Deiodination Reaction Research Articles

Structural Insights into the Iodothyronine Deiodinase 2 Catalytic Core and Deiodinase Catalysis and Dimerization

Iodothyronine deiodinases (Dio) are selenocysteine-containing membrane enzymes that activate and inactivate the thyroid hormones (TH) through reductive iodide eliminations. The three deiodinase isoforms are homodimers sharing highly conserved amino acid sequences, but they differ in their regioselectivities for the deiodination reaction and regulatory features. We have now solved a crystal structure of the mouse deiodinase 2 (Dio2) catalytic domain. It reveals a high overall similarity to the deiodinase 3 structure, supporting the proposed common mechanism, but also Dio2-specific features, likely mediating its unique properties. Activity studies with an artificially enforced Dio dimer further confirm that dimerization is required for activity and requires both the catalytic core and the enzyme’s N-terminus. Cross-linking studies reveal the catalytic core’s dimerization interface, providing insights into the architecture of the complete, active Dio homodimer.

Mechanisms of iopamidol transformation catalyzed by a copper corrosion product (c-Cu2O) during peroxymonosulfate disinfection

Peroxymonosulfate (PMS) is an alternative disinfectant for drinking water. This study aimed to investigate the transformation of iopamidol (IPM) catalyzed by a main copper corrosion product (c-Cu2O) with PMS as a disinfectant. The observed pseudo-first-order constant (kobs) for the IPM degradation in the c-Cu2O/PMS system (0.033 min−1) was 3 times that in the CuO/PMS system (0.011 min−1). The quenching tests and the electron paramagnetic resonance (EPR) experiments indicate that O2•− and 1O2 contributed to IPM degradation in the c-Cu2O/ PMS system. The complexation of metastable Cu(II) with a PMS molecule polarized the OO bond and then facilitated the electron transfer from the PMS molecule to other PMS and O2 molecules, which directly and indirectly promoted the yield of O2•− and 1O2. The iodine balance indicated that 26.0% of initial TOI was converted to IO3−, and CHI3 only accounted for 0.6% of the residual TOI. In the c-Cu2O/PMS system, IPM conversion was started with amide C−N bond breakage, deiodination reaction and hydrogen abstraction. This study helps to better understand the conversion mechanisms of iodine-containing organic micropollutants when PMS is deployed as a disinfectant in copper pipes.

Nitrogen-doped CNTs enhance heterogeneous Fenton reaction for IOH removal by FeOCl: Role of NCNTs and mechanism

Heterogeneous Fenton has already been usedextensively to remove emerging contaminants, however, sluggish Fe(III)/Fe(II) circulation and high mass-transport resistance are its two major limitations. In this study, a novel heterogeneous N-doped carbon nanotubes loaded nano-FeOCl (NCF) catalyst was synthesized by partial thermal decomposition to enhance its catalytic performance. By incorporating NCNTs, the specific surface area of NCF was significantly increased in comparisontoFeOCl, which promotes the accumulation of contaminants on the catalyst surface. Similarly, the degradation rate constant (k) of IOH in the NCF/H2O2 system was observed 114 times greater than that of the FeOCl/H2O2 system. Besides not significantly increased k, excessive H2O2 substantially reduced H2O2 utilization. Electron paramagnetic resonance and electrochemical analysis reflected that the NCNTs facilitated the Fe(III)/Fe(II) circulation by improving electron transfer and enhanced •OH, O2•− and 1O2 availability by exerting a confinement effect. The major reactions assumed in IOH degradation include hydrogen atom abstract, amide hydrolysis, deiodination reaction, •OH radical adduct formation, and oxidation of C-OH. This study elucidates the degradation mechanism of IOH in the heterogeneous Fenton system with carbon-based co-catalysts and provides an efficient measure for removing emerging contaminants from the environment.

Degradation of iohexol in the Co(II)/peracetic acid system under neutral conditions: Influencing factors, degradation pathways and toxicity

Advanced oxidation processes based on peracetic acid (PAA) activation have received more attention in water treatment recently. In this study, the degradation of iohexol (IOH, a classical iodinated X-ray contrast media) in the Co(II)/PAA system under neutral conditions, which mainly produced carbon-centric radicals, was investigated. Results showed that IOH decomposition follows the pseudo-first-order kinetic with a rate constant of 0.283 min−1. Appropriately increasing concentrations of PAA or Co(II) could promote the removal of IOH, while elevating the dosage of H2O2 inhibits the elimination of IOH in the Co(II)/PAA system. The IOH elimination was affected by pH, with the best response in pH between 5 and 7 in the Co(II)/PAA system. Additionally, low Cl− doses have negligible effects whereas high Cl− impeded the breakdown of IOH. Br−, I−, HCO3−, H2PO4− and humic acid suppressed the degradation of IOH. Removal of IOH was significantly inhibited in three selected real water samples. Furthermore, six IOH degradation pathways, including H-abstraction, amide hydrolysis, amino oxidation, deiodination reaction, hydroxylate and elimination reaction, were proposed on the basis of the liquid chromatography-tandem mass spectrometry, ion chromatography and DFT theoretical calculations (Frontier electron densities and fukui functions) results. Finally, the ECOSAR assessment showed that some degradation byproducts were much more toxic than IOH parent, but were much more biodegradable. Overall, this study indicates a potential risk when applying the carbon-centric radicals involved in PAA-based AOPs to remediate halogenated organic pollutants in water.

Acid-tailored self-assembled perylene diimide supramolecular for visible-light-driven activation of peroxymonosulfate towards efficient degradation of iohexol

The presence of iohexol (IOX) in the environment has attracted widespread attention. Acetic acid, hydrochloric acid, and nitric acid tailored self-assembled perylene diimides (PA, PC and PN) were prepared and utilized in different visible-light-driven activation of peroxymonosulfate (PMS/Vis) systems for the degradation of IOX. As an electron acceptor, PMS can significantly hinder the recombination of photogenerated electron-hole pairs. The removal rate of 5 mg/L IOX by PC/PMS/Vis system reached 99.1% at 30 min, which was 2.0 times and 1.3 times higher than that of PA/PMS/Vis and PN/PMS/Vis system. The boosted oxidation activity with PC was due to the pH dependence of perylene diimide (PDI) self-assembly and the small amount of Cl− (0.56%) absorbed on PC, which can promote the transfer of electron-hole pairs, change the surface charge distribution and energy band position, and enhance π-electron conjugation. Based on density functional theory and electrostatic potential calculation, the Cl− adsorbed on the surface of PDI brings an effect on the electrostatic potential distribution. Furthermore, the built-in intermolecular electric field leads to accelerated charge transfer of PDI. In the PC/PMS/Vis system, holes, singlet oxygen and superoxide radical were perceived as the dominant contributors. The degradation of IOX carried out via pathways of amide hydrolysis, amino oxidation, hydrogen abstraction, deiodination reaction, and OH attack. This work provides a new method for the pollution control of IOX and scientific guidance for the tailored self-assembly of organic supramolecules.

Practical synthesis of 2-deoxy sugars via metal free deiodination reactions

2-Deoxy-glycosides, in which the C-2 hydroxyl group is replaced with a hydrogen atom, are important motifs in numerous bioactive natural products and pharmaceutical molecules. Herein, an improved dilauroyl peroxide-mediated radical deiodination reaction by using cyclohexane and ethyl acetate as co-solvent is reported. This is an environmentally benign protocol, which operates smoothly under mild conditions and allows efficient preparation of a series of 2-deoxy-glycosides in up to 98% yields.

α-Cyclodextrin Encapsulation of Bicyclo[1.1.1]pentane Derivatives: A Storable Feedstock for Preparation of [1.1.1]Propellane.

The bicyclo[1.1.1]pentane (BCP) scaffold is useful in medicinal chemistry, and many protocols are available for synthesizing BCP derivatives from [1.1.1]propellane. Here, we report (1) the α-cyclodextrin (α-CD) encapsulation of BCP derivatives, affording a stable, readily storable material from which BCPs can be easily and quantitatively recovered and (2) new and simple protocols for deiodination reaction of 1,3-diiodo BCP to afford [1.1.1]propellane in protic/aprotic/polar/non-polar solvents. The combination of these methodologies enables simple, on-demand preparation of [1.1.1]propellane in various solvents under mild conditions from α-CD capsules containing 1,3-diiodo BCP.

α‐Cyclodextrin Encapsulation of Bicyclo[1.1.1]pentane Derivatives: A Storable Feedstock for Preparation of [1.1.1]Propellane

AbstractThe bicyclo[1.1.1]pentane (BCP) scaffold is useful in medicinal chemistry, and many protocols are available for synthesizing BCP derivatives from [1.1.1]propellane. Here, we report (1) the α‐cyclodextrin (α‐CD) encapsulation of BCP derivatives, affording a stable, readily storable material from which BCPs can be easily and quantitatively recovered and (2) new and simple protocols for deiodination reaction of 1,3‐diiodo BCP to afford [1.1.1]propellane in protic/aprotic/polar/non‐polar solvents. The combination of these methodologies enables simple, on‐demand preparation of [1.1.1]propellane in various solvents under mild conditions from α‐CD capsules containing 1,3‐diiodo BCP.

Bioluminescence imaging of carbon monoxide in living cells based on a selective deiodination reaction.

d-Luciferin is a popular bioluminescent substrate of luciferase in the presence of ATP. It is used in luciferase-based bioluminescence imaging and cell-based high-throughput screening applications. Herein, the iodination of d-luciferin was undertaken and explored as a bioluminescence probe without the need for light excitation to sensitively trace and image carbon monoxide (CO) in liver cancer cells. The bioluminescent probe (7'-iodo-luciferin) exhibited excellent selectivity for CO detection in vitro. This new probe could image exogenous and endogenous CO in the luciferase-transfected cancer cells. This new probe might be used for evaluating the roles of CO in various biological processes.

Oxidation of iopamidol with ferrate (Fe(VI)): Kinetics and formation of toxic iodinated disinfection by-products

Presence of iodinated X-ray contrast media (ICMs) in source water is of high concern, because of their potential to form highly toxic iodinated disinfection by-products (I-DBPs). This study investigated kinetics, mechanisms and products for oxidation of one ICMs, iopamidol (IPM) by ferrate (Fe(VI)). The obtained apparent second-order rate constants for oxidation of IPM by Fe(VI) ranged from 0.7 M−1 s−1 to 74.6 M−1 s−1 at pH 6.0–10.0, which were highly dependent on pH. It was found that the oxidation of IPM by Fe(VI) led to the formation of highly toxic I-DBPs. Iodoform (IF), iodoacetic acid and triiodoacetic acid formations were observed during the oxidation and IF dominated the formed I-DBPs. The formation of I-DBPs was also governed by pH and the maximum formation of I-DBPs occurred at pH 9.0. Transformation pathways of IPM by Fe(VI) oxidation were speculated to proceed through deiodination, amide hydrolysis and oxidation of amine reactions. The deiodination reaction during the oxidation of IPM by Fe(VI) contributed to the formation of I-DBPs. The formation of I-DBPs during the oxidation of IPM by Fe(VI) was significantly higher than those of iohexol, diatrizoate and iopromide, which was consistent with the lowest molecular orbital energy gap of IPM. Although Fe(VI) is considered as a green oxidant, the formation of highly toxic I-DBPs during the oxidation of IPM should receive great attention.

Dehalogenation of aromatic halides by polyaniline/zero-valent iron composite nanofiber: Kinetics and mechanisms

Dehalogenation of aryl halides was demonstrated using polyaniline/zero valent iron composite nanofiber (termed as PANI/Fe0) as a cheap, efficient and environmentally friendly heterogeneous catalyst. The catalyst was prepared via rapid mixing polymerization of aniline monomers with Fe(III) chloride as an oxidant followed by reductive deposition of nano-sized Fe0onto the PANI nanofiber using the by-products (Fe(II)/Fe(III)) present in the polymerization system as the Fe precursor. The catalyst was characterized by various physico-chemical techniques: ATR-FTIR, FE-SEM, HR-TEM, XRD, XPS and VSM. A mild reductive dehalogenation process of a wide range of aromatic bromides was explored in the presence of PANI/Fe0 catalyst. The catalyst was active and manifested a high reactivity (84% GC yield of naphthalene for 7h at 40°C) with four equivalents of t-BuMgCl. Deiodination reaction was proved to be more facile in comparison with their corresponding halides. Kinetic studies at different temperatures (30, 40, 50, and 60°C) revealed an overall pseudo-first-order behaviour with rate constants 0.00281, 0.00893, 0.01137 and 0.02421min−1, respectively. The reaction profile diagram of substrate consumption and the product formation rate indicated that there is no additional induction period was involved in the catalytic cycle. Activation energy (Ea) was calculated to be 56.3kJ/mol through Arrhenius plot. Several deuteration experiments were conducted with different Grignard reagents to understand the mechanism of the reaction. These studies explained that the hydride incorporated product was obtained through β-hydride elimination of t-BuMgCl. The catalyst was tested up to three cycles whereas the full conversion of the product was obtained for a prolonged period. PANI/Fe0 could be an alternative suitable catalyst for dehalogenation of environmentally poisonous aromatic halides.

Efficient Construction of Azaspiro[4.5]trienone Libraries via Tandem Ugi 4CC/Electrophilic ipso-Iodocyclization in One-Pot.

A solution-phase parallel synthesis of pharmaceutically important azaspiro[4.5]trienones has been developed by performing tandem Ugi four-component condensation (U4CC), involving substituted p-anisidines, aldehydes, 3-alkyl/aryl-propiolic acids, and isocyanides, and iodine-mediated ipso-iodocyclization in one-pot. This highly atom economical process produced functionalized azaspiro[4.5]trienones in good to excellent overall yields and products were easily isolated by precipitation followed by crystallization. These vinyl-iodide bearing azaspiro[4.5]trienones were utilized for further modifications through Suzuki coupling and deiodination reaction to demonstrate the suitability of these products for various palladium catalyzed modifications. The present method provides an easy access to highly functionalized azaspiro[4.5]trienones that can be useful in drug discovery research.

Mechanism and Scope of the Base‐Induced Dehalogenation of (E)‐Diiodoalkenes

AbstractA wide range of nucleophiles have induced the elimination of iodine from (E)‐diiodoalkenes to form alkynes under surprisingly mild conditions. The iodide anion is particularly efficient, and can drive the reaction to completion in less than 1 hour at room temperature in a polar aprotic solvent. Detailed investigations have suggested the reaction has a bimolecular polar mechanism. The deiodination reaction can be driven to completion with 1 equiv. of nucleophile and is partially catalytic with substoichiometric amounts of deiodinating reagent. Kinetic analysis of the stoichiometric iodide‐induced reaction indicated an overall pseudo‐first‐order behavior. The reaction exhibited strong solvent effects, with much slower reactions observed in protic solvents than in polar aprotic solvents. The substrate dimethyl (2E)‐2,3‐diiodobutene‐2‐dioate demonstrated orthogonal reactivity for either elimination or hydrolysis, depending on the solvent and nucleophile used. This reaction is a major pathway for all the diiodoalkenes examined, and represents a challenge and an opportunity for using these substrates in organic synthesis.

A fluorescence turn-on sensor for the detection of palladium ions that operates through in situ generation of palladium nanoparticles

A simple and straightforward fluorescence method for the detection of palladium ions at low concentrations has been developed. The mode of operation of the sensor involves in situ generation of palladium nanoparticles (PdNPs), which promote a selective deiodination reaction of iodo-BODIPY that forms highly fluorescent H-BODIPY.

Deiodination of iodinated aromatic compounds with electrospray ionization mass spectrometry

Dehalogenation of iodinated X-ray contrast media (ICM) has been reported using electrochemical and bioelectrochemical systems. Correspondingly, dehalogenation of aromatic halogens has also been reported in mass spectrometry (MS) using different ionization techniques like chemical ionization (CI), thermospray, fast-atom bombardment (FAB) and FAB-liquid secondary ionization mass spectrometry (LSIMS). The aim of the present work was to study deiodination of iodinated aromatic compounds in MS with electrospray ionization (ESI). The iodinated aromatic compounds were characterized by liquid chromatography/tandem mass spectrometry (LC/MS/MS) using a quadrupole time-of-flight (QTof)-micro MS instrument and ESI in both positive and negative ion mode. The effect of mobile phase additives like formic acid, acetic acid, trifluoroacetic acid, ammonium formate and ammonium acetate on the negative and positive ESI mass spectra of the iodinated aromatic compounds was studied. Formic acid and ammonium formate induced deiodination of the iodinated aromatic compounds with ESI-MS. Neither acetic acid, trifluoroacetic acid nor ammonium acetate induced the deiodination reaction. The effect was most pronounced with negative ESI where the HI product of the deiodination reaction easily adhered to the aromatic compounds giving rise to HI adducts in the mass spectra. The deiodination reaction was shown to take place in the ESI capillary, since the extent of the reaction was largely dependent on the capillary voltage. The calculated heat of reaction for deiodination of the iodinated aromatic compounds was significantly exothermic for formic acid. This was not the case for acetic acid and trifluoroacetic acid. Care should be taken when using formic acid as a mobile phase additive in LC/MS analyses of iodinated aromatic compounds, since the interpretation of the mass spectra might be influenced by potential dehalogenation reactions taking place in the ESI capillary.

In Situ Fourier Infrared Spectroscopy Studies on Electrochemical Deiodination Reaction of 2-Iodobenzoic Acid

Electrochemical reduction of 2-iodobenzoic acid(OIBA) in NaOH solution was investigated by cyclic voltammetry.To compared with Pt and Ti electrodes,Ag and Cu electrodes exhibited good electrocatalytic activity for the electroreduction of OIBA,and the electrochemical deiodination reaction could take place at more positive potentials on Ag and Cu electrodes.The study on the mechanism of OIBA by in situ FTIR spectroscopy showed that there were different between Ag and Cu electrodes during electrocatalytic reductive deiodination reaction of OIBA at the potentials positive than -800 mV,the absorption state of R…I…Ag was formed on Ag electrode initially,while OIBA existed as negative ions on Cu electrode.Then OIBA was processed by a series of deiodination and hydrogenation reactions at more negative potentials at Ag and Cu electrodes,and benzoic acid was obtained finally.

Thyronamines Are Isozyme-Specific Substrates of Deiodinases

3-Iodothyronamine (3-T 1 AM) and thyronamine (T AM) are novel endogenous signaling molecules that exhibit great structural similarity to thyroid hormones but apparently antagonize classical thyroid hormone (T(3)) actions. Their proposed biosynthesis from thyroid hormones would require decarboxylation and more or less extensive deiodination. Deiodinases (Dio1, Dio2, and Dio3) catalyze the removal of iodine from their substrates. Because a role of deiodinases in thyronamine biosynthesis requires their ability to accept thyronamines as substrates, we investigated whether thyronamines are converted by deiodinases. Thyronamines were incubated with isozyme-specific deiodinase preparations. Deiodination products were analyzed using a newly established method applying liquid chromatography and tandem mass spectrometry (LC-MS/MS). Phenolic ring deiodinations of 3,3',5'-triiodothyronamine (rT3AM), 3',5'-diiodothyronamine (3',5'-T2AM), and 3,3'-diiodothyronamine (3,3'-T2AM) as well as tyrosyl ring deiodinations of 3,5,3'-triiodothyronamine (T3AM) and 3,5-diiodothyronamine (3,5-T2AM) were observed with Dio1. These reactions were completely inhibited by the Dio1-specific inhibitor 6n-propyl-2-thiouracil (PTU). Dio2 containing preparations also deiodinated rT(3)AM and 3',5'-T2AM at the phenolic rings but in a PTU-insensitive fashion. All thyronamines with tyrosyl ring iodine atoms were 5(3)-deiodinated by Dio3-containing preparations. In functional competition assays, the newly identified thyronamine substrates inhibited an established iodothyronine deiodination reaction. By contrast, thyronamines that had been excluded as deiodinase substrates in LC-MS/MS experiments failed to show any effect in the competition assays, thus verifying the former results. These data support a role for deiodinases in thyronamine biosynthesis and contribute to confining the biosynthetic pathways for 3-T 1 AM and T 0 AM.

Iodotyrosine dehalogenase 1 (DEHAL1) is a transmembrane protein involved in the recycling of iodide close to the thyroglobulin iodination site.

In the thyroid, iodotyrosine dehalogenase acts on the mono and diiodotyrosines released during the hydrolysis of thyroglobulin to liberate iodide, which can then reenter the hormone-producing pathways. It has been reported that the deiodination of iodotyrosines occurs predominantly in the microsomes and is mediated by NADPH. Recently, two cDNAs, 7401- and 7513-base pairs long that encode proteins with a conserved nitroreductase domain were published in GenBank as iodotyrosine dehalogenase 1 (DEHAL1) and iodotyrosine dehalogenase 1B (DEHAL1B), respectively. We report here our investigation of the localization and activity of one of these isoforms, DEHAL1. DEHAL1 mRNA is highly expressed in the thyroid, is up-regulated by cAMP, and encodes a transmembrane protein that efficiently catalyzes the NADPH-dependent deiodination of mono (L-MIT) and diiodotyrosine (L-DIT), with greater activity vs. L-MIT. Iodotyrosine deiodinase was active in HEK293 cells transfected by DEHAL1 cDNA, but not in CHO cells. A fraction of DEHAL1 protein is exposed to the cell surface, as indicated by biotinylation experiments. Immunohistochemistry studies showed that DEHAL1 proteins accumulate at the apical pole of thyrocytes. Taken together, these findings indicate that the deiodination reaction occurs at the apical pole of the thyrocyte and is involved in a rapid iodide recycling process at and/or close to the organification site.

Radiolysis of an aqueous [11C]iomazenil solution

Summary Radiolysis of [11C]iomazenil was investigated in an aqueous solution. Preparation of [11C]iomazenil with [11C]CH3I produced a good radiochemical yield, however, its radiochemical purity was always less than 90 without additives. This poor radiochemical purity was attributed to radiolysis of [11C]iomazenil. The degradation of [11C]iomazenil via radiolysis was markedly facilitated in the presence of HCOONa (strong selective hydroxyl radical and hydrogen atom scavenger). On the other hand, the radiolysis was suppressed effectively in the presence of NaNO3 (selective hydrated electron scavenger), suggesting participation of hydrated electrons in the radiolysis of [11C]iomazenil. LC/MS analysis of the degradation product suggested that the major degradation product by radiolysis had a molecular weight of 285 corresponding to the deiodinated compound. The present study showed that a decrease in the radiochemical purity of [11C]iomazenil was attributed to the radiolysis via the deiodination reaction by hydrated electron.

Impact of Gene Cloning, Disruption and Over-Expression of Iodothyronine Deiodinases on Thyroid Hormone Homeostasis

Thyroxine (T4) is the main product of thyroid secretion, a pro-hormone that must be activated by deiodination to T3 in order to initiate thyroid hormone action. This deiodination reaction occurs in the phenolic-ring (outer-ring deiodination, ORD) of the T4 molecule and is catalyzed by two selenocysteine-containing deiodinases, i.e. D1 and D2. As a counter point to the activation pathway, both T4 and T3 can be irreversibly inactivated by deiodination of the thyrosyl-ring (inner-ring deiodination, IRD), a reaction catalyzed by D3, the third member of the selenodeiodinase group. Due to its substantial physiological plasticity, D2 is considered the critical T3-producing deiodinase in humans. Recently, the observations made in the D1-deficient C3H mouse mice were expanded by the development of mice with generalized targeted disruption or cardiac-specific over-expression of the D2 gene. The results obtained indicate that the selenodeiodinases constitute a physiological system contributing with the thyroid hormone homeostasis during adaptation to changes in iodine supply, cold exposure, in patients with thyroid dysfunction and perhaps during starvation and illness.