Search Results (67)

The complex of hypofluorous acid with acetonitrile—HOF•CH₃CN—is the only substance possessing a truly electrophilic oxygen. This fact makes it the only tool suitable for transferring oxygen atoms to sites that are not accessible to this vital element. We will review here most of the known organic reactions with this complex, which is easily made by bubbling dilute fluorine through aqueous acetonitrile. The reactions of HOF•CH₃CN with double bonds produce epoxides in a matter of minutes at room temperature, even when the olefin is electron-depleted and cannot be epoxidized by any other means. The electrophilic oxygen can also substitute deactivated tertiary C-H bonds via electrophilic substitution, proceeding with full retention of configuration. Using this complex enables transferring oxygen atoms to a carbonyl and oxidizing alcohols and ethers to ketones. The latter could be oxidized to esters via the Baeyer–Villiger reaction, proving once again the validity of the original Baeyer mechanism. Azines are usually avoided as protecting groups for carbonyl since their removal is problematic. HOF•CH₃CN solves this problem, as it is very effective in recreating carbonyls from the respective azines. A bonus of the last reaction is the ability to replace the common ¹⁶O isotope of the carbonyl with the heavier ¹⁷O or ¹⁸O in the simplest and cheapest possible way. The reagent can transfer oxygen to most nitrogen-containing molecules. Thus, it turns practically any azide or amine into nitro compounds, including amino acids. This helps to produce novel α-alkylamino acids. It also attaches oxygen atoms to most tertiary nitrogen atoms, including certain aromatic ones, which could not be obtained before. HOF•CH₃CN was also used to make five-member cyclic poly-NO derivatives, many of them intended to be highly energetic materials. The nucleophilic sulfur atom also reacts very smoothly with the reagent in a wide range of compounds to form sulfone derivatives. While common sulfides are easily converted to sulfones by many orthodox reagents, electron-depleted ones, such as R_f-S-Ar, can be oxidized to R_f-SO₂-Ar only with this reagent. The mild reaction conditions also make it possible to synthesize a whole range of novel episulfones and offer, as a bonus, a very easy way to make S^xO₂, x being any isotope variation of oxygen. These mild conditions also helped to oxidize thiophene to thiophen-S,S-dioxide without the Diels–Alder dimerizations, which usually follow such dioxide formation. The latter reaction was a prelude to a series of preparations of [all]-S,S-dioxo-oligothiophenes, which are important for the efficient preparation of active layers in field-effect transistors (FETs), as such oligomers are considered to be important for organic semiconductors for light-emitting diodes (LEDs). Several types of these oligothiophenes were prepared, including partly or fully oxygenated ones, star-oligothiophenes, and fused ones. Several [all]-S,S-dioxo-oligo-thienylenevinylenes were also successfully prepared despite the fact that they also possess carbon–carbon p centers in their molecules. All oxygenated derivatives have been prepared for the first time and have lower HOMO-LUMO gaps compared to their parent compounds. HOF•CH₃CN was also used to oxidize the surface of the nanoparticles of oligothiophenes, leaving the core of the nanoparticle unchanged. Several highly interesting features have been detected, including their ability to photostimulate the retinal neurons, especially the inner retinal ones. HOF•CH₃CN was also used on elements other than carbon, such as selenium and phosphor. Various selenides were oxidized to the respective selenodioxide derivatives (not a trivial task), while various phosphines were converted efficiently to the corresponding phosphine oxides. Full article

New secondary alcohols of type Ar-CHOH-hetaryl and MeCHOH-hetaryl, the radical hetaryl being a pyrroloazine, were investigated in solid state by X-ray single-crystal diffraction analysis, Hirshfeld analysis and DFT methods to assess their crystallographic features. One of the most important features is the presence of the hydroxyl group bonded to an asymmetric carbon atom which was involved in strong hydrogen bonds. The driving force of crystal packing is H-bond with the O-H···O=C/N≡C bonds being considered as strong comparative to carboxylic acids. These structural properties and binding affinity might lead to enhanced bioavailability of these particular pyrrolo-azines Full article

Azine compounds have recently gained significant attention due to the interesting properties that they display, which could be relevant in fields such as Pharmacology and Material Sciences. These types of ligands stand out in Coordination Chemistry because of the facilities that they exhibit that make it easy to coordinate transition and post-transition metal ions. Furthermore, to the azine skeleton (C=N-N=C), the addition of other donor atoms such as sulfur, oxygen or phosphorus in the ligand increases the coordination possibilities. In this sense, we are interested in azine ligands as precursors of novel metallosupramolecular architectures. The research herein reported is focused on the synthesis and characterization of a potentially tetradentate [P₂O₂] organic phosphine-azine ligand (LP). The addition of the phosphine group to the azine skeleton allows for the stabilization of soft metal ions and the assembly of functional structures. The azine ligand LP⁸ has been prepared by a condensation reaction between two equivalents of (diphenylphosphino)benzaldehyde and one equivalent of azine monohydrate, and it was fully characterized by using several techniques such as elemental analysis, mass spectrometry, infrared spectroscopy, ¹H NMR spectroscopy and X-ray diffraction. Full article

1,2,3,4,5-pentathiepines (PTEs) are naturally occurring polysulfides of increasing scientific interest based on their identified pharmacological activities. Artificial PTEs with N-heterocyclic backbones are efficiently synthesized via mediation by a molybdenum–oxo-bistetrasulfido complex. A common feature of all precursor alkynes successfully used to date in this reaction is the presence of a –CH(OEt)₂ group since the previously postulated mechanism requires the presence of one OEt^– as the leaving group, and the second must become a transient ethoxonium moiety. This raised the question of whether there really is a need for two, maybe only one, or possibly even zero ethoxy substituents. This research problem was systematically addressed by respective variations in the precursor-alkyne derivatives and by employing one related allene species. It was found that the total absence of ethoxy substituents prevents the formation of PTEs entirely, while the presence of a single ethoxy group results in the possibility to distinctly functionalize the position on the resulting N-heterocyclic pyrrole five ring in the target compound. This position was previously exclusively occupied by an –OEt for all products of the molybdenum-mediated reaction. The allene was applied with similar success as precursor as with the related alkyne. The now-employable significant change in precursor composition gives access to a whole new PTE subfamily, allowing further modulation of (physico)-chemical properties such as solubility, and provides additional insight into the mechanism of PTE formation; it comprises a merely partial validation of the previous hypothesis. The new alkyne precursors and pentathiepines were characterized by a variety of instrumental analyses (NMR, mass spec, UV–vis) and in six cases (one alkyne precursor, one unexpected side product, and four PTEs) by single-crystal X-ray diffraction. Syntheses, isolation procedures, analytical data, and the impact of the findings on the previously proposed mechanism are described in detail herein. Full article

Borane–trimethylamine complex (Me₃N·BH₃; BTM) is the most stable of the amine–borane complexes that are commercially available, and it is cost-effective. It is a valuable reagent in organic chemistry with applications in the reduction of carbonyl groups and carbon–nitrogen double bond reduction, with considerable examples in the reduction of oximes, hydrazones and azines. The transfer hydrogenation of aromatic N-heterocycles and the selective N-monomethylation of primary anilines are further examples of recent applications, whereas the reduction of nitrobenzenes to anilines and the reductive deprotection of N-tritylamines are useful tools in the organic synthesis. Moreover, BTM is the main reagent in the regioselective cleavage of cyclic acetals, a reaction of great importance for carbohydrate chemistry. Recent innovative applications of BTM, such as CO₂ utilization as feedstock and radical chemistry by photocatalysis, have extended their usefulness in new reactions. The present review is focused on the applications of borane–trimethylamine complex as a reagent in organic synthesis and has not been covered in previous reviews regarding amine–borane complexes. Full article

The use of privileged scaffolds as a starting point for the construction of libraries of bioactive compounds is a widely used strategy in drug discovery and development. Scaffold decoration, morphing and hopping are additional techniques that enable the modification of the chosen privileged framework and better explore the chemical space around it. In this study, two series of highly functionalized pyrimidine and pyridine derivatives were synthesized using a scaffold morphing approach consisting of triazine compounds obtained previously as antiviral agents. Newly synthesized azines were evaluated against lymphoma, hepatocarcinoma, and colon epithelial carcinoma cells, showing in five cases acceptable to good anticancer activity associated with low cytotoxicity on healthy fibroblasts. Finally, ADME in vitro studies were conducted on the best derivatives of the two series showing good passive permeability and resistance to metabolic degradation. Full article

The reactivity of the complex [(dpp-bian)GaNa(DME)₂] (1) (dpp-bian = 1,2-bis[(2,6-di-isopropylphenyl)imino]acenaphthene) towards isocyanates, benzophenone, diphenylketene, and 1,2-dibenzylidenehydrazine has been studied. Treatment of 1 with isocyanates led to derivatives of imidoformamide [(dpp-bian)Ga{C(=NPh)₂}₂–NPh][Na(DME)₃] (2), biuret [(dpp-bian)Ga(NCy)₂(CO)₂NCy][Na(DME)] (3), or carbamic acids [(dpp-bian)GaN(Cy)C(O)O]₂[Na(THF)(Et₂O)] (4), [(dpp-bian)GaC(=NCy)N(Cy)C(O)O][Na(Py)₃] (5). Treatment of 1 with 2 equiv. of Ph₂CO resulted in gallium pinacolate [(dpp-bian)GaO(CPh₂)₂O][Na(Py)₂] (9), while the reaction of 1 with 2 equiv. Ph₂CCO gave divinyl ether derivative [(dpp-bian)Ga{C(=CPh₂)O}₂][Na(DME)₃] (10). Complex 1 treated with 2 equiv. 1,2-dibenzylidenehydrazine underwent [1+2+2] cycloaddition to give C–C coupling product [(dpp-bian)Ga{N(NCHPh)}₂(CHPh)₂][Na(DME)₃] (11). When complex 1 was sequentially treated with 1 equiv. of 1,2-dibenzylidenehydrazine and 1 equiv. of pyridine or pyridine-d5; it gave [1+2+2] cycloaddition product [(dpp-bian)GaN(NCHPh)C(Ph)CN][Na(DME)₃] (12). Compounds 2–12 were characterized by NMR and IR spectroscopy, and their molecular structures were established by single-crystal X-ray diffraction analysis. Full article

A series of hydrazones, azoles, and azines bearing a 4-dimethylaminophenyl-5-oxopyrrolidine scaffold was synthesized. Their cytotoxic effect against human pancreatic carcinoma Panc-1 and triple-negative breast cancer MDA-MB-231 cell lines was established by MTT assay. Pyrrolidinone derivatives 3c and 3d, with incorporated 5-chloro and 5-methylbenzimidazole fragments; hydrazone 5k bearing a 5-nitrothien-2-yl substitution; and hydrazone 5l with a naphth-1-yl fragment in the structure significantly decreased the viability of both cancer cell lines. Compounds 3c and 5k showed the highest selectivity, especially against the MDA-MB-231 cancer cell line. The EC₅₀ values of the most active compound 5k against the MDA-MB231 cell line was 7.3 ± 0.4 μM, which were slightly higher against the Panc-1 cell line (10.2 ± 2.6 μM). Four selected pyrrolidone derivatives showed relatively high activity in a clonogenic assay. Compound 5k was the most active in both cell cultures, and it completely disturbed MDA-MB-231 cell colony growth at 1 and 2 μM and showed a strong effect on Panc-1 cell colony formation, especially at 2 μM. The compounds did not show an inhibitory effect on cell line migration by the ‘wound-healing’ assay. Compound 3d most efficiently inhibited the growth of Panc-1 spheroids and reduced cell viability in MDA-MB-231 spheroids. Considering these different activities in biological assays, the selected pyrrolidinone derivatives could be further tested to better understand the structure–activity relationship and their mechanism of action. Full article

In order to look for the origins of tautomeric preferences in neutral creatinine in vacuo, we examined prototropic conversions for model azoles, namely mono-hydroxy and mono-amino imidazoles, and also for their selected 1-methyl derivatives. All possible isomeric forms of creatinine and model compounds, resulting from intramolecular proton transfer (prototropy), conformational isomerism about –OH, and configurational isomerism about =NH, were studied in the gas phase (model of non-polar environment) by means of quantum-chemical methods. Because the bond-length alternation is a consequence of the resonance phenomenon, it was measured for all DFT-optimized structures by means of the harmonic oscillator model of electron delocalization (HOMED) index. Important HOMED analogies were discussed for investigated azoles and compared with those for previously studied cyclic azines, including pyrimidine nucleic acid bases. The internal effects were taken into account, and the stabilities of the investigated tautomers-rotamers were analyzed. Significant conclusions on the favored factors that can dictate the tautomeric preferences in creatinine were derived. Full article

In primary Sjögren’s syndrome (pSS) patients, salivary gland (SG) epithelial cells (SGECs) could be exposed to chronic hyperosmotic stress (HOS), consecutive to their destruction and deregulation, that exacerbates an inflammatory response. The aims of this study were to assess the mechanism accounting for C-C motif chemokine ligand 2 (CCL2) expression in an immortalized human salivary gland epithelial acinar cell line (NS-SV-AC) subjected to HOS, as well as the involvement of CCL2 in pSS. CCL2 mRNA and protein levels were determined via RT-qPCR and ELISA. Reporter plasmids and a promoter pull-down assay were used to identify transcription factors associated with CCL2 mRNA increase. Our data showed that HOS-induced CCL2 mRNA increase was independent of the nuclear factor of activated T-cells 5 (NFAT5) and nuclear factor-kappa B (NFkB) but involved Kruppel-like factor 5 (KLF5). CCL2 protein levels, quantified by enzyme-linked immunosorbent assay (ELISA) in sera samples from pSS patients, correlated with the European Alliance of Associations for Rheumatology’s Sjogren’s syndrome disease activity index (ESSDAI) score for systemic activity. In addition, CCL2 protein levels were higher in patients with biological activity, cutaneous manifestations, and ESSDAI score superior or equal to five. Our data suggest that chronic HOS could exacerbate pSS disease by contributing to the inflammatory process induced by the expression and secretion of CCL2. Full article

An efficient, economical, and green, sustainable synthesis of fused azines using Mg-Al hydrotalcite under a high-pressure Q-Tube reactor has been developed. This reaction proceeds through the aza-Michael addition of α,β-unsaturated ketone with different aminoazoles. This method offered excellent yields in a short reaction time that economically saved energy in addition to the protocol showing the reuse of the catalyst seven times without losing its catalytic activity. Full article

In this review, the complete tautomeric equilibria are derived for disubstituted pyrimidine nucleic acid bases starting from phenol, aniline, and their model compounds—monosubstituted aromatic azines. The differences in tautomeric preferences for isolated (gaseous) neutral pyrimidine bases and their model compounds are discussed in light of different functional groups, their positions within the six-membered ring, electronic effects, and intramolecular interactions. For the discussion of tautomeric preferences and for the analysis of internal effects, recent quantum-chemical results are taken into account and compared to some experimental ones. For each possible tautomer-rotamer of the title compounds, the bond length alternation, measured by means of the harmonic oscillator model of electron delocalization (HOMED) index, is examined. Significant HOMED similarities exist for mono- and disubstituted derivatives. The lack of parallelism between the geometric (HOMED) and energetic (ΔG) parameters for all possible isomers clearly shows that aromaticity is not the main factor that dictates tautomeric preferences for pyrimidine bases, particularly for uracil and thymine. The effects of one-electron loss (positive ionization) and one-electron gain (negative ionization) on prototropy and bond length alternation are also reviewed for pyrimidine bases and their models. Full article

Canine lymphoma (CL) is one of the most common malignant tumors in dogs. The cause of CL remains unclear. Genetic mutations that have been suggested as possible causes of CL are not fully understood. Whole-exome sequencing (WES) is a time- and cost-effective method for detecting genetic variants targeting only the protein-coding regions (exons) that are part of the entire genome region. A total of eight patients with B-cell lymphomas were recruited, and WES analysis was performed on whole blood and lymph node aspirate samples from each patient. A total of 17 somatic variants (GOLIM4, ITM2B, STN1, UNC79, PLEKHG4, BRF1, ENSCAFG00845007156, SEMA6B, DSC1, TNFAIP1, MYLK3, WAPL, ADORA2B, LOXHD1, GP6, AZIN1, and NCSTN) with moderate to high impact were identified by WES analysis. Through a Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of 17 genes with somatic mutations, a total of 16 pathways were identified. Overall, the somatic mutations identified in this study suggest novel candidate mutations for CL, and further studies are needed to confirm the role of these mutations. Full article

The development of new approaches for the synthesis of new bioactive heterocyclic derivatives is of the utmost importance for pharmaceutical industry. In this regard, the present study reports the green synthesis of new benzaldazine and ketazine derivatives via the condensation of various carbonyl compounds (aldehydes and ketones with the 3-(1-hydrazineylideneethyl)-1H-indole using the grinding method with one drop of acetic acid). Various spectroscopic techniques were used to identify the structures of the synthesized derivatives. Furthermore, the anticancer activities of the reported azine derivatives were evaluated against colon, hepatocellular, and breast carcinoma cell lines using the MTT technique with doxorubicin as a reference medication. The findings suggested that the synthesized derivatives exhibited potential anti-tumor activities toward different cell lines. For example, 3c, 3d, 3h, 9, and 13 exhibited interesting activity with an IC₅₀ value of 4.27–8.15 µM towards the HCT-116 cell line as compared to doxorubicin (IC₅₀ = 5.23 ± 0.29 µM). In addition, 3c, 3d, 3h, 9, 11, and 13 showed excellent cytotoxic activities (IC₅₀ = 4.09–9.05 µM) towards the HePG-2 cell line compared to doxorubicin (IC₅₀ = 4.50 ± 0.20 µM), and 3d, 3h, 9, and 13 demonstrated high potency (IC₅₀ = 6.19–8.39 µM) towards the breast cell line (MCF-7) as compared to the reference drug (IC₅₀ = 4.17 ± 0.20 µM). The molecular interactions between derivatives 3a-h, 7, 9, 11, 13, and the CDK-5 enzyme (PDB ID: 3IG7) were studied further using molecular docking indicating a high level of support for the experimental results. Furthermore, the drug-likeness analysis of the reported derivatives indicated that derivative 9 (binding affinity = −8.34 kcal/mol) would have a better pharmacokinetics, drug-likeness, and oral bioavailability as compared to doxorubicin (−7.04 kcal/mol). These results along with the structure–activity relationship (SAR) of the reported derivatives will pave the way for the design of additional azines bearing indole with potential anticancer activities. Full article

A two-dimensional and bifunctional pillar-layered metal–organic framework (MOF)—with the molecular formula [Zn(cba)(bpdb)]·DMF (2DTMU-1), H₂cba = 4,4′-methylenedibenzoic acid, bpdb = 1,4-bis(4-pyridyl)-2,3-diaza-1,3-butadiene—was obtained via the reaction of zinc(II) nitrate with H₂cba as the carboxylate linker and bpdb as the N-donor pillar. 2DTMU-1 is based on a binuclear paddlewheel Zn(II) unit complexed by four bridging bidentate (dicarboxylate) V-shaped ligands, which combine to from H₂cba; this tetragonal array, which is connected by bpdb with a bridging azine group, presents a pore size of 18 × 12 Ų. Full article