bis-Schiff Base Research Articles

Synthesis, molecular modeling, and biomedical applications of oxovanadium(IV) complexes of Schiff bases as a good SARS-CoV-2 inhibitor

Oxovanadium(IV) complexes of dibasic symmetrical bis-Schiff bases synthesized from 1,6-hexanediamine and orthohydroxy aldehydes or diketones. Their formation was confirmed with the help of elemental analysis, FTIR, 1H NMR, UV-visible and mass spectra, magnetic susceptibility, and conductance measurements. Quantum mechanical calculations are indicative to the proposed structures of the complexes. Most of the ligands and complexes have considerable inhibition capacity on mycelia growth against selected pathogenic fungi and bacteria and show good antioxidant property too. Complexes showed good larvicidal activity against the mosquito larvae (Culex quinquefasciatus). Molecular docking of a Schiff base, (BzA-HD-BzAH2) with SARS-CoV-2 Mpro revealed the best binding affinity with the receptor protein compared to the approved medicine hydroxychloroquine (HCQ) and favipiravir (FVP). The ADMET analysis showed that ligand is non-carcinogenic and less toxic than standards, HCQ or FVP. However, these in silico studies proved BzA-HD-BzAH2 to be a good candidate for development as a therapeutic drug against SARS-CoV-2.

Synthesis, in-vitro and in-silico studies of triazinoindole bearing bis-Schiff base as β-glucuronidase inhibitors

Triazinoindole bearing bis-Schiff base analogs (1–20) were synthesized by triazinoindole-thione ring formation, triazinoindole-thiol-phenylethanone, followed by triazinoindole bis-Schiff base formation. Synthesized analogs showed β-glucuronidase potential with IC50 value ranging between 2.60 ± 0.10 to 55.40 ± 1.60 µM as compared to standard d-saccharic acid 1,4-lactone (IC50 = 48.10 ± 1.2 µM). Analog 20 was the most potent one with IC50 value 2.60 ± 0.10 µM. Analogs 17, 4 showed IC50 values 5.20 ± 0.20 and 5.70 ± 0.20 µM respectively and withstand 2nd and 3rd ranked scaffolds among the synthesized analogs. All other sixteen analogs showed many-fold better potency with IC50 values ranging from 7.9 ± 0.2 to 48.1 ± 1.2 µM. The structure-activity relationship was established and confirmed of binding interactions through molecular docking studies.

Quantum mechanical study on the activation mechanism of human carbonic anhydrase VII cluster model with bis-histamine schiff bases and bis-spinaceamine derivatives

The activation mechanism of human carbonic anhydrase (hCA) isoform VII, hCA VII, with histamine, histamine bis-Schiff bases and bis-spinaceamine derivatives has been investigated using quantum mechanical calculations. The DFT-D3 method has been employed to calculate in detail the electronic structure and electronic energy of different compounds and complexes throughout the reaction pathway. The model system of hCA VII included the core catalytic center, the Zn2+ ion, its three histidine ligands and a hydroxide ion or water molecule coordinated to it. Furthermore, Thr199, Glu106 and the deep water molecule were considered in the model. Five activators of this enzyme, including histamine as standard, in complex with the cluster model of hCA VII were investigated. Thermodynamic functions for the overall reaction and for the complexation between activators and hCA VII were evaluated. Our results demonstrate that the protonatable moiety of these activators participates in proton transfer reactions from the zinc-bound water molecule to the reaction medium, promoting the formation of the catalytically active zinc hydroxide species of the enzyme. The QM analysis revealed that the electrostatic interactions between activators and hCA VII are the driving force of the enzyme-activator complex formation.

Functionalization of SBA-15 mesoporous silica with bis-schiff base for the selective removal of Pb(II) from water

The SBA-15 type mesoporous silica functionalized by the bis-Schiff base was designed and prepared through three surface modification steps. The obtained nanohybrid, MS-AP, was systematically characterized by a series of analytical techniques, and these thereby confirmed that the bis-Schiff ligand was successfully immobilized and the hexagonal pore structure of SBA-15 was well kept after the modification. Once modified, adsorption tests for Pb(II) were carried out in a bath under various conditions. Kinetic analyses demonstrated that adsorption kinetic was better represented by the pseudo-second-order model and besides this, the adsorption isotherms were well-fitted to the Freundlich model. Under optimal conditions, the theoretical maximum amount of Pb(II) that could be adsorbed by the MS-AP was measured to be 151.5 ​mg ​g−1, which suggested an excellent ions removal performance by the adsorbent. The thermodynamic study confirmed the spontaneous and endothermic nature of Pb(II) sorption with enhanced randomness. In the binary or the multiple mixed ions solutions, the MS-AP exhibited enhanced selectivity for Pb(II) with respect to Cu(II), Cd(II), Mn(II), Mg(II), Co(II) and Ni(II), when compared with the commonly used amine-grafted SBA-15. Furthermore, the ionic strength of the solution had no significant inhibition effect on Pb(II) sorption. Considering the good regeneration ability and reusability of the adsorbent, MS-AP could be promising for the selective removal of Pb(II) from water.

Theoretical and experimental investigations of new bis (amino triazole) schiff base ligand: Preparation of its UO2(II), Er (III), and La (III) complexes, studying of their antibacterial, anticancer, and molecular docking

UO2(II), Er (III), and La (III) complexes were prepared from new bis (amino triazole) Schiff base ligand. The ligand was synthesized by condensation of 1,3‐bis(4‐amino‐5‐phenyl‐1,2,4‐triazol‐3‐ylsulfanyl)propane with benzaldehyde. The structure of the prepared compounds was confirmed by some spectroscopic tools such as1H‐NMR, UV‐Vis, and IR, as well as molar conductance, mass spectrometry, elemental analysis, thermogravimetric analysis (TG), differential thermogravimetric (DTG), and differential thermal analysis (DTA) studies. The data revealed coordination of the complexes with tetradentate Schiff base. All complexes were octahedral. Computational studies for the prepared ligand by using DFT/B3LYP method were reported. The theoretical results described its bond lengths, angles, and dipole moment, and other parameters were calculated. The theoretical studies were supported the experimental data of the ligand and confirmed its successful preparation. Also, their antibacterial activities against four types of bacteria species (Pseudomonas aeruginosa,Escherichia coli,Bacillus subtilis, andStaphylococcus aureus) were investigated. The prepared complexes were biologically active compounds. The synthesized compounds were estimated for their anticancer activities against two cell lines (MCF‐7 and HepG2). The lowest IC50values were 17.6 and 23 μM for uranyl complex against MCF‐7 and ligand against HepG2 cell lines, respectively, which make them very important materials as anticancer drugs in the future researches. Finally, molecular docking studies were checked up for all prepared compounds with different protein receptors (3HB5 and 2GYT) to confirm their anticancer activities data.

Ni(II)-selective PVC membrane sensor based on 1,2,4-triazole bis Schiff base ionophore: Synthesis, characterization and application for potentiometric titration of Ni2+ ions against EDTA

This study involves the preparation and investigation of a novel and highly selective poly(vinyl chloride)-based membrane of 2-((5-(2-hydroxy-3-methoxybenzylideneamino)-2H-1,2,4-triazol-3-ylimino)methyl)-6-methoxyphenol Schiff base ligand (HMBT), which is a neutral ionophore with sodium tetraphenyl borate (STB) in the form of an excluder and o -nitrophenyloctyl ether ( o -NPOE) in the form of solvent mediators (plasticizing) as a Ni(II)-selective electrode. The observation of optimal performance was done wherein the membrane was shown to have the HMBT–PVC–NPOE-STB composition of 4:32:63:1.It worked effectively across a broad range of concentration (1.0 × 10 −8 to 1.0 × 10 −2 mol L −1 ). Meanwhile, the Nernstian slope was recorded as 29.3 mV per decade of activity between pH 3.0 and 8.0. The response time of this electrode was fast at 11 s which was used for a span of 100 days with sound reproducibility. According to the selectivity coefficients for trivalent, divalent, and monovalent cations, excellent selectivity was indicated for Ni(II) ions across a large number of citations, whereas no interference was caused by anions like PO 4 3− , SO 4 2− and Cl − . The proposed method in this study was applied successfully to determine Ni(II) content in different samples of water, obtaining suitable recoveries. Additionally, the probed sensor is utilized as indicator electrode when considering Ni 2+ ion potentiometric titration against EDTA. In addition, the chelate’s geometry and structure of the complex formed between Ni 2+ ions and HMBT, abbreviated as HMBT-Ni 2 , was evaluated by separating the solid product. Complex structure was confirmed based on alternative analytical and spectral methods to be structured in the bimetallic form with the formula [Ni 2 (HMBT)(H 2 O) 2 Cl 2 ]. The diamagnetic nature of the complex, which was concluded from the room temperature magnetic moment measurement combined with the UV–Vis measurement, suggested the square planar geometry around the Ni centers.

Synthesis, Molecular Structure from the X-ray Diffraction Data of the Powder (1E,1'E)-1,1'-(1,4-Phenylene)Bis(N-(Adamantan-1-yl)methanimine)

The title compound was synthesized by 2:1 condensation between adamantan-1-ylamine and benzene-1,4- dicarbaldehyde in n-BuOH and produced a good yield 87% of new bis Schiff base. The compound skeleton was affirmed by FTIR, 1H NMR, LC-MS, and X-ray powder diffraction. The structure was solved by a parallel tempering process and refined by using Rietveld refinement. Two adamantan-1-ylimino groups are connected in the anti-positions to the planar central 1,4-dimethylbenzene group. All rings of the adamantyl group possess normal chair conformation.

Optoelectronic and photonic properties of π-conjugated benzonitrile derivative bis-Schiff base by solution technique

In the present study, FT-IR and UV spectra of the 4,4′-((1,4 phenylenebis(methaneylylidene))bis(azaneylylidene))dibenzonitrile denoted as, PMAD were investigated in solution phase. PMAD exhibits two absorption bands near UV region. 1,4-Dioxane solvent gives rise to large shift in infrared frequency by the way of dipole-induced dipole interaction type. Optoelectronic and photonic properties were investigated experimentally in 1,4-dioxane, chloroform and THF solvents by solution technique. The significant parameters such as molar/mass extinction coefficient, optical band gap, transmittance, refractive index, angle of incidence and refraction, contrast, molecular absorption cross-section, dielectric constant, loss factors, optical and electric conductance were determined experimentally in 1,4-dioxane, chloroform and THF solutions of PMAD. It is observed that the investigated parameters are sensitive to the solvent. The results indicate that PMAD is promising molecule for electronic and optoelectronic devices.

Crystal Engineering of Schiff Base Zn(II) and Cd(II) Homo- and Zn(II)M(II) (M = Mn or Cd) Heterometallic Coordination Polymers and Their Ability to Accommodate Solvent Guest Molecules.

Based on solvothermal synthesis, self-assembly of the heptadentate 2,6-diacetylpyridine bis(nicotinoylhydrazone) Schiff base ligand (H2L) and Zn(II) and/or Cd(II) salts has led to the formation of three homometallic [CdL]n (1), {[CdL]∙0.5dmf∙H2O}n (2) and {[ZnL]∙0.5dmf∙1.5H2O}n (3), as well as two heterometallic {[Zn0.75Cd1.25L2]∙dmf∙0.5H2O}n (4) and {[MnZnL2]∙dmf∙3H2O}n coordination polymers. Compound 1 represents a 1D chain, whereas 2–5 are isostructural and isomorphous two-dimensional structures. The entire series was characterized by IR spectroscopy, thermogravimetric analysis, single-crystal X-ray diffraction and emission measurements. 2D coordination polymers accommodate water and dmf molecules in their cage-shaped interlayer spaces, which are released when the samples are heated. Thus, three solvated crystals were degassed at two temperatures and their photoluminescent and adsorption–desorption properties were recorded in order to validate this assumption. Solvent-free samples reveal an increase in volume pore, adsorption specific surface area and photoluminescence with regard to synthesized crystals.

Synthesis, in vitro Antimicrobial assay and Molecular Docking Studies of some new Symmetrical Bis-Schiff Bases and their 2-Azetidinones.

Synthesis, in vitro Antimicrobial assay and Molecular Docking Studies of some new Symmetrical Bis-Schiff Bases and their 2-Azetidinones.

Computational investigation of molecular structures, spectroscopic properties, cholinesterase inhibition and antibacterial activities of triazole Schiff bases endowed metal chelates

The aim of this project was to introduce novel bioactive compounds through the design and synthesis of two mono-Schiff bases, 4- [(5-amino-1H-1,2,4-triazol-3-yl)imino]methylbenzene-1,3-diol(L1) and 2- [(5-amino-1H-1,2,4-triazol-3-yl)imino]methyl}-6-methoxyphenol(L2) and one bis-Schiff base, 2,2′-{1H-1,2,4-triazole-3,5-diylbis [nitrilomethylylidene]}bis(6-methoxyphenol)(L3) together with their complexes of transition metals [VO(IV), Cr(III), Mn(II), Fe(II), Co(II), Ni(II), Cu(II), and Zn(II)]. The molecular structures of as-synthesized Schiff bases were explicitly confirmed by physical, spectral, analytical and computational studies. Quantum chemical calculations based on density functional theory (DFT) were performed at B3LYP/6-311+G(d.p) level to explore the optimized geometrical structures, molecular electrostatic potential (MEP), Mulliken atomic charges (MAC) and frontier molecular orbital (FMO) analysis of the as-synthesized ligands. The FMO energy gaps were rationalized to be 0.162, 0.158 and 0.138 eV for ligands (L1), (L2) and (L3), respectively which can efficiently polarize their chemical structures. As-synthesized metal complexes have good agreement with their purposed structures with octahedral geometry except vanadium complexes, which have square pyramidal geometry. As-synthesized compounds were also evaluated through thermogravimetry and fluorescence analysis. Additionally, the compounds were also scrutinized for antibacterial activity against five bacterial strains (Halomonas halophila, Chromohalobacter israelensis, Escherichia coli, Chromohalobacter salexigens and Halomonas salina) and enzyme inhibition bioassay against butyrylcholinesterase (BChE) and acetylcholinesterase (AChE). The results showed that the complexes (15) and (1) were the most active inhibitors of BChE and AChE enzymes with 94.60% and 90.90% activity, respectively. Moreover, all the compounds also exhibited significant antibacterial activity. It has been found that the metal complexes displayed more biological activity in contrary to parent ligands as a result of chelation.

A mesoporous silica-based fluorescent chemosensor bearing bis-Schiff base for the sensitive detection of Cu2+ ions

A new type of fluorescent chemosensor has been designed and prepared by immobilizing a bis-salicylaldehyde Schiff base on the surface of SBA-15 mesoporous silica for the sensitive determination of Cu2+ ions in water. The characterization of nanosensor Saloph-SBA confirmed that the bis-Schiff base was successfully anchored, and the ordered mesopore channel structure was well-maintained after surface modification. Upon the addition of Cu2+ ions, the fluorescence of the Saloph-SBA suspension was quenched dramatically, and a good linear relation was observed for the detection of Cu2+ over concentration ranging 0–2 ​mg/L. The nanosensor had a low detection limit of 8.4 ​× ​10−3 ​mg/L for Cu2+. In addition, the sensing selectivity study showed that the prepared probe had a good selectivity for Cu2+ over other interfering cations. Considering the effective regenerative ability and applicability of the nanosensor, Saloph-SBA could potentially be used as an effective nanosensor for the sensitive detection of Cu2+ ions in water.

Schiff Bases: Interesting Scaffolds with Promising Antitumoral Properties

Schiff bases, named after Hugo Schiff, are highly reactive organic compounds broadly used as pigments and dyes, catalysts, intermediates in organic synthesis, and polymer stabilizers. Lots of Schiff bases are described in the literature for various biological activities, including antimalarial, antibacterial, antifungal, anti-inflammatory, and antiviral. Schiff bases are also known for their ability to form complexes with several metals. Very often, complexes of Schiff bases with metals and Schiff bases alone have demonstrated interesting antitumor activity. Given the innumerable vastness of data regarding antitumor activity of all these compounds, we focused our attention on mono- and bis-Schiff bases alone as antitumor agents. We will highlight the most significant examples of compounds belonging to this class reported in the literature.

4-vinylpyridine derivatives: Protonation, methylation and silver(I) coordination chemistry

( E)-4-[2-(Pyridin-4-yl)vinyl]benzaldehyde, containing both a 4-vinylpyridine and an aldehyde functionality, is utilized to develop new, highly conjugated chalcone compounds and a bis-Schiff base azine compound. The chalcone-containing compounds are further explored for their protonation, methylation and silver(I) coordination chemistry using the pyridine moiety. In parallel, a cyano-containing analogue, ( E)-4-[2-(pyridin-4-yl)vinyl]benzonitrile is also synthesized and studied for its silver(I) coordination chemistry. These new compounds are fully characterized by mass spectrometry, elemental analysis and spectroscopic techniques. The methylated product of ( E)-1-(9-anthryl)-3-{4-[2-(pyridin-4-yl)vinyl]phenyl}prop-2-en-1-one and a silver complex of ( E)-4-[2-(pyridin-4-yl)vinyl]benzonitrile are structurally determined by X-ray crystallography.

N,N'-1,10-Bis(Naringin) Triethylenetetraamine, Synthesis and as a Cu(II) Chelator for Alzheimer's Disease Therapy.

The bis-Schiff base of N,N'-1,10-bis(naringin) triethylenetetraamine (1) was prepared, as a copper(II) ion chelator, compound 1 was used for Alzheimer's disease therapy in vitro. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay of compound 1 showed that this Schiff base could promote PC12 cells proliferation, and also, compound 1 could inhibit Cu2+-amyloid-β (Aβ)1-42 mediated cytotoxicity on PC12 cells. The thioflavine T (ThT) assay showed that 1 can effectively attenuate Cu2+-induced Aβ1-42 aggregation. In addition, compound 1 is determined to be potent antioxidants on the basis of in vitro antioxidant assay, it can effectively decease the level of reactive oxygen species (ROS) in Cu2+-Aβ1-42-treated PC12 cells and elevate the superoxide dismutase (SOD) activity in Cu2+-Aβ1-42-treated PC12 cells. The results show that N,N'-1,10-bis(naringin) triethylenetetraamine is a potential agent for therapy of Alzheimer's disease.

QSAR Study of α-Glucosidase Inhibitors for Benzimidazole Bearing Bis-Schiff Bases Using CoMFA, CoMSIA, and Molecular Docking

A new class of benzimidazoles bearing bis-Schiff bases as α-glucosidase inhibitory was studied based on the combination of two computational techniques such as 3D-QSAR and molecular docking. The CoMFA and CoMSIA QSAR models were developed from fifteen compounds in the training set and four compounds in the test set giving Q2 values of 0.587 and 0.597 respectively, and R2 values of 0.970 and 0.990 respectively. The adapted alignment method with the suitable parameters resulted in reliable models. The CoMFA and CoMSIA contour maps allowed the authors to recognize regions where the activity can be increased or decreased by suitable substitutions. According to these contour maps they have proposed three new compounds with high predicted activities. Moreover, to confirm the stability of these newly designed molecules in the receptor with PDB: 3A4A, a Surflex-docking was applied.

A dihydrazone based conjugated bis Schiff base chromogenic chemosensor for selectively detecting copper ion

A simple dihydrazone based bis Schiff base receptor L has been presented for the first time for colorimetric selective detection of Cu2+ ion in methanol-H2O (1:1 v/v, pH = 7.4 in HEPES buffer) with detection limit value 5.3 × 10−7 M. The binding stoichiometry was obtained as 1:1 from job’s plot analysis, 1H NMR and ESI-MS spectra with the association constant value 1.3 × 104 M−1. The chemosensor L can be applied for the recovery of contaminated water samples and also successfully used to detect Cu2+ ion using a test kit coated with L.

Potent antiproliferative active agents: novel bis Schiff bases and bis spiro β-lactams bearing isatin tethered with butylene and phenylene as spacer and DNA/BSA binding behavior as well as studying molecular docking

A [2+2]-cycloaddition of bis-isatin Schiff bases 5a–b and 7 with activated aryloxyacetic acid derivatives 8a–d afforded bis-spiroisatino β-lactams with aliphatic and aromatic spacers. The structures of the synthesized 2-oxindoles and spirooxindoles were determined based on Fourier-transform infrared spectroscopy, proton-1 and carbon-13 nuclear magnetic resonance spectroscopies and CHN analysis. Our interest in these bis-Schiff bases and bis-spiroisatino β-lactams is for their potential anticancer capabilities. In vitro bioactivity testing against the cervical adenocarcinoma (HeLa) and breast cancer (MCF-7) cell lines as well as noncancerous NIH/3T3 fibroblast cell was investigated applying the MTT assay. Bis-isatin derivatives 5a, 5b, 9h, 10a, and 10b showed promising antiproliferative activity toward these two cancer cell lines. Two of the bis-isatin Schiff bases, 5a and 5b, displayed IC50 values less than that of the clinically-used anticancer agent cisplatin towards both the MCF-7 and HeLa cells, while several of the bis-isatin β-lactams showed similar bioactivity to that of cisplatin. All of the oxindoles and spirooxindoles displayed a selective anticancer effect except 10b. To study the possible mechanism for this bioactivity, DNA and BSA binding analyses were performed using fluorescence and UV–visible spectroscopic techniques. The isatin adducts displayed excellent interaction propensity to CT-DNA as well as BSA. Molecular docking investigation carried out on DNA and BSA with promising molecules to show the possible mechanism of cytotoxicity activities.

Titanium (IV) complexes of some tetra-dentate symmetrical bis-Schiff bases of 1,6-hexanediamine: Synthesis, characterization, and in silico prediction of potential inhibitor against coronavirus (SARS-CoV-2).

Symmetrical bis‐Schiff bases (LH 2) have been synthesized by the condensation of 1,6‐hexanediamine (hn) and carbonyl or dicarbonyl. One of the synthesized Schiff bases has been subjected to the molecular docking for the prediction of their potentiality against coronavirus (SARS‐CoV‐2). Molecular docking revealed that tested Schiff base possessed high binding affinity with the receptor protein of SARS CoV‐2 compared with hydroxychloroquine (HCQ). The ADMET analysis showed that ligand is non‐carcinogenic and less toxic than standard HCQ. Schiff bases acting as dibasic tetra‐dentate ligands formed titanium (IV) complexes of the type [TiL(H2O)2Cl2] or [TiL(H2O)2]Cl2 being coordinated through ONNO donor atoms. Ligands and complexes were characterized by the elemental analysis and physicochemical and spectroscopic data including FTIR, 1H NMR, mass spectra, UV‐Visible spectra, molar conductance, and magnetic measurement. Optimized structures obtained from quantum chemical calculations supported the formation of complexes. Antibacterial, antifungal, and anti‐oxidant activity assessments have been studied for synthesized ligands and complexes.

Synthesis, crystal structures, and antimicrobial activities of copper(II) complexes with bis-Schiff bases

Three newly synthesized copper(II) complexes with the general formula [CuL], where L is the dianionic form of N,N′-bis(3,5-difluorosalicylidene)ethane-1,2-diamine (H2L1) for 1, N,N′-bis(3,5-difluorosalicylidene)propane-1,3-diamine (H2L2) for 2, and N,N′-bis(3,5-difluorosalicylidene)-2-hydroxy-1,3-propanediamine (H2L3) for 3, have been obtained and structurally characterized by spectroscopic method and single-crystal X-ray determination. The Cu atoms in the complexes are in square planar coordination, with the two imino N and two phenolate O atoms of the Schiff base ligands. The in vitro antimicrobial activities of the compounds indicate that they are interesting antibacterial agents.