Evidence for Trans-Oligoene Chain Formation in Graphene Induced by Iodine.

Functionalization of pristine graphene by hydrogen and fluorine is well studied, resulting in graphane and fluorographene structures. In contrast, functionalization of pristine graphene with iodine has not been reported. Here, the functionalization of graphene with iodine using photochemical activation is presented, which is thermally reversible at 400 °C. Additional dispersive dominant Raman modes that are probed by resonance Raman spectroscopy are observed. Additionally, iodinated graphene is probed by Kelvin probe force microscopy and by transport measurements showing p-doping surpassing non-covalent iodine doping by charge transfer-complex formation. The emergent Raman modes combined with strong p-doping indicate that iodine functionalization is distinct from simple iodine doping. A reaction mechanism based on these findings is proposed, identifying the large size of iodine atoms as the probable cause governing regiochemically controlled addition due to steric hinderance of reactive sites. The modification of the electronic structure is explained by the confinement of 1D trans-oligoene chains between sp3-defects. These results demonstrate the uniqueness of iodine reactivity toward graphene and the modification of the electronic structure of iodinated graphene, highlighting its dependence on the spatial arrangement of substituents.

Formation to Transportation: En-Route Fission-Facilitated Formation of Spheres in a Phosphorus-Based Porous Organic Polymer for Transportation of Iodine.

Despite its potential as a clean power source to meet rising electricity demands, nuclear energy generates radioactive waste, including isotopes of iodine, that pose significant environmental and health risks. There is a growing demand to capture radioactive iodine and repurpose it effectively. However, achieving this dual functionality with a single material remains a significant challenge. This study explores phosphorus-based porous organic polymers (P-POPs) as probes for these dual functionalities. By employing 4-formyl(triphenyl)phosphine (BB1) and phenyl-1,4-diacetonitrile (BB2) under the Knoevenagel polycondensation method, P-POPs (PKPOPs) have been synthesized that exhibit a smooth spherical morphology, which efficiently captures and release iodine under ambient conditions, facilitating efficient transportation of molecular iodine. This novel approach aims to potentially transform nuclear waste into valuable organic feedstock via an iodination reaction. The innovative application of PKPOP has also been demonstrated for iodination reactions using ball mills and under continuous flow conditions, showcasing its potential for safer waste management and utilization.

Enrichment of Geogenic Organoiodine Compounds in Alluvial-Lacustrine Aquifers: Molecular Constraints by Organic Matter.

Organoiodine compounds (OICs) are the dominant iodine species in groundwater systems. However, molecular mechanisms underlying the geochemical formation of geogenic OICs-contaminated groundwater remain unclear. Based upon multitarget field monitoring in combination with ultrahigh-resolution molecular characterization of organic components for alluvial-lacustrine aquifers, we identified a total of 939 OICs in groundwater under reducing and circumneutral pH conditions. In comparison to those in water-soluble organic matter (WSOM) in sediments, the OICs in dissolved organic matter (DOM) in groundwater typically contain fewer polycyclic aromatics and polyphenol compounds but more highly unsaturated compounds. Consequently, there were two major sources of geogenic OICs in groundwater: the migration of the OICs from aquifer sediments and abiotic reduction of iodate coupled with DOM iodination under reducing conditions. DOM iodination occurs primarily through the incorporation of reactive iodine that is generated by iodate reduction into highly unsaturated compounds, preferably containing hydrophilic functional groups as binding sites. It leads to elevation of the concentration of the OICs up to 183 µg/L in groundwater. This research provides new insights into the constraints of DOM molecular composition on the mobilization and enrichment of OICs in alluvial-lacustrine aquifers and thus improves our understanding of the genesis of geogenic iodine-contaminated groundwater systems.

Standard Radio-Iodine Labeling Protocols Impaired the Functional Integrity of Mesenchymal Stem/Stromal Cell Exosomes.

Mesenchymal stem/stromal cells (MSCs) are an extensively studied cell type in clinical trials due to their easy availability, substantial ex vivo proliferative capacity, and therapeutic efficacy in numerous pre-clinical animal models of disease. The prevailing understanding suggests that their therapeutic impact is mediated by the secretion of exosomes. Notably, MSC exosomes present several advantages over MSCs as therapeutic agents, due to their non-living nature and smaller size. However, despite their promising therapeutic potential, the clinical translation of MSC exosomes is hindered by an incomplete understanding of their biodistribution after administration. A primary obstacle to this lies in the lack of robust labels that are highly sensitive, capable of directly and easily tagging exosomes with minimal non-specific labeling artifacts, and sensitive traceability with minimal background noise. One potential candidate to address this issue is radioactive iodine. Protocols for iodinating exosomes and tracking radioactive iodine in live imaging are well-established, and their application in determining the biodistribution of exosomes has been reported. Nevertheless, the effects of iodination on the structural or functional activities of exosomes have never been thoroughly examined. In this study, we investigate these effects and report that these iodination methods abrogate CD73 enzymatic activity on MSC exosomes. Consequently, the biodistribution of iodinated exosomes may reflect the biodistribution of denatured exosomes rather than functionally intact ones.

Freeze-induced acceleration of iodide oxidation and consequent iodination of dissolved organic matter to form organoiodine compounds.

Freeze-induced acceleration of I- oxidation and the consequent iodination of dissolved organic matter (DOM) contribute to the formation of organoiodine compounds (OICs) in cold regions. The formed OICs may be a potentially important source of risk and are very closely with the environment and human health. Herein, we investigated the acceleration effects of the freeze process on I- oxidation and the formation of OICs. In comparison to reactive iodine species (RIS) formed in aqueous solutions, I- oxidation and RIS formation were greatly enhanced in frozen solution and were affected by pH, and the content of I- and O2. Freeze-thaw process further promoted I- oxidation and the concentration of RIS reached 45.7 µmol/L after 6 freeze-thaw cycles. The consequent products of DOM iodination were greatly promoted in terms of both concentration and number. The total content of OICs ranged from 0.02 to 2.83 µmol/L under various conditions. About 183-1197 OICs were detected by Fourier transform ion cyclotron resonance mass spectrometry, and more than 96.2% contained one or two iodine atoms. Most OICs had aromatic structures and were formed via substitution and addition reactions. Our findings reveal an important formation pathway for OICs and shed light on the biogeochemical cycling of iodine in the natural aquatic environment.

Iodinated Electron Acceptor with Significantly Extended Exciton Diffusion Length for Efficient Organic Photovoltaic Cells.

Iodination has unlocked new potentials in organic photovoltaics (OPVs). A newly designed and synthesized iodinated non-fullerene acceptor, BO-4I, showcases exceptional excitation delocalization property with the exciton diffusion length increased to 80 nm. The enhanced electron delocalization property is attributed to the larger atomic radius and electron orbit of the iodine atom, which facilitates the formation of intra-moiety excitations in the acceptor phase. This effectively circumvents the charge transfer state-related recombination mechanisms, leading to a substantial reduction in non-radiative energy loss (ΔEnr ). As a result, OPV cell based on PBDB-TF : BO-4I achieves an impressive efficiency of 18.9 % with a notable ΔEnr of 0.189 eV, markedly surpassing their fluorinated counterparts. This contribution highlights the pivotal role of iodination in reducing energy loss, thereby affirming its potential as a key strategy in the development of advanced next-generation OPV cells.

Tracking SF5 I in the Iodopentafluorosulfanylation of Alkynes.

In the vibrant field of SF5 chemistry, SF5 X reagents (X=F, Cl, Br) are at the heart of current investigations in radical pentafluorosulfanylation reactions. SF5 I is the missing link whose existence has not been reported despite its potential as SF5 donor. This study reports the formal addition of the hitherto unknown SF5 I reagent to alkynes by means of a combination of SF5 Cl/KI/18-crown-6 ether. The exclusive regio- and stereoselective synthesis of unprecedented (E)-1-iodo-2-(pentafluoro-λ6 -sulfanyl) alkenes was achieved. A consensus was reached through computational and mechanistic studies for the realistic formation of SF5 - anion but not SF5 I in solution and the rational involvement of SF5 ⋅ and iodine radicals in the iodo pentafluorosulfanylation reaction.

Palladium-Catalyzed Directed Atroposelective C-H Iodination to Synthesize Axial Chiral Biaryl N-Oxides via Enantioselective Desymmetrization Strategy.

The discovery of enantioselective desymmetrization reactions to provide practical synthesis of enantio-enriched atropisomeric biaryls is a challenging topic in the field of asymmetric catalysis. Herein, we report a highly enantioselective desymmetrization reaction for the synthesis of axially chiral biaryl N-oxides by atroposelective C-H iodination by using Pd(II) coordinated by N-benzoyl-l-phenylalanine as a chiral catalyst at room temperature. A broad range of products were obtained in high yields (up to 99 %) with excellent enantioselectivities (up to 98 % ee). The products could be synthesized in gram scale, one of which was proved to be a powerful organocatalyst in asymmetric allylation reaction. Mechanistic evidence as well as DFT calculations point towards the factors that lead to high reactivity and excellent enantiocontrol in this reaction.

Silk fibroin-based embolic agent for transhepatic artery embolization with multiple therapeutic potentials.

BACKGROUND: The excellent physicochemical and biomedical properties make silk fibroin (SF) suitable for the development of biomedical materials. In this research, the silk fibroin microspheres (SFMS) were customized in two size ranges, and then carried gold nanoparticles or doxorubicin to evaluate the performance of drug loading and releasing. Embolization efficiency was evaluated in rat caudal artery and rabbit auricular artery, and the in vivo distribution of iodinated SFMS (125I/131I-SFMS) after embolization of rat hepatic artery was dynamically recorded by SPECT. Transhepatic arterial radioembolization (TARE) with 131I-SFMS was performed on rat models with liver cancer. The whole procedure of selective internal radiation was recorded with SPECT/CT, and the therapeutic effects were evaluated with 18 F-FDG PET/CT. Lastly, the enzymatic degradation was recorded and followed with the evaluation of particle size on clearance of sub-micron silk fibroin. RESULTS: SFMS were of smooth surface and regular shape with pervasive pores on the surface and inside the microspheres, and of suitable size range for TAE. Drug-loading functionalized SFMS with chemotherapy or radio-sensitization, and the enhanced therapeutic effects were proved in treating HUH-7 cells as lasting doxorubicin release or more lethal radiation. For artery embolization, SFMS effectively blocked the blood supply; when 131I-SFMS serving as the embolic agent, the good labeling stability and embolization performance guaranteed the favorable therapeutic effects in treating in situ liver tumor. At the 5th day post TARE with 37 MBq/3 mg 131I-SFMS per mice, tumor activity was quickly inhibited to a comparable glucose metabolism level with surrounding normal liver. More importantly, for the fragments of biodegradable SFMS, smaller sized SF (< 800 nm) metabolized in gastrointestinal tract and excreted by the urinary system, while SF (> 800 nm) entered the liver within 72 h for further metabolism. CONCLUSION: The feasibility of SFMS as degradable TARE agent for liver cancer was primarily proved as providing multiple therapeutic potentials.

Electrochemical Iodination through the In Situ Generation of Iodinating Agents: A Promising Green Approach.

The synthesis of iodinated compounds using cheap, simple, and green strategies is of fundamental importance. Iodination reactions are mainly used to synthesize useful intermediates, especially in the pharmaceutical field, where they are employed for the production of contrast media or of iodinated active pharmaceutical ingredients. Traditional synthetic methods suffer from the use of erosive, toxic, or hazardous reactants. Approaches which involve the use of molecular iodine as an iodinating agent require the addition of an oxidizing agent, which is often difficult to handle. Electrochemistry can offer a valid and green alternative by avoiding the addition of such oxidizing agents, transforming the iodine source in the active species through the use of electrons as the main reactants. Herein, we report the electrochemical iodination with the generation of iodinating species in situ in water by using iodides as the source of iodine atoms. First of all, the electrochemical behavior of iodide and iodine in water on carbonaceous anodes was studied and, after selecting the suitable potential, in situ electrochemical iodination was successfully applied to 5-hydroxyisophthalic acid and 5-sulfosalicylic acid, comparing the iodinating power of I2 and iodonium species.

Palladium-Catalyzed Enantioselective Isodesmic C-H Iodination of Phenylacetic Weinreb Amides.

Isodesmic reactions represent mild alternatives to other chemical transformations that require harsh oxidizing agents or highly reactive intermediates. However, enantioselective isodesmic C-H functionalization is unknown and enantioselective direct iodination of inert C-H bond is very rare. Rapid synthesis of chiral aromatic iodides is of significant importance for synthetic chemistry. Herein, we report an unprecedented highly enantioselective isodesmic C-H functionalization to access chiral iodinated phenylacetic Weinreb amides via desymmetrization and kinetic resolution with PdII catalysis. Importantly, further transformations of the enantioenriched products are readily available at the iodinated or the Weinreb amide position, paving the way of related studies for synthetic and medicinal chemists.

Consecutive four-component synthesis of trisubstituted 3-iodoindoles by an alkynylation-cyclization-iodination-alkylation sequence.

A library of 19 differently substituted 3-iodoindoles is generated by a consecutive four-component reaction starting from ortho-haloanilines, terminal alkynes, N-iodosuccinimide, and alkyl halides in yields of 11-69%. Initiated by a copper-free alkynylation, followed by a base-catalyzed cyclizive indole formation, electrophilic iodination, and finally electrophilic trapping of the intermediary indole anion with alkyl halides provides a concise one-pot synthesis of 3-iodoindoles. The latter are valuable substrates for Suzuki arylations, which are exemplified with the syntheses of four derivatives, some of them are blue emitters in solution and in the solid state, in good yield.

Fibril Structure Demonstrates the Role of Iodine Labelling on a Pentapeptide Self-Assembly.

Iodination has long been employed as a successful labelling strategy to gain structural insights into proteins and other biomolecules via several techniques, including Small Angle X-ray Scattering, Inductively Coupled Plasma Mass Spectrometer (ICP-MS), and single-crystal crystallography. However, when dealing with smaller biomolecular systems, interactions driven by iodine may significantly alter their self-assembly behaviour. The engineering of amyloidogenic peptides for the development of ordered nanomaterials has greatly benefitted from this possibility. Still, to date, iodination has exclusively been applied to aromatic residues. In this work, an aliphatic bis-iodinated amino acid was synthesized and included into a custom pentapeptide, which showed enhanced fibrillogenic behaviour. Peptide single crystal X-ray structure and powder X-ray diffraction on its dried water solution demonstrated the key role of iodine atoms in promoting intermolecular interactions that drive the peptide self-assembly into amyloid fibrils. These findings enlarge the library of halogenated moieties available for directing and engineering the self-assembly of amyloidogenic peptides.

Freeze-Thaw Cycle-Enhanced Transformation of Iodide to Organoiodine Compounds in the Presence of Natural Organic Matter and Fe(III).

The formation of organoiodine compounds (OICs) is of great interest in the natural iodine cycle as well as water treatment processes. Herein, we report a pathway of OIC formation that reactive iodine (RI) and OICs are produced from iodide oxidation in the presence of Fe(III) and natural organic matter (NOM) in frozen solution, whereas their production is insignificant in aqueous solution. Moreover, thawing the frozen solution induces the further production of OICs. A total of 352 OICs are detected by Fourier transform ion cyclotron resonance mass spectrometry in the freeze-thaw cycled reactions of Fe(III)/I-/humic acid solution, which are five times as many as OICs in aqueous reactions. Using model organic compounds instead of NOM, aromatic compounds (e.g., phenol, aniline, o-cresol, and guaiacol) induce higher OIC formation yields (10.4-18.6%) in the freeze-thaw Fe(III)/I- system than those in aqueous (1.1-2.1%) or frozen (2.7-7.6%) solutions. In the frozen solution, the formation of RI is enhanced, but its further reaction with NOM is hindered. Therefore, the freeze-thaw cycle in which RI is formed in the frozen media and the resulting RI is consumed by reaction with NOM in the subsequently thawed solution is more efficient in producing OICs than the continuous reaction in frozen solution.

Formation Mechanism of Iodinated Aromatic Disinfection Byproducts: Acid Catalysis with H2OI.

Iodinated aromatic disinfection byproducts (I-DBPs) are a group of nonregulated but highly toxic DBPs. The formation of I-DBPs is attributed mainly to HOI because it is the most abundant reactive iodine species in chloraminated water. In this study, we used computational modeling of thermodynamics to examine the mechanism of iodination of aromatic contaminants, e.g., dipeptides and phenols. Computational prediction of the energy barriers of the formation of iodinated tyrosylglycine (I-Tyr-Gly) (66.9 kcal mol-1) and hydroxylated Tyr-Gly (OH-Tyr-Gly) (46.0 kcal mol-1) via iodination with HOI favors the formation of OH-Tyr-Gly over I-Tyr-Gly. Unexpectedly, mass spectrometry experiments detected I-Tyr-Gly but not OH-Tyr-Gly, suggesting that I-Tyr-Gly formation cannot be attributed to HOI alone. To clarify this result, we examined the thermodynamic role of the most reactive iodine species H2OI+ in the formation of aromatic I-DBPs under chloramination. Computational modeling of thermodynamic results shows that the formation of a loosely bonded complex of aromatic compounds with H2OI+ is the key step to initiate the iodination process. When H2OI+ serves as an acid catalyst and an iodinating agent, with HOI or H2O acting as a proton acceptor, the energy barrier of I-DBP formation was significantly lower (10.8-13.1 kcal mol-1). Therefore, even with its low concentration, H2OI+ can be involved in the formation of I-DBPs. These results provide insight into the mechanisms of aromatic I-DBP formation and important information for guiding research toward controlling I-DBPs in drinking water.

Preferential Halogenation of Algal Organic Matter by Iodine over Chlorine and Bromine: Formation of Disinfection Byproducts and Correlation with Toxicity of Disinfected Waters.

The increasing occurrence of harmful algal blooms (HABs) in surface waters may increase the input of algal organic matter (AOM) in drinking water. The formation of halogenated disinfection byproducts (DBPs) during combined chlorination and chloramination of AOM and natural organic matter (NOM) in the presence of bromide and iodide and haloform formation during halogenation of model compounds were studied. Results indicated that haloform/halogen consumption ratios of halogens reacting with amino acids (representing proteins present in AOM) follow the order iodine > bromine > chlorine, with ratios for iodine generally 1-2 orders of magnitude greater than those for chlorine (0.19-2.83 vs 0.01-0.16%). This indicates that iodine is a better halogenating agent than chlorine and bromine. In contrast, chlorine or bromine shows higher ratios for phenols (representing the phenolic structure of humic substances present in NOM). Consistent with these observations, chloramination of AOM extracted from Microcystis aeruginosa in the presence of iodide produced 3 times greater iodinated trihalomethanes than those from Suwannee River NOM isolate. Cytotoxicity and genotoxicity of disinfected algal-impacted waters evaluated by Chinese hamster ovary cell bioassays both follow the order chloramination > prechlorination-chloramination > chlorination. This trend is in contrast to additive toxicity calculations based on the concentrations of measured DBPs since some toxic iodinated DBPs were not identified and quantified, suggesting the necessity of experimentally analyzing the toxicity of disinfected waters. During seasonal HAB events, disinfection practices warrant optimization for iodide-enriched waters to reduce the toxicity of finished waters.

Systematic study of the iodinated rectal hydrogel spacer material discrepancy on accuracy of proton dosimetry.

PURPOSE: Iodination of rectal hydrogel spacer increases the computed tomography (CT) visibility. The effect of iodinated hydrogel spacer material on the accuracy of proton dosimetry has not been fully studied yet. We presented a systematic study to determine the effect of iodination on proton dosimetry accuracy during proton therapy (PT). METHODS: PT plans were designed for 20 prostate cancer patients with rectal hydrogel spacer. Three variations of hydrogel density were considered. First, as the ground truth, the true elemental composition of hydrogel true material (TM), verified by our measurement of spacer stopping power ratio, was used for plan optimization and Monte Carlo dose calculation. The dose distribution was recalculated with (1) no material (NM) override based on the CT intensity of the iodinated spacer, and (2) the water material (WM) override, where spacer material was replaced by water. The plans were compared with the ground truth using the metrics of gamma index (GI) and dosimetric indices. RESULTS: The iodination of hydrogel spacer affected the proton dose distribution with the NM scenario showing the most deviation from the ground truth. The iodination of spacer resulted in a notable increase in CT intensity and led to the treatment planning systems mistreating the iodinated spacer as a high-density material. Among the structures adjacent to the target, neurovascular bundles showed the largest dose difference, up to 350 cGy or about 5% of the prescribed dose with NM. Compared to the WM scenario, dose distribution similarity and GI passing ratios were lower in the NM scenario. CONCLUSION: The inaccurate CT intensity-based material for iodinated spacer resulted in errors in PT dose calculation. We found that the error was negligible if the iodinated spacer was replaced with water. Water density can be used as a clinically accessible and convenient alternative material override to true spacer material.

Fluorescent Indolo[3,2-a]phenazines against Toxoplasma gondii: Concise Synthesis by Gold-Catalyzed Cycloisomerization with 1,2-Silyl Migration and ipso-Iodination Suzuki Sequence.

A gold-catalyzed cycloisomerization of 2-indolyl-3-[(trimethylsilyl)ethynyl)]quinoxalines with concomitant 1,2-silyl shift forms 6-(trimethylsilyl)indolo[3,2-a]phenazines in moderate to excellent yield. These silylated heterocycles are readily transformed into 6-aryl-indolo[3,2-a]phenazines in moderate to good yield by one-pot ipso-iodination Suzuki coupling. The title compounds represent a novel type of tunable luminophore. Structure-property relationships for 6-aryl-indolo[3,2-a]phenazines obtained from Hammett correlations with σp+ substituent parameters indicate that emission maxima, Stokes shifts, and fluorescence quantum yields can be fine-tuned by the remote para-aryl substituent. Furthermore, indolo[3,2-a]phenazines were found to exhibit interesting activities against medically relevant pathogens such as the Apicomplexa parasite Toxoplasma gondii with an IC50 of up to 0.67±0.13 µM. Thus, these compounds are promising candidates for novel anti-parasitic therapies.

Highly transparent and conductive p-type CuI films by optimized solid-iodination at room temperature.

p-type CuI films with optimized optoelectronic performance were synthesized by solid-phase iodination of Cu3N precursor films at room temperature. The effects of the deposition power of Cu3N precursors on the structural, electrical, and optical properties of the CuI films were systematically investigated. X-ray diffraction results show that all the CuI films possess a zinc-blende structure. When the deposition power of Cu3N precursors was 140 W, the CuI films present a high transmittance above 84% in the visible region, due to their smaller root-mean-square roughness values of 9.23 nm. Moreover, these films also have a low resistivity of 1.63 × 10-2Ω·cm and a boosted figure of merit of 140.7 MΩ-1. These results are significant achievements among various p-types TCOs, confirming the promising prospects of CuI as a p-type transparent semiconductor applied in transparent electronics.

Deprotometalation-Iodolysis and Direct Iodination of 1-Arylated 7-Azaindoles: Reactivity Studies and Molecule Properties.

Five protocols were first compared for the copper-catalyzed C-N bond formation between 7-azaindole and aryl/heteroaryl iodides/bromides. The 1-arylated 7-azaindoles thus obtained were subjected to deprotometalation-iodolysis sequences using lithium 2,2,6,6-tetramethylpiperidide as the base and the corresponding zinc diamide as an in situ trap. The reactivity of the substrate was discussed in light of the calculated atomic charges and the pKa values. The behavior of the 1-arylated 7-azaindoles in direct iodination was then studied, and the results explained by considering the HOMO orbital coefficients and the atomic charges. Finally, some of the iodides generated, generally original, were involved in the N-arylation of indole. While crystallographic data were collected for fifteen of the synthesized compounds, biological properties (antimicrobial, antifungal and antioxidant activity) were evaluated for others.