Reactive Iodine Research Articles

Heterogenous Chemistry of I2O3 as a Critical Step in Iodine Cycling.

Global iodine emissions have been increasing rapidly in recent decades, further influencing the Earth's climate and human health. However, our incomplete understanding of the iodine chemical cycle, especially the fate of higher iodine oxides, introduces substantial uncertainties into atmospheric modeling. I2O3 was previously deemed a "dead end" in iodine chemistry; however, we provide atomic-level evidence that I2O3 can undergo rapid air-water or air-ice interfacial reactions within several picoseconds; these reactions are facilitated by prevalent chemicals on seawater such as amines and halide ions, to produce photolabile reactive iodine species such as HOI and IX (X = I, Br, and Cl). The heterogeneous chemistry of I2O3 leads to the rapid formation of iodate ions (IO3-), which is the predominant soluble iodine and its concentration cannot be well explained by current chemistry. These new loss pathways for atmospheric I2O3 can further explain its absence in field observations and its presence in laboratory experiments; furthermore, these pathways represent a heterogeneous recycling mechanism that can activate the release of reactive iodine from oceans, polar ice/snowpack, or aerosols. Rapid reactive adsorption of I2O3 can also promote the growth of marine aerosols. These findings provide novel insights into iodine geochemical cycling.

Enhanced bactericidal effects of povidone-iodine in the presence of silver ions

The rising prevalence of antibiotic-resistant infections worldwide necessitates the development of innovative antimicrobial systems for effective pathogen control. This study investigates the synergistic bactericidal effects of a combined system comprising povidone-iodine (PVP-I) and silver ions (Ag(I)). The PVP-I/Ag(I) system exhibited enhanced bactericidal activity against four key surrogate bacterial species: two Gram-negative bacteria, Escherichia coli (E. coli) and Pseudomonas aeruginosa (P. aeruginosa), and two Gram-positive bacteria, Staphylococcus aureus (S. aureus) and Bacillus subtilis (B. subtilis). Our experiments revealed that Ag(I) interacts with iodide ions (I−) to form silver iodide (AgI). This reaction promotes the formation of hypoiodous acid (HOI), a more potent bactericidal agent than other reactive iodine species (RIS), by shifting the equilibrium of RIS released from PVP-I. Under representative conditions ([PVP-I]0 = 1 mg/L, [Ag(I)]0 = 5 μM, pH = 7.3), the concentration of HOI in the PVP-I/Ag(I) system was 2.4−3.9 times higher than in the PVP-I system alone, aligning with theoretical predictions. The bactericidal efficacy of the PVP-I/Ag(I) system was influenced by pH variations, affecting HOI formation. This system represents a promising tool for rapid and effective microbial control, potentially enhancing public health outcomes.

Revisiting iodide species transformation in peracetic acid oxidation: unexpected role of radicals in micropollutants decontamination and iodate formation

Peracetic acid (PAA) is an alternative disinfectant for saline wastewaters, and hypohalous acids are typically regarded as the reactive species for oxidation and disinfection. However, new results herein strongly suggest that reactive radicals instead of HOI primarily contributed to decontamination during PAA treatment of iodine-containing wastewater. The presence of I- could greatly accelerate the micropollutants (e.g., sulfamethoxazole (SMX)) transformation by PAA. Chemical probes experiments and electron paramagnetic resonance analysis demonstrate acetylperoxyl radical rather than reactive iodine species primarily responsible for SMX degradation. The kinetic model was developed to further distinguish and quantify the contribution of radicals and iodine species, as well as to elucidate the transformation pathways of iodine species. Density functional theory calculations indicated that the nucleophilic attack of I- on the peroxide bond of PAA could form unstable O−I bond, with the transition state energy barrier for radical generation lower than that for HOI formation. The transformation of iodine species was regulated by acetylperoxyl radical to generate nontoxic IO3-, greatly alleviating the iodinated DBPs formation in saline wastewaters. This work provides mechanistic insights in radical-regulated iodine species transformation during PAA oxidation, paving the way for the development of viable and eco-friendly technology for iodide containing water treatment.

Enhanced degradation of sulfathiazole by ionizing radiation activated persulfate and periodate: Performances and mechanisms

Ionizing radiation has attracted significant interests in water purifying. However, it suffers from poor mineralization performance during the decontamination of organic micropollutants such as antibiotics. Herein, the radiolytic degradation of sulfathiazole (STZ) by gamma radiation was investigated. STZ could be completely degraded at 2.0 kGy absorbed dose but TOC removal efficiency was only 22.62 %. Quenching experiments demonstrated that •OH was the main reactive species. Toxicity assessment and phytotoxicity experiments indicated that gamma radiation can comprehensively decrease the toxicity of STZ. Significant enhancements of degradation and mineralization were observed in gamma/persulfate (Gamma/PS) and gamma/periodate (Gamma/PI) processes. The rate constant (k) increased by 1.08 times and TOC removal efficiency increased by 2.01 times with PS addition (1 mM). The k value enhanced by 4.05 times and TOC removal ratio enhanced by 2.66 times with the presence of PI (1 mM). Mechanistic investigation indicated that 1O2 played a major role in STZ degradation in the Gamma/PS and Gamma/PI systems. PI was almost completely transferred into the nontoxic iodate (IO3-), and no toxic reactive iodine species were produced in the Gamma/PI process. Moreover, Gamma/PS and Gamma/PI systems showed a broad-spectrum ability to remove a series of antibiotics. The removal performances and the costs of these systems were competitive compared with other advanced oxidation processes for antibiotics elimination. This study supplied an efficient and sustainable choice for the degradation of antibiotics, and clarified the intrinsic reaction mechanisms in the ionizing radiation-activated PS and PI systems.

Degradation of emerging contaminants in synthetic hydrolyzed urine by UV/peracetic acid: Free radical chemistry, and toxicity analysis

The ecological impact of emerging contaminants (ECs) in aquatic environments has raised concerns, particularly with regards to urine as a significant source of such contaminants in wastewater. The current investigation used the UV/Peracetic Acid (UV/PAA) processes, an innovative advanced oxidation technology, to effectively separate two emerging pollutants from urine at its source, namely, ciprofloxacin (CIP) and bisphenol A(BPA). The research findings demonstrate that the presence of the majority of characteristic ions has minimal impact on the degradation of ECs. However, in synthetic hydrolyzed urine, only NH4+ inhibits the degradation of two types of ECs, with a more pronounced effect observed on CIP degradation compared to BPA.The impact of halogen ions, specifically Cl− and I−, on the degradation of CIP in synthetic hydrolyzed urine was a complex phenomenon. When these two halogen ions are present individually, the generation of reactive halogen species (RHS) within the system enhances the degradation of CIP. However, when both types of ions coexist, the formation of diatomic radical species partially inhibits degradation. In terms of BPA degradation, while the production of reactive chlorine species (RCS) to some extent hinders the reaction rate, the generation of reactive iodine species (RIS) promotes the overall process. CIP undergoes fragmentation of the piperazine and quinoline rings, decarboxylation, defluorination reactions, as well as substitution reactions, leading to the formation of products with simplified structures. The degradation of BPA occurs gradually through hydroxyl and halogen substitution as well as isopropyl cleavage. The preliminary toxicity analysis confirmed that the presence of halogen ions in urine resulted in the formation of halogenated products in two types of ECs, albeit with an overall reduction in toxicity. The UV/PAA processes was considered to be an effective and relatively safe approach for the separation of ECs in urine.

Hidden Role of Organic Matter in the Immobilization and Transformation of Iodine on Fe-OM Associations.

The biogeochemical processes of iodine are typically coupled with organic matter (OM) and the dynamic transformation of iron (Fe) minerals in aquifer systems, which are further regulated by the association of OM with Fe minerals. However, the roles of OM in the mobility of iodine on Fe-OM associations remain poorly understood. Based on batch adsorption experiments and subsequent solid-phase characterization, we delved into the immobilization and transformation of iodate and iodide on Fe-OM associations with different C/Fe ratios under anaerobic conditions. The results indicated that the Fe-OM associations with a higher C/Fe ratio (=1) exhibited greater capacity for immobilizing iodine (∼60-80% for iodate), which was attributed to the higher affinity of iodine to OM and the significantly decreased extent of Fe(II)-catalyzed transformation caused by associated OM. The organic compounds abundant in oxygen with high unsaturation were more preferentially associated with ferrihydrite than those with poor oxygen and low unsaturation; thus, the associated OM was capable of binding with 28.1-45.4% of reactive iodine. At comparable C/Fe ratios, the mobilization of iodine and aromatic organic compounds was more susceptible in the adsorption complexes compared to the coprecipitates. These new findings contribute to a deeper understanding of iodine cycling that is controlled by Fe-OM associations in anaerobic environments.

Novel CQDs/BiOI Microspheres with Gradient Oxygen Vacancies for Efficient Photocatalytic Performance Boosting by the Synergism of Reactive Oxygen and Iodine Species

AbstractThe synergy of reactive oxidative species (ROSs: ⋅OH, ⋅O2− and 1O2) and reactive iodine species (RISs: ⋅I and ⋅I2−) is conclusive to driving organic pollutant degradation in various aquatic environments. Over the past years, rational design of Vis‐NIR responsive photocatalyst with enhanced photocatalytic performance has attracted drawing attention. Herein, CQDs/BiOI composites with up‐conversion photoluminescence (UCPL) properties and oxygen vacancies was constructed for tetracycline (TC) and oxytetracycline (OTC) degradation. The apparent kinetic constant of the 4‐CQDs/BiOI is 2.13 and 2.38 times on pure BiOI. The excellent photodegradation efficiency can be attributed to the enhanced light absorption originated from the up‐conversion property and improved charge separation efficiency. Furthermore, the iodine free radicals (⋅I) and superoxide free radicals (⋅O2−) played a crucial role in the photodegradation procedure. I− from BiOI could be partially oxidized to form ⋅I. At the same time, the electron capture traps formed by Oxygen vacancies can promote the production of ⋅O2−. Remarkably, the removal efficiency of TC and OTC was still maintained at 80 % by 4‐CQDs/BiOI under different water quality conditions due to the synergy of ⋅O2− with ⋅I. This work sheds light on a new treatment for the synergistic degradation of pollutants in complex water by RISs and ROSs.

Metal-Free Electrocatalytic Synthesis of Fused Azabicycles from N-Allyl Enamine Carboxylates.

An electrocatalytic approach to access structurally significant azabicyclic scaffolds from N-allyl enamine carboxylates is illustrated. This metal-free method functions exclusively with a catalytic amount of iodide, strategically employed to electrochemically generate a reactive hypervalent iodine species, which facilitates the cascade bicyclization processes with enhanced precision and efficiency. Excellent functional group compatibility was observed, enabling the synthesis of a series of azabicycle derivatives. Detailed mechanistic and electrochemical studies enhance the comprehension of the reaction sequence.

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.

Sustainable bioelectric activation of periodate for highly efficient micropollutant abatement

The periodate (PI)-based advanced oxidation process is valued for environmental remediation, but current activation methods involve high costs, secondary contamination risks, and limited applicability due to external energy inputs (e.g., UV), catalyst incorporation (e.g., Fe2+), or environmental modifications (e.g., freezing). In this work, novel bioelectric activation of PI using the electrons generated by electroactive bacteria was developed and investigated for rapid removal of carbamazepine (CBZ), achieving 100 %, 100 %, and 76 % removal efficiency for 4.22 µM of CBZ in 20 min at pH 2, 120 min at pH 6.4, and HRT of 30 min at pH 8.5, respectively, with a 1 mM PI dose and without an input voltage. It was deduced that electrons derived from bacteria could directly activate PI using Ti mesh electrodes and generate •IO3 via single electron transfer under strongly acidic conditions (e.g., pH 2). Nevertheless, under weak alkaline conditions (e.g., pH 8.5), biogenic electrons indirectly activated PI by generating OH−via 4e−reduction at the Ti mesh cathode, resulting in the formation of •O2− and 1O2. In addition to the metal cathode, a carbon-based cathode finely modulates the 2e−reduction, yielding H2O2 and activating PI to mainly form •OH. Moreover, primarily non-toxic IO3− was produced during treatment, while no detectable reactive iodine species (HOI, I2, and I3−) were observed. Furthermore, the bioelectric activation of PI demonstrated its capability to remove various micropollutants present in secondary-treated municipal wastewater, showcasing its broad-spectrum degradation ability. This study introduces a novel, cost-effective, and environmentally friendly PI activation technique with promising applicability for micropollutant elimination in water treatment.

How I– alters UV and UV/VUV processes' redox capacities: Evidences from iodine species evolution, hydrogen peroxide formation, and oxyhalides degradation?

Although UV and/or VUV tandem I– are often proposed as advanced reduction processes (ARPs) to eliminate micropollutants by generating eaq–, the fate of I– and its byproducts formation remain to be explored. Therefore, this study investigated the iodine species evolution during UV/I– and UV/VUV/I– processes under different influencing factors. Results show that UV/VUV oxidized most of I– to IO3– whereas UV only oxidized a portion of I– to intermediate reactive iodine species (RISs, including I2, HOI, and I3–); meanwhile, substantial H2O2 was generated only in UV/VUV/I– process but not in UV/I– process, proving that UV/VUV owns stronger oxidation ability than UV alone. Spiking I– into water exerted triple-sided effects by consuming •OH, generating eaq–, and shielding light, thus complicating the systems. Holistically, increasing pH or decreasing dissolved oxygen converted oxidizing environment into reducing condition and caused less RISs formation, especially for UV/VUV/I–. For oxyhalides, neither UV/I– nor UV/VUV/I– degraded ClO4–. While UV/I– cannot remove ClO3–, UV/VUV/I– reduced ClO3– to Cl–. Expectedly, both UV/I– and UV/VUV/I– reduced BrO3– to Br– more efficiently than UV and UV/VUV, confirming that I– can enhance the reduction capacities of UV/VUV and UV technologies.

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.

The diverse roles of halide ions in the degradation of bisphenol A via UV/peracetic acid process at different pH values: Radical chemistry, and transformation pathways

UV/Peracetic Acid (UV/PAA), as an innovative advanced oxidation process (AOP), is employed to treat bisphenol A (BPA) in water through the generation of hydroxyl radicals (•OH) and carbon-centered radicals (R−C•). The impact of halide ions (Cl−; Br−; I−) on the efficiency of UV/PAA was investigated for the first time under varying pH levels. The presence of halide ions exerted an influence on the reactivity of •OH and R−C•, exhibiting varying degrees of impact across different pH conditions. It was discovered that pH exerts a significant influence on its efficiency, with optimal removal performance observed at a pH 9. The degradation of BPA was inhibited by Cl− through the generation of reactive chlorine species (RCS), which triggers the interconversion between •OH and R−C•. Reactive bromine species (RBS) were produced in the presence of Br−, facilitating BPA degradation and generating HOBr as a supplementary source of •OH radicals. I− primarily generate reactive iodine species (RIS) through photolysis, which facilitates the degradation of BPA. The transformation of BPA involves hydroxylation, demethylation, halogenation, and cleavage reactions to form various products and pathways. The toxicity test demonstrates that the UV/PAA treatment of BPA exhibits lower toxicity, thereby indicating its environmentally friendly.

Freezing-Enhanced Photoreduction of Iodate by Fulvic Acid.

Iodate is a stable form of iodine species in the natural environment. This work found that the abiotic photosensitized reduction of iodate by fulvic acid (FA) is highly enhanced in frozen solution compared to that in aqueous solution. The freezing-induced removal of iodate by FA at an initial pH of 3.0 in 24 h was lower than 10% in the dark but enhanced under UV (77.7%) or visible light (31.6%) irradiation. This process was accompanied by the production of iodide, reactive iodine (RI), and organoiodine compounds (OICs). The photoreduction of iodate in ice increased with lowering pH (pH 3-7 range) or increasing FA concentration (1-10 mg/L range). It was also observed that coexisting iodide or chloride ions enhanced the photoreduction of iodate in ice. Fourier transform ion cyclotron resonance mass spectrometric analysis showed that 129 and 403 species of OICs (mainly highly unsaturated and phenolic compounds) were newly produced in frozen UV/iodate/FA and UV/iodate/FA/Cl- solution, respectively. In the frozen UV/iodate/FA/Cl- solution, approximately 97% of generated organochlorine compounds (98 species) were identified as typical chlorinated disinfection byproducts. These results call for further studies of the fate of iodate, especially in the presence of chloride, which may be overlooked in frozen environments.

Updates on microbial Iodine Cycling in snotty Biofilms of a prealpine Mineral Spring Cavern

We have previously described the massive, methane-oxidizing microbial biofilms discovered in the cavern of an iodine-rich former medicinal spring in prealpine southern Germany (Karwautz et al. 2017). Next to up to 3000 ppm of methane in the cavern atmosphere, the mineral spring water can contain up to 23 mM of iodine, ~thousand-fold higher than in natural freshwaters. Since reactive iodine species can be toxic for microbes, the massive microbial growth in this cave is a fascinating phenomenon. We postulate that microbes capable of utilizing different iodine species should be prevalent in the cavern. Here, we present our recent work investigating the possible involvement of biofilm microbiota in either oxidative or reductive iodine cycling. Gradient tubes set up with iodide and oxygen as redox partners showed ample microbial growth and the formation of elemental iodine. Amplicon sequencing suggested different Alpha- (Magnetospirillum spp.) and Gammaproteobacteria (Aeromonas spp.) to be capable of iodide oxidation. Moreover, we address a possible iodate-dependent methane oxidation hosted within biofilm microbiota. Metagenomes allowed to assemble the MAGs of a novel member of the recently discovered anaerobic Methylomirabilota methanotrophs, Candidatus Methylomirabilis iodofontis. Its genetic repertoire included not only known markers of oxygenic denitrification and aerobic methane oxidation, but also of iodate respiration (Zhu et al. 2022). Our ongoing work will provide further evidence of the still largely uncharted iodine-cycling ecophysiologies of the biofilm microbiota of this unique microbe-dominated subsurface ecosystem.

Ultraefficient OG-Mediated Photodynamic Inactivation Mechanism for Ablation of Bacteria and Biofilms in Water Augmented by Potassium Iodide under Blue Light Irradiation.

While photodynamic inactivation (PDI) has emerged as a novel sterilization strategy for drinking water treatment that recently attracted tremendous attention, its efficiency needs to be further improved. In this study, we aimed to clarify the ultraefficient mechanism by which potassium iodide (KI) potentiates octyl gallate (OG)-mediated PDI against bacteria and biofilms in water. When OG (0.15 mM) and bacteria were exposed to blue light (BL, 420 nm, 210 mW/cm2), complete sterilization (>7.5 Log cfu/mL of killing) was achieved by the addition of KI (250 mM) within only 5 min (63.9 J/cm2). In addition, at lower doses of OG (0.1 mM) with KI (100 mM), the biofilm was completely eradicated within 10 min (127.8 J/cm2). The KI-potentiated mechanism involves in situ rapid photogeneration of a multitude of reactive oxygen species, especially hydroxyl radicals (•OH), reactive iodine species, and new photocytocidal substances (quinone) by multiple photochemical pathways, which led to the destruction of cell membranes and membrane proteins, the cleavage of genomic DNA and extracellular DNA within biofilms, and the degradation of QS signaling molecules. This multitarget synergistic strategy provided new insights into the development of an environmentally friendly, safe, and ultraefficient photodynamic drinking water sterilization technology.

Target-prepared sludge biochar-derived synergistic Mn and N/O induces high-performance periodate activation for reactive iodine radicals generation towards ofloxacin degradation

Converting waste activated sludge into catalysts for the removal of antibiotics in water fulfils the dual purpose of waste-to-resource and hazardous pollution elimination. In this study, sludge-derived biochar (SDB) for efficient periodate (PI) activation was first prepared via one-step pyrolysis of potassium permanganate-polyhexamethylenebiguanide conditioned sludge without additional modification. The SDB (750 °C)-PI system degraded 100% ofloxacin (OFL, 41.5 μM) within 6 min and was almost undisturbed by inorganic ions or humic acids. The experimental results confirmed that the predominant role of reactive iodine species (RIS) and the auxiliary involvement of singlet oxygen (1O2) jointly contributed to the OFL degradation. Theoretical calculations further indicated that the synergy between Mn and N/O induced local charge redistribution and improved electron transfer capability of SDB, leading to the formation of electron-rich Mn sites and enhanced Mn(II)↔Mn(III)↔Mn(IV) redox to promote PI activation. More importantly, the enhanced adsorption and charge transfer of PI on the Mn site of the Mn-N/O-C structures induced the I-O bond stretching and the rapid generation of RIS. This study offered a cost-effective strategy for developing SDB-based catalysts, further advancing the comprehension of sludge management and the intricate mechanisms underlying RIS formation in PI-advanced oxidation processes.

Iodide-mediated selective photocatalytic treatment of phenolic pollutants

Photocatalysis is a promising approach for environmental remediation. However, the intensively studied •OH and h+-based oxidation processes often miss the target pollutants due to their poor selectivity. The potential formation of toxic degradation byproducts from the oxidation of matrix species is a real concern in photocatalytic treatment. Here, we describe an innovative application of iodide-based photocatalytic process towards efficient degradation of phenolic pollutants even in complex water matrixes. Due to the presence of iodide, the degradation rate of our target pollutant, bisphenol A (BPA), was enhanced by 29 times on g-C3N4, and as much as 130 times on CdS. With evolved reactive iodine species (RIS) as oxidants, the iodide-based photocatalysis could selectively oxidize phenolic pollutants, thus, avoiding the inhibition by ubiquitous anions and organics in wastewater. Quenching experiments and measurements of RIS demonstrated that the diiodide (•I2-) was the dominant oxidant for degradation of phenolic pollutants, while iodine atom (•I) and triiodide (I3-) play minor roles. This work sheds light on the practical application of iodide-based photocatalysis for water treatment.

Peptide‐Hypervalent Iodine Reagent Chimeras: Enabling Peptide Functionalization and Macrocyclization**

AbstractHerein, we report a novel strategy for the modification of peptides based on the introduction of highly reactive hypervalent iodine reagents—ethynylbenziodoxolones (EBXs)—onto peptides. These peptide‐EBXs can be readily accessed, by both solution‐ and solid‐phase peptide synthesis (SPPS). They can be used to couple the peptide to other peptides or a protein through reaction with Cys, leading to thioalkynes in organic solvents and hypervalent iodine adducts in water buffer. Furthermore, a photocatalytic decarboxylative coupling to the C‐terminus of peptides was developed using an organic dye and was also successful in an intramolecular fashion, leading to macrocyclic peptides with unprecedented crosslinking. A rigid linear aryl alkyne linker was essential to achieve high affinity for Keap1 at the Nrf2 binding site with potential protein‐protein interaction inhibition.

Peptide-Hypervalent Iodine Reagent Chimeras: Enabling Peptide Functionalization and Macrocyclization.

Herein, we report a novel strategy for the modification of peptides based on the introduction of highly reactive hypervalent iodine reagents-ethynylbenziodoxolones (EBXs)-onto peptides. These peptide-EBXs can be readily accessed, by both solution- and solid-phase peptide synthesis (SPPS). They can be used to couple the peptide to other peptides or a protein through reaction with Cys, leading to thioalkynes in organic solvents and hypervalent iodine adducts in water buffer. Furthermore, a photocatalytic decarboxylative coupling to the C-terminus of peptides was developed using an organic dye and was also successful in an intramolecular fashion, leading to macrocyclic peptides with unprecedented crosslinking. A rigid linear aryl alkyne linker was essential to achieve high affinity for Keap1 at the Nrf2 binding site with potential protein-protein interaction inhibition.