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Journal of Flow Chemistry 2024Azo compounds find use in many areas of science, displaying crucial properties for important applications as photoconductive organic pigments, fluorescent quenchers,... (Review)
Review
Azo compounds find use in many areas of science, displaying crucial properties for important applications as photoconductive organic pigments, fluorescent quenchers, paints, cosmetics, inks, and in the large and valuable dye industry. Due to the unstable intermediates, and the exothermic and fast reactions used in their synthesis, high value azo compounds are excellent candidates for continuous flow manufacturing. This comprehensive review covers the progress made to date on developing continuous flow systems for azo synthesis and reflects on the main challenges still to be addressed, including scale up, conversion, product purity, and environmental impact. The further development of integrated continuous flow processes has the potential to help tackle these challenges and deliver improved methods for azo compound generation.
PubMed: 38882391
DOI: 10.1007/s41981-024-00307-2 -
Chemistry (Weinheim An Der Bergstrasse,... Jun 2024The photocatalytic C-N borylation and C-H arylation mostly depend on the ruthenium and iridium complexes or eosin Y and the use of porphyrin catalysts is still in...
The photocatalytic C-N borylation and C-H arylation mostly depend on the ruthenium and iridium complexes or eosin Y and the use of porphyrin catalysts is still in infancy. A series of novel 21-thiaporphyrins (A2B2 and A3B type) were synthesized having carbazole/phenothiazine moieties at their meso-positions and screened as catalysts for C-N borylation and C-H arylation. This paper demonstrates the 21-thiaporphyrin catalyzed C-N borylation and het-arylation of anilines under visible light. The method utilizes only 0.1 mol% of 21-thiaporphyrin catalyst under blue light for the direct C-N borylation and het-arylation reactions. A variety of substituted anilines were used as source for expensive and unstable aryl diazonium salts in the reactions. The heterobiaryls and aryl boronic esters were obtained in decent yields (up to 88%). Versatility of the 21-thiaporphyrin catalyst was tested by thiolation and selenylation of anilines under similar conditions. Mechanistic insight was obtained from DFT studies, suggesting that 21-thiaporphyrin undergo an oxidative quenching pathway. The photoredox process catalyzed by 21-thiaporphyrins offers a mild, efficient and metal-free alternative for the formation of C-C, C-S, and C-Se bonds in aryl compounds; it can also be extended to borylation reaction.
PubMed: 38825798
DOI: 10.1002/chem.202401623 -
Chemical Research in Toxicology Jun 2024Nitrosamines are in the cohort of concern (CoC) as determined by regulatory guidance. CoC compounds are considered highly potent carcinogens that need to be limited...
Nitrosamines are in the cohort of concern (CoC) as determined by regulatory guidance. CoC compounds are considered highly potent carcinogens that need to be limited below the threshold of toxicological concern, 1.5 μg/day. Nitrosamines like NDMA and NDEA require strict control, while novel nitrosamine drug substance-related impurities (NDSRIs) may or may not be characterized as potent carcinogens. A risk assessment based on the structural features of NDSRIs is important in order to predict potency because they lack substance-specific carcinogenicity. Herein, we present a quantum mechanical (QM)-based analysis on structurally diverse sets of nitrosamines to better understand how structure influences the reactivity that could result in carcinogenicity. We describe the potency trend through activation energies corresponding to α-hydroxylation, aldehyde formation, diazonium intermediate formation, reaction with DNA base, and hydrolysis reactions, and other probable metabolic pathways associated with the carcinogenicity of nitrosamines. We evaluated activation energies for selected cases such as -nitroso pyrrolidines, -nitroso piperidines, -nitroso piperazines, -nitroso morpholines, -nitroso thiomorpholine, -methyl nitroso aromatic, fluorine-substituted nitrosamines, and substituted aliphatic nitrosamines. We compare these results to the recent framework of the carcinogenic potency characterization approach (CPCA) proposed by health authorities which is meant to give guidance on acceptable intakes (AI) for NDSRIs lacking substance-specific carcinogenicity data. We show examples where QM modeling and CPCA are aligned and examples where CPCA both underestimates and overestimates the AI. In cases where CPCA predicts high potency for NDSRIs, QM modeling can help better estimate an AI. Our results suggest that a combined mechanistic understanding of α-hydroxylation, aldehyde formation, hydrolysis, and reaction with DNA bases could help identify the structural features that underpin the potency of nitrosamines. We anticipate this work will be a valuable addition to the CPCA and provide a more analytical way to estimate AI for novel NDSRIs.
Topics: Nitrosamines; Quantum Theory; Carcinogens; Molecular Structure; Humans
PubMed: 38804898
DOI: 10.1021/acs.chemrestox.4c00087 -
Molecules (Basel, Switzerland) May 20241-(3-aryl)-3-(dimethylamino)prop-2-en-1-one (enaminones) derivatives and the diazonium salt of -chloroaniline were used to synthesize several novel disperse azo dyes...
1-(3-aryl)-3-(dimethylamino)prop-2-en-1-one (enaminones) derivatives and the diazonium salt of -chloroaniline were used to synthesize several novel disperse azo dyes with high yield and the use of an environmentally friendly approach. At 100 and 130 °C, we dyed polyester fabrics using the new synthesized disperse dyes. At various temperatures, the dyed fabrics' color intensity was assessed. The results we obtained showed that dyeing utilizing a high temperature method at 130 °C was enhanced than dyeing utilizing a low temperature method at 100 °C. Reusing dye baths once or twice was a way to achieve two goals at the same time. The first was obtaining a dyed product at no cost, and the second was a way to treat the wastewater of dyeing bath effluents and reuse it again. Good results were obtained for the fastness characteristics of polyester dyed with disperse dyes. When the disperse dyes were tested against certain types of microbes and cancer cells, they demonstrated good and encouraging findings for the potential to be used as antioxidants and antimicrobial agents.
Topics: Polyesters; Coloring Agents; Textiles; Humans; Anti-Infective Agents; Azo Compounds; Microbial Sensitivity Tests
PubMed: 38792089
DOI: 10.3390/molecules29102227 -
Organic & Biomolecular Chemistry May 2024The Lewis acid mediated reaction of allyltributylstannane compounds with β-hydroxy-α-diazo carbonyls gives β-allyl-α-diazo carbonyl products in good yields. This...
The Lewis acid mediated reaction of allyltributylstannane compounds with β-hydroxy-α-diazo carbonyls gives β-allyl-α-diazo carbonyl products in good yields. This reaction proceeds a vinyl diazonium ion intermediate which is intercepted by the allylstannane nucleophile. Importantly, the diazo functional group is retained over the course of the reaction to give diazo-containing scaffolds with increased molecular complexity. Methallyltrimethylsilane also serves as a functional allyl transfer reagent in this reaction.
PubMed: 38747167
DOI: 10.1039/d4ob00254g -
Molecular Diversity May 2024In the present work, we successfully synthesized Se-alkyl selenopyridines 1 and 3, selenopheno[2,3-b]pyridine 2, and bis-selenopyridine 4 derivatives using an...
In the present work, we successfully synthesized Se-alkyl selenopyridines 1 and 3, selenopheno[2,3-b]pyridine 2, and bis-selenopyridine 4 derivatives using an eco-friendly method by utilizing NaHSe instead of toxic hydrogen selenide. The effect of the temperature on the reaction was screening at various temperatures. The regiospecific reaction of selenopyridine 1 with bromine afforded an unexpected product 4,6-diamino-5-bromo-2-[(cyanomethyl)selenyl]-pyridine-3-carbonitrile (5), which was cyclized to selenopheno[2,3-b]pyridine (7) by refluxing in the presence of TEA. While its treatment with thiophenol and/or p-chlorothiophenol gave 8a, b. On the other hand, its reaction with aminothiophenol afforded 2-(benzo[d]-thiazol-2-yl)-5-bromoselenopheno[2,3-b]pyridine-3,4,6-triamine (9). Also, N-(2-cyano-4-methyl-5H-1-seleno-3,5,8-triazaacenaphthylen-7-yl)acetamide (11) and a novel series of selenoazo dyes 12a-d were synthesized by treatment of selenopheno[2,3-b]pyridine 2 with acetic anhydride and/or diazonium chlorides of aromatic amines, respectively. Then, we ascertained the potential activity of synthesized compounds against highly metastatic prostate cancer cells (PC-3) and osteosarcoma cells (MG-63) and found that 12a, 12b, 12c, and 12d were more cytotoxic than doxorubicin in both tested cell lines, showing nearly the same anticancer activity with IC values ranging from 2.59 ± 0.02 µM to 3.93 ± 0.23 µM. Mechanistically, the most potent compounds 12a and 12b proved to be potent EGFR inhibitors with IC values of 0.301 and 0.123 µM, respectively, compared to lapatinib as a positive reference (IC = 0.049 µM). Moreover, the docking results are in good agreement with the anticancer activity as well as the EGFR inhibitory activity, suggesting these two compounds as promising EGFR anticancer candidates.
PubMed: 38739230
DOI: 10.1007/s11030-024-10872-2 -
Journal of the American Chemical Society May 2024Peptide-receptor interactions play critical roles in a wide variety of physiological processes. Methods to link bioactive peptides covalently to unmodified receptors on...
Peptide-receptor interactions play critical roles in a wide variety of physiological processes. Methods to link bioactive peptides covalently to unmodified receptors on the surfaces of living cells are valuable for studying receptor signaling, dynamics, and trafficking and for identifying novel peptide-receptor interactions. Here, we utilize peptide analogues bearing deactivated aryl diazonium groups for the affinity-driven labeling of unmodified receptors. We demonstrate that aryl diazonium-bearing peptide analogues can covalently label receptors on the surface of living cells using both the neurotensin and the glucagon-like peptide 1 receptor systems. Receptor labeling occurs in the complex environment of the cell surface in a sequence-specific manner. We further demonstrate the utility of this covalent labeling approach for the visualization of peptide receptors by confocal fluorescence microscopy and for the enrichment and identification of labeled receptors by mass spectrometry-based proteomics. Aryl diazonium-based affinity-driven receptor labeling is attractive due to the high abundance of tyrosine and histidine residues susceptible to azo coupling in the peptide binding sites of receptors, the ease of incorporation of aryl diazonium groups into peptides, and the relatively small size of the aryl diazonium group. This approach should prove to be a powerful and relatively general method to study peptide-receptor interactions in cellular contexts.
Topics: Diazonium Compounds; Humans; Receptors, Peptide; Peptides; Animals
PubMed: 38693710
DOI: 10.1021/jacs.4c04672 -
Science and Technology of Advanced... 2024Electrochemical grafting of organic molecules to metal surfaces has been well-known as an efficient tool enabling tailored modification of surface at the nanoscale....
Electrochemical grafting of organic molecules to metal surfaces has been well-known as an efficient tool enabling tailored modification of surface at the nanoscale. Among many compounds with the ability to undergo the process of electrografting, iodonium salts belong to less frequently used, especially when compared with the most popular diazonium salts. Meanwhile, due to their increased stability, iodonium salts may be used in situations where the use of diazonium salts is constrained. The aim of this study was to examine the effect of the electrochemical reduction of iodonium salts on the physicochemical properties of Pt electrodes, and the possibility to form pro-adhesive layers facilitating further functionalization purposes. Consequently, we have selected four commercially available iodonium salts (diphenyliodonium chloride, bis(4-tertbutylphenyl)iodonium hexafluorophosphate, (4-nitrophenyl)(2,4,6-trimethylphenyl)iodonium triflate, bis(4-methylphenyl)iodonium hexafluorophosphate), and attached them to the surface of Pt electrodes by means of an electrochemical reduction process. As-formed layers were then extensively characterized in terms of wettability, roughness and charge transfer properties, and used as pro-adhesive coatings prior to the deposition of poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate), PEDOT:PSS. Due to the increase in hydrophilicity and roughness, modified electrodes increased the stability of PEDOT:PSS coating while maintaining its high capacitance.
PubMed: 38680949
DOI: 10.1080/14686996.2024.2338786 -
Journal of the American Chemical Society May 2024MicroRNAs (miRNAs) play indispensable roles in post-transcriptional gene regulation. The identification of target mRNAs is essential for dissecting the recognition...
MicroRNAs (miRNAs) play indispensable roles in post-transcriptional gene regulation. The identification of target mRNAs is essential for dissecting the recognition basis, dynamics, and regulatory mechanism of miRNA-mRNA interactions. However, the lack of an unbiased method for detecting weak miRNA-mRNA interactions remains a long-standing obstacle for miRNA research. Here, we develop and provide proof-of-concept evidence demonstrating a chemical G-clamp-enhanced photo-cross-linking strategy for covalent capture of intracellular miRNA targets in different cell lines. This approach relies on an yl-dizirine--clamp-mdified-ucleoside (ARAGON) miRNA probe containing an alkynyl group that improves the thermal stability of miRNA-target mRNA duplex molecules and can rapidly cross-link with the complementary strand upon UV 365 nm activation, enhancing the transient capture of mRNA targets. After validating the accuracy and binding properties of ARAGON-based miRNA probes through the successful enrichment for the known targets of miR-106a, miR-21, and miR-101, we then extend ARAGON's application to screen for previously unknown targets of different miRNAs in various cell lines. Ultimately, results in this study uncover GAB1 as a target of miR-101 in H1299 lung cancer cells and show that miR-101 silencing of GAB1 can promote apoptosis in H1299 cells, suggesting an oncogenic mechanism of GAB1. This study thus provides a powerful and versatile tool for enhanced screening of global miRNA targets in cells to facilitate investigations of miRNA functions in fundamental cellular processes and disease pathogenesis.
Topics: MicroRNAs; Humans; Photochemical Processes; RNA, Messenger; Diazomethane; Cross-Linking Reagents; Cell Line, Tumor; Ultraviolet Rays
PubMed: 38679963
DOI: 10.1021/jacs.4c02901 -
Journal of the American Chemical Society Apr 2024Substituting precious elements in luminophores and photocatalysts by abundant first-row transition metals remains a significant challenge, and iron continues to be...
Substituting precious elements in luminophores and photocatalysts by abundant first-row transition metals remains a significant challenge, and iron continues to be particularly attractive owing to its high natural abundance and low cost. Most iron complexes known to date face severe limitations due to undesirably efficient deactivation of luminescent and photoredox-active excited states. Two new iron(III) complexes with structurally simple chelate ligands enable straightforward tuning of ground and excited state properties, contrasting recent examples, in which chemical modification had a minor impact. Crude samples feature two luminescence bands strongly reminiscent of a recent iron(III) complex, in which this observation was attributed to dual luminescence, but in our case, there is clear-cut evidence that the higher-energy luminescence stems from an impurity and only the red photoluminescence from a doublet ligand-to-metal charge transfer (LMCT) excited state is genuine. Photoinduced oxidative and reductive electron transfer reactions with methyl viologen and 10-methylphenothiazine occur with nearly diffusion-limited kinetics. Photocatalytic reactions not previously reported for this compound class, in particular the C-H arylation of diazonium salts and the aerobic hydroxylation of boronic acids, were achieved with low-energy red light excitation. Doublet-triplet energy transfer (DTET) from the luminescent LMCT state to an anthracene annihilator permits the proof of principle for triplet-triplet annihilation upconversion based on a molecular iron photosensitizer. These findings are relevant for the development of iron complexes featuring photophysical and photochemical properties competitive with noble-metal-based compounds.
PubMed: 38598280
DOI: 10.1021/jacs.4c00605