Iodo Groups Research Articles

Octanuclear Zinc Clusters in Microporous Organic Polymers: Network-Enhanced Reductive CO2 Fixation to Formamides at Room Temperature.

A building block containing eight zincs and eight iodo groups (8Zn) is obtained by the Zn complexation of a salen ligand bearing two additional hydroxy groups. Through the Sonogashira-Hagihara coupling of 8Zn with 1,3,5,7-tetra(4-ethynylphenyl) adamantane, microporous organic polymers bearing octanuclear zinc clusters (MOP-8Zn) are prepared, exhibiting a high surface area of 562 m2g-1, microporosity, and a particulate morphology with an average diameter of 249nm. The MOP-8Zn exhibits significantly enhanced catalytic performance, compared to molecular counterparts, in the reductive carbon dioxide fixation to formamides, possibly due to the cooperative adsorption and confinement effect of networks on substrates.

Visible-Light-Promoted Radical gem-Selenosulfonylation or -Iodosulfonylation of 2,2,2-Trifluorodiazoethane under Photosensitizer-Free Conditions.

A visible-light-promoted radical gem-difunctionalization of trifluorodiazoethane with RSO2X (X = SeR', I) for the synthesis of α-seleno or α-iodo trifluoroethyl sulfones is described. This atom-economical reaction is external-photocatalyst- and additive-free and uses nontoxic ethyl acetate as the solvent. The resultant products, which incorporate sulfonyl, trifluoromethyl, and iodo or selenyl functional groups onto one carbon atom, can serve as versatile building blocks. A major synthetic application was demonstrated by ATRA reactions with various terminal alkynes.

AgSCF3 Radical Addition Based on an Oxidant-Free α,β-Amide (Trifluoromethyl)sulfanylation Reaction

Abstract(Trifluoromethyl)sulfanylamides are an important class of organic compounds that are common among natural products and drug molecules. Here, we report a (trifluoromethyl)sulfanylation reaction using silver(I) (trifluoromethyl)sulfide as a free-radical (trifluoromethyl)sulfanylation reagent for β-amide compounds. This reaction does not require stoichiometric oxidants or additional transition-metal catalysts, and can be achieved by adding common organic acids. This method has excellent applicability and can accommodate several functional groups, including ester groups, acyl groups, and even bromo or iodo groups. Heterocyclic α,β-amides can also be readily converted into the corresponding products. This reaction also provides a new method for the synthesis of deuterated (trifluoromethyl)sulfanylamides.

Structure-Activity Relationship and Voltage Dependence for the Drug-Drug Interaction between Amiodarone Analogs and MNI-1 at the L-type Cav Channel.

The drug-drug interaction (DDI) between amiodarone (AMIO) and sofosbuvir (SOF), a direct-acting hepatitis-C NS5B nucleotide polymerase inhibitor, has been associated with severe bradyarrhythmia in patients. Recent cryo-EM data has revealed that this DDI occurs at the α-subunit of L-type Cav channels, with AMIO binding at the fenestration site and SOF [or MSD nucleotide inhibitor #1 (MNI-1): analog of SOF] binding at the central cavity of the conductance pathway. In this study, we investigated the DDI between 21 AMIO analogs, including dronedarone (DRON) and MNI-1 (or SOF) in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and hCav1.2 models. Our findings indicate that among the tested AMIO analogs in hiPSC-CMs at clinically relevant concentrations, only three analogs (AA-9, AA-10, and AA-17) were able to effectively substitute for AMIO in this DDI with 1 µM MNI-1. This highlights the importance of the diethyl amino group of AMIO for interacting with MNI-1. In the hCav1.2 model, desethylamiodarone (AA-12) demonstrated synergy with 90 µM MNI-1, while three other analogs with modifications to the position of the diethyl amino group or removal of iodo groups showed weaker synergy with 90 µM MNI-1. Interestingly, DRON did not exhibit any interaction with 270 µM SOF or 90 µM MNI-1, suggesting that it could safely replace AMIO in patients requiring SOF treatment, other clinically relevant differences considered. Overall, our functional data align with the cryo-EM data, highlighting that this DDI is dependent on the structure of AMIO and cardiomyocyte resting membrane potential. SIGNIFICANCE STATEMENT: Our findings point to specific residues in the AMIO molecule playing a critical role in the DDI between AMIO and MNI-1 (SOF analog), confirming cryo-EM results. Applied at clinically relevant AMIO's concentrations or projected MNI-1's concentrations at the resting potentials mimicking the sinoatrial node, this DDI significantly slowed down or completely inhibited the beating of hiPSC-CMs. Finally, these in vitro results support the safe replacement of AMIO (Cordarone) with DRON (Multaq) for patients requiring SOF treatment, other clinical caveats considered.

6-Aminocoumarin-derived Schiff base gelators: aggregation and sensing of CN-, Fe3+, Cu2+ and CO2 under different conditions.

Herein, we report the synthesis, characterization, supramolecular gelation and multiple applications of 6-aminocoumarin-derived Schiff bases 1 and 2. Both Schiff bases underwent gelation in DMF-H2O (2 : 1, v/v), DMSO-H2O (2 : 1, v/v) and dioxane-H2O (2 : 1, v/v) involving weak forces. Furthermore, the gels were stable and exhibited good viscoelastic properties. The storage modulus (G') of each gel was considerably higher than its loss modulus (G''). The higher value of the crossover point and lower value of tan δ for the gel of Schiff base 2 compared to the gel of Schiff base 1 demonstrated the better gelation behaviour of 2 than that of 1 in DMF-H2O (2 : 1, v/v). Further, iodo-analogue 2 exhibited cross-linked helical morphology, whereas non-iodo analogue 1 exhibited long chain fibrous morphology, as observed via FESEM. These differences in morphology and viscoelastic behaviors were attributed to the iodo group present in 2, which influenced its aggregation involving halogen bonding. To demonstrate their application, the DMF-H2O (2 : 1, v/v) gels of both 1 and 2 recognized CN- over a series of other anions by exhibiting a gel-to-sol phase change. Besides anion sensing, gels 1 and 2 selectively detected Fe3+ and Cu2+ ions over other metal ions via a gel-to-gel colour change. Finally, CN--treated solutions of 1 and 2 allowed the successful detection of CO2 by the naked eye. Moreover, the detection was possible using a test-kit method.

Rhodium‐Catalyzed Intramolecular Cyclization and Rearrangement of 1‐Azido‐2‐(2,2‐Dihalovinyl)arenes and 1‐Azido‐2‐[(2,2‐Dihalovinyl)(Boc)amino]arenes for the Preparation of 2,3‐Dihaloindoles and 2‐Haloquinoxalines

AbstractTreatment of 1‐azido‐2‐(2,2‐dihalovinyl)arenes with a catalytic amount of Rh2(esp)2 afforded various 2,3‐dihaloindoles in 51–74% yields. This reaction progressed via the intramolecular cyclization of rhodium nitrene generated in situ and the rearrangement of one halogen group. For the 2‐chloro‐2‐iodovinyl group, the iodo group selectively rearranged to yield 2‐chloro‐3‐iodoindoles as single isomers. Moreover, 1‐azido‐2‐[(2,2‐dihalomovinyl)(Boc)amino]arenes were reacted with a catalytic amount of Rh2(oct)4, which produced 2‐haloquinoxaline in 55–92% yields.

Development of probes for radiotheranostics with albumin bindingmoiety to increase the therapeutic effects of astatine-211 (211At).

We have developed probes for multiradionuclides radiotheranostics using RGD peptide ([67Ga]Ga-DOTA-c[RGDf(4-I)K] ([67Ga]1) and Ga-DOTA-[211At]c[RGDf(4-At)K] ([211At]2)) for clinical applications. The introduction of an albumin binding moiety (ABM), such as 4-(4-iodophenyl)-butyric acid (IPBA), that has high affinity with the blood albumin and prolongs the circulation half-life can improve the pharmacokinetics of drugs. To perform more effective targeted alpha therapy (TAT), we designed and synthesized Ga-DOTA-K([211At]APBA)-c(RGDfK) ([211At]5) with 4-(4-astatophenyl)-butyric acid (APBA), which has an astato group instead of an iodo group in IPBA. We evaluated whether APBA functions as ABM and [211At]5 is effective for TAT. In addition, we prepared 67Ga-labeled RGD peptide without ABM, [67Ga]Ga-DOTA-K-c(RGDfK) ([67Ga]3), and 125I-labeled RGD peptide with ABM, Ga-DOTA-K([125I]IPBA)-c(RGDfK) ([125I]4), to compare with [211At]5. Biodistribution experiments of [67Ga]3 without ABM, [125I]4 and [211At]5 with ABMwere conducted in normal mice and U-87 MG tumor-bearing mice. In addition, two doses of [211At]5 (370 or 925kBq) were administered to U-87 MG tumor-bearing mice to confirm the therapeutic effects. The blood retention of [125I]4 and [211At]5 was remarkably increased compared to [67Ga]3. Also, [125I]4 and [211At]5 showed similar biodistribution and significantly greater tumor accumulation and retention compared to [67Ga]3. In addition, [211At]5 inhibited tumor growth in a dose-dependent manner. The functionality of APBA as ABM like IPBA, and the usefulness of [211At]5 as the radionuclide therapy agent for TAT was revealed.

Ag-Catalyzed para-Selective Sulfenyl Group Transfer Reactions of N-Sulfenylanilides.

Ag-catalyzed reactions of N-sulfenylanilides afforded the corresponding p-sulfenylanilides in good to high yields with good para selectivity. The present transformation has a high compatibility of functional groups, such as ester, bromo, and iodo groups. Mechanistic studies indicate that the rearrangement reaction proceeds via intermolecular transfer of the sulfenyl group.

Halo-Jacobsen Rearrangement Induced by Steric Repulsion between peri-Iodo Groups.

The naphthalene ring is distorted due to steric repulsion between iodo groups at the peri-positions. Due to the distortion, 1,8-diiodonaphthalene underwent a halo-Jacobsen rearrangement when treated with trifluoromethanesulfonic acid, producing 1,5-diiodonaphthalene and 1,4-diiodonaphthalene. In this reaction, acid-induced dehalogenative homocoupling also proceeded to form 4,4'-diiodo-1,1'-binaphthyl. The reaction selectivity could be controlled by varying the reaction temperature. DFT calculations and some control experiments revealed that these compounds were formed by different pathways.

Design, Synthesis, and Antimycobacterial Evaluation of Novel Tetrahydroisoquinoline hydrazide Analogues.

A series of novel 2-substituted-5,7-dichloro-1,2,3,4-tetrahydroisoquinoline-6-carbohydrazide were designed, synthesized and structures were confirmed by analytical methods viz.,1H NMR, 13C NMR and Mass spectrometry. Synthesized derivatives were evaluated for their anti-mycobacterial activity against Mycobacterium tuberculosis (Mtb) H37Ra. Among all the evaluated compounds, 10A25 contaning biphenyl moiety exhibited significant inhibition with IC50 4.7 μM. 10A19, with an electron-withdrawing Iodo group in the ortho position of the phenyl exhibited significant anti-tubercular activity with IC50 8.8 µM. IC50 values of the remaining compounds ranged from 9.2 to 73.6 μM. Molecular docking study of the significantly active compound 10A25 was performed to determine the putative binding position of the test ligand at the active site of the selected target proteins Mycobacterium tuberculosis enoyl reductase (InhA) PDB - 4TZK and peptide deformylase PDB -3E3U. A suitable single crystal for one of the active compounds, 10A12, was generated and analysed to further confirm the structure of the compounds.

Transition-Metal-Free Difunctionalization of Sulfur Nucleophiles.

Efficient protocols for accessing iodo-substituted diaryl and aryl(vinyl) sulfides have been developed using iodonium salts as reactive electrophilic arylation and vinylation reagents. The reactions take place under transition-metal-free conditions, employing odorless and convenient sulfur reagents. A wide variety of functional groups are tolerated in the S-diarylation, enabling the regioselective late-stage application of several heterocycles and drug molecules under mild reaction conditions. A novel S-difunctionalization pathway was discovered using vinyliodonium salts, which proceeds under additive-free reaction conditions and grants excellent stereoselectivity in the synthesis of aryl(vinyl) sulfides. A one-pot strategy combining transition-metal-free diarylation and subsequent reduction provided facile access to electron-rich thioanilines and a direct synthesis of a potential drug candidate derivative. The retained iodo group allows a wide array of further synthetic transformations. Mechanistic insights were elucidated by isolating the key intermediate, and the relevant energy profile was substantiated by DFT calculations.

Transition‐Metal‐Free Difunctionalization of Sulfur Nucleophiles**

AbstractEfficient protocols for accessing iodo‐substituted diaryl and aryl(vinyl) sulfides have been developed using iodonium salts as reactive electrophilic arylation and vinylation reagents. The reactions take place under transition‐metal‐free conditions, employing odorless and convenient sulfur reagents. A wide variety of functional groups are tolerated in theS‐diarylation, enabling the regioselective late‐stage application of several heterocycles and drug molecules under mild reaction conditions. A novelS‐difunctionalization pathway was discovered using vinyliodonium salts, which proceeds under additive‐free reaction conditions and grants excellent stereoselectivity in the synthesis of aryl(vinyl) sulfides. A one‐pot strategy combining transition‐metal‐free diarylation and subsequent reduction provided facile access to electron‐rich thioanilines and a direct synthesis of a potential drug candidate derivative. The retained iodo group allows a wide array of further synthetic transformations. Mechanistic insights were elucidated by isolating the key intermediate, and the relevant energy profile was substantiated by DFT calculations.

Inserting Single-Atom Zn by Tannic Acid Confinement To Regulate the Selectivity of Pd Nanocatalysts for Hydrogenation Reactions.

Precisely controlling the selectivity of nanocatalysts has always been a hot topic in heterogeneous catalysis but remains difficult owing to their complex and inhomogeneous catalytic sites. Herein, an effective strategy to regulate the chemoselectivity of Pd nanocatalysts for selective hydrogenation reactions by inserting single-atom Zn into Pd nanoparticles is reported. Taking advantage of the tannic acid coating-confinement strategy, small-sized Pd nanoparticles with inserted single-atom Zn are obtained on the O-doped carbon-coated alumina. Compared with the pure Pd nanocatalyst, the Pd nanocatalyst with single-atom Zn insertion exhibits prominent selectivity for the hydrogenation of p-iodonitrobenzene to afford the hydrodeiodination product instead of nitro hydrogenation ones. Further computational studies reveal that the single-atom Zn on Pd nanoparticles strengthens the adsorption of the nitro group to avoid its reduction and increases the d-band center of Pd atoms to facilitate the reduction of the iodo group, which leads to enhanced selectivity. This work provides new guidelines to tune the selectivity of nanocatalysts with guest single-atom sites.

Phenolic furanochromene hydrazone derivatives: Synthesis, antioxidant activity, ferroptosis inhibition, DNA cleavage and DNA molecular docking studies

Twenty-four phenolic furanochromene hydrazone derivatives were designed and synthesized in order to evaluate structure–activity relationships in a series of antioxidant-related assays. The derivatives have varying substitution patterns on the phenol ring, with some compounds having one, two or three hydroxy groups, and others containing one hydroxy group in combination with methoxy, methyl, bromo, iodo and/or nitro groups. Antioxidant activity was determined using the DPPH free radical scavenging and CUPRAC assays. Compounds containing ortho-dihydroxy and para-dihydroxy patterns had the highest free radical scavenging activity, with IC50 values ranging from 5.0 to 28 μM. Similarly, derivatives with ortho-dihydroxy and para-dihydroxy patterns, together with a 4-hydroxy-3,5‑dimethoxy pattern, displayed strong copper (II) ion reducing capacity, using Trolox as a standard. Trolox equivalent antioxidant capacity (TEAC) coefficients for these derivatives ranged from 1.75 to 3.97. As further evidence of antioxidant potential, greater than half of the derivatives reversed erastin-induced ferroptosis in HaCaT cells. In addition, twenty-three of the derivatives were effective at cleaving supercoiled plasmid DNA in the presence of copper (II) ions at 1 mM, with the 3,4‑dihydroxy derivative showing cleavage to both the linear and open circular forms at 3.9 uM. The interaction of the phenolic furanochromene derivatives with DNA was confirmed by molecular docking studies, which revealed that all the derivatives bind favorably in the minor groove of DNA.

A general strategy for in situ assembly of light-up fluorophores via bioorthogonal Suzuki-Miyaura cross-coupling

Herein we presented a general strategy for in situ assembly of intramolecular charge-transfer (ICT)-based light-up fluorophores via bioorthogonal Suzuki-Miyaura cross-coupling reaction. By introducing iodo group at the appropriate position, five fluorophores with different scaffolds including naphthalimide, coumarin, naphthalene sulfonate, nitrobenzoxadiazole, and acetonaphthone, were designed as bioorthogonal multicolor fluorogenic probes, which could produce significant fluorescence enhancement and high fluorescence quantum yield after Suzuki-Miyaura reaction with aryl boronic acid or boronate. Manipulating the substituents and π scaffold in the fluorophores allows fine-tuning of their photophysical properties. With this strategy, we succeeded in peptide conjugation, no-wash fluorogenic protein labeling, and mitochondria-selective bioorthogonal imaging in live cells.

Screening of anti-cancerous potential of classical Raudra rasa and modified Raudra rasa modified with hiraka bhasma (nanodiamond) through FTIR & LC-MS analysis.

Raudra rasa is an ayurvedic medicine explicitly prescribed for the treatment of arbuda (cancer), whereas hiraka bhasma has the potential to promote cancer healing properties. Together, these two medicines provide multifunction benefits. This paper analyses the functional groups of Raudra rasa modified with hiraka bhasma and compares it with the classically prepared raudra rasa. To identify the functional group, organic ligands, and active compounds present in samples of raudra rasa (CRR) and modified raudra rasa with hiraka bhasma (MRR) contributing to cancer alleviation by using Fourier transform infrared spectroscopy (FTIR) & LC-MS analysis. Classical raudra rasa (CRR), its ingredients, shadguna kajjali (SK); decoction of Piper betel Linn. (PBD); Amaranthus spinosus Linn. (ASD); Boerhaavia diffusa Linn. (BDD); Piper longum Linn. (PLD); cow urine (GM), & similarly modified raudra rasa (MRR), its ingredients,hiraka bhasma (HB); shadguna rasasindura (SHR); water-soluble extract of Piper betel Linn. (PBE); Amaranthus spinosus Linn. (ASE); Boerhaavia diffusa Linn. (BDE); cow urine ark (GA); Piper Longum Linn. (PLE) were subjected to FTIR and LC-MS analysis. Among all 15 samples studied, maximum numbers of peaks (21) were seen in MRR indicating a greater number of functional groups. Further, in MRR, a maximum peak in the double bond region is suggestive of its higher stability compared to CRR. Both the compound is preliminarily a mixture of the number of functional groups like; fluoro, methyl, amino, hydroxy, nitro, methylamino, carbonyl, and iodo groups, having known anti-proliferative activities. By the FT-IR analysis, the biologically active compounds in aqueous and methanol extract of CRR & MRR were identified that have anti-cancerous compounds. In the present study, a total of 40 major compounds like alkaloids, amino acid, carboxylic acid, Flavonoids, Nucleoside, Nucleotide, phenylpropanoid, Sphingosine, stilbenoid, sugar, phosphate, terpenoids, vitamin from aqueous & methanol extract of CRR & MRR were identified by LC-MS. This research paper highlights the presence of different functional groups and bioactive compounds known to have anti-cancer activities. Thus, this review suggests future recommendations for the design and development of improved anticancer drugs with higher efficacy.

Treatment of iodine-containing water by the UV/NH2Cl process: Dissolved organic matters transformation, iodinated trihalomethane formation and toxicity variation

UV/NH2Cl process is becoming increasingly important for water treatment, while its impact on iodine-containing water remains unknown. In this study, the structure transformation of dissolved organic matters (DOMs), generation of iodinated trihalomethanes (I-THMs), and variation of acute toxicity were evaulated during the UV/NH2Cl treatment of iodine-containing water. The combination of exciation emission matrix-parallel factor analysis and two-dimensional correlation spectroscopy integrated with synchronous fluorescence and infrared absorption spectroscopy showed that fulvic-like fraction of DOM was more susceptible to UV/NH2Cl process and particularly iodo and polysaccharide groups gave the fastest resopnses. Consequently, UV fluence lower than 60 mJ/cm2 promoted the production of I-THMs, while excessive UV exhausted NH2Cl and reactive iodine species and subsequently reduced I-THM generation. Moreover, DOM concentration and source, NH2Cl dosage, and I− concentration had significant impacts on I-THM formation in the UV/NH2Cl process. Additionally, a positive correlation was found between acute toxicity variation and I-THM formation when treating iodine-containing waters with UV/NH2Cl. These results together provide a comprehensive understanding on UV/NH2Cl treatment of iodine-containing water.

External Photocatalyst-Free Visible Light-Promoted 1,3-Addition of Perfluoroalkyl Iodides to Vinyldiazoacetates

External Photocatalyst-Free Visible Light-Promoted 1,3-Addition of Perfluoroalkyl Iodides to Vinyldiazoacetates

Pd-Catalyzed ipso,meta-Dimethylation of ortho-Substituted Iodoarenes via a Base-Controlled C-H Activation Cascade with Dimethyl Carbonate as the Methyl Source.

A methyl group can have a profound impact on the pharmacological properties of organic molecules. Hence, developing methylation methods and methylating reagents is essential in medicinal chemistry. We report a palladium-catalyzed dimethylation reaction of ortho-substituted iodoarenes using dimethyl carbonate as a methyl source. In the presence of K2CO3 as a base, iodoarenes are dimethylated at the ipso- and meta-positions of the iodo group, which represents a novel strategy for meta-C-H methylation. With KOAc as the base, subsequent oxidative C(sp3)-H/C(sp3)-H coupling occurs; in this case, the overall transformation achieves triple C-H activation to form three new C-C bonds. These reactions allow expedient access to 2,6-dimethylated phenols, 2,3-dihydrobenzofurans, and indanes, which are ubiquitous structural motifs and essential synthetic intermediates of biologically and pharmacologically active compounds.

Studies in the rearrangement reactions involving camphorquinone.

Skeletal rearrangements of camphor are well-known, however, those involving camphorquinone, its sibling, are rare. We have found that the diol derived from allylated camphorquinone undergoes iodine or bromine mediated deep-seated skeletal rearrangement to provide an interesting tricyclic ring system. The iodo group in the rearranged product provided convenient leverage for further functionalization. For example, it was converted into an azide and the azide was subjected to copper(i) mediated Huisgen 1,3-dipolar cycloaddition with acetylenes to obtain a terpene–triazole conjugate.