Search Results (27)

Two new 2-N-phenylamino-5-nitropyridine—4-methyl (2PA5N4MP) and 2-N-phenylamino-5-nitropyridine-6-methyl (2PA5N6MP) isomers were synthesized and comprehensively characterized by single-crystal X-ray diffraction, IR/Raman spectroscopy, UV–Vis absorption, and photoluminescence measurements. DFT and TD-DFT calculations were also carried out to support the experimental results. The X-ray analysis revealed significant structural differences: 2PA5N6MP adopted an almost planar conformation (pyridine–phenyl dihedral ~3°), whereas 2PA5N4MP was markedly twisted (~45°), leading to distinct hydrogen-bonding motifs (N–H⋯N dimers vs. N–H⋯O interactions). These geometric disparities influenced their electronic properties: 2PA5N6MP exhibited a narrower HOMO–LUMO gap (≈2.45 eV) than 2PA5N4MP (≈3.77 eV), which was consistent with a pronounced bathochromic shift in absorption. Both isomers showed broad UV–Vis absorption (200–520 nm), but the 6-methyl derivative featured an additional low-energy charge–transfer band around 460 nm (with a maximum at ~500 nm) compared to ~355 nm in the 4-methyl isomer. Likewise, their photoluminescence spectra differed as follows: 2PA5N4MP emitted in the violet–blue region (bands at ~415 and 450 nm), whereas 2PA5N6MP had an extra orange band peaking at ~560 nm (in addition to a ~450 nm band). The red-shifted 560 nm emission of 2PA5N6MP was attributed to intersystem crossing into triplet states, in line with TD-DFT predictions. Furthermore, both isomers readily formed complexes with Eu³⁺ ions, and the Eu³⁺ chelates exhibited the characteristic red f–f emissions (⁵D₀ → ⁷F transitions ~590–700 nm), demonstrating efficient sensitization of Eu³⁺ luminescence. Overall, the position of the methyl substituent strongly modulates the compounds’ optical behavior, and these isomers show promise as tunable organic dyes and effective ligands for luminescent lanthanide complexes. Full article

Pyridines are one of the most important and promising classes of N-heterocycles actively studied in modern organic and medicinal chemistry; in particular, pyridine is a privileged structural motif in drug design. From a synthetic organic chemistry perspective, nitropyridines can be considered as convenient and readily available precursors for a wide range of mono- and polynuclear heterocyclic systems demonstrating diverse activities, such as antitumor, antiviral, anti-neurodegenerative, etc. This review is an analysis of the literature on the use of nitropyridines for the synthesis of biologically active compounds, covering the period from 2015 to the present. Full article

Two new 2-N-phenylamino-(4 or 6)-methyl-3-nitropyridine derivatives were synthesized. Their structures were characterized on the basis of X-ray diffraction, IR, and Raman spectra as well as electron UV-Vis and emission spectra measurements. The experimental results were analyzed in terms of theoretical data in which the quantum chemical DFT and NBO calculations were applied. To elucidate the relaxation pathways of electronically excited states, multiple excitation wavelengths were employed to probe energy dissipation mechanisms in the studied compounds. A systematic analysis was conducted to evaluate how variations in methyl substituent positioning modulate both the structural architecture and photophysical behavior of the isomeric systems. The spectroscopic, structural and theoretical considerations allow us to propose the potential technological applications derived from the unique properties of these isomers. Full article

Background: CY1-4, 9-nitropyridine [2′,3′:4,5] pyrimido [1,2-α] indole -5,11- dione, is an indoleamine 2,3-dioxygenase (IDO) inhibitor and a poorly water-soluble substance. It is very important to increase the solubility of CY1-4 to improve its bioavailability and therapeutic effect. In this study, the mesoporous silica nano-skeleton carrier material Sylysia was selected as the carrier to load CY1-4, and then the CY1-4 nano-skeleton drug delivery system (MSNM@CY1-4) was prepared by coating the hydrophilic polymer material Hydroxypropyl methylcellulose (HPMC) and the lipid material Distearoylphosphatidyl-ethanolamine-poly(ethylene glycol)₂₀₀₀ (DSPE-PEG₂₀₀₀) to improve the anti-tumor effect of CY1-4. Methods: The solubility and dissolution of MSNM@CY1-4 were investigated, and its bioavailability, anti-tumor efficacy, IDO inhibitory ability and immune mechanism were evaluated in vivo. Results: CY1-4 was loaded in MSNM@CY1-4 in an amorphous form, and MSNM@CY1-4 could significantly improve the solubility (up to about 200 times) and dissolution rate of CY1-4. In vivo studies showed that the oral bioavailability of CY1-4 in 20 mg/kg MSNM@CY1-4 was about 23.9-fold more than that in 50 mg/kg CY1-4 suspension. In B16F10 tumor-bearing mice, MSNM@CY1-4 significantly inhibited tumor growth, prolonged survival time, significantly inhibited IDO activity in blood and tumor tissues, and reduced Tregs in tumor tissues and tumor-draining lymph nodes to improve anti-tumor efficacy. Conclusions: The nano-skeleton drug delivery system (MSNM@CY1-4) constructed in this study is a potential drug delivery platform for improving the anti-tumor effect of oral poorly water-soluble CY1-4. Full article

Long-range proton transfer in several conjugated proton cranes, originating from 7-hydroxy quinoline as a proton transfer platform, has been investigated theoretically by means of DFT and TD-DFT methodology. Major emphasis was given to their applicability to provide clean switching upon irradiation. The border conditions require the existence of a single enol tautomer in the ground state, which under excitation through a series of consecutive exited and ground state intramolecular proton transfer steps is transferred to the keto tautomer. It was shown that the most suitable candidates are based on using iso-quinoline, pyrimidine and 4-nitropyridine as proton crane units. Their suitability is a function of aromaticity changes, the basicity of the nitrogen atom from the proton crane unit and the structural effects originating from their conjugation with 7-hydroxy quinoline. Full article

A large number of the thin-film organic structures (polyimides, 2-cyclooctylarnino-5-nitropyridine, N-(4-nitrophenyl)-(L)-prolinol, 2-(n-Prolinol)-5-nitropyridine) sensitized with the different types of the nano-objects (fullerenes, carbon nanotubes, quantum dots, shungites, reduced graphene oxides) are presented, which are studied using the holographic technique under the Raman–Nath diffraction conditions. Pulsed laser irradiation testing of these materials predicts a dramatic increase of the laser-induced refractive index, which is in several orders of the magnitude greater compared to pure materials. The estimated nonlinear refraction coefficients and the cubic nonlinearities for the materials studied are close to or larger than those known for volumetric inorganic crystals. The role of the intermolecular charge transfer complex formation is considered as the essential in the refractivity increase in nano-objects-doped organics. As a new idea, the shift of charge from the intramolecular donor fragment to the intermolecular acceptors can be proposed as the development of Janus particles. The energy losses via diffraction are considered as an additional mechanism to explain the nonlinear attenuation of the laser beam. Full article

4-Nitroquinoline-N-oxide (NQO) and 4-nitropyridine-N-oxide (NPO) are important precursors for the synthesis of substituted heterocycles while NQO is a popular model mutagen and carcinogen broadly used in cancer research; intermolecular interactions are critical for their reactions or functioning in vivo. Herein, the effects of the coordination of N-oxide’s oxygen atom to Lewis acids on multicenter donor–acceptor bonding were explored via a combination of experimental and computational studies of the complexes of NQO and NPO with a typical π-electron donor, pyrene. Coordination with ZnCl₂ increased the positive electrostatic potentials on the surfaces of these π-acceptors and lowered the energy of their LUMO. Analogous effects were observed upon the protonation of the N-oxides’ oxygen or bonding with boron trifluoride. The interaction of ZnCl₂, NPO, or NQO and pyrene resulted in the formation of dark co-crystals comprising π-stacked Zn-coordinated N-oxides and pyrene similar to that found with protonated or (reported earlier) BF₃-bonded N-oxides. Computational studies indicated that the coordination of N-oxides to zinc(II), BF₃, or protonation led to the strengthening of the multicenter bonding of the nitro-heterocycle with pyrene, and this effect was related both to the increased electrostatic attraction and molecular–orbital interactions in their complexes. Full article

Disubstituted isothiazolo[4,3-b]pyridines are known inhibitors of cyclin G-associated kinase. Since 3-substituted-7-aryl-isothiazolo[4,3-b]pyridines remain elusive, a strategy was established to prepare this chemotype, starting from 2,4-dichloro-3-nitropyridine. Selective C-4 arylation using ligand-free Suzuki-Miyaura coupling and palladium-catalyzed aminocarbonylation functioned as key steps in the synthesis. The 3-N-morpholinyl-7-(3,4-dimethoxyphenyl)-isothiazolo[4,3-b]pyridine was completely devoid of GAK affinity, in contrast to its 3,5- and 3,6-disubstituted congeners. Molecular modeling was applied to rationalize its inactivity as a GAK ligand. Full article

The multicomponent reaction of 2-nitroacetophenone (or nitroacetone), acetaldehyde diethyl acetal, β-dicarbonyl compound, and ammonium acetate in an acetic acid solution allowed the acquisition of previously undescribed 4-methyl-substituted derivatives of 5-nitro-1,4-dihydropyridine in satisfactory yields. The oxidation of the obtained 5-nitro-1,4-dihydropyridine derivatives resulted in the corresponding 2,4-dimethyl-5-nitropyridines. In addition, for the first time in the synthesis of unsymmetrical 1,4-dihydropyridines by the Hantzsch reaction acetaldehyde, diethyl acetal was used as a source of acetaldehyde. The use of more volatile and sufficiently reactive acetaldehyde in this reaction did not lead to a controlled synthesis of unsymmetrical 5-nitro-1,4-dihydropyridines. The proposed multicomponent approach to the synthesis of 4-methyl-substituted 5-nitro-1,4-dihydropyridines and their subsequent aromatization into pyridines made it possible to obtain previously undescribed and hardly accessible substituted 5(3)-nitropyridines. Full article

An efficient method for the synthesis of pyrazolo [4,3-b]pyridines has been developed on the basis of readily available 2-chloro-3-nitropyridines via a sequence of SNAr and modified Japp–Klingemann reactions. The method offers a number of advantages including utilization of stable arenediazonium tosylates, operational simplicity as well as combining the azo-coupling, deacylation and pyrazole ring annulation steps in a one-pot manner. An unusual rearrangement (C-N-migration of the acetyl group) was observed and a plausible mechanism was proposed based on the isolated intermediates and NMR experiments. In addition, the developed protocol was successfully applied to the synthesis of 1-arylindazoles combining the Japp–Klingemann reaction and cyclization of the resulting hydrazone as a one-pot procedure. Full article

In this work, we report on the catalytic activity of a manganese complex [(Cl)₂Mn(RCOOET)], where RCOOET is ethyl-5-methyl-1-(((6-methyl-3-nitropyridin-2-yl)amino)methyl)-1H-pyrazole-3-carboxylate, in the oxidation of phenol or catechol by atmospheric oxygen to form o-quinone. The [(Cl)₂Mn(RCOOET)] catalyzes the oxidation of catechol at a rate of 3.74 µmol L⁻¹ min⁻¹ in tetrahydrofuran (THF), in a similar manner to catecholase or tyrosinase. Full article

As part of our ongoing scaffold-hopping work on an antiplasmodial 2-trichloromethylquinazoline scaffold, we aimed to explore the 1-trichloromethylphthalazine scaffold as a potential new antimalarial series. Using previously chlorination conditions described by our lab to obtain a trichloromethyl group from a methyl group, we did not obtain the target compound; instead, we obtained a dichloro methylphosphonic dichloride side product 3. The nature of this compound was then characterized by NMR, HRMS and X-ray crystallography. The same issue was previously reported by Kato et al., starting from the 2-methyl-3-nitropyridine. Finally, compound 3, although not cytotoxic, was not active against P. falciparum, the parasite responsible for human malaria. Full article

A number of new 2-methyl- and 2-arylvinyl-3-nitropyridines were synthesized and their reactions with thiols were studied. It was found that 3-NO₂ tends to be selectively substituted under the action of sulfur nucleophiles in the presence of another nucleofuge in position 5. Correlations between the substitution pattern and regioselectivity as well as photophysical properties were established. Some synthesized compounds possessed a large Stokes shift. Full article

Multidrug resistance (MDR), having a multifactorial nature, is one of the major clinical problems causing the failure of anticancer therapy. The aim of this study was to examine the antitumour effects of selected pyridinium salts, 1-methyl-3-nitropyridine chloride (MNP) and 3,3,6,6,10-pentamethyl-3,4,6,7-tetrahydro-[1,8(2H,5H)-dion]acridine chloride (MDION), on sensitive leukaemia HL60 cells and resistant topoisomerase II-defective HL60/MX2 cells. Cell growth was determined by the MTT test. Intracellular ROS level was measured with the aid of 2′,7′-DCF-DA. The cell cycle distribution was investigated by performing PI staining. DSB formation was examined using the γ-H2AX histone phosphorylation assay. The activity of caspase-3 and caspase-8 was measured with the use of the FLICA test. The assays for examining the lysosome membrane permeabilization were carried out with the aid of LysoTracker Green DND-26. Both studied compounds exerted very similar cytotoxic activities towards sensitive HL60 cells and their MDR counterparts. They modulated the cellular ROS level in a dose-dependent and time-dependent manner and significantly increased the percentage of sensitive HL60 and resistant HL60/MX2 cells with sub-diploid DNA (sub-G1 fraction). However, the induction of DSB formation was not a significant mechanism of action of these pyridinium salts in studied cells. Both examined compounds triggered caspase-3/caspase-8-dependent apoptosis of sensitive HL60 cells and their MDR counterparts. Additionally, the findings of the study indicate that lysosomes may also participate in the programmed death of HL60 as well as HL60/MX2 cells induced by MDION. The data obtained in this work showed that both examined pyridinium salts, MNP and MDION, are able to retain high antileukaemic effects against multidrug resistant topoisomerase II-defective HL60/MX2 cells. Full article