Molecular Iodine Research Articles

Iodine-Mediated α-C-H Amination of Carbonyl Compounds via Nitrogen-Directed Oxidative Umpolung.

A new synthetic strategy for direct C(sp3)-H amination of carbonyl compounds at their α-carbon has been established employing molecular iodine and nitrogen-directed oxidative umpolung. In this transformation, iodine acts not only as an iodinating reagent but also as a Lewis acid catalyst, and both the nitrogen-containing moiety and the carbonyl group in the substrate play important roles. This synthetic approach is applicable to a broad variety of carbonyl substrates, including esters, ketones, and amides. Its features also include no requirement for transition metals, mild reaction conditions, short reaction times, and gram-scale synthesis.

Synthesis of anthracene linked polycyclic pyridine derivatives fused with coumarin and pyrazole by one‐pot multicomponent strategy followed by oxidation

AbstractA simple, metal‐free, and effective methodology has been developed for the synthesis of coumarin and pyrazole‐fused polycyclic pyridine derivatives. This synthesis was achieved in two steps. In the first step, polycyclic fused dihydropyridine derivatives were synthesized by a one‐pot three‐component reaction of 9‐anthracene carboxaldehyde/2‐naphthaldehyde, 4‐hydroxycoumarin, and 3‐amino pyrazole in acetonitrile using a catalytic amount of p‐TSA under reflux conditions. Then, these synthesized products were further oxidized into their corresponding pyridine derivatives using 10 mol% of molecular iodine as a catalyst in DMSO at 100°C. Metal‐free reaction conditions, good yields, simple purification process, operational simplicity, and inclusion of more than one bioactive moiety such as coumarin, pyrazole, pyridine, and anthracene/naphthalene in the product are the distinguishing features of this methodology.

An effective room temperature nuclear iodination of aromatic compounds using molecular iodine and ammonium acetate

An effective room temperature nuclear iodination of aromatic compounds using molecular iodine and ammonium acetate

Iodoform Reaction-Based Turbidimetry for Analysis of Alcohols in Hand Sanitizers

This work presents the first development of an analytical turbidimetric method for the determination of legal alcohols in alcohol-based hand sanitizer products. A typical iodoform reaction is exploited to form a yellow product in the form of precipitates. An iodoform test shows a positive result as yellow precipitates in the presence of ethanol and isopropanol; therefore, the test can only be used to distinguish between methanol and those legal alcohols. In the presence of molecular iodine (I2) and a strong alkaline solution, the legal alcohol is converted to the corresponding carbonyl compound (i.e., ethanol to acetaldehyde, isopropanol to acetone). The susceptibility of this intermediate towards the reaction with hydroxide ions (strong alkaline condition) results in formations of yellow precipitation of iodoform (CHI3) and a water-soluble carboxylate salt in the solution. Therefore, this change allows for the detection of legal alcohols through either naked-eye observation (as semi-quantitative analysis) or a common benchtop/portable photometer/spectrophotometer (as quantitative analysis) by means of turbidimetric analysis. In this work, turbidimetry is employed, which is a useful alternative detection method in analytical practice, especially with colored samples in hand sanitizing products. This is because they can employ wavelengths at which the colored solution does not absorb light. As a result of our developed method, the calibration plots are in the range of 30 to 100% (v/v) for both ethanol and isopropanol. The limit of detection (LOD) (3SD of y-intercept/slope) was found to be 7.4% (v/v) ethanol and 6.5% (v/v) isopropanol. Direct analysis of the non-pretreatment of the sample is achieved. The results indicate that our new proposed analytical method is fit for purpose and valid to detect the legal alcohols in alcohol-based hand sanitizing products for both international and Thai regulations (at least 70% (v/v)). Our quantitative results were also comparable to a standard analytical method, such as the use of a gas chromatography-flame ionization detector (GC-FID). Our developed method and analytical operation could potentially be developed into a practically portable analysis.

Iodine loaded nanoparticles with commercial applicability increase survival in mice cancer models with low degree of side effects.

The recorded use of iodine in medicine, dates to 5000 BC. Molecular iodine (I2 ) has been claimed to exert an antineoplastic effect that triggers apoptotic and re-differentiation mechanisms in different types of cancer cells in animal studies. Hitherto, all experiments published have been carried out with I2 diluted in water preparations resulting in the administration of ionized iodide, either alone or in combination with low levels of I2 . To maximize the levels of I2 by avoiding water solutions we have managed to develop a colloidal nano particle (NP) loaded with I2 with a Z-average of 7-23 nm with remarkable stability, preferable osmolality and commercial applicability. Here we report the results from formulation and pre-clinical studies with the rationale: a) to find a tolerable dose of the I2 NP system delivered intravenously or per-orally, and b) to determine if the tolerable doses are efficacious in murine models of cancer. A novel drug delivery system with I2 NP was formulated and murine cancer models with CT26, MDA-MB-231 and LL/2 cells were used to analyse the efficacy. Despite the formulation challenges we were successful in constructing stable NPs loaded with I2 which have convincing commercial applicability. We conclude that administration of the NP I2 drug delivery system: 1. Blunted tumour growth in a xenograft breast cancer model; 2. Had a significant effect on survival in the orthotopic, syngeneic lung metastasis model; 3. Showed reduced tumour burden in post-mortem evaluation and; 4. Was associated with low degree of side effects. Taken all together, our findings indicate that the NP I2 drug delivery system may serve as a novel effective cancer treatment with low degree of side effects. This is something which needs further exploration including confirmation in future clinical trials.

Molecular Iodine Mediated Spectrophotometric Determination of Tolfenamic Acid in Pharmaceutical and Veterinary Formulations

Molecular Iodine Mediated Spectrophotometric Determination of Tolfenamic Acid in Pharmaceutical and Veterinary Formulations

Comparing the Use of Molecular Iodine and Copper(II) Compounds as an Oxidizing Agent of Metals and Alloys under Regeneration thereof in the Course of Processing

Comparing the Use of Molecular Iodine and Copper(II) Compounds as an Oxidizing Agent of Metals and Alloys under Regeneration thereof in the Course of Processing

A density functional theory analysis of the adsorption and surface chemistry of inorganic iodine species on graphitea

In the event of a nuclear accident, fission products may be released into the environment. The release of 131I is of particular concern to human health. Iodine can be captured using a number of materials and frequently, this is accomplished with activated carbon impregnated with organic bases. Previous studies have used DFT and the graphite (0001) surface as a surrogate for adsorption, those studies focus on the species I•, I2, and CH3I. In this work we perform an ab initio study of the adsorption onto the surface of a graphite sheet of I2, CH3I, and inorganic acidic iodine species (HI, HOI, HIO2, and HIO3), which were selected to examine the possible effect of oxidation state on adsorption. The PBE exchange-correlation functional with D3 dispersion was employed. It was found that for molecular iodine, the iodine atoms tended to either situate above the center of a hexagonal site on the graphite or directly atop a carbon atom with the lighter components resting closer to the graphite. For each species the relative binding energies spanned the range of 21–33 kJ mol-1 and graphite-iodine distance was in the range of 3.52–3.93 Å. In all cases we found no significant charge transfer between the iodine species and the graphite, thus we conclude that all the iodine species studied undergo strong physisorption to the graphite.

Protective effects of iodine on rat prostate inflammation induced by sex hormones and on the DU145 prostate cancer cell line treated with TNF

Molecular iodine (I2) prevents oxidative stress and prostate hyperplasia induced by hyperandrogenism and reduces cell viability in prostate cancer cell lines. Here, we aimed to evaluate the protective effect of I2 and testosterone (T) on hyperestrogenism-induced prostate inflammation. Additionally, the effects of I2 and/or tumor necrosis factor (TNF) on cell viability and interleukin 6 (IL6) secretion were evaluated in a prostate cancer cell line (DU145). We also investigated whether the effects of I2 on viability are peroxisome proliferator-activated receptor gamma (PPARG)-dependent. Castrated (Cx) rats received pellets of either 17β estradiol (E2) or E2 and T and were treated with I2 (0.05%) in the drinking water for four weeks. The experimental groups were sham, Cx, Cx + E2, Cx + E2+I2, Cx + E2+T, and Cx + E2+T + I2. As expected, inflammation was triggered in the Cx + E2 group (high inflammation score; increase in TNF and transcriptional activity of RELA [nuclear factor-kappa B p65 subunit]), and this effect was diminished in the Cx + E2+T group (medium inflammation score and decrease in TNF). The lowest inflammation score (decrease of TNF and RELA and increase of PPARG) was obtained in the Cx + E2+T + I2 group. In DU145 cells, I2 (400 μM) and TNF (10 ng/ml) additively reduced cell viability, and I2 reduced the production of TNF-stimulated IL6. The PPARG antagonist (GW9662) did not inhibit the effects of I2 on the loss of cell viability. In summary, our data suggest that I2 and T exert a synergistic anti-inflammatory action on the normal prostate, and the interrelationship between I2 and TNF leads to anti-proliferative effects in DU145 cells. PPARG does not seem to participate in the I2-induced cell viability loss in the prostate.

Stabilizing Frequency of a Diode Laser to a Reference Transition of Molecular Iodine through Modulation Transfer Spectroscopy

We report the frequency stabilization of an external cavity diode laser (ECDL) to a reference molecular iodine (I2) transition at 13,531.18 cm−1 (739.03382 nm). Using the Modulation Transfer Spectroscopy (MTS) method for the highly sensitive detection of weak absorption signals, the Doppler-free absorption peaks of I2 corresponding to the hot band transition R(78) (1–11) are resolved. The ECDL’s frequency is stabilized with respect to one of the lines lying within the reference absorption band. For this, the iodine vapor cell is heated to 450 °C and the corresponding circularly polarized pump and probe beam powers are maintained at 10 mW and 1 mW, respectively, to avoid power broadening. The short (100 ms) and long-term (50 h) linewidths of the frequency stabilized laser are measured to be 0.75(3) MHz and 0.5(2) MHz, respectively, whereas the natural linewidth of the specific I2-transitions lie within a range of tens of MHz.

I2‐Mediated Oxidation of Amines in Water toward Imines and Amides

AbstractA sustainable oxidation reaction of amines in water is established for the synthesis of imines and amides employing environmentally benign molecular iodine as the sole oxidant. The features of the present reaction also include no use of transition metals, operational simplicity and gram‐scale synthesis. It provides a facile access to imine and amide derivatives including bioactive molecules from readily accessible amine precursors.

An Efficient Route towards Quinazolinone Derivatives via I2/DMSO-Promoted Oxidative Decarboxylation of α-Amino Acids and Subsequent Oxidative Annulation Reaction

AbstractAn efficient and straightforward strategy to synthesize a wide range of quinazolinone derivatives from commercially inexpensive 2-aminobenzamides and various amino acids via molecular iodine promoted oxidative decarboxylation of α-amino acids, followed by oxidative cyclization reaction, is revealed. Operational simplicity, consistent yield, functional group tolerance and sustainability are the other noteworthy features of the reaction. A large number of quinazolinone derivatives were conveniently prepared employing the current strategy. The synthesis of other related heteroarenes, such as benzoxazole and benzothiazole derivatives, following the same reaction conditions broadens the scope of the method.

ИСПОЛЬЗОВАНИЕ СЕРЕБРОСОДЕРЖАЩИХ НАНОКОМПОЗИТОВ ДЛЯ ОПРЕДЕЛЕНИЯ ЙОДИД-ИОНОВ

At present, the interest of analytical chemists in metal-containing nanocomposites has increased significantly. This is primarily due to the possibility of their application as optical sensors. The operation of such sensors is based on the phenomenon of surface plasmon resonance (SPR). The result of this study is the development of a new sensitive method for the determination of iodide ions based on the use of paper modified with silver nanoparticles (NPs). Iodides, oxidized under the action of special reagents, form molecular iodine, which is extracted by an air flow and transferred to a sensitive paper layer containing NPs. The interaction of NPs with iodine leads to traceable optical changes. The limit of detection (0.01 mg/L) and the range of determined concentrations (0.03–0.3 mg/L) of iodide ions were determined.

Molecular Iodine Mouthrinse Antimicrobial Activity Against Periodontopathic Bacteria.

This study compared two molecular iodine mouthrinses for their in vitro bactericidal effects against subgingival biofilm bacteria from severe periodontitis patients. In a subgingival biofilm eradication assay, dilution aliquots of subgingival microbial specimens from 32 adults with severe periodontitis were mixed in vitro with either a mouthrinse containing 100 parts per million (ppm) molecular iodine (Iorinse®) or one containing 150 ppm molecular iodine (iClean®), followed by mouthrinse neutralization after 60 seconds with 3% sodium thiosulfate. The mixtures, along with unexposed subgingival biofilm aliquots, were inoculated onto enriched Brucella blood agar and incubated anaerobically for 7 days to quantitate total viable bacterial counts and selected red/orange complex periodontal pathogens (Porphyromonas gingivalis, Tannerella forsythia, Prevotella intermedia/nigrescens, Parvimonas micra, Campylobacter rectus, and Fusobacterium nucleatum). Both molecular iodine mouthrinses significantly reduced total viable bacterial counts in the subgingival biofilm samples, with iClean® providing significantly greater in vitro suppression than Iorinse®. Both molecular iodine mouthrinses also significantly reduced total red/orange complex periodontal pathogens, with significantly greater suppression also exhibited by iClean®. The molecular iodine mouthrinses exerted marked bactericidal activity in vitro against human subgingival biofilm microbial species, including red/orange complex periodontal pathogens associated with severe periodontitis, with iClean® providing significantly better antimicrobial activity than Iorinse®. These findings suggest potential value of molecular iodine mouthrinses in the treatment and prevention of periodontal diseases.

One-pot tandem synthesis of carbazole-1,4-quinone from Fischer-Borsche ring using molecular iodine/periodic acid

An efficient method for the synthesis of carbazole-1,4-quinones has been achieved from the Fischer-Borsche ring using a combination of a catalytic amount of molecular iodine and periodic acid. The developed protocol displayed a broad range of substrate scope and good tolerance to a variety of substituents. The key step of the develop protocol involved double-oxidation of Fischer-Borsche ring. Moreover, the effectiveness of this method has been extended to the concise synthesis of bioactive Murrayaquinone A and Koeniginequinone A.

Design and characterization of a multi-frequency semi-pilot ultrasonic reactor: Application to the extraction and oxidation of flaxseed-gum

The aim of this study was to design and study a new multi-frequency ultrasonic semi-pilot tank by evaluating the operational parameters with respect to calorimetric efficiency and sonochemical activity. The device was then applied to the extraction of flax-gum from the seeds and its oxidation by TEMPO method. The ultrasonic tank was used in single and multi-frequency modes (20 kHz, 40 kHz and 100 kHz). It has been shown that in single mode, the geometry and location of the ultrasonic transducers had a direct impact on the energy transfer efficiency and that the immersed radial probes gave transfer rates in the range of 66.9–82.8%. The production rate of molecular iodine was found to be better at a frequency of 100 kHz whatever the output powers used. The extraction of polysaccharides from flax seeds is proportional to the power density and can be done under mild conditions to preserve the integrity of macromolecules. Ultrasound assisted oxidation is efficient and we have highlighted that this could be done at low acoustic powers thank to the 100 kHz frequency. Thus, the results show that ultrasonic vessels are relevant for the scaling up of pretreatment of biomass and chemical processes.

Molecular Docking, Microwave-Assisted Synthesis, Characterization and Pharmacological Evaluation of 2,4,5-trisubstituted Imidazole’s

Introduction: Nitrogen containing heterocycles such as azoles have gained popularity in me-dicinal chemistry research due to their versatile pharmacological activities. Imidazole’s are one such class of adaptable compounds. The aim of the study was to explore pharmacological activities of 2,4,5-trisubstituted imidazole’s and also to develop a novel method of synthesis using microwave chemistry. Methods: In the present study, the in-silico studies of 2,4,5-trisubstituted imidazole’s was carried out to predict their anti-leishmanial as well as COX-2 inhibitory activity. Although, the results are not satisfacto-ry for the anti-leishmanial activity, the molecules showed comparable docking scores with standard celecoxib for the COX-2 inhibitory activity. Later, the microwave-assisted green synthesis of tri-substituted imidazole’s was attempted using green catalyst and solvent, molecular iodine and ethanol respectively. The synthesised derivatives (TG-1-4) were purified and characterised. Results: The derivatives were subjected to in-vitro COX-2 inhibitory assay, which showed good results. The molecules under study showed exemplary results against COX-2 PDB in molecular docking studies. A novel microwave-irradiation method was developed for the synthesis and also the in-vivo studies car-ried out for testing COX-2 inhibition was fruitful. Conclusion: In conclusion, the selected derivatives can be further studied in-vivo to develop new COX-2 inhibitors.

Production of Molecular Iodine via a Redox Reaction between Iodate and Organic Compounds in Ice.

The abiotic mechanism of molecular iodine (I2) production from iodate (IO3-) remains largely unknown. Here, we demonstrate the production of I2 in the presence of IO3- and organic compounds in ice. When the solution containing IO3- (100 μM) and furfuryl alcohol (100 μM) at pH 3.0 was frozen at -20 °C, 13.1 μM of I2 was produced with complete degradation of furfuryl alcohol after 20 min. However, there was little change in the IO3- and furfuryl alcohol concentrations in water at 25 °C. The production of I2 in ice is due to the freeze concentration effect, which induces the accumulation of IO3-, furfuryl alcohol, and protons in the ice grain boundaries. This behavior facilitated the production of I2 via a redox reaction between IO3- and organic compounds. The production of I2 increased with increasing furfuryl alcohol concentration and decreasing pH. However, freezing temperature had a minor effect on the maximum production of I2. The production of I2 is highly dependent on the type of organic compounds. It was higher for organic compounds with higher electron-donating properties. This study suggests a new mechanism for I2 production, which is helpful for predicting precisely the atmospheric I2 budget in cold regions.

Diiodine–Triethylsilane System: Formation of N-Alkylsulfonamides from Aldehydes or Ketones and Sulfonamides

AbstractReductive amination has not been commonly used in the preparation of N-alkylsulfonamides because of the low nucleophilicity of sulfonamides. In this work, a protocol for the synthesis of N-alkylsulfonamides from aldehydes or ketones and sulfonamides was developed. Molecular iodine, triethylsilane, and ethyl acetate were used as the initiator, reductant, and solvent, respectively. The key role of triethyl(iodo)silane in the reaction was confirmed through control experiments.

Solid-State Preparation and Characterization of 2-Hydroxypropylcyclodextrins-Iodine Complexes as Stable Iodophors

The use of iodine as antiseptic poses some issues related to its low water solubility and high volatility. Stable solid iodine-containing formulations are highly advisable and currently limited to the povidone-iodine complex. In this study, complexes of molecular iodine with 2-hydroxypropyl α-, β- and γ-cyclodextrins were considered water-soluble iodophors and prepared in a solid state by using three different methods (liquid-assisted grinding, co-evaporation and sealed heating). The obtained solids were evaluated for their iodine content and stability over time in different conditions using a fully validated UV method. The assessment of the actual formation of an inclusion complex in a solid state was carried out by thermal analysis, and the presence of iodine was further confirmed by SEM/EDX and XPS analyses. High levels of iodine content (8.3-10.8%) were obtained with all the tested cyclodextrins, and some influence was exerted by the employed preparation method. Potential use as solid iodophors can be envisaged for these iodine complexes, among which those with 2-hydroxypropyl-α-cyclodextrin were found the most stable, regardless of the preparation technique. The three prepared cyclodextrin-iodine complexes proved effective as bactericides against S. epidermidis.