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ACS Omega Aug 2023A series of 6-monohalo (Cl, Br, and I) β-cyclodextrin derivatives with various types of methylations were synthesized via a diazotization/nucleophilic displacement...
A series of 6-monohalo (Cl, Br, and I) β-cyclodextrin derivatives with various types of methylations were synthesized via a diazotization/nucleophilic displacement reaction from the corresponding methylated cyclodextrin amines. All four starting compounds (6-amino-6-deoxy derivatives of native β-CD, per-6--methyl-, per-2,3--methyl-, and per-2,3,6--methyl-β-CD) were found to have different reactivities under the same reaction conditions. Unsubstituted and fully per-O-methylated cyclodextrin amines undergo fast transformation, giving lower yields of the monohalogenated product. The selectively methylated cyclodextrin amines react remarkably slower and provide almost complete conversion into the desired monohalogenated compound. A pure product was, in several cases, successfully isolated with simple purification techniques (extraction and precipitation), allowing large-scale preparations. This new method opens the way for preparing poorly investigated monofunctionalized selectively methylated cyclodextrins.
PubMed: 37576619
DOI: 10.1021/acsomega.3c01950 -
Chembiochem : a European Journal of... Aug 2023Aryl diazonium cations are versatile bioconjugation reagents due to their reactivity towards electron-rich aryl residues and secondary amines, but historically their...
Aryl diazonium cations are versatile bioconjugation reagents due to their reactivity towards electron-rich aryl residues and secondary amines, but historically their usage has been hampered by both their short lifespan in aqueous solution and the harsh conditions required to generate them in situ. Triazabutadienes address many of these issues as they are stable enough to endure multiple-step chemical syntheses and can persist for several hours in aqueous solution, yet upon UV-exposure rapidly release aryl diazonium cations under biologically-relevant conditions. This paper describes the synthesis of a novel maleimide-functionalized triazabutadiene suitable for site-selectively installing aryl diazonium cations into proteins at neutral pH; we show reaction with this molecule and a surface-cysteine of a thiol disulfide oxidoreductase. Through photoactivation of the site-selectively installed triazabutadiene motifs, we generate aryl diazonium functionality, which we further derivatize via azo-bond formation to electron-rich aryl species, showcasing the potential utility of this strategy for the generation of photoswitches or protein-drug conjugates.
Topics: Hydrogen-Ion Concentration; Membrane Proteins; Maleimides
PubMed: 37311168
DOI: 10.1002/cbic.202300313 -
Bioinorganic Chemistry and Applications 2023A series of divalent and one trivalent metal chelates of the azo ligand resulting from coupling of sulfafurazole diazonium chloride with resorcinol have been designed...
A series of divalent and one trivalent metal chelates of the azo ligand resulting from coupling of sulfafurazole diazonium chloride with resorcinol have been designed and synthesized. Structure investigation of the isolated chelates have been achieved by applying spectroscopic and analytical tools which collaborated to assure the formation of the metal chelates in the molar ratios of 1L: 1M for Ni(II), Co(II), and Fe(III) chelates, where Cu(II) and Zn(II) complexes formed in the ratio 2L : 1M. The geometrical arrangement around the metal canters was concluded from UV-Vis spectra to be octahedral for all metal chelates. The attachment of the ligand to the metal ions took place through the azo group nitrogen and o-hydroxyl oxygen through proton displacement leading to the ligand being in monobasic bidentate binding mode. Antimicrobial and antitumor activities of the interested compounds have been evaluated against alternative microorganisms and cancer cells, respectively, in a trial to investigate their extent of activity in addition to docking studies. The mode of interaction of the compounds with SS-DNA has been examined by UV-Vis spectra and viscosity studies.
PubMed: 37274083
DOI: 10.1155/2023/2239976 -
Molecules (Basel, Switzerland) Mar 2023The lack of a practical "fit for the purpose" analytical protocol is the main limitation that has hampered the exploitation of the EFSA analytical health claim on the...
Evaluation of Novel Rapid Analytical Methods to Categorize Extra Virgin Olive Oil Based on the Coulometrically Determined Antioxidant Capacity and on the Spectrophotometric Assessment of Phenolic Compounds.
The lack of a practical "fit for the purpose" analytical protocol is the main limitation that has hampered the exploitation of the EFSA analytical health claim on the extra virgin olive oil (EVOO) biophenols, more than ten years since its introduction. In this work, two analytical methods recently developed in our laboratories for categorizing EVOO have been evaluated on a set of 16 samples from Cilento (Campania Region, southern Italy) and compared to other commonly used quality indexes. The Coulometrically Determined Antioxidant Capacity (CDAC) is associated with the component responsible for the health-promoting properties and oxidative stability of EVOO. The Fast Blue BB (FBBB) assay consists of the spectrophotometric (420 nm) determination of biophenols-FBBB diazonium coupling products generated in unfractionated EVOO. The FBBB assay and HPLC-UV reference method provide values highly correlated to each other. Fourteen of sixteen EVOO samples with CDAC > 10 mmol kg and FBBB absorbance > 0.5 had HPLC-determined biophenols > 250 mg kg, and therefore eligible for the EFSA health claim. Consistently, two EVOO samples with HPLC-determined biophenols < 250 mg kg had CDAC values and FBBB absorbance below the respective thresholds. CDAC and FBBB assays are proposed individually or in combination as methods to categorize EVOO samples in alternative to HPLC-UV.
Topics: Olive Oil; Phenols; Principal Component Analysis; Fatty Acids; Antioxidants; Spectrophotometry; Time Factors
PubMed: 37049871
DOI: 10.3390/molecules28073108 -
Food Chemistry. Molecular Sciences Jul 2023Brown seaweeds () are a rich source of polyphenols (up to 20% dry weight) with a structure based on phloroglucinol (1,3,5-trihydroxybenzene). To-date the determination...
Brown seaweeds () are a rich source of polyphenols (up to 20% dry weight) with a structure based on phloroglucinol (1,3,5-trihydroxybenzene). To-date the determination of total phenolics content (TPC) involves a redox reaction with the Folin-Ciocalteu (FC) reagent. However, side reactions with other reducing substances preclude accurate, direct measurement of TPC. This research reports a novel microplate assay involving a coupling reaction between phloroglucinol with Fast Blue BB (FBBB) diazonium salt, at basic pH, to form a stable tri-azo complex with maximum absorbance at 450 nm. Linear regression correlation values (R) were ≥0.99 with phloroglucinol as standard. Direct quantification of TPCs (phloroglucinol equivalents, PGEs) in crude aqueous and ethanolic extracts from demonstrated that the new FBBB assay is not subject to side-redox interference and provides a more accurate estimate of TPC (1.2-3.9-fold lower than with the FC assay) in a relatively rapid (30 min), cost-effective (0.24€/test) microplate format.
PubMed: 36875799
DOI: 10.1016/j.fochms.2023.100166 -
Materials (Basel, Switzerland) Feb 2023Water-soluble azo derivatives of lignin were synthesized by the azo coupling reaction using organosolv ethanol lignin and diazonium salts based on sulfanilic acid and...
Water-soluble azo derivatives of lignin were synthesized by the azo coupling reaction using organosolv ethanol lignin and diazonium salts based on sulfanilic acid and p-nitroaniline. The structure of azo derivatives of lignin were studied by nuclear magnetic resonance, Fourier-transform infrared spectroscopy, and gel permeation chromatography. It was found that the azobenzene bonds formed in the azo coupling reaction of macromolecules impart the photosensitive properties to the synthesized polymers via cis-trans photoisomerization of the diazobenzene group. It was shown experimentally that the synthesized polymers exhibited good solubility both in the aqueous media in a wide (2-12) pH range and in DMSO and THF organic solvents, which opens up new prospects for their application.
PubMed: 36837154
DOI: 10.3390/ma16041525 -
Molecules (Basel, Switzerland) Feb 2023In materials (polymer) science and medicinal chemistry, heteroaromatic derivatives play the role of the central skeleton in development of novel devices and discovery of... (Review)
Review
In materials (polymer) science and medicinal chemistry, heteroaromatic derivatives play the role of the central skeleton in development of novel devices and discovery of new drugs. On the other hand, (3-trifluoromethyl)phenyldiazirine (TPD) is a crucial chemical method for understanding biological processes such as ligand-receptor, nucleic acid-protein, lipid-protein, and protein-protein interactions. In particular, use of TPD has increased in recent materials science to create novel electric and polymer devices with comparative ease and reduced costs. Therefore, a combination of heteroaromatics and (3-trifluoromethyl)diazirine is a promising option for creating better materials and elucidating the unknown mechanisms of action of bioactive heteroaromatic compounds. In this review, a comprehensive synthesis of (3-trifluoromethyl)diazirine-substituted heteroaromatics is described.
Topics: Photoaffinity Labels; Diazomethane; Chemistry, Pharmaceutical; Proteins; Nucleic Acids
PubMed: 36771073
DOI: 10.3390/molecules28031408 -
Molecules (Basel, Switzerland) Jan 2023SARS-CoV-2 M is a chymotrypsin-like cysteine protease playing a relevant role during the replication and infectivity of SARS-CoV-2, the coronavirus responsible for...
SARS-CoV-2 M is a chymotrypsin-like cysteine protease playing a relevant role during the replication and infectivity of SARS-CoV-2, the coronavirus responsible for COVID-19. The binding site of M is characterized by the presence of a catalytic Cys145 which carries out the hydrolytic activity of the enzyme. As a consequence, several M inhibitors have been proposed to date in order to fight the COVID-19 pandemic. In our work, we designed, synthesized and biologically evaluated , a novel inhibitor of SARS-CoV-2 M bearing a trifluoromethyl diazirine moiety. displayed in vitro inhibition activity against SARS-CoV-2 M at a low micromolar level (IC = 4.1 μM) in a FRET-based assay. Moreover, an inhibition assay against PL revealed lack of inhibition, assuring the selectivity of the compound for the M. Furthermore, the target compound was docked within the binding site of the enzyme to predict the established intermolecular interactions in silico. was subsequently tested on the HCT-8 cell line to evaluate its effect on human cells' viability, displaying good tolerability, demonstrating the promising biological compatibility and activity of a trifluoromethyl diazirine moiety in the design and development of SARS-CoV-2 M binders.
Topics: Antiviral Agents; Diazomethane; Molecular Docking Simulation; Protease Inhibitors; SARS-CoV-2
PubMed: 36677572
DOI: 10.3390/molecules28020514 -
Philosophical Transactions of the Royal... Feb 2023Non-ribosomal peptide synthetases (NRPSs) biosynthesize many pharmaceuticals and virulence factors. The biosynthesis of these natural peptide products from biosynthetic...
Non-ribosomal peptide synthetases (NRPSs) biosynthesize many pharmaceuticals and virulence factors. The biosynthesis of these natural peptide products from biosynthetic gene clusters depends on complex regulations in bacteria. However, our current knowledge of NRPSs is based on enzymological studies using full NRPS systems and/or a single NRPS domain in heterologous hosts. Chemical and/or biochemical strategies to capture the endogenous activities of NRPSs facilitate studies on NRPS cell biology in bacterial cells. Here, we describe a chemical scaffold for the rapid and selective photoaffinity labelling of NRPSs in purified systems, crude biological samples and living bacterial cells. We synthesized photoaffinity labelling probes coupled with 5'--(phenylalanyl)sulfamoyladenosine with clickable alkyl diazirine or trifluoromethyl phenyl diazirine. We found that a trifluoromethyl phenyl diazirine-based probe cross-linked the Phe-activating domain of a GrsA-NRPS with high selectivity and sensitivity at shorter ultraviolet (UV) irradiation times (less than 5 min) relative to a prototypical benzophenone-based probe. Our results demonstrated that this quick labelling protocol can prevent damage to proteins and cells caused by long UV irradiation times, providing a mild photoaffinity labelling method for biological samples. This article is part of the theme issue 'Reactivity and mechanism in chemical and synthetic biology'.
Topics: Diazomethane; Bacteria; Peptide Synthases; Multigene Family
PubMed: 36633280
DOI: 10.1098/rstb.2022.0026 -
RSC Advances Dec 2022Cinnamic acids are an important class of phenolic compounds, which have many beneficial effects on human health but are also interesting synthetic intermediates thanks...
Cinnamic acids are an important class of phenolic compounds, which have many beneficial effects on human health but are also interesting synthetic intermediates thanks to the presence of several reactive sites. While studying the reactivity of cinnamic acids with diazonium salts from aromatic amines, an unexpected reactivity has been discovered, leading to the formation of 1,2-diaza-1,3-dienes instead of traditional diazo-coupling products. The new compounds have been fully characterized by mono and bidimensional NMR spectroscopy and mass spectrometry. Preliminary studies on the biological activity of the compounds have been carried out testing both their antibacterial and antitumor activity, leading to promising results.
PubMed: 36605622
DOI: 10.1039/d2ra07515f