Nitro Substituents Research Articles

Effects of Polar Substituents and Media on the Performance of N,N′‐Di‐tert‐Butoxycarbonyl‐Indigos as Photoswitches

AbstractThe N,N′‐di‐tert‐butoxycarbonylindigo parent compound and four symmetrically substituted derivatives alternatively containing methoxy and nitro substituents in positions 5 and 6 were synthesized. The photochromic behavior was studied in solvents ranging in polarity from toluene to acetonitrile/water mixtures and characterized in terms of trans and cis isomer spectra, conversion quantum yields and thermal half‐lives of the metastable cis isomers. The half‐lives at 21 °C varied from a few seconds (5‐nitro in polar solvents) to several days (6‐methoxy in apolar media) and can be described by the substituents’ Hammett constants. Spectroscopic and photochemical parameters, in contrast, are governed largely by the substituents’ resonance effects according to a scheme well known from thioindigos and these are termed here favorable and unfavorable resonance effects (FRE and URE, respectively). The title photoswitches show little propensity to quenching by protons and may be operated in aqueous media.

RETRACTED ARTICLE: Three-Dimensional Ni(II)-MOF Containing an Asymmetric Pyridyl-Carboxylate Ligand: Catalytic Cyanosilylation of Aldehydes and Inhibits Human Promyelocytic Leukemia Cancer Cells

A new Ni(II)-based metal–organic framework with the chemical formula of (Me2NH2)[Ni3(L)2(μ3-OH)(H2O)]·2DMF (1) have been designed and synthesized by the reaction of 3-phenylpyridine polycarboxylic (H3L) ligands and Ni(NO3)2·6H2O in a mixed solvent of DMF and water under the solvothermal conditions. The resulting solvent-free 1a was found to be catalytically active for the cyanosilylation reaction of aromatic aldehydes with nitro substituent in varying positions in the presence of trimethylsilyl cyanide to afford cyanohydrin trimethylsilyl ethers in a shape and size selective manner. The as-prepared 1 did not exhibit catalytic activities for the same reaction. Based on the experimental results, a possible catalytic mechanism has also been proposed. We next examined the cell viability with CCK-8 assay and the cell proliferation with plate colony formation assay. Both experiments suggested the inhibitory effect of compound 1a on human promyelocytic leukemia cancer HL-60 cells. For the mechanism exploration, the ROS content in HL-60 cancer cells was measured with detection kit, results also indicated the compound 1a increased the level of ROS in HL-60 cells, which may the reason of the compound’s anti-cancer activity.

Substituent effect on colorimetric detection of biologically and environmentally relevant anions: Insight in real-life applications.

A new set of chromogenic anion receptors R1-R4 have been synthesized with a different substituent, including electron withdrawing (nitro moiety in R1), conjugated group (naphthyl in R2), and electron donating (methyl in R3), respectively. The receptors R1-R4 exhibited very good sensitivity towards the F- and AcO- anions in the DMSO. In addition, R1 showed selectivity towards H2PO4- ions over other tested anions. R1 especially acted as an effective sensor for sodium salts of F-, AcO-, AsO2-, and AsO42- ions in an aqueous medium due to the presence of two electron-withdrawing nitro substituents, which showed hydrogen bond donor tendency and acidity of the OH proton. This result indicates that R1 is highly capable of competing with an aqueous medium to detect anions without counter Na+ ion interference. Interestingly, R1 displays solvatochromic property in the presence of AcO- ions in different aprotic solvents. Additionally, the receptor R1 shows high binding affinity towards AcO- ions in the buffer medium (DMSO: HEPES, 9:1 v/v), which displayed remarkable colour change from pale yellow to blue with a large ∆λred shift of 170 nm. The CV studies reveal the deprotonation of the -NH proton upon interaction with the AcO- ions. The receptor R1 is subjected to practical application to sense F- and AsO2- ions using the test strip. In addition, the receptor R1 proves itself as a potential applicant for the detection of F- ions quantitatively in commercially available mouthwash.

Synthesis, Spectral and Electrochemical Redox Properties of EAA-Appended Porphyrins

Porphyrins having nitro substituents at β-position can act as excellent synthons for further functionalization of porphyrins having wide range of applications [1]. β-Nitro-meso-tetraarylporphyrins can be further functionalized in presence of Michael donor such as active methylene compounds which result in the formation of porphyrins and chlorins depending on reaction conditions and bulkiness of the Michael donor [2-5]. A wide variety of active methylene compounds such as 1,3-dicarbonyls, diketoesters and malonates can undergo Michael addition reactions under mild basic conditions [6]. In this regard, we report the selective synthesis of 2-EAA-5,10,15,20-tetraphenylporphyrins and their metal complexes (Fig. 1a) [7]. All of the synthesized EAA-appended porphyrins exhibited enol tautomeric form in solution predominantly. However, there is no keto-enol tautomerism in it as there is no peak for -CH in 1H NMR spectrum. EAA-appended porphyrins have shown multiple oxidations and reductions in cyclic voltammograms possibly due presence of EAA group on porphyrin ring (Fig. 1b).MTPP(EAA) where M = 2H, Co(II), Ni(II), Cu(II) and Zn(II) exhibited a remarkable red shift (10-15 nm) in the B and Q bands as compared to the corresponding MTPPs, whereas all these porphyrins have bands which are blue-shifted by ∼10-14 nm as compared to their precursor, i.e., MTPP(NO2). In this presentation, we will present the synthesis, spectral and electrochemical redox properties of EAA-appended porphyrins. Figure 1. (a) Molecular structures of synthesized porphyrins and (b) Cyclic voltammograms (CVs) of CuTPP, CuTPP(NO2) and CuEAA complexes in CH2Cl2 at 298 K.

Analysis of Bisulfite Via a Nitro Derivative of Cyanine-3 (NCy3) in the Microfluidic Channel.

NCy3, a derivative of Cyanine 3 with a nitro substituent, showed a high reactivity to bisulfite in aqueous media, instantly leading to ratiometric change of absorption spectra and significant fluorescence quenching. Applied in the microfluidic channel, NCy3 functionalize as a sensitive approach for quantitative detection of bisulfite, particularly for samples with a small volume.

Antibacterial Activity and Mode of Action of a Sulfonamide-Based Class of Oxaborole Leucyl-tRNA-Synthetase Inhibitors.

Benzoxaboroles are a class of boron-containing compounds with a broad range of biological activities. A subset of benzoxaboroles have antimicrobial activity due primarily to their ability to inhibit leucyl-tRNA synthetase (LeuRS) via the oxaborole tRNA-trapping mechanism, which involves the formation of a stable tRNALeu-benzoxaborole adduct in which the boron atom interacts with the 2'- and 3'-oxygen atoms of the terminal 3' tRNA adenosine. We sought to identify other antibacterial targets for this promising class of compounds by means of mode-of-action studies, and we selected a nitrophenyl sulfonamide based oxaborole (PT638) as a probe molecule because it had potent antibacterial activity (MIC of 0.4 μg/mL against methicillin-resistant Staphylococcus aureus) but did not inhibit LeuRS (IC50 > 100 μM). Analogues of PT638 were synthesized to explore the importance of the sulfonamide linker and the impact of altering the functionalization of the phenyl ring. These structure-activity-relationship studies revealed that the nitro substituent was essential for activity. To identify the target for PT638, we raised resistant strains of S. aureus, and whole-genome sequencing revealed mutations in leuRS, suggesting that the target for this compound was indeed LeuRS, despite the lack of enzyme inhibition. Subsequent analysis of PT638 metabolism demonstrated that bacterial nitroreductases readily converted this compound into the amino analogue, which inhibited LeuRS with an IC50 of 3.0 ± 1.2 μM, demonstrating that PT638 is thus a prodrug.

A bio-inspired O2-tolerant catalytic CO2 reduction electrode

The electrochemical reduction of CO2 to give CO in the presence of O2 would allow the direct valorization of flue gases from fossil fuel combustion and of CO2 captured from air. However, it is a challenging task because O2 reduction is thermodynamically favored over that of CO2. 5% O2 in CO2 near catalyst surface is sufficient to completely inhibit the CO2 reduction reaction. Here we report an O2-tolerant catalytic CO2 reduction electrode inspired by part of the natural photosynthesis unit. The electrode comprises of heterogenized cobalt phthalocyanine molecules serving as the cathode catalyst with >95% Faradaic efficiency (FE) for CO2 reduction to CO coated with a polymer of intrinsic microporosity that works as a CO2-selective layer with a CO2/O2 selectivity of ∼20. Integrated into a flow electrolytic cell, the hybrid electrode operating with a CO2 feed gas containing 5% O2 exhibits a FECO of 75.9% with a total current density of 27.3 mA/cm2 at a cell voltage of 3.1 V. A FECO of 49.7% can be retained when the O2 fraction increases to 20%. Stable operation for 18 h is demonstrated. The electrochemical performance and O2 tolerance can be further enhanced by introducing cyano and nitro substituents to the phthalocyanine ligand.

Electrochemical Study of Poly(aryloxyphosphazenes) Functionalized with COOH and NO2 Groups. In Search of New Applications

An electrochemical study of poly(aryloxyphosphazenes) substituted with COOH and NO2 groups is reported here for the first time. In order to develop new applications, a glassy carbon electrode was coated with the compound in non-aqueous media, and it behavior was studied using Cyclic Voltammetry, Differential Pulse Voltammetry and Electrochemical Impedance Spectroscopy techniques. The analysis showed that the current intensity of the electrochemical response increases when the substitution degree in COOH− as NO2−functionalized poly(aryloxyphosphazenes) increases, therefore is it possible to predict the degree of substituent for this kind of polymer. Subsequently the morphology of glassy carbon electrodes modified with COOH− and NO2−functionalized poly(aryloxyphosphazenes) was characterized using Scanning electron microscopy. The COOH−functionalized poly(aryloxyphosphazenes) can act as pH sensing electrodes. Furthermore, the present research demonstrates that the electrochemical synthesis of NH2−functionalized poly(aryloxyphosphazenes) is a suitable methodology for the reduction of nitro substituents avoiding the generation of hazardous wastes. The reduction of NO2−functionalized poly(aryloxyphosphazenes) degree is reported.

Synthesis and optical studies of Y-shaped imidazole derivatives.

A novel series Y-shaped π-expanded imidazole based chromophores was designed and synthesized. The series contains thirteen 2-aryl-4,5-bis[2-(aryl)vinyl)]-1H-imidazoles (6a-6m), which were characterized by spectroscopic analysis. The structures of compounds 6d and 6j were also confirmed by X-ray crystallographic analysis. The optical studies were investigated using absorption and emission measurements in dichloromethane. The fluorescence quantum yields were observed varying in 0.22-0.59 range, but the compounds with nitro substituent did not show the fluorescence. The absorption and emission study of the series helped us to understand the effect of substituents on the optical properties of compounds as well.

Synthesis of 1-(5-Chloro-2-hydroxyphenyl)-5-oxopyrrolidine-3-carboxylic Acid Derivatives and Their Antioxidant Activity.

A series of novel 1-(5-chloro-2-hydroxyphenyl)-5-oxopyrrolidine-3-carboxylic acid derivatives containing chloro, hydroxyl, isopropyl, nitro, nitroso, and amino substituents at benzene ring and 1-(5-chloro-2-hydroxyphenyl)-5-oxopyrrolidine-3-carbohydrazide derivatives bearing heterocyclic moieties were synthesized. Antioxidant activity of the synthesized compounds was screened by DPPH radical scavenging method and reducing power assay. A number of compounds were identified as potent antioxidants. Antioxidant activity of 1-(5-chloro-2-hydroxyphenyl)-4-(5-thioxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)pyrrolidin-2-one has been tested to be 1.5 times higher than that of a well-known antioxidant ascorbic acid. 1-(5-Chloro-2-hydroxyphenyl)-4-(4-methyl-5-thioxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)pyrrolidin-2-one has shown 1.35 times higher antioxidant activity than that of vitamin C by DPPH radical scavenging method and optical density value of 1.149 in reducing power assay. The structure of 1-(5-chloro-2-hydroxyphenyl)-N-(1,3-dioxoisoindolin-2-yl)-5-oxopyrrolidine-3-carboxamide was unambiguously assigned by means of X-ray diffraction analysis data.

Tuning the recognition properties of urea based receptor towards cyanide in aqueous medium: Effect of fluorine substitution on strength and selectivity of the anion receptor.

In this report, we have successfully tuned the selectivity and sensitivity of an anion receptor L1 by substituting electron withdrawing natured fluorine atoms directly on to the rim of the phenyl ring. Despite the fact that, we have two electron withdrawing natured nitro substituents on the other side of receptor L1; two fluorine substitutions made dramatic change in the sensing ability as well as the selectivity of the receptor L1 towards anions. The acetonitrile solution contains L1 with tetrabutyl ammonium salts of fluoride, cyanide, acetate and dihydrogen phosphate results sudden color changes from yellow to brown; almost negligible spectral/color change for azide and bifluoride, where as there is no color change observed with any other anionic guests with L1. Solution state binding studies of L1 are carried out by UV-Vis spectrometry titration in 100% acetonitrile and it is found to be the receptor L1 selectively binds cyanide, phosphate and fluoride stronger than acetate; it is also found that receptor binds fluoride 100 times stronger than that of the receptor L and L1 has almost similar efficiency in binding towards acetate ion (AcO-). The strength of the receptor L1 towards fluoride, cyanide, acetate and dihydrogen phosphate bindings are found to be in the order of 1.271 × 105 M-1 > 1.245 × 105 M-1 > 1.368 × 103 M-1, 1.23 × 103 M-1 respectively. When we used aqueous environment (10% of water in acetonitrile) as testing solvent system, the receptor L1 selectively sense cyanide ion. Over all, strength of the receptor is increased towards anions with an increasing the number of fluorine atom onto the receptors. Here in we have also prepared a reference compound L2 in which the receptor molecule is substituted with only one fluoride atom. The acetonitrile solution of reference receptor L2 with help of naked-eye colorimetric experiment and spectrometric ammonium salts of fluoride, cyanide, acetate and bifluoride results sudden color changes from faint-yellow to brown in color. Unlike receptor L1, receptor L2 does not recognize H2PO4-, but instead of H2PO4-, it recognizes bifluoride as evidenced from UV-Vis spectroscopic and naked-eye colorimetric studies.

A study towards drug discovery for the management of type 2 diabetes mellitus through inhibition of the carbohydrate-hydrolyzing enzymes α-amylase and α-glucosidase by chalcone derivatives.

The inhibition of carbohydrate-hydrolyzing enzymes, α-amylase and α-glucosidase, is one of the major therapeutic strategies for the treatment of type 2 diabetes mellitus. Chalcones have been recognized for their multiple biological activities, including antidiabetic properties, through unclear mechanisms. In the present work, a panel of chalcones bearing hydroxy, methoxy, methyl, nitro, chloro, fluoro and bromo substituents were evaluated against α-amylase and α-glucosidase activities, most of them for the first time. The results showed that the substitution patterns and the type of substituents of chalcones influence their inhibitory activity. The presence of hydroxy groups at C-2'- and C-4' of the A ring and at C-3 and C-4 of the B ring favors the intended effect. Chalcones holding nitro groups and chloro substituents, together with a hydroxy group in the chalcone scaffold, showed strong inhibition of the α-glucosidase activity. The present study provides related scaffolds that may serve as the basis for the design and synthesis of new structures in order to obtain the ideal antidiabetic chalcone.

Influence of nitro substituents on the redox, electronic, and proton reduction catalytic behavior of phenolate-based [N2O3]-type cobalt(iii) complexes.

We report on the synthesis, redox, electronic, and catalytic behavior of two new cobalt(iii) complexes, namely [CoIII(L1)MeOH] (1) and [CoIII(L2)MeOH] (2). These species contain nitro-rich, phenolate-based pentadentate ligands and present dramatically distinct properties associated with the position in which the -NO2 substituents are installed. Species 1 displays nitro-substituted phenolates, and exhibits irreversible redox response and negligible catalytic activity, whereas 2 has fuctionalized phenylene moieties, shows much improved redox reversibility and catalytic proton reduction activity at low overpotentials. A concerted experimental and theoretical approach sheds some light on these drastic differences.

СИНТЕЗ ТА ФОТОВОЛЬТАЇЧНІ ВЛАСТИВОСТІ СИМЕТРИЧНИХ БІС-АЗОМЕТИНІВ З АКЦЕПТОРНИМИ ЗАМІСНИКАМИ У 4,4'-ПОЛОЖЕННІ

Two new symmetric azomethine dyes capable of photoinduced isomerization were synthesized by condensing symmetric bis-aldehyde (obtained by the reaction of epichlorohydrin with 4-oxybenzaldehyde) with 4-nitroaniline and 4-chloroaniline, respectively. The yield of the target products decreases with the transition from nitro-substituted azomethine to chlorine-substituted. This is due to the greater basicity of the starting amines with nitro-substitution when increasing the acceptor force of the substituent complicates the course of the reaction. Azomethines are characterized by absorption with a maximum at 400–410 nm, which makes them sensitive to radiation with a blue component of the spectrum. The photoelectric properties of azomethines upon irradiation were investigated by the method of measuring the surface potential with the help of a Kelvin dynamic probe. The maximum value of the electric potential of the photosensitive films free surface during irradiation with white LED at I = 60 W/m2 is about 270 mV in the case of azomethine with a nitro group in the 4,4' position and about 125 mV in the case of azomethine with chlorine as a substituent. That is, the magnitude of the electric potential of the free surface decreases approximately twice during the transition from nitro substituent to chlorine. This may be explained by the fact that the photoinduced changes in azomethine with a higher acceptor substituent flow more quickly and with greater efficiency. But at the same time, the reverse changes when turning off the light are just as fast. For chlorine substituted azomethine samples, the reverse process proceeds rather slowly, which may indicate greater stability over time of the photochemically modified form in case of chlorine substitution compared to the nitro-substituted analogue. Thus, the synthesized azomethines can be used in the development of new photovoltaic media and recording media for optical information recording.

Supramolecular cage encapsulation as a versatile tool for the experimental quantification of aromatic stacking interactions.

The widespread presence of aromatic stacking interactions in chemical and biological systems, combined with their relatively small energetic contribution, have led to a plethora of theoretical and experimental studies for their quantification and rationalization. Typically, π-π aromatic interactions are studied as a function of substituents to gather information about the interaction mechanism. While experiments suggest that aromatic interactions are dominated by local electrostatic contacts between π-electron density and CH groups, theoretical work has raised the possibility that direct electrostatic interactions between local dipoles of the substituents may play a role. We describe a supramolecular cage that binds two aromatic carboxylates in a stacked geometry such that the aromatic substituents are remote in space. Chemical Double Mutant Cycles (DMCs) were used to measure fifteen different aromatic stacking interactions as a function of substituent (NMe2, OMe, Me, Cl and NO2). When both aromatic rings have electron-withdrawing nitro substituents, the interaction is attractive (-2.8 kJ mol-1) due to reduced π-electron repulsion. When both aromatic rings have electron-donating di-methylamino substituents, the interaction is repulsive (+2.0 kJ mol-1) due to increased π-electron repulsion. The results show that aromatic stacking interactions are dominated by short range electrostatic contacts rather than substituent dipole interactions.

Design and Synthesis of Some New Benzimidazole Containing Pyrazoles and Pyrazolyl Thiazoles as Potential Antimicrobial Agents

A new class of bis heterocycles‐benzimidazolyl pyrazoles were prepared from the Michael acceptor (E)‐3‐(1H‐benzimidazol‐2‐yl)‐1‐aryl‐prop‐2‐en‐1‐one. The thiamide group was exploited to develop thiazole ring on treatment with p‐fluorophenacyl bromide to get tris heterocycles. All the lead compounds were tested for antimicrobial activity. The compound 7d having nitro substituent on the aromatic ring showed greater antimicrobial activity particularly against Pseudomonas aeruginosa and Penicillium chrysogenum.

The first target specific, highly diastereoselective synthesis, design and characterization of pyranoquinolinyl acrylic acid diastereomers as potential α-glucosidase inhibitors

In the present investigation we report the first target specific, highly diastereoselective synthesis of new class of pyranoquinolinyl/furoquinolinyl-acrylic acid diastereomers and evaluation of their invitro α-glucosidase inhibitory activity. All the products were thoroughly characterized by 1H NMR, 13C NMR, FT-IR, Mass spectral and CHN analysis. A highly diastereoselective target specific route of synthesis for the biologically active diastereomers were developed by usingchiral catalyst Europium tris[3-heptafluoropropylhydroxyl methylene]-(−)-camphorate (A) or Europiumtris[3-(trifluoromethyl)hydroxylmethylene]-(+)-camphorate (B). It was found that among a set of 4 diastereomeric products obtained, exodiasteromers of pyranoquinolinyl acrylic acid adducts exhibited relatively high α-glucosidase inhibitory activity. The newly synthesized compounds exhibited IC50 values in the range of (0.40 ± 0.02–30.3 ± 0.84 μM) as compared to standard acarbose (IC50 = 0.65 ± 0.02 μM). It was found that compounds 11a, 11c, 11d and 12d were found to be more active than standard acarbose. It was also found that unsubstituted compound (11a) or compounds with chlorine or methoxy substituent (11c, 11d, 12d) showed potential α-glucosidase inhibitory activity. However a reversal in activity was observed with Nitro substituent (11b, 13b) wherein the endodiastereomers were found to be more active than exodiastereomers. Molecular docking studies were used for design of the compound and understand the mode of binding between the compound and target enzyme. A plausible mechanism for the diastereoselective synthesis was also proposed.

Nitromethane as a Carbanion Source for Domino Benzoannulation with Ynones: One‐Pot Synthesis of Polyfunctional Naphthalenes and a Total Synthesis of Macarpine

AbstractA one‐pot, transition‐metal‐free, domino Michael/SNAr protocol of general applicability has been devised for the regioselective synthesis of polyfunctional naphthalenes by employing nitromethane and ortho‐haloaryl ynones. Utilization of nitromethane as a one carbon carbanion source that is incorporated into a variety of ynones, ends up as an aromatic nitro substituent. The application of this domino process towards a total synthesis of the polycyclic alkaloid macarpine demonstrate for the efficacy of this methodology. The conceptually simple approach to affect regioselective, multifunctional benzoannulation of ynones displays wide substrate scope and functional‐group tolerance and has been implemented with substituted nitromethanes, as well as with alicyclic o‐haloynones.

Nitromethane as a Carbanion Source for Domino Benzoannulation with Ynones: One-Pot Synthesis of Polyfunctional Naphthalenes and a Total Synthesis of Macarpine.

A one-pot, transition-metal-free, domino Michael/SN Ar protocol of general applicability has been devised for the regioselective synthesis of polyfunctional naphthalenes by employing nitromethane and ortho-haloaryl ynones. Utilization of nitromethane as a one carbon carbanion source that is incorporated into a variety of ynones, ends up as an aromatic nitro substituent. The application of this domino process towards a total synthesis of the polycyclic alkaloid macarpine demonstrate for the efficacy of this methodology. The conceptually simple approach to affect regioselective, multifunctional benzoannulation of ynones displays wide substrate scope and functional-group tolerance and has been implemented with substituted nitromethanes, as well as with alicyclic o-haloynones.

Design of Cu-based intermetallic nanocrystals for enhancing hydrogenation selectivity

Motivated by the high performance of intermetallic compounds with their ordered structures, developing synthetic methods for preparing intermetallic compounds is highly desired. Herein, we report facile syntheses and rational design of the structurally ordered Cu-based intermetallic compounds (CuM (M = Pt, Pd, Au)). To achieve this, intermetallic nanoparticles were synthesized in solution by a butyllithium co-reduction method at 240 °C. The developed wet-chemistry syntheses of ordered intermetallic CuM nanoparticles avoided solid annealing process, and thus relatively small intermetallic nanocrystals were formed. The ordered PtCu nanocatalysts displayed enhanced chemoselectivity relative to the PtCu solid-solution alloy and individual monometallic nanocatalysts for catalytic hydrogenations of a series of substituted nitroaromatics. The DFT-based theoretical calculations for hydrogenations of halonitrobenzenes suggest that the surface geometry of ordered PtCu structures favor the hydrogenation of nitro substituent and disfavor the hydrodechlorination by-reaction, resulting in enhanced chemoselectivity.