Azine Derivatives Research Articles

First oxidative coupling of cyclazine heterocycle via regioselective dimerization of 1,2-dicarbomethoxy-3-phenylcycl[3.2.2]azine: Synthesis, theoretical aspects and physicochemical studies

The first covalently linked dimer has been prepared for cyclazine systems by regioselective oxidative homocoupling of 1,2-dicarbomethoxy-3-phenylcycl[3.2.2]azine. The regioselectivity of this reaction at 4-position, having been confirmed by X-ray diffraction analysis and NMR spectroscopy, has been also reliably predicted within the model of average local ionization energy on the molecular surface of the starting monomer at the BP86/def2-TZVP level of theory. Due to the planar π-π interaction of the cycl[3.2.2]azine subunits, the dimer is a green fluorophore (λem = 527 nm, toluene), characterized by a bathochromic shift of the main bands in the UV–vis and fluorescence spectra relative to the monomer by 41 and 71 nm, respectively. Furthermore, the dimer demonstrates an increased fluorescence quantum yield relative to the monomer (55 % vs. 35 % in toluene), and according to the data of X-ray diffraction analysis, DFT calculations and variable temperature 1D and 2D 1H NMR spectroscopy, is characterized by hindered rotation of the S1-state-involved cycl[3.2.2]azine cores along the C4–C4′ bond axis. Such prerequisites determine good application potential of the 4-4′ coupled cycl[3.2.2]azine derivatives as turn-on fluorescent, i.e. fluorogenic probes for advanced bioimaging in living systems. Finally, unlike the monomer, the dimer shows reversibility of both one- and two-electron reduction and oxidation processes, and therefore can become the basis of both n- and p-type semiconductors.

Molecular Design Strategy for Microorganism Discrimination Based on Keto-Salicylaldehyde Azine Derivatives

Molecular Design Strategy for Microorganism Discrimination Based on Keto-Salicylaldehyde Azine Derivatives

2-Cyano-N-(2,5-dioxopyrrolidin-1-yl) acetamide as a building block for developing new azole and azine derivatives and assessing their biological properties

2-Cyano-N-(2,5-dioxopyrrolidin-1-yl) acetamide as a building block for developing new azole and azine derivatives and assessing their biological properties

An interesting aggregation induced red shifted emissive and ESIPT active hydroxycoumarin tagged symmetrical azine: Colorimetric and fluorescent turn on–off–on response towards Cu2+ and Cysteine, real sample analysis and logic gate application

We report a newly synthesized 7-diethylamino-4-hydroxycoumarin tagged symmetrical azine derivative (SHC), with an interesting color transformation from yellowish green to orange via aggregation induced red shifted emissive (117 nm) feature in THF-H2O mixture. Interestingly, the single crystal X-ray analysis of this molecule demonstrates that two hydroxycoumarin moieties were present in azine unit, among them one of the coumarin units was exist as enol form and another one transferred to keto form via ground state proton transfer reaction. The optical responses of the compound in different solvents exposed the observation of dual emissive bands which corresponds to the presence of ESIPT phenomenon in SHC molecule. Further, this characteristic was confirmed by absorption, emission, solid state structure and time resolved fluorescence decay measurements. Furthermore, the fluorophore, SHC was exploited as a colorimetric and turn on–off–on fluorescent probe for detection of Cu2+ ions and Cysteine (Cys). The 1:1 binding ratio of the probe with Cu2+ and Cys with SHC-Cu2+, was established via Job plot analysis, mass spectral technique and the DFT calculations. The probe, SHC was employed for the detection of copper ions in the environmental real water samples. Finally, the reversible fluorescent turn on–off–on character of the probe, SHC was established to construct the IMPLICATION logic gate application.

Discovering the DPPH Free Radical Scavenging Activity of Azine Derivatives Bearing Ethyl Phenyl Ketone Moiety

Discovering the DPPH Free Radical Scavenging Activity of Azine Derivatives Bearing Ethyl Phenyl Ketone Moiety

Novel benzimidazole-based azine derivatives as potent urease inhibitors: synthesis, in vitro and in silico approach.

Aim: In light of various biological activities of benzimidazole and azines, this study focuses on reporting novel derivatives of benzimidazole nucleus.Methods: Twenty novel azines of benzimidazole were synthesized, characterized and tested for in vitro urease inhibitory activity.Results: All these derivatives showed excellent to good inhibition in the range of IC50 values 14.21±1.87 to 76.11±1.81μM by comparing with standard thiourea 21.14±0.42μM. Docking studies were performed for the targeted benzimidazole derivatives to understand the binding mechanics. The results indicated higher binding efficacy compared with the reference inhibitor.Conclusion: This work identifies potential lead candidates for novel urease inhibitors, which with industrial support may be harnessed for the development of new drugs.

Uncovering excited state behaviours associated with electron-withdrawing CN and electron-donating TPA moieties on SAA derivatives: a theoretical study

Inspired by the excellent photochemical characteristics exhibited by salicylaldehyde azine (SAA) derivatives, our current endeavour primarily revolves around delving into the intricacies of photo-induced excited state reactions for its electron-donating and electron-withdrawing moieties derivatives (i.e. CN-SAA-CN, CN-SAA-TPA and TPA-SAA-TPA). Our simulations reveal push–pull-substituted-dependent photoexcitation that could significantly affect excited state intramolecular proton transfer (ESIPT) reaction for SAA derivatives. Constructing potential energy surfaces (PESs), we unveil the ultrafast ESIPT mechanism due to the low potential barriers. Additionally, by comparing the differences of barriers among CN-SAA-CN, CN-SAA-TPA and TPA-SAA-TPA, we present regulative manner for SAA derivatives by substituting electron-donating and electron-withdrawing moieties. We sincerely anticipate that the modulation of push–pull substitutions on excited state behaviours will pave the way for ground-breaking advancements in luminescent materials.

Synthesis, Crystal Structure, Computational Investigation of Vanillin Azine Derivative as Potent Blocker of the N‐Terminal Ras‐Binding Domain (RBD) in Human a‐Raf Kinase

AbstractVanillin is the main component of natural vanilla extract and is responsible for its flavoring properties. Besides its well‐known applications as an additive in food and cosmetics. In this, we have synthesized a new vanillin derivative. Its structure was characterized by IR, MS, NMR and confirmed by single‐crystal X‐ray analysis. The asymmetric unit of the title molecule consists of two independent half molecules, each having crystallographically imposed centrosymmetry. Reticular layers approximately parallel to the bc plane are generated from one molecule through O−H⋅⋅⋅N hydrogen bonds. The layers are linked by the second molecule through O−H⋅⋅⋅O hydrogen bonds to form a 3‐D network structure. We carried out density functional investigations to understand the compound‘s molecular reactivity and chemical stability. Frontier molecular orbital (FMO) analysis, global reactivity, and Fukui parameters were calculated at the B3LYP/6‐31+G(d,p) method. In 20 % to 30 % of human malignancies, RAS genes are activated ontogenetically by point mutations. New strategies to block this oncogenic protein are needed since it has proven difficult to create efficient RAS inhibitors. The above‐titled compound shows better structural activity relationship studies against Ras‐binding domine, based on this molecular docking simulation as well as the drug‐likeness analysis carried out for our newly synthesized compound.

Chitosan-sulfonic acid-catalyzed green synthesis of naphthalene-based azines as potential anticancer agents.

Aim: This study focuses on advancing green chemistry in anticancer drug discovery, particularly through the synthesis of azine derivatives with a naphthalene core using CS-SO3H as a catalyst. Methods: Novel benzaldazine and ketazine derivatives were synthesized using (E)-(naphthalen-1-ylmethylene)hydrazine and various carbonyl compounds. The methods employed included thermal and grinding techniques, utilizing CS-SO3H as an eco-friendly and cost-effective catalyst. Results: The approach resulted in high yields, short reaction times and demonstrated catalyst reusability. Cytotoxicity tests highlighted compounds 3b, 11 and 13 as potent against the HEPG2-1. Conclusion: This study successfully aligns with the objectives of eco-conscious drug development in organic chemistry. Molecular docking and in silico studies further indicate the potential of these ligands as antitumor medicines, with favorable oral bioavailability properties.

Crystal-to-crystal polymorphic phase transition in a cocrystal accompanied by expansion and surface wettability change

Cocrystal of n-propylparaben and a bipyridine-based azine derivative exhibit heat-induced crystal-to-crystal polymorphic phase transition accompanied by expansion and cracking of the single crystals with distinct wettability properties.

Cu-catalysed diversity-oriented synthesis of isoxazole and imidazo[1,2-a]azine conjugates

The first synthesis of diversely substituted isoxazole linked imidazo[1,2-a]azine derivatives via application of the Groebke-Blackburn-Bienayme (GBB) reaction with excellent yields is reported. This protocol proceeds via Cu(OTf)2-catalysed cascade three component reaction of isoxazole C-3(5) carbaldehydes and 2-aminopyridines/2-aminopyrimidines/2-aminopyrazines in the presence of isonitriles by forming one C–C, and three C–N bonds in a single-operation. The synthetic utility of this transformation is also extended through a gram scale synthesis. The salient features like clean reactions, short reaction time, good to excellent yields, high atom economy and easy purification procedures enacted this protocol as a practical contribution to the synthesis of medicinally valuable heterocycles.

Molecular Revealing the High‐stable Polycyclic Azine Derivatives for Long‐Lifetime Aqueous Organic Flow Batteries

AbstractSoluble organic molecules with diverse and highly tunable structures are receiving more and more attention as redox‐active materials for aqueous organic flow batteries (AOFBs). However, the undesirable parasitic reactions of redox‐active molecules restrict their practical application. Herein, a general molecular stabilization strategy is proposed by introducing amino groups on 3,7‐positions of polycyclic azine derivatives (phenothiazine and phenoxazine compounds) to effectively enhance the redox activity and electrochemical stability of molecules. The theoretical calculation and a series of electrochemical analyses revealed that the 3,7‐substituted amino groups serving as the redox active sites can stabilize the intermediate radicals by delocalizing the electron density in the acidic solution, preventing nucleophilic/electrophilic attack. As a result, the designed 3,7‐bis‐((2‐hydroxyethyl)(methyl)amino)phenothiazin‐5‐ium bromide not only achieved the remarkable electrochemical cycling performance in the flow cell with an ultra‐low‐capacity fade rate of 0.00029% per cycle for 18000 cycles (62 days) and but also delivered a stable high capacity of 47 Ah L−1 (with capacity fade 0.0056% per cycle, 0.077% per day) under ambient condition. Such finding undoubtedly provides a guidance to design stable redox‐active molecules for AOFBs.

Synthesis, Cytotoxic, and Antioxidant Activity of Some Benzoquinoline-Based Heterocycles

A series of benzoquinoline-based heterocycles was synthesized using 2-((3-chlorobenzo[f]quinolin-2-yl)methylene)hydrazine-1-carbothioamide as a key material via condensation of 3-chlorobenzo[f]quinoline-2-carbaldehyde with thiosemicarbazide. The titled thiosemicarbazone scaffold was conducted with some carbon electrophilic reagents such as acetic anhydride, chloroacetyl chloride, chloroacetic acid, 2-bromo-1-(3-nitrophenyl)ethan-1-one, 2-chloro-N-phenylacetamide, and dimethyl but-2-ynedioate to obtain triazole thione, imidazolone, thiazolidinone, and thiazole derivatives. On the other hand, hydrazinolysis of thiosemicarbazone did not proceed as expected but it gave the azine derivative. The in vitro antitumor and antioxidant activity of the synthesized compounds were screened and revealed that triazole thione and thiazole derivatives were the most potent.

Novel Triangulenes: Computational Investigations of Energy Thresholds for Photocatalytic Water Splitting.

Organic materials with Inverted Singlet-Triplet (INVEST) gaps are interesting for their potential use in photocatalytic small molecule transformations such as the entirely solar-driven water splitting reaction. However, only a few INVEST emitters are thermodynamically able to split water requiring a first singlet excited dark state, S1 , above 1.27 or 1.76 eV, and absorption near solar the maximum, 2.57 eV. These requirements and the INVEST character are key for achieving a long-lived photocatalyst for water splitting. The only known INVEST emitters that conform to these criteria are large triangular boron carbon nitrides with unknown synthesis pathways. Using ADC(2), a quantum-mechanical method, we describe three triangulenes. 3 a is a cyano azacyclopenta[cd]phenalene derivative while 3 b and 3 c are cycl[3.3.3]azine derivatives. 3 b has a previously undescribed disulfide bridge. Overall, 3 a fulfills requirements for photocatalytic four-electron reduction of water while the S1 states of 3 b and 3 c are likely slightly low for the two-electron reduction process. By analyzing impacts of ligands, we find that there are guidelines describing how S1 -S5 energies and oscillator strengths, T1 energies, and ΔES1T1 gaps are affected, requiring deep-learning algorithms for which studies will be presented by us in due time. The impact of ground-state geometries, solvation effects, as well as reduced-cost ADC(2) algorithms on our findings are also discussed.

Solvent-dependent isomerization of a chromogenic trefoil-shaped salicylaldehyde azine derivative

A chromogenic trefoil-shaped salicylaldehyde azine derivative displayed solvent-dependent isomerism of the C3h and CS symmetries. An azine derivative was prepared from triformylphloroglucinol and 3,5-di-tert-butylsalicylaldehyde hydrazone. The trefoil structure was established using single-crystal X-ray diffraction. UV–vis absorption spectroscopy revealed that solvent-dependent isomerization was accompanied by a bathochromic shift. Isomerization was controlled by adjusting the strength of the intramolecular hydrogen bonding of the azine derivative by solvent polarity. This unusual solvent-dependent isomerization can be utilized for creation azine-based new solvatochromic materials.

Synthesis and Antioxidant Activity of Some Benzoquinoline-Based Heterocycles Derived from 2-((3-Chlorobenzo[f]quinolin-2-yl)methylene)hydrazine-1-carbothioamide

A new series of benzoquinoline-based heterocycles was synthesized utilizing the building block synthon, 2-((3-chlorobenzo[f]quinolin-2-yl)methylene)hydrazine-1-carbothioamide via the condensation of 3-chlorobenzo[f]quinoline-2-carbaldehyde with thiosemicarbazide. The titled thiosemicarbazone scaffold was conducted with some carbon-centered electrophilic reagents such as acetic anhydride, chloroacetyl chloride, chloroacetic acid, 2-bromo-1-(3-nitrophenyl)ethan-1-one, 2-chloro-N-phenylacetamide, and dimethyl but-2-ynedioate to achieve triazolethione, imidazolone, thiazolidinone, and thiazole derivatives. In turn, the hydrazinolysis of this substrate did not proceed as expected but it afforded the azine derivative. The antioxidant activity screening of the produced compounds revealed that thiazole and triazolethione derivatives were the most potent.

Discovery of (S)-flurbiprofen-based novel azine derivatives as prostaglandin endoperoxide synthase-II inhibitors: Synthesis, in-vivo analgesic, anti-inflammatory activities, and their molecular docking

The anti-inflammatory and analgesic drugs currently used are associated with several adverse effects and found to be highly unsafe for long-term use. Currently, nineteen novel bis-Schiff base derivatives (1–19) of flurbiprofen have been designed, prepared and assessed for in-vivo analgesic, anti-inflammatory and in vivo acute toxicity evaluation. The structures of the acquired compounds were deduced through modern spectroscopic techniques including HR-ESI-MS, 13C-, and 1H NMR. Amongst the series, compounds 7, 9, and 10 attributed potent activities with 93.89, 92.50, and 90.47% decreased edema, respectively compared to flurbiprofen (90.01%), however, compounds 11 and 15 exhibited significant activity of 90.00% decrease. Out of them, fourteen compounds (1–6, 8, 12–14, and 16–19) displayed good activity in the range of 68.96–86.95%. In case of an analgesic study, all the derivatives significantly (p 0.001) increased the pain threshold time particularly compound 7 had the best analgesic effect (24 ± 2.08 s) in comparison with flurbiprofen (21.66 ± 2.02 s) using hot plate test. Similarly, in the acetic acid-induced writhing test, compound 7 determined a potent inhibitory effect (60.47 %) close to flurbiprofen (59.28%). All the synthesized derivatives were found safe up to the dose of 30 mg/kg, in acute toxicity study. On a molecular scale, the synthesized compounds were modeled through a ligand-based pharmacophore study and molecular docking to have insight into the different possible interactions leading to high inhibition levels against the COX-2 enzyme.

Starch nanoparticles modified with ionic liquid: A novel and efficient catalyst for the synthesis of symmetrical azine derivatives at room temperature

Starch nanoparticles modified with ionic liquid were prepared by the reaction of starch nanoparticles with N-methyl-N-propyltrimethoxysilane imidazolium chloride. They were used as a new reusable and green heterogeneous nanocatalyst for the synthesis of symmetrical azines. Different azine derivatives were prepared using this quick procedure with satisfying yields. The reaction proceeded at room temperature in solvent-free conditions with a simple work-up, short reaction times, and an easy purification technique. All products were characterized using Fourier transform infrared spectroscopy (FT-IR) and nuclear magnetic resonance spectroscopies. Also, the catalyst itself was characterized by FT-IR, scanning electron microscopy, and thermal gravimetric analysis.

Spectral studies of synthetic symmetric syringaldehyde di-Schiff azine with β-cyclodextrin inclusion complexes as a fluorescent probe for the detection of metal ions

In the past few years, organic fluorescent probes play a crucial role in sensor fields due to their magnificent selectivity and detection ability towards various transition metals and alkali ions. Herein, A facile and profitable Schiff-based symmetrical azine derivative of 4,4′ ((1E,1′E)-hydrazine-1,2-diylidenebis(methanylylidene)) bis2,6-methoxyphenyl, dihydrazone or syringaldehyde Azine (SyA) has been synthesized which was rapidly detected dual metal ions (Cu2+ and Pb2+) in different mechanism pathway via Chelation Enhanced Fluorescence Mechanism (CHEF) and Ligand to Metal Charge Transfer (LMCT) approach in optimized physiological conditions under ACN medium. Simultaneously, the interaction mechanism between the SyA and both metals was studied with the help of Benesi-Hildebrand and 1H NMR spectroscopy. Afterward, we prepared the inclusion complex of β-cyclodextrin with SyA (β-CD:SyA) to enhance water solubility and sensing probability. The complex for the observed surprising result was that complexation not only enhanced their properties and detected the new metal ion of Al3+ (may be due to β-CD hydroxyl group interaction with metal ions) without disturbance detection of Cu2+ and Pb2+. The LOD and binding constant values of SyA and β-CD:SyA towards Cu2+, and Al2+ were calculated by absorbance and fluorescence titration profile. From an application point of view, the antibacterial activity and biological activities were evaluated.

Synthesis, electrochemistry, and in vitro antileishmanial efficacy of novel ferrocenylazines

Leishmaniasis is a zoonotic disease prevalent in 83–92 countries. This disease's current treatments are unsatisfactory because of a variety of shortcomings, including serious toxicity, variable efficacy, painful administration, and the occurrence of parasite resistance to these antileishmanial agents. The abovementioned limitations have urged the development of novel, reliable, and affordable agents to treat leishmaniasis. Ferrocenylazine derivatives were therefore synthesized for activity screening against Leishmania major and Leishmania donovani cell cultures. This emphasizes the urgent need for new effective antileishmanial agents. In search for such therapeutics, we synthesized and evaluated in vitro the antileishmanial activity of a series of azine derivatives based on the organometallic compound ferrocene. Two ferrocenylaldazines, 2l and 2q, were uncovered as mammalian cell nontoxic antileishmanial early leads, expressing submicromolar activity with IC50 values of 0.78 ± 0.03 and 0.46 ± 0.03 μM, respectively, against amastigote of L. donovani. Ferrocenylazines may therefore act as potential new antileishmanial agents, and the next objective will be the identification of the involved biological targets.