Hypoiodite Research Articles

Novel Phosphoryloxylactonisation of Pentenoic Acids Mediated by Ammonium Iodide

Using ammonium iodide as a catalyst and m-chloroperbenzoic acid as the oxidant, a novel and efficient procedure has been developed for phosphoryloxylactonisation of alkenoic acids in CH3CN at room temperature, which provides the corresponding phosphoryloxylactones in good yields. In this protocol, it is proposed that ammonium iodide catalyst is first oxidised to hypoiodous acid, which reacts with the alkenoic acid to afford the corresponding iodolactone. Then, the iodolactone is further transformed into a hypervalent iodine intermediate by continuing oxidation, and finally the in situ generated active iodine species reacts with a diaryl phosphate to furnish the phosphoryloxylactone end product.

Novel α-tosyloxylation of ketones catalyzed by the in situ generated hypoiodous acid from alkyl iodide

Using a catalytic amount of 1-iodopropane, a novel and efficient procedure has been developed for direct preparation of α-tosyloxyketones from ketones. In this protocol, 1-iodopropane is first oxidized into iodosylpropane, which decomposes to form the key catalyst hypoiodous acid. With this method, not only α-tosyloxyketones, but also other α-sulfonyloxyketones have been prepared in moderate to good yields, which extends the application of alkyl substituted hypervalent iodine reagents in organic synthesis.

HOI versus HOIO selectivity of a molten-type AgI electrode.

AgI electrode is often applied not only to determine iodine concentration but also to follow oscillations in the weakly acidic medium of the Bray-Liebhafsky and Briggs-Rauscher reactions where it partly follows the hypoiodous acid (HOI) concentration. It is known that HOI attacks its matrix in the corrosion reaction: AgI + HOI + H(+) ⇆ Ag(+) + I2 + H2O and the AgI electrode measures the silver ion concentration produced in that reaction. The signal of the electrode can be the basis of sensitive and selective HOI concentration measurements only supposing that an analogous corrosive reaction between AgI and iodous acid (HOIO) can be neglected. To prove that assumption, the authors calibrated a molten-type AgI electrode for I(-), Ag(+), HOI, and HOIO in 1 M sulfuric acid and measured the electrode potential in the disproportionation of HOIO, which is relatively slow in that medium. Measured and simulated electrode potential versus time diagrams showed good agreement, assuming that the electrode potential is determined by the HOI concentration exclusively and the contribution of HOIO is negligible. An independent and more direct experiment was also performed giving the same result. HOIO was produced with a new improved recipe. an AgI electrode can be applied to measure the HOI concentration selectively above the so-called solubility limit potential.

An Efficient Monochlorination of Electron-rich Aromatic Compounds Catalysed by Ammonium Iodide

An efficient monochlorination of electron-rich aromatic compounds is developed, with which a series of regioselective monochlorinated products are obtained in good yields. In the reaction, ammonium iodide is used as catalyst and m-chloroperbenzoic acid is used as the terminal oxidant. Ammonium iodide is first oxidised to hypoiodous acid by m-chloroperbenzoic acid. The in situ generated active iodine species then reacts with the aromatic compound to form the active hypervalent iodine intermediate in two steps and this reacts with lithium chloride to afford eventually the chlorinated compounds.

Molecular Profiles of Papillary Thyroid Tumors Have Been Changing in the Last Decades: How Could We Explain It?

The molecular profile of thyroid tumors can be discovered today in at least 70–80% of cases. The most common alterations are point mutations of BRAF and RAS followed by RET/PTC rearrangements. Other less frequent oncogenes involved are PIK3CA, TP53, TSHR, PTEN, GNAS, and CTNNB1 (1), but taken together they are still not able to account for 100% of cases. According to the data reported and collected so far (http://www.sanger.ac.uk/genetics/CGP/), BRAFV600E point mutations are present in about 45% of papillary thyroid cancer (PTC), with a higher rate in classical and tall cell variants and a rather low prevalence in follicular variant (2). There are exceptions with higher prevalence of BRAFV600E in PTC found in areas of China with a very high iodine content in the drinking water (3) and PTC found in the volcanic area of Mount Etna in Sicily where the drinking water is particularly rich in several elements, such as boron, iron, manganese, and vanadium, often present in concentrations exceeding usual maximum limits (4). The observations of Jung et al (5), showing a high prevalence of BRAFV600E mutation in a series of PTC diagnosed in the United States over a 35-year period, from 1974 to 2009, are of great relevance in this regard, associated with a significant increase of its prevalence in the classical variant of PTC over these last decades. The first study that indicated an increase of the prevalence of BRAFV600E mutation was reported in 2005 in a UK series, and the authors hypothesized that some environmental/etiological agent(s) could be responsible for the changing molecular features of PTC over time (6). Similar results were reported 6 years later by Mathur et al (7) in a series of PTC patients reported from California, and the hypothesis in this study was that the increased prevalence of the BRAFV600E mutation could be responsible for the increasing rate of PTC. In 2012, we also reported a significant increasing rate of BRAFV600E mutation in an Italian multicenter study (8), and it was interesting to observe that the increase was similar when the analysis was separately performed in the four different groups of PTC patients (from Pisa, Milan, Perugia, and Catania). Because the reported series are really very heterogeneous from a geographical point of view, it is conceivable that the increased prevalence of BRAFV600E mutation is a worldwide phenomenon, making it plausible that only a common, or very similar, reason could explain this trend. It is known that higher iodine intake has been found to be associated with a higher incidence of PTC (9), and it is notable that programs of iodine prophylaxis appear to be associated with an increase in the prevalence of PTC and a decrease in follicular histology (follicular thyroid cancer [FTC]) (10–12). This evidence and the Chinese report (3) may raise the question of a link between iodine intake, BRAFV600E mutation, and the development of increased incidence of PTC, but up to now, no experimental evidence that iodine can induce somatic gene alterations in follicular cells has been reported. Nevertheless, it is known that the iodine radical (I●), iodinium ion (I ) and the hypoiodous acid intermediate (IO[IOH]) are commonly formed in the follicular cell and represent reactive elements that together or as an alternative to H2O2 can determine cell oxidative stress, which is required to create conditions for thyroid cell proliferation (13–15). Further experimental studies on this putative relationship between

Perturbations of the Dushman Reaction with Piroxicam: Experimental and Model Calculations

AbstractPerturbation of the BrayLiebhafsky non‐oscillating subsystem (mixture of KIO3 and H2SO4), i.e., Dushman reaction (DR), by piroxicam (PX), was observed in an open reactor, i.e., in the continuously fed well‐stirred tank reactor (CSTR). Monitoring the response of DR to perturbations by different concentrations of PX allows developing a simple procedure for quantitative determination of this analyte in both bulk drug and pharmaceutical preparation (injection). A tentative perturbation mechanism of PX action on the DR matrix, based on a kinetic scheme that was suggested by Agreda et al., is proposed. The PX reactivity in DR has been generally related to the reaction of PX with hypoiodous acid (HIO) present in the matrix.

Effects of bromide and iodide ions on the formation of disinfection by-products during ozonation and subsequent chlorination of water containing biological source matters

This study aims to investigate the influence of the coexistence of halogen ions (bromide/iodide) and biological source matters on the speciation and yield of trihalomethanes (THMs), haloacetic acids (HAAs), and N-nitrosodimethylamine (NDMA) during the ozonation and subsequent chlorination of water. The results show that the concentrations of brominated THMs and iodinated THMs increased with increasing bromide and iodide concentration. These results may be attributed to the higher reactivity of hypobromous acid and hypoiodous acid generated from the ozonation and subsequent chlorination in the presence of bromide or iodide ions. The presence of bromide increased the species of brominated HAAs. There was a shift from chlorinated HAAs to brominated HAAs after increasing the concentration of bromide. The effect of iodide on HAA formation was more complex than bromide. For most samples, the concentration of total HAAs (T-HAAs) increased to the maximum and then decreased with increasing iodide concentration. The components of the organic precursors also significantly influenced the formation of brominated and iodinated disinfection by-products (Br-DBPs and I-DBPs). Humic acids produced more CHBr3 (596.60 μg/L) than other organic materials. Microcystis aeruginosa cells produced the most tribromoacetic acid (TBAA, 84.16 μg/L). Furthermore, the yield of NDMA decreased with increasing bromide concentration, indicating that the formation of NDMA was inhibited by the high concentration of bromide.

Modification of Ozone Deposition and I2 Emissions at the Air–Aqueous Interface by Dissolved Organic Carbon of Marine Origin

The reaction between gaseous ozone (O3) and aqueous iodide (I(-)) at the surface microlayer (SML) is believed to be a major chemical contributor to the oceanic dry deposition of O3 over open ocean waters and has also recently been shown to produce environmentally significant quantities of gaseous molecular iodine (I2). Here we investigate how this reaction is affected by the presence of dissolved organic carbon (DOC) of marine origin, using a heterogeneous flow reactor and detection of gaseous I2 by solvent trapping and UV/vis spectroscopy. Ozone deposition measurements over coastal seawater implied an O3 reactivity (λ) toward coastal marine DOC of ∼500 (420-580) s(-1), 2-5 times higher than that toward iodide at typical ocean concentrations (∼0.5-1 × 10(-7) M). We added varying amounts of highly concentrated DOC extracted from coastal seawater to I(-) solutions (1 × 10(-5) M) such that the relative reactivities of DOC and I(-) toward O3 (λDOC/λI) were in the expected range for natural seawater. The evolution of gaseous I2 and the loss of aqueous I(-) both reduced as DOC concentrations increased, with an overall suppression of I2 emissions of about a factor of 2 under conditions of λDOC/λI representative of open ocean waters (0.5-1). A kinetic model of the SML suggested that neither competition of DOC with I(-) for reaction with interfacial O3, nor direct loss of I2 and hypoiodous acid (HOI) through reaction with increasing quantities of DOC, can fully explain these results. We conclude that the suppression of I2 emissions by DOC is largely a physical effect arising from a decrease in the net transfer of I2 from the aqueous to gas phase, as suggested by recent laboratory studies.

Increased Concentration of Iodide in Airway Secretions Is Associated with Reduced Respiratory Syncytial Virus Disease Severity

Recent studies have revealed that the human and nonrodent mammalian airway mucosa contains an oxidative host defense system. This three-component system consists of the hydrogen peroxide (H2O2)-producing enzymes dual oxidase (Duox)1 and Duox2, thiocyanate (SCN(-)), and secreted lactoperoxidase (LPO). The LPO-catalyzed reaction between H2O2 and SCN(-) yields the bactericidal hypothiocyanite (OSCN(-)) in airway surface liquid (ASL). Although SCN(-) is the physiological substrate of LPO, the Duox/LPO/halide system can generate hypoiodous acid when the iodide (I(-)) concentration is elevated in ASL. Because hypoiodous acid, but not OSCN(-), inactivates respiratory syncytial virus (RSV) in cell culture, we used a lamb model of RSV to test whether potassium iodide (KI) could enhance this system in vivo. Newborn lambs received KI by intragastric gavage or were left untreated before intratracheal inoculation of RSV. KI treatment led to a 10-fold increase in ASL I(-) concentration, and this I(-) concentration was approximately 30-fold higher than that measured in the serum. Also, expiratory effort, gross lung lesions, and pulmonary expression of an RSV antigen and IL-8 were reduced in the KI-treated lambs as compared with nontreated control lambs. Inhibition of LPO activity significantly increased lesions, RSV mRNA, and antigen. Similar experiments in 3-week-old lambs demonstrated that KI administration was associated with reduced gross lesions, decreased RSV titers in bronchoalveolar lavage fluid, and reduced RSV antigen expression. Overall, these data indicate that high-dose KI supplementation can be used in vivo to lessen the severity of RSV infections, potentially through the augmentation of mucosal oxidative defenses.

Determination of iodide, iodate and organo-iodine in waters with a new total organic iodine measurement approach

The dissolved iodine species that dominate aquatic systems are iodide, iodate and organo-iodine. These species may undergo transformation to one another and thus affect the formation of iodinated disinfection byproducts during disinfection of drinking waters or wastewater effluents. In this study, a fast, sensitive and accurate method for determining these iodine species in waters was developed by derivatizing iodide and iodate to organic iodine and measuring organic iodine with a total organic iodine (TOI) measurement approach. Within this method, organo-iodine was determined directly by TOI measurement; iodide was oxidized by monochloramine to hypoiodous acid and then hypoiodous acid reacted with phenol to form organic iodine, which was determined by TOI measurement; iodate was reduced by ascorbic acid to iodide and then determined as iodide. The quantitation limit of organo-iodine or sum of organo-iodine and iodide or sum of organo-iodine, iodide and iodate was 5 μg/L as I for a 40 mL water sample (or 2.5 μg/L as I for an 80 mL water sample, or 1.25 μg/L as I for a 160 mL water sample). This method was successfully applied to the determination of iodide, iodate and organo-iodine in a variety of water samples, including tap water, seawater, urine and wastewater. The recoveries of iodide, iodate and organo-iodine were 91–109%, 90–108% and 91–108%, respectively. The concentrations and distributions of iodine species in different water samples were obtained and compared.

Conversion of Iodide to Hypoiodous Acid and Iodine in Aqueous Microdroplets Exposed to Ozone

Halides are incorporated into aerosol sea spray, where they start the catalytic destruction of ozone (O3) over the oceans and affect the global troposphere. Two intriguing environmental problems undergoing continuous research are (1) to understand how reactive gas phase molecular halogens are directly produced from inorganic halides exposed to O3 and (2) to constrain the environmental factors that control this interfacial process. This paper presents a laboratory study of the reaction of O3 at variable iodide (I(-)) concentration (0.010-100 μM) for solutions aerosolized at 25 °C, which reveal remarkable differences in the reaction intermediates and products expected in sea spray for low tropospheric [O3]. The ultrafast oxidation of I(-) by O3 at the air-water interface of microdroplets is evidenced by the appearance of hypoiodous acid (HIO), iodite (IO2(-)), iodate (IO3(-)), triiodide (I3(-)), and molecular iodine (I2). Mass spectrometry measurements reveal an enhancement (up to 28%) in the dissolution of gaseous O3 at the gas-liquid interface when increasing the concentration of NaI or NaBr from 0.010 to 100 μM. The production of iodine species such as HIO and I2 from NaI aerosolized solutions exposed to 50 ppbv O3 can occur at the air-water interface of sea spray, followed by their transfer to the gas-phase, where they contribute to the loss of tropospheric ozone.

Disproportionation reaction of iodous acid, HOIO. Determination of the concentrations of the relevant ionic species H+, H2OI+, and IO3 −

The pseudo-equilibrium concentrations of the H+, IO3 −, and H2OI+ ions, kinetically very important species in the disproportionation reaction of iodous acid, have been determined from the equilibrium dissociation reactions of sulfuric and iodous acids in the quasi-stationary state. The values observed were higher than the concentration of the protonated ion of hypoiodous acid.

Uptake of iodide in the marine haptophyte Isochrysis sp. (T.ISO) driven by iodide oxidation.

Uptake of iodide was studied in the marine microalga Isochrysis sp. (isol. Haines, T.ISO) during short-term incubations with radioactive iodide ((125) I(-) ). Typical inhibitors of the sodium/iodide symporter (NIS) did not inhibit iodide uptake, suggesting that iodide is not taken up through this transport protein, as is the case in most vertebrate animals. Oxidation of iodide was found to be an essential step for its uptake by T.ISO and it seemed likely that hypoiodous acid (HOI) was the form of iodine taken up. Uptake of iodide was inhibited by the addition of thiourea and of other reducing agents, like L-ascorbic acid, L-glutathione and L-cysteine and increased after the addition of oxidized forms of the transition metals Fe and Mn. The simultaneous addition of both hydrogen peroxide (H2 O2 ) and a known iodide-oxidizing myeloperoxidase (MPO) significantly increased iodine uptake, but the addition of H2 O2 or MPO separately, had no effect on uptake. This confirms the observation that iodide is oxidized prior to uptake, but it puts into doubt the involvement of H2 O2 excretion and membrane-bound or extracellular haloperoxidase activity of T.ISO. The increase of iodide uptake by T.ISO upon Fe(III) addition suggests the nonenzymatic oxidation of iodide by Fe(III) in a redox reaction and subsequent influx of HOI. This is the first report on the mechanism of iodide uptake in a marine microalga.

ChemInform Abstract: Hypoiodous Acid Initiated Rearrangement of Tertiary Propargylic Alcohols to α‐Iodoenones.

AbstractIn situ generated hypoiodous acid initiates the rearrangement of tertiary propargylic alcohols to α‐iodoenones under mild conditions and in good yields.

Atmospheric iodine levels influenced by sea surface emissions of inorganic iodine

Naturally occurring bromine- and iodine-containing compounds substantially reduce regional, and possibly even global, tropospheric ozone levels1,2,3,4. As such, these halogen gases reduce the global warming effects of ozone in the troposphere5, and its capacity to initiate the chemical removal of hydrocarbons such as methane. The majority of halogen-related surface ozone destruction is attributable to iodine chemistry2. So far, organic iodine compounds have been assumed to serve as the main source of oceanic iodine emissions1,6,7,8,9. However, known organic sources of atmospheric iodine cannot account for gas-phase iodine oxide concentrations in the lower troposphere over the tropical oceans3,4. Here, we quantify gaseous emissions of inorganic iodine following the reaction of iodide with ozone in a series of laboratory experiments. We show that the reaction of iodide with ozone leads to the formation of both molecular iodine and hypoiodous acid. Using a kinetic box model of the sea surface layer and a one-dimensional model of the marine boundary layer, we show that the reaction of ozone with iodide on the sea surface could account for around 75% of observed iodine oxide levels over the tropical Atlantic Ocean. According to the sea surface model, hypoiodous acid—not previously considered as an oceanic source of iodine—is emitted at a rate ten-fold higher than that of molecular iodine under ambient conditions.

In situ generated hypoiodous acid in an efficient and heterogeneous catalytic system for the homo-oxidative coupling of thiols

Supported hydrogen peroxide on polyvinylpolypyrrolidone (PVPH2O2), silica sulfuric acid (SiO2-OSO3H) and catalytic amounts of potassium iodide (KI) has been developed as a heterogeneous medium for the rapid oxidative coupling of thiols into symmetrical homodisulfides. This oxidizing system proceeds under extremely mild conditions and gives no other oxidized side products.

Laccase-Catalyzed Oxidation of Iodide and Formation of Organically Bound Iodine in Soils

Laccase oxidizes iodide to molecular iodine or hypoiodous acid, both of which are easily incorporated into natural soil organic matter. In this study, iodide sorption and laccase activity in 2 types of Japanese soil were determined under various experimental conditions to evaluate possible involvement of this enzyme in the sorption of iodide. Batch sorption experiment using radioactive iodide tracer ((125)I(-)) revealed that the sorption was significantly inhibited by autoclaving (121 °C, 40 min), heat treatment (80 and 100 °C, 10 min), γ-irradiation (30 kGy), N(2) gas flushing, and addition of reducing agents and general laccase inhibitors (KCN and NaN(3)). Interestingly, very similar tendency of inhibition was observed in soil laccase activity, which was determined using 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate) (ABTS) as a substrate. The partition coefficient (K(d): mL g(-1)) for iodide and specific activity of laccase in soils (Unit g(-1)) showed significant positive correlation in both soil samples. Addition of a bacterial laccase with an iodide-oxidizing activity to the soils strongly enhanced the sorption of iodide. Furthermore, the enzyme addition partially restored iodide sorption capacity of the autoclaved soil samples. These results suggest that microbial laccase is involved in iodide sorption on soils through the oxidation of iodide.

Ozonation of iodide-containing waters: Selective oxidation of iodide to iodate with simultaneous minimization of bromate and I-THMs

The presence of iodinated disinfection by-products (I-DBPs) in drinking water poses a potential health concern since it has been shown that I-DBPs are generally more genotoxic and cytotoxic than their chlorinated and brominated analogs. I-DBPs are formed during oxidation/disinfection of iodide-containing waters by reaction of the transient hypoiodous acid (HOI) with natural organic matter (NOM). In this study, we demonstrate that ozone pre-treatment selectively oxidizes iodide to iodate and avoids the formation of I-DBPs. Iodate is non-toxic and is therefore a desired sink of iodine in drinking water. Complete conversion of iodide to iodate while minimizing the bromate formation to below the guideline value of 10 μg L−1 was achieved for a wide range of ozone doses in five raw waters with DOC and bromide concentrations of 1.1–20 mg L−1 and 170–940 μg L−1, respectively. Lowering the pH effectively further reduced bromate formation but had no impact on the extent of iodate and bromoform formation (the main trihalomethane (THM) formed during ozonation). Experiments carried out with pre-chlorinated/post-clarified samples already containing I-DBPs, showed that ozonation effectively oxidized I-THMs. Therefore, in iodide-containing waters, in which I-DBPs can be produced upon chlorination or especially chloramination, a pre-ozonation step to oxidize iodide to iodate is an efficient process to mitigate I-DBP formation.

Bromoform production from seawater treated with bromoperoxidase

Bromoform (CHBr3; 11–486 fmol L−1 h−1), dibromomethane (CH2Br2; 0–9.4 fmol L−1 h−1), and low amounts of chloride‐substituted chlorobromomethanes were produced from southern California coastal surface seawater upon the addition of algal bromoperoxidase (BrPO) and hydrogen peroxide. Production was greater from water collected near shore than 16 km offshore, presumably reflecting the difference in the reactive dissolved organic matter (DOMreact) concentrations. In the spring, there was an increase in phytoplankton abundance, and CHBr3 production from BrPO incubations was greater, presumably due to increased DOMreact. In the winter, CH2Br2 production was enhanced, although still lower than CHBr3, suggesting a qualitative change in DOM composition due to terrestrial runoff. During the month of the highest precipitation, CHBr3 and CH2Br2 production was enhanced in samples obtained from the mouth of an urban river, suggesting a higher concentration of DOMreact of terrestrial origins. DOM was fractionated by ultrafiltration and subject to the BrPO incubation. The higher molecular weight fractions contained a higher concentration of DOM that was susceptible to BrPO bromination, yielding polybromomethanes. Polybromomethane and iodomethane production associated with phytoplankton blooms results from the reaction between the surrounding DOM, and hypobromous acid (HOBr) and hypoiodous acid released from extracellular (apoplastic) BrPO. The reaction of HOBr and DOM (biological bleaching) could represent a significant DOM degradation pathway. Cell‐free BrPO, derived from dead cells, could remain catalytically active in seawater and produce low amounts of polyhalomethanes prior to biological degradation.

Hypoiodite‐Mediated Metal‐Free Catalytic Aziridination of Alkenes

Look, no metal: A metal-free catalytic procedure for aziridination of alkenes using tetrabutylammonium iodide as the catalyst, m-chloroperoxybenzoic acid (mCPBA) as the terminal oxidant, and N-aminophthalimide as the nitrenium precursor has been developed (see scheme; right: X-ray structure of one of the products). Control experiments suggests that the active oxidant is in situ generated hypoiodous acid (HIO).