CN Bond Formation Research Articles

Effect of tannic acid modification on antioxidant activity, antibacterial activity, environmental stability and release characteristics of quercetin loaded zein-carboxymethyl chitosan nanoparticles

The stability of quercetin remains a challenge for their application in industrial food production. In order to solve this shortcoming, zein-tannic acid covalent complex was prepared. Fourier transform infrared spectroscopy demonstrated the formation of CN bond between zein and tannic acid. Quercetin loaded nanoparticles (QZTC) were prepared by zein-tannic acid complex and carboxymethyl chitosan by anti-solvent co-precipitation and pH migration method. The structure of the nanoparticles was characterized and the effects of tannic acid modification and carboxymethyl chitosan addition on the encapsulation efficiency, oxidation resistance, antibacterial property, environmental stability and microstructure of the nanoparticles were studied. The results showed that compared with zein nanoparticles, QZTC had higher encapsulation rate, smaller and more uniform spherical microstructure. Compared with free quercetin and the other two nanoparticles, QZTC showed higher light, heat, storage stability, antioxidant and antibacterial abilities (p < 0.05). It was also found that the improvement of stability mainly depended on the formation of CN covalent bond, hydrogen bond, electrostatic interaction and hydrophobic interaction between components. This study provides new ideas for improving the environmental stability, antioxidant and antibacterial properties of quercetin and for developing nanoparticles that can be used in food processing.

Microbubble-enhanced cold plasma activation (MB-CPA) for surface functionalization of polymer nanoparticles from nanoprecipitation

Cold plasma activation has been considered as a green and effective technological approach for functionalization of solid surfaces. In the current study, we introduce a versatile technique known as microbubble-enhanced cold plasma activation (MB-CPA) for surface modification of polymer plates and nanoparticles in flowing liquid phase. Corona plasma is generated at the inlet of a venturi tube, thereby creating a highly excited state in the air. Reactive nitrogen and oxygen species (RNOS) are transferred from the gas phase to the suspension flow in the form of plasma microbubbles. Two types of polymer-based nanoparticles in the suspension, namely polymethyl methacrylate (PMMA) of 16–154 nm and polycaprolactone (PCL) of 30–225 nm, are synthesized using nano-precipitation method. Through the degradation of model compounds, the polar organic solvent, acetone and ethanol, is found to promote or suppress the production of active species. In addition, the efficiency of the MB-CPA treatment depends on the solvent composition, making this technology a controllable and efficient strategy for the surface modification of nanoparticles. The findings indicate that plasma activation effectively reduces the negative surface zeta-potentials and induces aggregation and separation in the suspensions. The infrared spectra of the treated nanoparticles reveal that plasma activation leads to the formation of NH and CN bonds situated on the surface of PMMA. Our work demonstrates that organic-solvent involved MB-CPA emerges as a promising method for the surface modification of nanoparticles in the flow condition.

Synthesis and anti-breast cancer evaluation of fused imidazole-imidazo[1,2-c][1,2,3]triazoles: PEG-400 mediated one-pot reaction under ultrasonic irradiation

Synthetic chemists have organized easy and effective ways for perfect synthesis in response to the requirement for scaffolds that are crucial for medical applications. To investigate the synthesis of fused 1,2,3-triazoles in the presence of ultrasound, the [3 + 2] cycloaddition followed by CN bond formation reaction between 2-chloro-N-(1-methyl-1H-imidazol-2-yl)acetamide and substituted aryl iodoalkynes was carried out ourpreviously reported condition. The cancer activity of the synthesized compounds were then tested in vitro against two breast cancer cell lines MCF-7 and MDA-MB231 and some of the compounds 5g and 5j showed more potent activity against MCF-7 compared to standard erlotinib (IC50 = 4.70 ± 0.11 μM) with IC50 values 4.02 ± 0.74 and 4.23 ± 0.65 μM. Later, in vitro EGFR results revealed that compound 5g (IC50 = 0.38 ± 0.02 μM) have shown more effective than the conventional medicine erlotinib (IC50 = 0.42 ± 0.04 μM). Compounds 5j (IC50 = 0.42 ± 0.05 μM) have shown equipotent, 5i (IC50 = 0.53 ± 0.02 μM) and 5k (IC50 = 0.58 ± 0.02 μM) were shown good activity compared to the standard erlotinib. In silico investigations of more potent compounds (5g, 5i, 5j, 5k, and 5q) and erlotinib on the EGFR protein indicated that all five compounds had comparable binding energies and inhibition constants than the erlotinib.

Copper-catalyzed C–C bond cleavage coupling with C[tbnd]N bond formation toward mild synthesis of lignin-based benzonitriles

N-participated lignin depolymerization is of great importance for the transformation of waste lignin into value-added chemicals. The vast majority of developed strategies employ organic amines as nitrogen source, and considerable methods rely on excessive use of strong base, which suffers severe environmental issues. Herein, benzonitrile derivatives are synthesized from oxidized lignin β-O-4 model compounds in the presence of solid nitrogen source (NH4)2CO3 under mild, base-free conditions over commercially available copper catalyst. Mechanism studies suggest the transformation undergoes a one-pot, highly coupled cascade reaction path involving oxidative C-C bond cleavage and in-situ formation of CN bond. Of which, Cu(OAc)2 catalyzes the transfer of hydrogen from Cβ (Cβ-H) to Cα, leading to the cleavage of Cα-Cβ bonds to offer benzaldehyde derivative, this intermediate then reacts in-situ with (NH4)2CO3 to afford the targeted aromatic nitrile product. Tetrabutylammonium iodide (TBAI), acting as a promoter, plays a key role in breaking the Cα-Cβ bonds to form the intermediate benzaldehyde derivative. With this protocol, the feasibility of the production of value-added syringonitrile from birchwood lignin has been demonstrated. This transformation provides a sustainable approach to benzonitrile chemicals from renewable source of lignin.

Ambient electrosynthesis of urea from carbon dioxide and nitrate over Mo2C nanosheet

Electrocatalytic synthesis of urea through CN bond formation, converting carbon dioxide (CO2) and nitrate (NO3–), presents a promising, less energy-intensive alternative to industrial urea production process. In this communication, we report the application of Mo2C nanosheets-decorated carbon sheets (Mo2C/C) as a highly efficient electrocatalyst for facilitating CN coupling in ambient urea electrosynthesis. In CO2-saturated 0.2 mol/L Na2SO4 solution containing 0.05 mol/L NO3–, the Mo2C/C catalyst achieves an impressive urea yield of 579.13 µg h–1 mg–1 with high Faradaic efficiency of 44.80% at –0.5 V versus the reversible hydrogen electrode. Further theoretical calculations reveal that the multiple Mo active sites enhance the formation of *CO and *NH2 intermediates and facilitate their CN coupling. This research propels the use of Mo2C-based electrodes in electrocatalysis and accentuates the capabilities of binary metal-based catalysts in CN coupling reactions.

Fabrication of gelatin-polyester based biocomposite scaffold via one-step functionalization of melt electrowritten polymer blends in aqueous phase

The rapid manufacturing of biocomposite scaffold made of saturated-Poly(ε-caprolactone) (PCL) and unsaturated Polyester (PE) blends with gelatin and modified gelatin (NCO-Gel) is demonstrated. Polyester blend-based scaffold are fabricated with and without applying potential in the melt electrowriting system. Notably, the applied potential induces phase separation between PCL and PE and drives the formation of PE rich spots at the interface of electrowritten fibers. The objective of the current study is to control the phase separation between saturated and unsaturated polyesters occurring in the melt electro-writing process and utilization of this phenomenon to improve efficiency of biofunctionalization at the interface of scaffold via Aza-Michael addition reaction. Electron-deficient triple bonds of PE spots on the fibers exhibit good potential for the biofunctionalization via the aza-Michael addition reaction. PE spots are found to be pronounced in which blend compositions are PCL-PE as 90:10 and 75:25 %. The biofunctionalization of scaffold is monitored through CN bond formation appeared at 400 eV via X-ray photoelectron spectroscopy (XPS) and XPS chemical mapping. The described biofunctionalization methodology suggest avoiding use of multi-step chemical modification on additive manufacturing products and thereby rapid prototyping of functional polymer blend based scaffolds with enhanced biocompatibility and preserved mechanical properties. Additionally one-step additive manufacturing method eliminates side effects of toxic solvents and long modification steps during scaffold fabrication.

Computational insights into the reaction mechanism of the synthesis of quinazoline derivatives via the cyclocondensation reaction between methyl 2-amino-4-(2-diethylaminoethoxy)-5-methoxybenzoate and formamide

In this work, the cyclocondensation reaction mechanism between methyl 2-amino-4-(2-diethylaminoethoxy)-5-methoxybenzoate (MAD, 1) and formamide (FME, 2) was theoretically explored at the DFT level using the B3LYP/6-311++G(d,p) computational method. The two paths (a and b) involved in this reaction take place through four steps. CDFT results show the most favourable electrophilic/nucleophilic interaction between the C3 electrophilic center of MAD (1) and the N4 nucleophilic center of FME (2). Activation energy analysis predicts the formation of quinazoline derivative as the main product, in reasonable agreement with experimental results. BET allowed a deeper understanding of the reaction mechanism by revealing the existence of four structural stability domains (SSD) during the processes of CN and OH bond formation. The bond process is as follows: depopulation of V(N) basin with the formation of first CN bond (appearance of V(C,N) basin), cleavage of NH bond with the creation of V(N) and V(H) monosynaptic basins, and finally the appearance of V(H,O) disynaptic basin related to the OH bond. In the case of dehydration, the transition from SSD-I to SSD-II corresponds to the cleavage of the CO bond, whose electron population is transferred to the V(O3) basin. The cleavage of N7-H9 bond with the formation of V(N) and V(H) basins is the first stage, followed by the formation of the OH bond as the second stage.

Copper(I) complexes of 1,2-bis(diphenylphosphino)benzene as efficient catalysts for alkyne hydroamination and azide-alkyne cycloaddition

This paper reports the synthesis of a small group of three copper(I) complexes using 1,2-bis(diphenylphosphino)benzene, abbreviated as dppbz, and their utilization as catalyst for CN bond formation reactions. Reaction of dppbz has been carried out with three different copper(I) sources. While reaction with [Cu(CH3CN)4]ClO4 affords [CuI(dppbz)2]ClO4 (complex 1), that with CuI and CuSCN affords di-copper complexes [{CuI(dppbz)I}2] and [{CuI(dppbz)(SCN)}2] (complexes 2 and 3) respectively. Bulk characterization on the complexes has been done by elemental (C, H, N) analysis, magnetic susceptibility measurement, and spectroscopic (IR, NMR and UV–vis) methods. Crystal structures of all three complexes have been determined. In [CuI(dppbz)2]ClO4, copper(I) is having a highly distorted tetrahedral CuP4 core. In [{CuI(dppbz)I}2] and [{CuI(dppbz)(SCN)}2], the tetrahedral CuP2I2 and CuP2SN cores are relatively less distorted. These copper complexes have been found to serve as efficient catalyst precursors for two types of CN bond formation reactions, viz. hydroamination and click reaction. Hydroamination of aryl alkynes with aryl amines has afforded selectively imine products of a single type (Markownikov product) in good yields under relatively mild condition. However, similar hydroamination with benzyl amines or alkyl amines has afforded selectively anti-Markownikov imine products. Click reaction between aryl alkynes and aryl azides yielding the cycloaddition products has also been brought about successfully with remarkable catalytic efficiency.

Photocatalyzed intermolecular C–N bond formation for the synthesis of imidazo[1,2-a]pyridines

Photocatalyzed intermolecular CN bond formation of 2-aminopyridines with ketones choosing NH4I as the catalyst was explored, affording imidazo[1,2-a]pyridines under milder conditions. The reaction induced by sunlight is able to provide the corresponding products. Our catalytic system is suitable for the reaction of 2-aminopyridine, ketones and sulfide derivatives. Furthermore, the protocol is also applicable for the reaction of 2-aminopyridine and sulfoxonium ylide.

Convenient synthesis of 6-Amino-2-naphthol by Copper-catalyzed Ullmann reaction

A strategic approach towards the synthesis of 6-amino-2-naphthol for energy efficient and consistent yield was exploited by two protocols: (a) a direct amination, and (b) a cascade synthetic approach involving methylation, amination, and demethylation of 2-bromo-6-naphthol by replacing naphthyl bromide with an –NH2 group. A modified copper-catalyzed Ullmann- type CN bond formation reaction at a controlled temperature (80–120 °C) was adopted for the amination reaction in both protocols. Amination reaction of two different substrates 2-bromo-6-methoxynapthalene and 2-bromo-6-naphthol were performed. Two different aminating reagents, namely, aq·NH3 (28–30%) and NaN3 were explored. Copper catalysts were elemental Cu, CuI, Cu2O, CuO, and CuSO4·5H2O. Extensive method optimization revealed that the combination of CuSO4•5H2O, l-proline, and Na-ascorbate is the superior catalyst when employed with NaN3 and NaOH at 120 °C affording the highest coupling yield of 61%. 6-amino-2-naphthol was obtained following both protocols however, the latter afforded a higher overall yield (53%). Thus, an Ullmann reaction strategy with a stable, environmentally friendly, earth-abundant, easy-to-handle, and inexpensive catalyst CuSO4•5H2O in combination with Na-ascorbate makes the amination reaction of bifunctional naphthyl bromide simple, sustainable, energy-efficient and convenient with consistent yield.

Synthesis and biological evaluation of coumarine-imidazo[1,2-c][1,2,3]triazoles: PEG-400 mediated one-pot reaction under ultrasonic irradiation

Synthetic chemists have organized easy and effective ways for perfect synthesis in response to the requirement for scaffolds that are crucial for medical applications. To investigate the synthesis of fused 1,2,3-triazoles in the presence and absence of ultrasound, the [3 + 2] cycloaddition followed by CN bond formation reaction between 3-(iodoethynyl)-2H-chromen-2-one and substituted 2-chloro-N-phenylacetamides was carried out under relatively optimized conditions. The cancer activity of the synthesized compounds were then tested in vitro against two MCF-7 and A-549 and the majority of the examined compounds 4e-4o showed significant activity, with compounds 4f, 4 g, and 4 h surpassing the standard drug against the A-549 line, and 4 m and 4n excelling it against MCF-7. Later, in vitro EGFR results revealed that compounds 4f (IC50 = 0.420 ± 0.08 μM), 4 g (IC50 = 0.367 ± 0.02 μM), and 4 h (IC50 = 0.453 ± 0.02 μM) were more effective than the conventional medicine Erlotinib (IC50 = 0.460±0.06 μM). In silico investigations of more potent compounds (4f, 4 g, 4 h, 4i, 4k, 4 m, and 4n) and erlotinib on the EGFR protein indicated that all seven compounds had much higher binding energies and inhibition constants than the erlotinib. Finally, the in silico pharmacokinetic profile of compounds 4f, 4 g, 4 h, 4i, 4k, 4 m, and 4n was estimated using SWISS/ADME and pkCSM, where all compounds followed Lipinski, Veber, Egan, and Muegge rules without deviation.

Spectroscopic, X-ray, mechanistic and DFT studies on formation of novel benzoimidazole-4-ones from cyclohexenyl carbothioamides

Spectroscopic studies of cyclohexenyl carbothioamides 2, obtained from condensation of 1,3-cyclohexandione with aryl isothiocyanates, predicted the proton transfer behaviour in solid, solution and gaseous phases. DFT studies in gaseous and solution phase shows good congruence with the experimental findings. Condensation of cyclohexenyl carbothioamide 2a with hydrazine hydrate unexpectedly embellished novel 2-(4-chlorophenyl)amino)-2,5,6,7-tetrahydro-4H-benzo[d]imidazol-4-one 4a and 2-(bis((4-chlorophenyl)amino)methylene)cyclohexane-1,3-dione 3a instead of the presumable 2H and 1H-indazole derivatives 5a and 6a, respectively. The proposed mechanism of formation of unconventional products 3a and 4a supported by experimental results is described. Spectroscopic investigations such as FT-IR, Mass and NMR (1H, 13C, DEPT-135, HSQC, COSY, NOESY) along with X-ray crystallographic results established the structure of two derived novel products 3a and 4a. The interesting feature of this study is NN bond cleavage of strained transit diazetidine ring and formation of CN bond leading to generation of novel benzoimidazol-4-one derivative 4a. Hirshfeld surface analysis of entitled compounds is reported.

Synthesis of acetyl deoxyvasicinone analogues from 2-(4-oxopentyl)quinazolin-4(3H)-ones via linear cyclizations

Two deoxyvasicinone analogues were obtained from 2-(4-oxopentyl)quinazolin-4(3H)-ones via different process of linear cyclizations. The first was 1-acetyl-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one analogue derived from direct cyclization in the presence of I2 in basic condition. The other was 1-acetylpyrrolo[2,1-b]quinazolin-9(3H)-one analogue obtained from two-step procedures beginning with geminal dichlorination in acidic condition, followed by intramolecular CN bond formation in the presence of para-toluenesulfonic acid.

Metal-free dearomative 2,3-difunctionalization of indoles via radical cascade

An oxidative dearomatization of protected indoles leading to 2-azido 3-arylselenyl indolines has been developed under metal-free conditions. The formation of CN and CSe bonds is believed to arise from the oxidation of indole via radical cascade. The reaction is regio and diastereo-selective and works under mild conditions.

Interaction dust–plasma in Titan's ionosphere: Feedbacks on the gas phase composition

Titan's organic aerosols are formed and spend some time in the ionosphere, an atmospheric layer ionized by solar VUV photons and energetic particles coming from the magnetosphere of Saturn, forming a natural N2-CH4-H2 plasma. Previous works showed some chemical evolution processes: VUV photons slightly alter the aerosols nitrile bands, hydrogen atoms tend to hydrogenate their surface and carbon-containing species participate to the growth of the aerosols. This work investigates the effect of the other plasma species, neglected until now, namely the N2-H2 derived ions, radicals and electronic or vibrational excited states. Industrial plasmas often use N2-H2 discharges to form ammonia-based fertilizers, for metal nitriding, and to erode organic surfaces. Consequently, these are likely to affect Titan's organic aerosols.We therefore developed the THETIS experiment (for Tholin Evolution in Titan's Ionosphere Simulation) to study the interactions between analogues of Titan's aerosols (tholins) and the erosive N2-H2 plasma species found in Titan's ionosphere. Following a first paper on the investigation of the evolution of the solid phase by Scanning Electron Microscopy and IR transmission spectroscopy (Chatain et al., 2020a), this second paper focuses on evolution of the gas phase composition, studied by neutral and ion mass spectrometry.In the presented experiments, newly formed HCN, NH3-CN and C2N2 are extracted in quantity from the tholins as well as some other carbon-containing species and their derived ions. On the other hand, the production of ammonia strongly decreases, probably because the H, NH and N radicals are rather used for the production of HCN at the surface of tholins. Heterogeneous processes are suggested based on the experimental observations: chemical processes induced by radicals at the surface would modify and weaken the tholin structure, while ion sputtering would desorb small molecules and highly unsaturated ions. The effect of plasma erosion on aerosols in Titan's ionosphere could therefore lead to the formation of CN bonds in the aerosol structure, as well as the production of HCN or R-CN species in the gas phase.

Twisted intramolecular charge transfer, nonlinear optical, antibacterial activity, and DFT analysis of ultrasound processed (E)-N′-(4-isopropylbenzylidene)nicotinohydrazide

Hydrazones have attracted considerable interest for their antimicrobial and nonlinear optical (NLO) applications. In the present work, a new hydrazone (E)-N′-(4-isopropylbenzylidene)nicotinohydrazide (INH) was synthesized by a condensation reaction of cuminaldehyde with nicotinic hydrazide via ultrasonication. The hydrazone was characterized by FT-IR spectroscopy, mass spectrometry, NMR (1H, 13C, HOMO-COSY, HSQC, and DEPT-135), elemental analysis, and FESEM analyses. Phase-pure and non-existent isomorphic phase transition in INH was demonstrated by X-ray diffraction and thermogravimetric analysis. The absorption maximum of INH in an aqueous solution was red-shifted compared to that of the reactant molecules, indicating that the CN bond formation efficiently enhances the resonance interaction towards the pyridine ring. Fluorescence emission of INH at a shorter wavelength is caused by a locally excited state. A longer wavelength band is caused by intramolecular proton transfer in nonpolar/aprotic solvents, while it is caused by TICT emission in protic solvents. The direct and indirect bandgaps of the INH crystals were assessed using Tauc plots and the Kubelka–Munk algorithm. The efficacy of INH for the inactivation of E. coli and B. subtilis were examined through a plate colony counting assay, and the inactivation was 62.7 ± 0.2 % and 98.3 ± 0.4 %, respectively. The geometrical structure, Mulliken, MEP surface, and electronic properties of INH are theoretically optimized using density functional theory (DFT) at the B3LYP/6-31G(d,p) level and showed good concurrence with the experimentally defined structure. The INH displays higher NLO properties compared to urea as a reference, as determined by molecular hyperpolarizability analysis. The frontier molecular orbitals and global reactivity descriptors showed that INH is more reactive and reasonably stable.

Flue gas to urea: A path of flue gas resourceful utilization through electrocatalysis

Flue gas has caused great damage to the environment and human health. At present, the treatment of flue gas requires high operating costs, accompanied by the loss of huge resources. In this regard, we designed a path to use the flue gas rich in NOx, SO2 and CO2 to obtain valuable fertilizer, urea. We demonstrate that HCOOH can be obtained from CO2 reduction by the hydrated electron generated by irradiated SO32−, a product from flue gas SO2 removal, and then urea can be synthesized by electrochemical coupling of HCOOH and NO on a Ag-Cu Janus nanoparticle electrocatalyst. The *NO hydrogenation (*NHO) preferentially occurs on the Ag-Cu Janus interface, promoting the formation of CN bonds. An average urea yield of 8098.5 μg h−1 mg−1 was achieved on Ag-Cu Janus nanoparticles catalyst at − 0.45 V versus the reversible hydrogen electrode (RHE) with a high Faradic efficiency of 55.45 %. Our work provides a feasible way for the resource utilization of flue gas.

Enhancing flame retardant property of graphene oxide via phosphorus and nitrogen co-doping

A simple and versatile method has been developed to efficiently enhance the flame retardant of graphene oxide (GO) by adding ammonium phosphate (AP) into GO. The as-made GO/AP exhibits excellent flame retardant properties, which emits some smoke at the beginning without catching any fire and any observable shrinkage. In contrast, the GO catches fire within several seconds and completely burns out. The improvement of flame retardancy can be attributed to the formation of CP and CN bonds with heat. This simple and effective technique of the introduction of P and N can be adopted for inexpensive mass production of GO/AP for many practical applications such as sensors, energy-storing materials, and nanomaterial electronics.

Synthesis of optical active tetramethyl-1,1′-spirobiindane-based iodoarenes and evaluation of their use as axially chiral organocatalysts

Three novel axially chiral iodoarenes based on the tetramethyl-1,1′-spirobiindane skeleton were successfully prepared starting from Bisphenol A. The reactivity and selectivity were evaluated in the asymmetric oxidative formation of CN bonds through an intramolecular desymmetrization strategy, resulting in ee’s up to 92% with high yield.

NHC-catalyzed [3 + 4] annulation between 2-dromoenal and aryl 1,2-diamine: Insights into mechanisms, chemo and stereoselectivities

We present a DFT study of the mechanisms, chemo- and stereoselectivities in the reaction of 2-bromoenal with aryl 1,2-diamine enabled by a chiral NHC. The catalytic reaction starts with NHC addition to 2-bromoenal, subsequent [1,2]-proton transfer results in the Breslow intermediate, which then undergoes sequential CBr bond breaking and [1,3]-proton transfer. The resulting acylazolium can transform to the [3 + 4] cycloadduct through subsequent CN bond formation, [1,3]-proton transfer and cyclization. Finally, elimination of catalyst provides 1,5-benzodiazepin-2-one. DFT results reveal that OAc− and HOAc play important roles respectively in the [1,2]- and [1,3]-proton transfer process. The CN bond formation step controls the enantioselectivity of the reaction, and preferably provides access to (R)-1,5-benzodiazepin-2-one. The computed enantioselectivity (97.5% ee) agrees well with experimental report (97% ee). Non-covalent NH···π, CH···N and CH···π interactions are the key factors for controlling the stereoselectivity. The NHC is demonstrated to play a role in CBr bond activation through reduce the electron density between the C and Br atoms, thus increases 2-bromoenal's electrophilicity and facilitates its subsequent reaction with diamines.