Aniline Nitrogen Research Articles

Synthesis and in vitro/in silico evaluation of the antimalarial activity of potential amino-quinoline derivatives

In this study, a series of N-arylamino-7-chloroquinolines were synthesized via an alkylation reaction involving aniline derivatives (2) and 4,7-dichloroquinoline (1). Additionally, the synthesis of a library of N-aryl-N-benzylamino-7-chloroquinoline analogues, modified on the aniline nitrogen, has also reported. A structure-activity relationship (SAR) study was conducted to evaluate the biological efficacy and safety of these derivatives against chloroquine-sensitive (Pf3D7) and chloroquine-resistant (PfW2) Plasmodium falciparum strains. Compounds 5i and 5c showed promising efficacy against the Pf3D7 strain with IC50 values of 0.25 μM and 0.54 μM, respectively, while compound 5l demonstrated significant activity against the PfW2 strain with an IC50 of 5.82 μM. The cytotoxicity of these compounds was also evaluated on HUVEC cell lines. Additionally, their pharmacological and pharmacokinetic (ADME) properties were studied to predict their fate and identify promising candidates for further clinical studies.

Comparison of Vinyldimethylaniline and Indolizine Donor Groups on Si‐Substituted Xanthene Core Shortwave Infrared Fluorophores

AbstractSmall organic molecules absorbing and emitting in the shortwave infrared (SWIR, 1000–2000 nm) region are desirable for biological imaging applications due to low auto‐fluorescence, reduce photon scattering, and good tissue penetration depth of photons which allows for in vivo imaging with high resolution and sensitivity. Si‐substituted xanthene‐based fluorophores with indolizine donors have demonstrated some of the longest wavelengths of absorption and emission from organic dyes. This work seeks to compare an indolizine heterocyclic nitrogen with dimethyl aniline nitrogen donors on otherwise identical Si‐substituted xanthene fluorophores via optical spectroscopy, computational chemistry and electrochemistry. Three donors are compared including an indolizine donor, a ubiquitous dimethyl aniline donor, and a vinyl dimethyl aniline group that keeps the number of π‐bonds consistent with indolizine. Significantly higher quantum yields and molar absorptivity are observed in these studies for a dimethylamine‐based donor relative to a simple indolizine donor absorbing and emitting at similar wavelengths (~1312 nm emission). Substantially longer wavelengths are obtainable by appending aniline‐based groups to the indolizine donor (~1700 nm) indicating longer wavelengths can be accessed with indolizine donors while stronger emitters can be accessed with anilines in place of indolizine.

Hydrogen bonding-promoted tunable approach for access to aza-bicyclo-[3.3.0]octanes and cyclopenta[b] pyrroles.

A unified strategy is disclosed that builds on successfully engaging the aniline nitrogen of 1,3-amphoteric γ-aminocyclopentenone for a tandem annulation with electron-poor alkynes, solely assisted by the H-bonding network of HFIP. This metal-free mild strategy provides access to medicinally relevant aza-bicyclo-octanes en route to another important scaffold: cyclopenta[b]pyrrole.

Elucidating the roles of Cr(VI)-Cu(II) Co-pollution in the stress of aniline degradation stress: Insights into metabolic pathways and functional genes

In order to examine the impact of Cu(II)-Cr(VI) co-pollution in printing and dyeing wastewater on the aniline biodegradation system (ABS), loading experiments were conducted on ABS at varying concentrations of Cu(II)-Cr(VI). The synergistic stress imposed by Cu(II)-Cr(VI) accelerated the deterioration of the systems, with only the C2-3 (2 mg/L Cr(VI)-3 mg/L Cu(II)) sustaining stable operation for 42 days. However, its nitrogen removal performance remained significantly impaired, resulting in a total nitrogen (TN) removal rate below 40%. High-throughput sequencing analysis revealed a stronger correlation between Cr(VI) and microbial diversity compared to Cu(II). Metagenomic sequencing results demonstrated that Cu(II) emerged as the dominant factor influencing the distribution of dominant bacteria in C2-3, as well as its contribution to contaminant degradation. The complex co-pollution systems hindered aniline degradation and nitrogen metabolism through the combined bio-toxicity of heavy metals and aniline, thereby disrupting the transport chain within the systems matrix.

Evolution of aniline degradation and nitrogen removal performance in electro-enhanced sequence batch reactor under salinity stress: Sludge characteristics and microbial diversity

To explore the influence mechanism of different concentrations of salinity on the electro-enhanced aniline biodegradation system, a control group and experimental groups (0%-NaCl, 0.5%-NaCl, 1.5%-NaCl, 2.5%-NaCl, 3.5%-NaCl) were established. The experimental results showed that the electric field strengthened the denitrification performance, while salinity had little effect on the degradation efficiency of aniline and chemical oxygen demand (COD). The removal rate of TN reached 79.6% and 74.9% in 0.5%-NaCl and 1.5%-NaCl, respectively, which were superior than 0%-NaCl. As salinity increased, the nitrogen removal effect was negatively affected. Microbial diversity analysis indicated that the microbial community structure was uniform in the control group, 0%-NaCl, and 0.5%-NaCl, with the dominant genus OLB8 ensuring the nitrogen removal performance. In contrast, in the 2.5%-NaCl and 3.5%-NaCl experimental groups, the organic degrading bacteria were still active, while nitrifiers and denitrifiers were severely damaged. In conclusion, this study suggested that low concentrations of salinity can improve the decontamination performance of the electro-enhanced aniline biodegradation system, while high concentrations of salinity could lead to the collapse of the decontamination mechanism.

Understanding the impacts of intermittent electro field on the bioelectrochemical aniline degradation system: Performance, microbial community and functional enzyme

On account of the lack of a sustainable electron donor source and the inhibitory effect of aniline on denitrogenation make it tough to achieve simultaneous removal of aniline and nitrogen. Herein, the strategy of adjusting electric field mode was applied to the electro-enhanced sequential batch reactors (E-SBRs: R1 (continuous ON), R2 (2 h-ON/2 h-OFF), R3 (12 h-ON/12 h-OFF), R4 (in the aerobic phase ON), R5 (in the anoxic phase ON)) to treat aniline wastewater. Aniline removal rate reached approximately 99% in the five systems. Decreasing electrical stimulation interval from 12 to 2 h significantly improved the electron utilization efficiency for aniline degradation and nitrogen metabolism. The total nitrogen removal was achieved from 70.31% to 75.63%. Meanwhile, the hydrogenotrophic denitrifiers of Hydrogenophaga, Thauera, and Rhodospirillales, enriched in reactors of minor electrical stimulation interval. Accordingly, the expression of functional enzyme related to electron transport was incremental with the proper electrical stimulation frequency.

The role of acceptor and π-bridge for donor-driven halochromism of D-π-A N,N-dialkylaminostyrylhetarenes

The photophysical properties of a series of D-π-A chromophores, where D is represented by di- or trialkylaniline moiety, π – vinylene, A - quinoxaline, quinoxalinone, quinoline, benzothiazole and thiophenecarboxaldehyde, have been analyzed upon acidification. In all cases, appearance of the second emission band is associated with protonation of the nitrogen atom in the donor fragment. Nevertheless, the simultaneous appearance of two emission bands at equal amounts of acid is observed only for dyes with a quinoxalinone acceptor fragment, which suggests the crucial role of the latter in providing dual emission upon acidification. The highest pH sensitivity has been achieved for the dye with an ethyl group at the ortho-position of benzene ring relative to the vinylene bridge. In contrast, the variation of substituents at the aniline nitrogen atom, the protonation of which causes the appearance of the emission under acidic conditions, does not lead to significant changes in pH sensitivity.

The changing C/N of aggressive aniline: Metagenomic analysis of pollutant removal, metabolic pathways and functional genes

In order to optimize the degradation of high-concentration aniline wastewater, the operation of sequencing batch bioaugmentation reactors with different aniline concentrations (200 mg/L, 600 mg/L, 1000 mg/L) was studied. The results showed that the removal rates of aniline and COD in the three reactors could reach 100%. When the aniline increased to 600 mg/L, the nitrogen removal efficiency reached the peak (51.85%). The increase of aniline inhibited the nitrification, while denitrification was enhanced due to the increase of C/N ratio. But this change was reversed by the toxicity of high concentrations of aniline. The metagenomic analysis showed that when the aniline concentration was 600 mg/L, the abundance distribution of microbial samples was more uniform. The improved of aniline concentration had led to the increase of aromatic compounds degradation metabolic pathways. In addition, the abundance of aniline degradation and nitrogen metabolism genes (dmpB, xylE, norB) was also promoted.

Comparative Analysis of a Series of pH‐Responsive Sulphonated Europium Complexes for Bioassays Monitoring Acidification

AbstractThe synthesis and photophysical evaluation of a series of hydrophilic sulphonated and pH responsive luminescent europium(III) probes are reported. The Eu emission intensities and lifetimes increase very significantly on lowering pH, leading to a ‘switching on’ of Eu luminescence in more acidic media. By varying the nature of the substituents at an integral aniline nitrogen atom located in the sensitising chromophore, the pKa value of the complex can be tuned to between 4.3 and 6.3 for a set of five Eu(III) complexes. These systems are designed to allow conjugation to targeting vectors permitting, for example, the monitoring of receptor internalisation in cells. This approach can be used to tag proteins selectively and allows the monitoring of uptake into acidic organelles, enabling the creation of time‐resolved internalisation assays to follow pH change in real time, both in vitro and in cellulo.

Discovery and synthesis of 1,2,4-oxadiazole derivatives as novel inhibitors of Zika, dengue, Japanese encephalitis, and classical swine fever virus infections.

Zika virus (ZIKV), an arbovirus of the Flaviviridae family, has emerged as a significant public health concern owing to its association with congenital abnormalities and severe neurological sequelae. Thus, there is an urgent need to develop effective therapeutic approaches to efficiently treat ZIKV infections. This study used phenotypic screening to identify a series of 1,2,4-oxadiazole derivatives that possess antiviral activity against ZIKV infection. Subsequently, 28 new derivatives were designed, synthesized, and evaluated for this purpose. Among these compounds, 4-(5-phenyl-1,2,4-oxadiazol-3-yl)-N-(pyridin-3-ylmethyl)aniline (5d) had potent antiviral activity against ZIKV infections. Furthermore, a structure-activity relationship analysis indicated that a benzyl substitution on the aniline nitrogen of this compound improved potency while augmenting its drug-like properties. In addition, 5d exhibited antiviral activity against various viruses of Flaviviridae family of worldwide public health importance, such as dengue, Japanese encephalitis and classical swine fever viruses, indicating its potential as a lead compound for generating 1,2,4-oxadiazole derivatives with broad-spectrum anti-flaviviral properties.

Synthesis of chiral N-alkylated indoles through replacement of aniline nitrogen by natural amino acids

Chiral N-alkylated indoles are privileged structural motifs found in many natural products and pharmaceuticals and a search for effective methods with which to prepare chiral N-alkylated indoles is ongoing. Efficient syntheses of enantioenriched N-alkylated indoles has been developed but not with standing these advances, the development of a facile method to prepare chiral N-alkylated indoles from simple and available starting materials under mild conditions is still needed. In this paper, we report a nitrogen replacement process driven by dearomatization that directly incorporates natural α-amino acids into 2-alkynylanilines leading to the formation of a variety of multi-functional chiral N-alkylated indoles.

Probing the Ni2+ -selective Response of Fluorescent Probe NiSensor-1 with the NiCast Photocaged Complex.

CTEA (N,N-bis[2-(carboxylmethyl)thioethyl]amine) is a mixed donor ligand that has been incorporated into multiple fluorescent sensors such as NiSensor-1 that was reported to be selective for Ni2+ . Other metal ions such as Zn2+ do not produce an emission response in aqueous solution. To investigate the coordination chemistry and selectivity of this receptor, we prepared NiCast, a photocage containing the CTEA receptor. Cast photocages undergo a photoreaction that decreases electron density on a metal-bound aniline nitrogen atom, which shifts the binding equilibrium toward unbound metal ion. The unique selectivity of CTEA was examined by measuring the binding affinity of NiCast and the CTEA receptor for Ni2+ , Zn2+ , Cd2+ and Cu2+ under different conditions. In aqueous solution, Ni2+ binds more strongly to the aniline nitrogen atom than Cd2+ ; however, in CH3 CN, the change in affinity virtually disappears. The crystal structure of [Cu(CTEA)], which exhibits a Jahn-Teller-distorted square pyramidal structure, was also analyzed to gain more insight into the underlying coordination chemistry. These studies suggest that the fluorescence selectivity of NiSensor-1 in aqueous solution is due to a stronger interaction between the aniline nitrogen atom and Ni2+ compared to other divalent metal ions except Cu2+ .

Control of aeration time in the aniline degrading-bioreactor with the analysis of metagenomic: Aniline degradation and nitrogen metabolism

The strategy of adjusting aeration time (5 h/6 h/7 h) was applied to the sequential batch reactors to optimize the treatment of aniline wastewater (600 mg/L) conveniently and economically. Three reactors degraded aniline effectively. The nitrogen removal ability of system with 6 h aeration time was better, performing the similar denitrification property as 5 h and nitrification performance as 7 h. Meanwhile, longer aeration time potentially damaged the sludge structure. The metagenomic analysis explained the micro-mechanism for the better performance of the system with 6 h aeration time. Appropriate aeration time was conducive to the enrichment of synergistic microflora, including aniline degrading-bacteria, heterotrophic nitrifiers and denitrifiers. Then, the tilt of environmental resources to these floras in the system was beneficial to the maximum value utilization of living substrates. Accordingly, these bacteria were more closely related to genes, resulting in higher expression of functional genes in the system.

Study on the Feasibility of Enhancing the Biodegradation of Aniline Wastewater by Polyvinyl Alcohol-Sodium Alginate Gel Pellets Embedded Activated Sludge

Embedded pellets obtained by means of embedding activated sludge in polyvinyl alcohol—sodium alginate were successfully adapted in aniline wastewater degradation system. The results of shake flask experiment showed that the combination of sludge and embedded pellets had the best performance in degrading aniline, compared with sludge system and pellet system. Moreover, the application of embedded pellets promoted the toxicity tolerance and operation performance of the reactor. The enhanced reactor could completely degrade aniline and ammonia nitrogen in 150 and 240 min, and the total nitrogen removal rate increased by 26.83%. Meanwhile, high-throughput sequencing results illustrated that the addition of embedded pellets can effectively protect the diversity of functional microbial community. The average relative abundances of main functional genera such as Hydrogenophaga (aromatic amine compounds degradation and heterotrophic nitrification-aerobic denitrification), Norank_f__ Microscillaceae (nitrification), Brevundimonas (heterotrophic nitrification-aerobic denitrification), and Flavobacterium (denitrification) increased by 50.63%, 73.45%, 99.71%, 89.6%, 72.01%, and 95.70%, respectively.

A metagenomic view of how different carbon sources enhance the aniline and simultaneous nitrogen removal capacities in the aniline degradation system

To cross nitrogen removal barrier, carbon sources (sodium succinate (Z1), sodium acetate (Z2) and glucose (Z3)) were applied in aniline degradation reactor to enrich heterotrophic nitrifiers and denitrifiers. The aniline was degraded almost completely and the nitrogen removal performance was improved in three systems. The total nitrogen (TN) removal efficiency of Z2 was the highest. The dominant bacteria were phylum Proteobacteria, class BetaProteobacteria, and genus Thauera (Z1, Z3), Leptothrix (Z2). Different aniline degrading bacteria, heterotrophic nitrifiers and denitrifiers were enriched, and Z2 had more high-abundance communities. Three systems followed the meta-cleavage pathway for the aniline degradation according to the genes annotation. Particularly, the contribution of each genus to nitrogen metabolism and aromatic compounds degradation in the Z2 was more evenly distributed, rather than relying mainly on the contribution of Thauera in Z1 and Z3 so that more functional genes related nitrogen metabolism and aniline degradation were more abundant in Z2.

NSSN-Type Group 4 Metal Complexes in the Ring-Opening Polymerization of l-Lactide.

A new class of zirconium and hafnium complexes coordinated by linear dianonic tetradentate NSSN ligands is reported. The ligands feature two amide functions coupled with two thioether groups linked by a central flexible ethane bridge and two lateral rigid phenylene bridges and differ for the substituents on the aniline nitrogen atoms, i.e., isopropyl, cyclohexyl, or mesityl substituents: NSSN-iPr, NSSN-Cy, or NSSN-Mes. They were prepared by reacting 2-aminothiophenol with dibromoethane to afford the NSSN ligands without substituents on the aniline nitrogen atoms, which were subsequently alkylated through a reductive amination of acetone or cyclohexanone or palladium-catalyzed cross-coupling reaction with mesityl bromide. The corresponding zirconium and hafnium complexes 1-5 were obtained through a transamination reaction between the neutral ligands and Zr(NMe2)4 or Hf(NMe2)4 [(NSSN-iPr)Zr(NMe2)2 (1), (NSSN-Cy)Zr(NMe2)2 (2), (NSSN-Mes)Zr(NMe2)2 (3), (NSSN-iPr)Hf(NMe2)2 (4), and (NSSN-Cy)Hf(NMe2)2 (5)]. They were characterized in solution by NMR spectroscopy and in solid state by X-ray diffraction analysis (except for 3). All complexes present an octahedral coordination geometry with a fac-fac ligand wrapping and a cis relationship between the other two monodentate ligands. The catalytic performances of 1-5 in the ring-opening polymerization of cyclic esters were investigated. Complex 1 was the most active: its polymerization activity was superior to those generally displayed by zirconium complexes featuring OSSO ligands and compared well with those of the most active group 4 complexes operating in a toluene solution.

A combined experimental and computational structural study of the N-(2-cyanophenyl)disulfonamides derived from 5-bromo- and 5-iodoanthranilamide

One-pot sulfonyl chloride-pyridine mediated disulfonylation of the aniline nitrogen atom and dehydration of the primary amide group of the 5-halogenoanthranilamide derivatives afforded the corresponding N-(2-cyanophenyl)disulfonamides, exclusively. This facile reaction makes use of readily available substrates and gives high yield of the products in short reaction time. The structures of these compounds were characterised using a combination of nuclear magnetic resonance (1H NMR & 13C NMR), infrared (IR) and mass spectrometric techniques. Their geometry was distinctly confirmed by single crystal X-ray diffraction (XRD) analysis of N-(4-bromo-2-cyanophenyl)-N-(methylsulfonyl)methanesulfonamide (2a) as representative model. The geometrical optimizations of structures of compounds 2a, 2b and 2c were also investigated by means of density functional theory (DFT) calculations. The optimized structural parameters (bond lengths, bond angles, and torsion angles) of 2a have been compared with those of the X-ray structure.

Iron-promoted dealkylative carbene aminocyclization of δ-arylamino-α-diazoesters.

Herein, we report a novel methodology to access N-aryl proline derivatives using amino-tethered α-diazoesters and cheap, readily available iron salts. Mechanistically, the aminocyclization reaction involves the initial formation of an iron-carbene complex followed by a nucleophilic attack of the aniline nitrogen atom to give an ammonium ylide intermediate, which finally undergoes the iron-promoted dealkylation.

D-π-A'-π-A chromophores with quinoxaline core in the π-electron bridge and charged heterocyclic acceptor moiety: Synthesis, DFT calculations, photophysical and electro-chemical properties

Chromophores with charged heterocyclic acceptor moiety in combination with divinylquinoxaline conjugated π-bridge show a significant solvatochromic shift, small energy gap value (determined by various methods), and large values of the first hyperpolarizability estimated by DFT. A quinoxaline-based chromophore with an indolium acceptor exhibits an outstanding solvatochromic shift (0.38 eV), probably a record one for D-π-A chromophores with a dialkyl aniline donor moiety. A good correlation between the above characteristics and the calculated NBO π-charge on the aniline nitrogen atom has been found. A change in the trend by opposite one in the characteristics in the series of quinolinium /benzothiazolium/ indolium chromophores is exhibited when passing from gas to solvent.

The 1H [formula omitted] dispersion curve of fentanyl citrate to identify NQR parameters

We report the 1H T1 dispersion curve between 0 and 5 ​MHz for the synthetic opioid fentanyl citrate (C28H36N2O8). The structures in the curve can be used to estimate the 14N nuclear quadrupole resonance (NQR) frequencies of the material. Density functional theory predictions of the NQR parameters of several fentanyl citrate compounds are also reported. The predictions for the aniline nitrogen are consistent with structures in the observed T1 data. To help interpret the fentanyl citrate results the T1 dispersion curve for the explosive ammonium nitrate is also presented.