiols which play a vital role in all living organisms. Conclusion: Selectivity of ClO2 between humans and bacteria is based not on their different biochemistry, but on their different size. We hope initiating clinical applications of this promising local antiseptic

Dynamics and mechanism studies of nonlinear chemical systems

The kinetics and mechanisms of oxidation of selected thiocarbamides (tetra-methylthiourea, trimethylthiourea, phenylthiourea, and 2-aminoethanethiolsulfuric acid) by chlorite in aqueous acidic media are investigated using UV/Vis, NMR, Stopped-flow techniques, and qualitative analysis. The reactions were extremely complex, with reaction dynamics strongly influenced by the pH of the reaction medium and formation of stable intermediates (sulfonic acids). Results revealed that oxidations of substituted thioureas do not always proceed via a stepwise oxidation of the sulfur center. Instead, reactions occurred in two stages: S-oxygenation of the sulfur center to yield the sulfinic acid, which then reacts in the second phase predominantly through an initial hydrolysis to produce a urea-type residue and the sulfoxylate anion. The sulfoxylate anion, a highly reducing species, is then rapidly oxidized to sulfate.;Experimental and numerical studies of local periodic forcing on an excitable Belousov-Zhabotinsky (BZ) medium in a thin gel layer are reported. Rather than the traditional suprathreshold perturbations giving rise to a local oscillatory state, waves were initiated in an excitable system via localized small amplitude variations in light intensity, without crossing into the oscillatory regime of the autonomous system. Initiation of waves in the initially quiescent medium was possible when the frequency of the sinusoidal perturbation was suitably tuned to that of the autonomous system. The region in phase space where wave initiation was possible depended on the parameter values of the perturbation, namely forcing frequency and forcing amplitude, and on the inherent properties of the autonomous system. Resonance patterns are found by relating the period between two waves to the period of the sinusoidal perturbation.;Experimental and theoretical studies of the peroxidase-oxidase (PO) reaction are reviewed. Numerical investigations into the initiation of trigger waves in an oscillatory one-dimensional PO reaction-diffusion system are presented. Trigger waves are initiated in the oscillatory system via localized perturbations in the concentration of one of the variables using the extended BFSO model. The chemical waves traveled with a sharp front and were not able to penetrate barriers to diffusion, which are properties characteristic of trigger waves

Risk of chlorine dioxide as emerging contaminant during SARS-CoV-2 pandemic: enzyme, cardiac, and behavior effects on amphibian tadpoles

Objective The use of chlorine dioxide (ClO2) increased in the last year to prevent SARS-CoV-2 infection due to its use as disinfectant and therapeutic human treatments against viral infections. The absence of toxicological studies and sanitary regulation of this contaminant represents a serious threat to human and environmental health worldwide. The aim of this study was to evaluate the acute toxicity and sublethal efects of ClO2 on tadpoles of Trachycephalus typhonius, which is a common bioindicator species of contamination from aquatic ecosystems. Materials and methods Median lethal concentration (LC50), the lowest-observed efect concentration (LOEC), and the noobserved efect concentration (NOEC) were performed. Acetylcholinesterase (AChE) and glutathione-S-transferase (GST) activities, swimming behavior parameters, and cardiac rhythm were estimated on tadpoles of concentrations≤LOEC exposed at 24 and 96 h. ANOVA and Dunnett’s post-hoc comparisons were performed to defne treatments signifcance (p≤0.05). Results The LC50 of ClO2 was 4.17 mg L−1 (confdence limits: 3.73–4.66). In addition, NOEC and LOEC values were 1.56 and 3.12 mg L−1 ClO2, respectively, at 48 h. AChE and GST activities, swimming parameters, and heart rates increased in sublethal exposure of ClO2 (0.78–1.56 mg L−1) at 24 h. However, both enzyme activities and swimming parameters decreased, whereas heart rates increased at 96 h. Conclusion Overall, this study determined that sublethal concentrations of ClO2 produced alterations on antioxidant systems, neurotoxicity refected on swimming performances, and variations in cardiac rhythm on treated tadpoles. Thus, our fndings highlighted the need for urgent monitoring of this chemical in the aquatic ecosystems.Fil: Peltzer, Paola. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; ArgentinaFil: Cuzziol Boccioni, Ana Paula. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; ArgentinaFil: Attademo, Andres Maximiliano. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Martinuzzi, Candela Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; ArgentinaFil: Colussi, Carlina Leila. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; ArgentinaFil: Lajmanovich, Rafael Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentin

Fundamental reaction mechanisms of chlorine dioxide during water treatment - Reactions with phenols and biomolecules during inactivation mechanisms

Two key elements of drinking water treatment are disinfection and pollution control. For this purpose, different chemical oxidants are used, for instance, chlorine (free available chlorine (FAC)), ozone (O₃), or chlorine dioxide (ClO₂). The presented work investigated the reaction mechanisms of ClO₂ during drinking water treatment. ClO₂ reacts mainly with activated aromatic compounds (e.g., phenols, anilines) and forms chlorite as major by-product (drinking water standard, 200 µg L⁻¹, Germany). It is increasingly implemented in drinking water treatment as a substitute for chlorination to avoid the formation of a halogenated disinfection by-product (DBP). However, recently it has been shown that FAC also forms in reactions of ClO₂ as a by-product. This results in a combined oxidation with ClO₂ and FAC, and both oxidants can work together synergistically in disinfection and pollutant degradation but may also form two sets of DBPs. The present study focuses on the intrinsic formation of FAC and other inorganic by-products (chloride, chlorite, and chlorate) in the ClO₂ reactions with phenols as representatives for reactive sites in natural organic matter (NOM) and biomolecules (amino acids). Furthermore, the contribution of FAC to disinfection in a ClO₂ water treatment model system has been investigated. The reaction of ClO₂ with amino acids was studied in the context of disinfection mechanisms. Thereby amino acids may be an important reaction partner for reaction with microbial cells during the disinfection. Therefore, reactions of ClO₂ with tyrosine and tryptophan were investigated regarding reaction kinetics and the formation of different chlorine species (FAC, chlorite, chloride, chlorate). Tyrosine and tryptophan displayed a very high reactivity towards ClO₂ (kapp = 3.16 × 10⁴ M⁻¹ s⁻¹ and 1.81 × 10⁴ M⁻¹ s⁻¹ at pH 7), and it seems likely that these represent a possible point of primary reaction of ClO₂ in microbial cells. Both investigated amino acids showed a significant formation of FAC (tyrosine ≈ 50 %, tryptophan ≈ 36 % of dosed ClO₂ concentration). Thereby FAC may serve as an additional reactive species contributing to cell inactivation. Since amino acids are the building blocks of peptides and proteins, it is possible that the reaction of ClO₂ with cell proteins during disinfection is not only causing the inactivation of the corresponding proteins but also forms FAC, which can cause further cell damage and may enhance the total cell inactivation. In ClO₂ based treatment ClO₂ is mainly consumed by NOM. The strong depletion can be explained by the different phenolic moieties, which show high reactivity towards ClO₂. Recently, it has been shown that the reaction of ClO₂ with NOM is forming 25 % FAC. Since phenol, the major reactive side in NOM, itself forms 50 % FAC in the reaction with ClO₂; it might be possible that the presence of different functional groups attached to the phenolic ring is causing a change in the reaction mechanism regarding the formation of inorganic chlorine species. Therefore, the yields of different chlorine species (chlorine balance) of different phenolic compounds with different substituents (e.g., alkyl, hydroxyl, or methoxy groups) in ortho-, meta-, and para-position were investigated. It could be shown that most substituents do not particularly affect the chlorine balance. However, para-substituted phenols seem to form ortho-benzoquinone, which is very reactive and causes a change in the chlorine balance over time (reduced FAC yields and increased chloride yields). This might explain the different reported yields of FAC in the literature. The substituents which strongly affect the chlorine balance of phenol are hydroxyl and amino groups in ortho- and para-position, which results in 100 % yields of chlorite and total hampering of FAC formation. The exact reason for this observation requires further investigation. Glycine has been frequently used to determine intrinsic FAC in ClO₂ reactions with phenols which have a low reaction kinetics with FAC (kapp = 10² M⁻¹ s⁻¹, at pH 7). Thus, FAC can be successfully scavenged by glycine, which reacts several orders of magnitude faster with FAC (kapp = 1.5 × 10⁵ M⁻¹ s⁻¹ at pH 7). The ensuing product of this reaction (chloro-glycine) can be determined to quantify FAC formation. However, if the compound under study reacts fast with FAC (e.g., cysteine kapp = 6.2 × 10⁷ M-¹ s-¹ at pH 7) glycine may not be able to quantitatively scavenge FAC resulting in an underestimation of intrinsic FAC. Examples of compounds with such high reaction kinetics with FAC are thiols (e.g., Glutathione (GSH)), which react fast with both oxidants ClO₂ and FAC (kapp ≥ 10⁷ M⁻¹ s⁻¹). The reaction of GSH with FAC is two orders of magnitudes faster than the reaction of FAC with glycine. Therefore, a new method was developed using methionine as a selective scavenger. Methionine is a sulfide-containing amino acid, which reacts fast with FAC (kapp = 6.8 × 10⁸ M⁻¹ s⁻¹ at pH 7) and forms chloride and methionine sulfoxide (MSO) in equal parts. The yields of chloride and MSO can be used to quantify the FAC yields. The reaction of methionine with ClO₂ was determined to be kapp = 10⁻² M⁻¹ s⁻¹ at pH 7. The method was successfully applied to qualitatively state that FAC is formed in the reaction of ClO₂ with the tripeptide GSH. However, in some cases, MSO formation was observed from a yet unknown source, which requires further investigation. Finally, the intrinsic FAC participation during ClO₂-based disinfection was investigated. First, a novel concept has been developed to determine different levels of microbial cell inactivation, which is based on the extension of the lag phase (initial growth phase preceding the exponential growth). Thereby an increase of the Escherichia coli inactivation results in a prolongation of the lag phase. Since the growth can be monitored online by an increase in optical density, this method is fast and enables the simultaneous measurement of several samples. With this method, it was possible to show that in ClO₂-based disinfection processes, the intrinsic formation of FAC may be very important. This was shown in experiments of E. coli elimination in the presence of NOM. The addition of methionine as a fast-reacting FAC-scavenger fully suppressed the inactivation of E. coli. This indicates that the observed E. coli inactivation on ClO₂-based processes with high loads of NOM may be mainly driven by FAC. Furthermore, it was shown that disinfection in the presence of NOM is pH-dependent (pH 6.5 > 7.5 > 8.5). This can be explained by the depletion of ClO₂, which is accelerated at higher pH values due to the dissociation of the phenolic moieties (pKa: 10) of the NOM (note that the deprotonated phenolate species reacts more than five orders of magnitude faster with ClO₂ compared to protonated phenol). With an increasing consumption rate of ClO₂, less ClO₂ will be available for disinfection. Additionally, the speciation of FAC (HOCl) might be responsible for the observed stronger inactivation at lower pH since HOCl is a stronger disinfectant than OCl⁻ (pKa: 7.54)

Mechanistic Studies on the Electrochemistry of Glutathione and Homocysteine

This research work has investigated the electrochemistry of glutathione (GSH)and homocysteine (HCSH) in order to develop sensors for these biological thiols.Ru(bpy)33+ and IrCl62− have been used as mediators for the electrooxidation of GSH andHCSH because direct oxidation of these thiols is slow at most conventional electrodes.The electrochemical detection of GSH and HCSH has been pursued because of their biological roles. Concerted proton electron transfer (CPET) and stepwise proton electron transfer(PT/ET) pathways have been observed in the electrooxidation of GSH and HCSH.Oxidation of GSH by Ru(bpy)33+ carried out in deuterated and undeuterated buffered (pH= pD = 5.0) and unbuffered solutions (pH = pD 5.0−9.0) indicates a CPET pathway. AtpH 7.0 buffered solution, the involvement of the buffer was obvious, with rate increasing as the buffer concentration increases − an indication of a general base catalysis. The oxidation of GSH by IrCl62− follows through CPET at pH 7.0 when the optimum concentration of the buffer is established. The plot of the rate vs. buffer concentration gave a curvature at lower buffer concentration and then a plateau at higher concentration,which implies a change in the rate determining step as the buffer concentration increases.At lower buffer concentration, proton transfer was seen to be the rate determining step asthe reduction current increases upon scan rate increase. In the oxidation of HCSH by IrCl62−, CPET was observed at pH = pD values of7.0 and 8.0, whereas PT/ET was seen at pH = pD values of 9.0 and 10. Increase in the buffer concentration at pH 7.0 revealed the contribution of the buffer, in that, the oxidation proceeds more efficiently, seeing that the catalytic peak current shifts more negatively and the peak broadness diminishes. Increase in the temperature for the electrooxidation of HCSH resulted in increase in the rate

Synthesis, Characterization and Reactivity of Some Selected Organosulfur Oxo-acids

The two major metabolites after S-Oxygenation of dimethylthiourea (N, N\u27-dimethylaminoiminomethanesulfinic acid (DMAIMSA) and N, N\u27-dimethylamino iminomethanesulfonic acid (DMAIMSOA)) were synthesized. Structural analysis by X-ray crystallography shows that DMAIMSA and DMAIMSOA exist as zwitterionic species in their solid form, with a positive charge delocalized around an sp2-hybridized carbon center flanked by two nitrogen atoms. Kinetics and mechanistic studies on the oxidation of DMAIMSA and DMAIMSOA by acidified iodate/iodine and bromate/bromine were studied. The results reveal that DMAIMSA, unlike DMAIMSOA, is highly reactive. DMAIMSOA is very inert and unreactive in low pH environments. The difference in reactivity is attributed to the fact that the C-S bond in DMAIMSA at 1.880(2) Å is longer than the theoretical prediction of 1.79 Å. This inordinate length renders the C-S bond in DMAIMSA relatively weak and easy to cleave. The more electronegative -SO3 group in DMAIMSOA, by inductive effects, strengthen the C-S bond thus making it more difficult to cleave. The major pathway in the oxidation of DMAIMSA proceeds through an unexpected early heterolytic cleavage of the C-S bond to yield the highly reducing sulfoxylate anion,SO2 2SO-. The observation of dithionite formation in aerobic DMAIMSA solutions clearly establishes the formation of SO22- as the leaving group in the initial stages of oxidation of DMAIMSA. The apparent inertness of DMAIMSOA indicates that the oxidation of DMAIMSA through DMAIMSOA represents a minor pathway in the oxidation of DMAIMSA. For comparative studies, the kinetics and mechanistic study of the oxidation of hydroxymethanesulfinic acid (HMSA) by acidified iodate and iodine was also performed. The first 2-electron oxidation of HMSA should yield hydroxymethanesulfonic acid (HMSOA). As with DMAIMSOA, further oxidation of HMSOA is very slow. The predominant pathway in the further oxidation of HMSOA and DMAIMSOA involves a slow initial hydrolysis of their C-S bond to yield bisulfite (HSO3-). Genotoxicity studies on some selected organosulfur oxo-acids were examined via DNA damage studies. The results reveal that oxo-acids of thiocarbamides are the reactive metabolites leading to the toxicity of their parent compounds. Analyses of the effect of scavengers reveal the involvement of hydroxyl radicals in the damage induced by DMAIMSA and DMAIMSOA

Діоксид хлору. Том 1. Хімія.

Книга присвячена актуальній проблемі застосування діоксиду хлору як ефективного окиснювача і дезінфектанта у технологіях водопідготовки. Перший том є докладною характеристикою фундаментальних основ хімічних реакцій діоксиду хлору у водному середовищі. Представлено узагальнюючі роботи щодо розуміння ролі діоксиду хлору як попереднього окиснювача та дезінфектанта; характеристики реакцій діоксиду хлору з неорганічними та органічними сполуками; докладної інформації щодо утворення побічних продуктів хлоритів та хлоратів; ролі первинних та вторинних оксидантів в процесах інактивації бактерій при дезінфекції води діоксидом хлору; хімічних та технологічних аспектів утворення, моделювання та мінімізації вмісту хлоритів та хлоратів після очищення води діоксидом хлору; переліку аналітичних методів визначення у питній воді діоксиду хлору, хлорит- і хлорат-аніонів. Книга розрахована на хіміків, технологів та інженерів в галузі очищення води, а також гігієністів, санітарних лікарів, викладачів і здобувачів вищої освіти ВНЗ

NON-EDIBLE BIOMASS RESIDUE TO HIGH VALUE-ADDED CHEMICALS: A LIGNIN-DERIVED CATALYST DESIGN FOR PRODUCTION OF CHLORINE DIOXIDE & PREPARATION OF SUSTAINABLE POLAR APROTIC SOLVENTS FROM CELLULOSE

The global production of plant biomass waste is in the order of 140 Gt per year which offers a promising alternative to petroleum and a sustainable resource to produce fuels and chemicals. Inspired by innovative advancement in biomass valorization, two catalytic processes have been developed to produce chlorine dioxide and polar aprotic solvents from non-edible biomass residues. The application of chlorine dioxide (ClO2) in water treatment is growing because of its superior antimicrobial properties and lower tendency to generate harmful chlorinated organic by-products. Most of the previously investigated catalysts for the one electron oxidation of chlorite to ClO2 are based on manganese or iron porphyrin complexes which suffer from expensive ligand and catalyst syntheses as well as the catalyst instability in oxidative environment. Chlorine dioxide chemistry and its catalytic production are explained in depth in chapter 1. Second chapter describes a novel catalyst design based on molecules that can be derived from lignin for catalytic production of ClO2 in water. A lignin-derived ligand bis(2-hydroxy-3-methoxy-5-propylbenzyl) glycine, (DHEG) was synthesized from 2-methoxy-4-propylphenol (dihydroeugenol (DHE)) and the amino acid glycine. Two mononuclear iron and manganese complexes of DHEG were prepared, characterized, and employed for the oxidation of chlorite to chlorine dioxide in aqueous solution. Peroxyacetic acid (PAA) was used as a ‘green’ oxidant in the redox reactions for the catalyst activation generating high valent Fe and Mn(IV)-OH intermediates. EPR studies verified the formation of a high valent MnIV species. Both Fe and Mn activated complexes catalyzed chlorite oxidation with bimolecular rate constants of 32 and 144 M-1 s-1, respectively, at pH 4.0 and 25 °C. The Mn complex was found to be more efficient for chlorite oxidation with a turnover frequency of 17 h-1 and remained active during subsequent additions of PAA. The rate of ClO2 formation with PAA/Mn-DHEG was first-order in PAA and showed acidic pH dependence. A mechanism that accounts for all observations is presented. Chapter 3 highlights the need of more environmentally benign polar aprotic solvents (PAS) from sustainable resources. Of particular interest for this work is the catalytic conversion of cellulose to short chain polyols and the coupling of these polyols with N,N-dimethylurea (DMU) to produce cyclic PAS. Detailed chemistry background for this transformation are presented within this chapter. In the final chapter, a green and catalytic process is described for the synthesis of N,N'-dimethylimidazolidinone (DMI) and 1,3,4-trimethylimidazolidin-2-one (TMI) from cellulose, the most abundant and non-edible component of biomass. The physical and chemical properties of DMI and TMI including high boiling point, remarkable chemical stability, and being more eco-friendly than DMF make them appealing for use in the pharmaceutical industry. Cellulose depolymerization and reaction of intermediate products with N,N-dimethylurea (DMU) to produce PAS have been investigated in a one-pot, two-step process at elevated temperature. Ru/C is an effective multifunctional catalyst for both C-C bond cleavage of cellulose and subsequent hydrogenation of the unsaturated products in the second step; the catalyst also promotes the condensation hydroxy ketone intermediates with DMU to create cyclic PAS concurrently. Such tandem reactions are challenging to achieve particularly when incompatible conditions are required for each step. Solvent selection is also challenging with the low solubility of cellulose in most common organic solvents. Herein, the overall 85% selectivity for PAS was achieved from the reactions of cellulose or sugar with DMU over Ru/C in DMI (the product) as a solvent. The optimized conditions for coupling of 1,2-propylene glycol with DMU was used in a mechanistic study for the production of PAS with both homogeneous and heterogenous Ru catalysts. Catalytic oxidation of 1,2-PG to hydroxy acetone is the key step to produce TMI with a higher yield obtained using electron-donating phosphine ligands on Ru