Electron-withdrawing Nitro Group Research Articles

A "Double-Locked" and Enzyme/pH-Activated Theranostic Agent for Accurate Tumor Imaging and Therapy.

Theranostic agents for concurrent cancer therapy and diagnosis have begun attracting attention as a promising modality. However, accurate imaging and identification remains a great challenge for theranostic agents. Here, we designed and synthesized a novel theranostic agent H6M based on the “double-locked” strategy by introducing an electron-withdrawing nitro group into 1-position of a pH-responsive 3-amino-β-carboline and further covalently linking the hydroxamic acid group, a zinc-binding group (ZBG), to the 3-position of β-carboline to obtain histone deacetylase (HDAC) inhibitory effect for combined HDAC-targeted therapy. We found that H6M can be specifically reduced under overexpressed nitroreductase (NTR) to produce H6AQ, which emits bright fluorescence at low pH. Notably, H6M demonstrated a selective fluorescence imaging via successive reactions with NTR (first “key”) and pH (second “key”), and precisely identified tumor margins with a high S/N ratio to guide tumor resection. Finally, H6M exerted robust HDAC1/cancer cell inhibitory activities compared with a known HDAC inhibitor SAHA. Therefore, the NTR/pH-activated theranostic agent provided a novel tool for precise diagnosis and efficient tumor therapy.

Dehydrative amination of benzhydrols with electron-withdrawing group-substituted 2-aminopyridines utilizing Au(III)/TPPMS catalyst system in water.

We report a method for gold(III)/sodium diphenylphosphinobenzene-3-sulfonate (TPPMS)-catalyzed direct amination of benzhydrols using 2-aminopyridines with poor nucleophilic character in water. Various functional groups such as electron-withdrawing nitro, cyano and halogen groups were tolerated well to form the desired N-benzylated 2-aminopyridine compounds. On the basis of mechanistic studies including kinetic profiles, Hammett study and isotope effects, we propose a pathway in which a Lewis acidic gold cation species activates the sp3 C-O bond of the alcohol in the rate-determining step.

Organic skin layer with carboxyl and electron-withdrawing nitro groups to chemically bind with residual Li and Ni cations on single-crystal LiNi0.8Co0.1Mn0.1O2

Interfacial issue is very critical to the electrochemical properties of LiNi0.8Co0.1Mn0.1O2 (NCM811) cathode, and it also poses a great challenge for successful commercialization of NCM811 via construction of a desirable surface layer. This work constructs a novel metal-organic interface by grafting organic 4-NBA (4-nitrobenzoic acid) layer onto singe-crystal NCM811 surface. The electron transfer from the interfacial Ni2+ to the electron-withdrawing nitro group of 4-NBA promotes the formation of metal-organic interface, which inhibits Ni dissolution into the organic electrolyte. The neutralization reaction between the carboxyl groups of 4-NBA and residual lithium compounds of NCM811 constructs an interfacial layer with improved Li+ conductivity. The 4-NBA organic layer also helps constructing a thin and stable cathode/electrolyte interphase by alleviating the side reactions of electrolyte. The electrochemical properties of single-crystal NCM811 cathode are remarkably enhanced. At a high discharge rate of 20C, a capacity of 141 mAh g−1 can be delivered, significantly higher than that of 101 mAh g−1 of the pristine cathode. After 200 cycles at 1C, the modified sample exhibits excellent capacity retention of 84.5%.

Theoretical insights into the enhancement of 1-Methyl-2,4,5-trinitroimidazole yield by exchanging of group introduction order

During the synthesis of 1-methyl-2,4,5-trinitroimidazole (MTNI), the product yield was affected by group introduction order. This phenomenon has not been explained in the reaction mechanism. In this paper, the DFT method was used to study the synthesis mechanism. For the nitration reaction, an N-H⋯O hydrogen bond was formed between the midazole ring and water molecule in the solution to promote the nitration reaction, so the nitration mechanism was affected by the introduction of methyl group at the N site. For the methylation reaction, the electrophilic attack of the methyl group was affected by the introduction of more electron-withdrawing nitro group.

Synthesis and Laccase-Mediated Oxidation of New Condensed 1,4-Dihydropyridine Derivatives

We describe herein the synthesis and laccase mediated oxidation of six novel 1,4-dihydropyridine (DHP)-based hexahydroquinolines (DHP1-DHP3) and decahydroacridines (DHP4-DHP6). We employed different laccase enzymes with varying redox potential to convert DHP1-DHP3 and DHP4-DHP6 to the corresponding pyridine-containing tetrahydroquinoline and octahydroacridine derivatives, respectively. Intensively coloured products were detected in all biocatalytic reactions using laccase from Trametes versicolor (TvLacc), possibly due to the presence of conjugated chromophores formed in products after oxidation. The NMR assessment confirmed that the oxidation product of DHP1 was its corresponding pyridine-bearing tetrahydroquinoline derivative. Laccase from Bacillus subtillis (BacillusLacc) was the most efficient enzyme for this group of substrates using HPLC assessment. Overall, it could be concluded that DHP2 and DHP5, bearing catecholic structures, were easily oxidized by all tested laccases, while DHP3 and DHP6 containing electron-withdrawing nitro-groups are not readily oxidized by laccases. DHP4 with decahydroacridine moiety consisting of three condensed six-membered rings that contribute not only to the volume but also to the higher redox potential of the substrate rendered this compound not to be biotransformed with any of the mentioned enzymes. Overall, we showed that multiple analytical approaches are needed in order to assess biocatalytical reactions.

Detection of small molecular toxins using azacalix[4]arene architecture and its theoretical investigations

We demonstrate an azacalix[4]arene based bifunctional probe, viz. bisnaphthylated-azacalix[4]arene (BNAC) for the selective recognition of molecular toxins such as monocrotophos (MCP) and N-methyl-4-nitroaniline (MNA). The photophysical properties, especially the emission studies were introduced for monitoring the host–guest complexation. Noteworthy, the emission responses of the host exclusively alter according to the functionalities attached to the guest molecules. For instance, MCP being electron-rich enhances the emission intensity of BNAC upon complexation by donating electrons to the electrophilic sites of the receptor. Inversely, MNA having electron-withdrawing nitro groups readily interacts with the highly conjugated naphthalene rings and suppresses the emission maxima of the receptor through photoinduced electron transfer (PET). Job’s plot reveals both MNA and MCP exhibit 1:1 stoichiometry upon complexation with BNAC. Computational studies including molecular docking and DFT calculations were carried out to predict the binding affinity, plausible host–guest interactions and to investigate the binding mechanism.

Curvature-regulated transmembrane anion transport by a trifluoromethylated bisbenzimidazole

In this paper, we demonstrate that modification of anion-transport active 1,3-bis(benzimidazol-2-yl)benzene with strongly electron-withdrawing trifluoromethyl and nitro groups leads to a dramatic increase in the anionophoric activity, and the activity may be greatly regulated by the curvatures of the liposomes used.

Simple Development of Novel Reversible Colorimetric Thermometer Using Urea Organogel Embedded with Thermochromic Hydrazone Chromophore

Thermochromic urea (U) organogel immobilized with a thermochromic tricyanofuran hydrazone (TCFH) chromophore was developed. Thermochromic TCFH chromophore bearing two nitro functional groups on a hydrazone recognition unit was synthesized via an azo-coupling reaction of tricyanofuran (TCF) heterocyclic moiety containing an active methyl group with the diazonium chloride salt of 2,4-dinitroaniline comprising two strongly electron-withdrawing nitro groups. The molecular structure of both intermediates and TCFH dye were characterized by several analytical methods, including 1H NMR, 13C NMR, IR, mass spectroscopy (MS), and elemental analysis. The thermochromic responsiveness could be attributed to the charge delocalization of TCFH as well as to the presence of an intramolecular charge transfer. The generated organogel displayed a thermoreversible sol–gel transition associated with color change. The origin of the monitored thermochromism is a conformational change of the tricyanofuran hydrazone backbone due to the temperature-driven deprotonation–protonation reversible process. The prepared urea–tricyanofuran hydrazone (UTCFH) thermometer acted as a diagnostic tool providing an instant color change between yellow, orange, red and purple upon changing the temperature of the UTCFH organogel in dimethyl sulfoxide (DMSO). This color change was proportionally correlated with increasing the temperature from 44 to 63 °C. The UTCFH organogel composed of urea and push-π-pull hydrazone type tricyanofuran chromophore immobilized physically in the urea organogel was found to function as a temperature-driven chromic thermometer. This chromogenic UTCFH organogel in DMSO displayed a phase transition at 41–48 °C. The morphological properties of the gel internal fibrous nanostructure (80–120 nm) were monitored by scanning electron microscopy (SEM). The colorimetric measurements were monitored by UV–Vis absorption spectroscopy. The chromogenic thermometer demonstrated a good reversibility without fatigue. The mechanism accounting for thermochromism of UTCFH organogel is proposed.

Michael addition of amines to sterically crowded ortho-benzoquinone completed with unprecedented 1,2-shift of a tert-butyl group

A strong electron-withdrawing nitro group introduced into the 6-position of 3,5-di-( tert -butyl)-1,2-benzoquinone provides for activation of the sterically blocked Michael addition reaction channel. Addition of amines to the quinone is followed by a concerted 1,2-migration of a tert -butyl group to afford derivatives of 4-amino-3-nitrocyclohexa-3,5-diene-1,2-dione system. The multistep reaction mechanism was examined using DFT computational methods. • Michael addition reaction channel blocked in sterically crowded o-quinones is activated. • 3,5-di-( tert -butyl)-6-nitro-1,2-benzoquinone reacts with amines to give cyclohexadienones. • The addition reaction is accompanied by 1,2-shift of a tert- butyl group along the ring. • The multistep mechanism of the reaction is unveiled by the DFT study.

Tuning Anion-Binding Properties of 22-Membered Unclosed Cryptands by Structural Modification of the Lariat Arm.

A series of 22-membered unclosed cryptands end-capped with intra-annular methyl (1), phenyl (2), p-tert-butylphenyl (3), and p-nitrophenyl (4) amide substituents (lariat arm) were synthesized to elucidate the effect of steric and electronic factors on their anion recognition behavior. The 1H NMR titrations in DMSO-d6 with 0.5% water reveal enhanced selectivity for H2PO4– vs Cl– and PhCO2–. The para-attachment of the electron-withdrawing nitro group (−NO2 vs −H and −t-Bu) was found to increase anion-binding affinity, whereas the steric bulkiness of lariat arm (methyl vs aryl) has a marginal effect. DFT calculations reveal that binding of H2PO4– is associated with minimal conformational change in the lariat arm moiety and involve four hydrogen bond acceptor and one donor sites of host.

Asymmetric Spirocyclization Enabled by Iridium and Brønsted Acid-Catalyzed Formal Reductive Cycloaddition

A catalytic, enantioselective spirocyclization of formanilides or formylindolines and enamides has been developed herein. The reaction proceeds through a sequential iridium-catalyzed hydrosilylatio...

Solid-state photochromic molecular switches based on axially chiral and helical spiropyrans

Solid-state photochromic switches with reversible luminescence modulation property have wide applications in optical data storage, anticounterfeiting, sensing, and bioimaging, however, it is a significant challenge to design and prepare such materials. In the present work, a novel class of chiral and helical binaphthyl-substituted spiropyrans has been synthesized and characterized. The introduction of binaphthyl can not only promote the solid-state luminescence but also achieve the interesting chiroptical switching properties for the potential applications in chiral recognition and circularly polarized luminescence. The single-crystal structures and density functional theory calculations reveal that the presence of strong electron-withdrawing nitro groups can promote photoswitch efficiency by stabilizing the electron-rich conjugated merocyanine with the lower electron cloud density and LUMO/HOMO levels. For charge transfer in excited states, π → π* transition would enhance emission, but n → π* transition and intramolecular charge transfer show the opposite effect. Therefore, these photochromic switches provide a novel paradigm in the design of multiple-responsive, chiral, and luminescent materials.

Comparison of sensitivity for methods of positive and negative ion mass spectrometry, exemplified by nitrotoluenes

For a model series of nitro aromatic compounds comprising mono-, di- and trinitrotoluenes, and dinitrobenzene, using the same commercial experimental set up consisting of gas chromato-graphy/mass spectrometry (GC/MS) instrument equipped with a quadrupole analyzer, the two types of mass spectra were recorded, of positive ions (in the conventional, standard mode of electron ionization at 70 eV) and of negative ions (NI, generated at low, pre-ionization electron energies by resonant electron capture, REC). The comparative analysis of characteristic fragmentation processes was carried out for molecular ions of both signs. The sensitivity of REC NI MS method was established to enhance upon increasing the number of electron-withdrawing nitro groups, reaching or even outperforming that of the classical method of electron ionization (EI). Thus, the detection limit for trinitrotoluene in a solution was estimated as 5 ppm, which is by an order of magnitude lower as compared to the conventional EI mode of analysis. Comparison of the ion composition of NI mass spectra and of the relative intensities of ion peaks with the corresponding data obtained previously for the studied group of compounds by means of different types of mass spectrometers, has revealed a satisfactory inter-instrumental reproducibility of the NI mass spectra. The results reported herein indicate that the NI generation/registration mode, which can technically be readily available even without modifications of design of commercial GC/MS instrument in their basic configuration, is suitable to be introduced in laboratory practice as the additional tool for increasing the selectivity and reliability in detection/identification of trace amounts of compounds possessing a high electron af nity and for solving extraordinary structural and analytical problems.

Thermochemistry and Initial Decomposition Pathways of Triazole Energetic Materials.

A thorough investigation of the initial decomposition pathways of triazoles and their nitro-substituted derivatives has been conducted using the MP2 method for optimization and DLPNO-CCSD(T) method for energy. Different initial thermolysis mechanisms are proposed for 1,2,4-triazole and 1,2,3-triazole, the two kinds of triazoles. The higher energy barrier of the primary decomposition path of 1,2,4-triazole (H-transfer path, ∼52 kcal/mol) compared with that of 1,2,3-triazole (ring-open path, ∼45 kcal/mol) shows that 1,2,4-triazole is more stable, consistent with experimental observations. For nitro-substituted triazoles, more dissociation channels associated with the nitro group have been obtained and found to be competitive with the primary decomposition paths of the triazole skeleton in some cases. Besides, the effect of the nitro group on the decomposition pattern of the triazole skeleton has been explored, and it has been found that the electron-withdrawing nitro group has an opposite effect on the primary dissociation channels of 1,2,4-triazole derivatives and 1,2,3-triazole derivatives.

Nickel‐Catalyzed C‐O Cross‐Coupling Reaction at Low Catalytic Loading with Weak Base Participation

Herein, we report a nickel‐catalyzed crossing‐coupling reaction for the synthesis of diaryl ethers. The desired products are achieved by coupling heterocyclic alcohols with aryl bromides bearing strong electron withdrawing nitro group under the catalyst system of NiCl2(PPh3)2 and weak base KHCO3. This mild reaction exhibits a broad functional group tolerance. Compound 4 as an important intermediate is suitable for further structural modification of MALT1 inhibitor MI‐2.

Robust therapeutic potential of carbazole-triazine hybrids as a new class of urease inhibitors: A distinctive combination of nitrogen-containing heterocycles

The inhibition of urease enzyme is very important as it plays a key role in the treatment of several urinary and gastrointestinal tract infections. This enzyme provides a suitable environment for Helicobacter pylori at the low pH of the stomach, a causative agent of gastric and peptic ulcer that may lead to cancer. In agriculture, the high urease content causes environmental and economic problems. In this pursuit, given the well-established importance of integrated pharmacophores in medicinal chemistry and to explore new inhibitors of urease featuring two distinct heterocyclic functionalities, we herein report a facile synthesis of carbazole-triazine hybrids (3a-j). These new propeller-shaped chemical scaffolds were evaluated for their urease inhibitory potential in order to identify suitable leads. The initial structure-activity survey work guided through in vitro bioactivity results recognized 3e and 3f as new starting point hits incorporating bulky iodo (3e) and strong electron-withdrawing nitro (3f) groups at the para-position of aryl amine component. The potent compounds (3e &3f) exhibited the highest activity with IC50 values of 5.6 and 6.7 µM, respectively. In the molecular docking analysis, these compounds depicted excellent binding interactions with the active site residues. The key interactions observed include hydrogen bonding, π–π interactions, π–cation and nickel atom coordination to the triazine nitrogen of both inhibitors.

The Nature of Charge Carriers in Polymeric Complexes of Nickel with Schiff Bases Containing Electron-Withdrawing Substituents

The data on polymeric complexes of nickel with salen-type Schiff bases containing electron-withdrawing nitro groups in ligand’s aromatic fragments are acquired by an in situ technique based on collecting electron paramagnetic resonance spectra simultaneously with absorption spectra in the UV, visible, and near IR regions in the course of oxidation-reduction of a polymer film on the surface of an optically transparent electrode under conditions of cyclic voltammetry. Based on the combined analysis of spectroscopic and electrochemical data, it is shown that as the potential of the polymer-modified electrode shifts in the positive region, the different types of charge carriers successively appear in the system (phenoxyl radical cations, radical pairs, and dications). The results obtained suggest that the positive charge can be delocalized either between aromatic rings in monomer fragments or between fragments of neighboring polymer chains.

Derivatization of Natural Compound β-Pinene Enhances Its In Vitro Antifungal Activity against Plant Pathogens.

Background: The development of new antifungal agents has always been a hot research topic in pesticide development. In this study, a series of derivatives of natural compound β-pinene were prepared, and the antifungal activities of these derivatives were evaluated. The purpose of this work is to develop some novel molecules as promising new fungicides. Methods: Through a variety of chemical reactions, β-pinene was transformed into a series of β-pinene-based derivatives containing amide moieties and acylthiourea moieties. The antifungal activities of these derivatives against five plant pathogens including Colletotrichum gloeosporioides, Fusarium proliferatum, Alternaria kikuchiana, Phomopsis sp. and Phytophthora capsici were tested; preliminary structure–activity relationship was discussed. Results: Some derivatives exhibited moderate or significant antifungal activity due to the fusion of the amide moiety or the acylthiourea moiety with the pinane skeleton. The structure–activity relationship analysis showed that the fluorine atom and the strong electron withdrawing nitro group, or trifluoromethyl group on the benzene ring of the derivatives had a significant effect on the improvement of the antifungal activity against Colletotrichum gloeosporioides, Fusarium proliferatum, Alternaria kikuchiana and Phomopsis sp. Meanwhile, the introduction of an ethyl group at the meta-position on the benzene ring of the derivatives could improve the antifungal activity against Phytophthora capsici. Compounds 4e, 4h, 4q, 4r exhibited broad-spectrum antifungal activity against the tested strains. Compound 4o had significant antifungal activity against Phytophthora capsici (IC50 = 0.18 μmol/L). These derivatives were expected to be used as precursor molecules for novel pesticide development in further research.

Quantum and Phonon Interference-Enhanced Molecular-Scale Thermoelectricity.

Simultaneous engineering of electron and phonon transport through nanoscale molecular junctions is fundamental to the development of high-performance thermoelectric materials for the conversion of waste heat into electricity and cooling. Here, we demonstrate a systematic improvement of the room-temperature thermoelectric figure of merit (ZT) of molecular junctions. This is achieved by phonon interference (PI)-suppressed thermal conductance and quantum interference-enhanced electrical conductance and Seebeck coefficient. This strategy leads to a significant enhancement of ZT from low values ca. 10–6 in oligo(phenylene-ethynylene) (OPE2) to the record values of 2.4 in dinitro-functionalized OPE2 (DOPE2). The dinitro functionalization also considerably enhances ZT of biphenyl-dithiol (BDT) and bipyridyl molecular junctions. Remarkably, the energy levels of electron-withdrawing nitro groups are hardly changed from one molecule to the other. Because of this generic feature, a resonance transport in the vicinity of Fermi energy of electrodes is formed leading to a significant improvement of Seebeck coefficient and ZT of all derivatives. For example, the Seebeck coefficient enhances from 10.8 μV/K in BDT to −470 μV/K in dinitro-BDT (DBDT). In addition, destructive PI due to the nitro groups suppresses phonon thermal conductance, for example, from 20 pW/K in BDT to 11 pW/K in DBDT at room temperature. We also demonstrate that quantum and PI-enhanced single-molecule thermoelectric efficiency is conserved when parallel molecules are placed between gold electrodes. These results promise to remove the key roadblocks and open new avenues to exploit functionalized organic molecules for thermoelectric energy harvesting and cooling.

Применение 1,3-диоксолана в синтезе замещенных 3,4-дигидрохиназолинов, диарилметанов или метилендиаминов

The interaction between 1,3-dioxolane with primary aromatic amine- sulfanilamide (streptocide), secondary aromatic amine-N-benzylaniline and also with amine of heterocyclic series – 4-aminopyridine. It is found that, sulfanilamide (streptocide), which has an electron withdrawing sulfonamide group in para position, reacts with 1,3-dioxolane in an atmosphere of benzol and trifluoroacetic acid producing 3-(4-sulfamoylphenyl)-3,4-dihydroquinazoline-6-sulphonamide, that is corresponding to the previous result obtained when 1,3-dioxolane reacts with para-nitroaniline (which also contains electron-withdrawing nitrogroup) resulting in 3-(p-nitrophenyl)-6-nitro-3,4-dihydroquinazoline. Under the same conditions the interaction between 1,3-dioxolane and N-benzylaniline results in producing 4,4'-bis(phenylmethyleneamino)diphenylmethane, which refers to a different class of compounds – diphenylmethane derivative. A primary amine of heterocyclic series 4-aminopyridine reacts with 1,3-dioxolane in the presence of concentrated hydrochloric acid producing N,Nʹ-di-(4-pyridinyl)methylenediamine. Antimicrobic properties of received compounds were studied on museum potentially pathogenic microorganism strains: Staphylococcusaureus (strain 906), Candid aalbicans (АТСС 24433), in FSBI «Scientific Centre for Expert Evaluation of Medicinal Products» of the Ministry of Health of the Russian Federation. Only N,Nʹ-di-(4-pyridyl)methylenediamine out of three investigated compounds showed microbiological activity. This compound inhibits growth of Staphylococcus aureus at concentration 62.5 µg/ml, culture death comes from the effect of concentration 125.0 µg/ml. The morphology of compounds was established according to mass spectrometry data, 1Н NMR spectroscopy, the structure of N,Nʹ-di-(4-pyridyl)methylenediamine in the form of chloride was proved using X-ray structural analysis.