Synthesis, characterization, antibiogram and DNA binding studies of novel Co(II), Ni(II), Cu(II), and Zn(II) complexes of Schiff base ligands with quinoline core

A series of Co(II), Ni(II), Cu(II), and Zn(II) complexes of Schiff base ligands L¹H₃ and L²H have been prepared. The ligands are synthesized by the condensation of 2-hydroxy-3-formylquinoline with salicyloylhydrazide and 2-hydrazinobenzothiazole in absolute ethanol. The prepared complexes were characterized by the analytical and spectral techniques. The stoichiometry of the complexes is found to be 1:1. The presence of coordinated and lattice water is confirmed by the TG and DTA studies. Subsequently all the prepared complexes were screened for antimicrobial activity against bacteria and fungi. The Cu(II) complexes have been found to be more active than the ligand. In addition the DNA binding/cleaving capacity of the compounds was analyzed by absorption spectroscopy, viscosity measurement, thermal denaturation, and gel electrophoresis methods.     

Synthesis, spectroscopic, thermal and antimicrobial studies of Co(II), Ni(II), Cu(II) and Zn(II) complexes with Schiff base derived from 4-amino-3-mercapto-6-methyl-5-oxo-1,2,4-triazine

Coordination complexes of Co(II), Ni(II), Cu(II) and Zn(II) with Schiff base derived from syringaldehyde and 4-amino-3-mercapto-6-methyl-5-oxo-1,2,4-triazine have been synthesized. These complexes have been characterized by elemental analysis, magnetic moment, spectroscopic (IR, Electronic, ¹H NMR, ESR) and thermogravimetric analysis. Magnetic and spectral data suggest octahedral geometry for Co(II), Ni(II) and Zn(II) complexes and square planar for Cu(II) complexes. The presence of coordinated water in metal complexes was confirmed by thermal and IR data. The Schiff base and its metal complexes have been screened for antibacterial (Pseudomonas aeruginosa, Bacillus subtilis, Escherichia coli, Staphylococcus aureus) and antifungal activities (Aspergillus niger, A. flavus). A comparison is made between activities of complexes with Schiff base and with the standard antibiotics.     

Synthesis, Characterization and Biocidal Activities of Some Schiff Base Metal Complexes

Some new mixed ligand complexes (1-5) of type ML''B (M(II)=Mn(II), Co(II), Ni(II), Cu(II) and Zn(II); HL''= o-vanillidene-2-aminobenzothiazole; B= 1,10-phenanthroline) and Schiff base metal complexes of types (ML₂") (6-10) and (M₂L") (11-15) (HL"= o-vanillidene-2-amino-N-(2-pyridyl)-benzene sulfonamide) were synthesized and characterized by elemental analysis and spectral (IR, ¹H NMR and ¹³C NMR) studies. The free ligands and their metal complexes have been screened for their in vitro biological activities against bacteria, fungi and yeast. The metal complexes show more potent activities compared with Schiff base ligands.     

Antimicrobial,DNA cleavage,and antioxidant properties of new series of metal(II) complexes derived from naphthofuran-2-carbohydrazide Schiff base: synthesis and physico-chemical studies

Metal complexes of the type [NiL₂Cl₂]·H₂O and ML₂Cl₂ [M = Co(II), Cu(II), Cd(II), Zn(II), and Hg(II)] where L = Schiff base, derived from condensation of naphthofuran-2-carbohydrazide and 2-chloro-3-formylquinoline have been synthesized. The chelation of the complexes have been inferred through elemental analyses, IR, electronic mass, ¹H NMR, ESR spectral data, magnetic and thermal studies. The measured low molar conductance values in DMF indicate the complexes to be non-electrolytic in nature. The cyclic voltammetric investigation suggested that, the Cu(II) complex is of single electron transfer quasi-reversible nature. The free ligand and its complexes have been evaluated for their in vitro antibacterial and antifungal activities by minimum inhibitory concentration method. The influence of DNA cleavage on all the complexes was analyzed by agarose gel electrophoresis method. The free ligand with its complexes has been studied for their antioxidant activity by DPPH method. The results of bioassay revealed that, the metal complexes are active than the free ligand and their biological activity increases on complexation.     

DNA cleavage and antimicrobial investigation of Co(II), Ni(II), and Cu(II) complexes with triazole Schiff bases: synthesis and spectral characterization

The Co(II), Ni(II), and Cu(II) complexes with Schiff bases derived from 3-substituted-4-amino-5-mercapto-1,2,4-triazole and fluvastatin have been synthesized. Schiff bases exhibited thiol–thione tautomerism and coordinated to metal ion through azomethine nitrogen and thiolate sulphur atoms. Square planar geometry for all the metal complexes of the type ML₂ has been proposed in the light of analytical, spectral (IR, UV–Vis., ESR, and FAB-mass), magnetic, and thermal studies. The antimicrobial studies of Schiff bases and their metal complexes against various antibacterial (Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Bacillus subtilis) and antifungal (Aspergillus niger, and Pencillium Chrysogenum) species by Minimum Inhibitory Concentration method revealed that, the metal complexes possess more healing antibacterial activity than the Schiff bases. Co(II), Ni(II), and Cu(II) complexes cleave the DNA isolated from A. niger.     

Synthesis, characterization, and antimicrobial activity of some new 2-diazo-benzimidazole derivatives and their Ni(II), Cu(II), and Ag(I) complexes

2-Aminobenzimidazole was diazotized and made to react with active methylene compounds viz: ethylcyanoacetate and malanonitrile. The ligands [IIIa and IIIb] were isolated, characterized, and then condensed with Ni(II) chloride, Cu(II) chloride, and Ag(I) nitrate. The ligands and complexes were characterized by elemental analysis, IR, ¹H NMR, ESR, UV–Visible spectral techniques, and along with thermal studies. The antimicrobial activity of the ligands [IIIa (C₁₂H₁₁N₅O₂) and IIIb (C₁₀H₆N₆)] and their metal complexes [IVa–IVf] against bacterial strains and fungal strains were investigated. The antimicrobial activity of the above metals and the ligands were discussed.     

Synthesis, characterization, antimicrobial, and DNA cleavage studies of metal complexes of coumarin Schiff bases

Co(II), Ni(II), Cu(II), and Zn(II) complexes of the Schiff bases formed by the condensation of 8-formyl-7-hydroxy-4-methyl-coumarin with 3-amino-pyridine (L ₁ ) and 3-amino-2-chloro-pyridine (L ₂ ) are synthesized and characterized by various physico-chemical methods. The FAB-mass spectra of the ligand L ₁ and its Zn(II) complex are reported herewith. Thermal studies with Co(II) and Ni(II) complexes of both the ligands L ₁ and L ₂ are also reported. From the above studies, it is concluded that the ligand L ₁ acts as a bidentate ligand coordinating through azomethine nitrogen and phenolic oxygen of coumarin moiety via deprotonation, and ligand L ₂ acts as a tridentate ligand coordinating through azomethine nitrogen, phenolic oxygen of coumarin, and chlorine of pyridine moiety. All the complexes showed an octahedral geometry with a slight distortion in Cu(II) complexes. The fluorescence studies are carried out for ligand L ₁ with its Co(II), Ni(II), Cu(II), and Zn(II) complexes. The ligands and the complexes were screened for antibacterial and antifungal activities in vitro. The antitubercular activities are carried out by middle Brook method for all the compounds. The MIC values, cytotoxicity properties, and DNA cleavage studies are carried out for most active ligand L ₂ , Co(II), and Cu(II) complexes.     

Synthesis, characterization, and thermal and biocidal aspects of drug-based metal complexes

Drug-based metal complexes [M(L)(A)(H₂O)₂] (M = Cu(II), Ni(II), Co(II), Zn(II), Cd(II), Mn(II), A = atenolol and L = ciprofloxacin) have been prepared and characterized using infrared spectra, electronic spectra, magnetic measurements, elemental analyses, and thermal investigation. Spectral investigations of metal complexes assume monomeric six-coordinate octahedral geometry. All the synthesized complexes exhibit higher biocidal activity against Bacillus subtilis, Escherichia coli, Bacillus cereus, Staphylococcus aureus, Salmonella typhi, and Serratia marcescens compared to parent compounds and standard drugs.     

Synthesis of metal(II) [M = Cu, Mn, Zn] Schiff base complexes and their Pro-apoptotic activity in liver tumor cells via caspase activation

Hepatocellular carcinoma is the fifth most common cancer responsible for more than 600,000 deaths per year. It is a typical vascular tumor which at earlier stages does not exhibit remarkable development of tumor; however, at advance stages, it is richly supplied by blood vessels and damages hepatocyte, the main functional cell types in the liver. Currently, surgery and chemotherapy are the main treatment strategies. However, the chemotherapeutic agents are usually unable to discriminate between normal and cancerous cells, and hence adverse effects of drug toxicities have become the major concerns in chemotherapy. Thus, inducing caspase dependent cytotoxicity in cancer cells via apoptosis has become one of the interesting and effective strategies for fighting this disease. The current study is an effort to further explore this area of research. Mn(II), Cu(II), and Zn(II) Schiff base complexes were prepared by condensation of 2-hydroxy-1-naphthaldehyde with either 4-nitrobenzene-1,2-diamine or 4-methylbenzene-1,2-diamine and characterized by Spectroscopic (FT-IR, UV–Vis, NMR, and MS) and microanalysis. The ligands, in comparison to their metal complexes, were evaluated for their anticancer and proapoptotic properties in human hepatocarcinoma (HepG2) cells. Results showed that the complexes are more potent proapoptotic agents than the parent ligands. All the tested compounds showed dose-dependent antiproliferative activity comparable with 5-fluorouracil (IC₅₀ = 4.6 μg/mL). All the synthesized Schiff base ligands and respective metal complexes showed potential anticancer activity. Out of them, some compounds showed IC₅₀ value as low as 1.24–3.56 μg/mL. Compounds 3 and 7 inhibited HepG2 cell proliferation by inducing apoptosis via activation of caspase cascade.     

Pyridine-2,5-dicarboxylate complexes with 2,2′-bipyridine and Co(II), Zn(II), Cu(II): syntheses, characterization, antimicrobial, and cytotoxic effects

In this study, three novel mononuclear M(II)-pyridine-2,5-dicarboxylate (M = Co(II), Cu(II), and Zn(II)) complexes with pyridine-2,5-dicarboxylic acid or (isocinchomeronic acid, H₂pydc) and 2,2′-bipyridine (bipy), [Co(pydc)(bipy)₂]·5H₂O (1), [Cu(pydc)(bipy)₂]·6H₂O (3), and [Zn(pydc)(bipy)₂]·6H₂O (4) have been synthesized. Elemental, thermal, and mass analysis; magnetic susceptibilities; molar conductance; IR and UV/vis spectroscopic studies have been performed to characterize the complexes. Subsequently, the results of antimicrobial activity of the two ligands H₂pydc and bipy, and the four compounds (1), (2), (3), and (4) were obtained by the agar disk diffusion method. Furthermore, the cytotoxic activity was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide viability assay for 24 and 48 h on rat glioma cells (C6).     

Synthesis of water soluble copper(II) complexes: crystal structures,DNA binding,oxidative DNA cleavage,and in vitro anticancer studies

Two ternary copper(II) complexes of dl-threonine and polypyridyl ligands with formula of [Cu(Thr)(Byp)Cl]·H₂O (1) and [Cu(Thr)(Phen)H₂O]Cl·2H₂O (2) were synthesized. The complexes were characterized by spectral (NMR, FT-IR, and UV–Vis), CHN elemental analysis and have been structurally elucidated by X-ray crystallography. Both of the complexes formed slightly distorted square-pyramidal coordination geometry. The electronic absorption spectra of the complexes showed a very low intensity d–d electronic band in the range of 610–620 nm in Tris–HCl/NaCl (5:5 mM) pH 7.2 buffer solution. The DNA binding interaction with calf-thymus DNA (CT-DNA) was investigated by electronic absorption spectral titration and viscosity measurements. The results revealed that the phenanthroline complex (2) interact with CT-DNA through intercalation while bipyridyl complex (1) through the groove binding mode. The calculated intrinsic binding constant (K _b) of (1) and (2) were 0.5 and 4.4 × 10⁵ M^?1, respectively. Both the complexes were found to promote efficient DNA cleavage activities at low concentration in the presence of H₂O₂. The results showed that (2) has the highest DNA binding and nuclease activity. Furthermore, both the complexes were tested against human colon cancer (HCT 116) and breast cancer (MCF-7) cell lines and showed a dose-dependent antiproliferation effect.     

Synthesis, characterization, and antibacterial activity of the ligands including thiophene/furan ring systems and their Cu(II), Zn(II) complexes

Carboxamide complexes having general formula as [ML]Cl₂·nH₂O (where M?=?Cu(II), Zn(II); n?=?0, 1/2) were synthesized using heterocyclic carboxamide ligands: 1,4-bis[3-(2-thiophenecarboxamido)propyl]piperazine (L¹) and 1,4-bis[3-(2-furancarboxamido) propyl]piperazine (L²). Their structures were characterized with elemental analysis, molar conductivity, magnetic susceptibility, and spectral methods (¹H-NMR, ¹³C-NMR, FT-IR, LC-MS). TGA and DTA curves were also performed. The structure–activity relationship for the ligands was investigated using PM3 semi-empirical method. The antibacterial activities of the carboxamides and their complexes were investigated against bacteria; Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 11230, Bacillus magaterium RSKK 5117, B. cereus RSKK 863, Salmonella enteritidis ATCC 13076, B. subtilis RSKK 244 using microdilution method.     

Synthesis, characterization, and antibacterial activity of a novel heterocyclic Schiff’s base and its metal complexes of first transition series

The synthesis of a series of some novel Schiff base complexes of Cu(II), Ni(II), Co(II), Mn(II), Zn(II) with a tetradentate Schiff base has been achieved by the reaction of malonyl hydrazide with dehydroacetic acid in ethanol under refluxing condition. All the synthesized metal complexes and ligand were characterized on the basis of elemental analysis, UV–Visible, ¹H and ¹³C NMR, IR spectroscopy and mass spectrometry. The IR spectral data suggest that azomethine N and enolic O atom are involved in coordination with metal ions, and the ligand behaves as a tetradentate ligand with ONNO donor atoms. The mass spectrum of the complexes reveals the formation of metal ligand bonding in stoichiometric ratio 1:1 (M:L). The UV–Visible data suggest the square planner geometry for the synthesized complexes. All compounds were screened for their antibacterial activity against gram-positive and gram-negative bacteria using Ampicillin as a standard drug. It has been found that metal complexes show enhanced activity as compared to ligand, and some modification in ligand structure may lead to better antibacterial agents in future.     

Synthesis, characterization, in vitro anticancer activity, and docking of Schiff bases of 4-amino-1,2-naphthoquinone

A series of Schiff bases of 4-amino-1,2-naphthoquinone were synthesized, purified, characterized, and evaluated for cytotoxicity against a panel of human cancer cell lines (Hep-G₂, MG-63, and MCF-7). The cells were dosed with these Schiff bases at varying concentrations, and cell viability was measured by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Significant anticancer activities were observed in vitro for some members of the series and compounds 4-(3,4,5-trimethoxybenzylideneamino)naphthalene-1,2-dione (S10) as well as 4-(4-hydroxy-3-methoxybenzylideneamino)naphthalene-1,2-dione (S13) are active cytotoxic agents against different cancer cell lines with IC₅₀ values in the range of 5.91–9.98 μM. The structures of synthesized compounds were established by spectroscopic (FT-IR, ¹H NMR, ¹³C NMR) and elemental analysis. To study the molecular basis of interaction and affinity of binding of the target molecules, all the compounds were docked into the ATPase domain of Topoisomerase-II (TP-II) by using Schrödinger molecular modeling software package. Docking experiments showed a good correlation between their predicted glide scores and the observed IC₅₀ values of synthesized compounds. Structure–activity relationships indicated that presence of electron donating groups on phenyl ring of Schiff bases enhances the activity but Schiff base with electron withdrawing substituents on phenyl ring shows diminished activity.     

Spectroscopic and structural studies on Ni-sulfadimethoxine complex

The new Ni complex of sulfadimethoxine (SDMX) is prepared and investigated by infrared spectroscopy. The X-ray powder diffraction patterns of the Ni(II) complex of (SDMX) (c), Ni(CH₃COO)₂ (b) and (SDMX) (a) are recorded and compared. It is shown that the proposed structure for this complex derived from the infrared spectrum are consistent with the X-ray powder diffraction measurements and the elemental analysis results. Investigation of the infrared spectrum of the sample indicates that the vibrations due to the amino and sulfonamido groups are shifted with respect to the free molecule in line with their coordination to the metal.     

Synthesis and Characterization of Cr(III), Mn(III), Fe(III), VO(IV), Zr(IV) and UO2(VI) Complexes of Schiff Base Derived from Isonicotinoyl Hydrazone

2-hydroxy-5-chloro-3-nitroacetophenone isonicotinoyl hydrazone as a Schiff base ligand and its complexes with Cr(III), Mn(III), Fe(III), VO(IV), Zr(IV) and UO₂(VI) metal ions have been synthesized. The ligands as well as their metal complexes were well characterized using various physicochemical techniques such as elemental analyses, molar conductance measurements, magnetic measurements, thermal analysis, electronic and IR spectral studies. On the basis of these studies, square pyramidal stereochemistry for Mn(III) and VO(IV) complexes while octahedral stereochemistry for all the other complexes have been suggested. The complexes were found to be stable up to 60-70° and thermal decomposition of the complexes ended with respective metal oxide as a final product. The thermal data have been analyzed for kinetic parameters using Broido and Horowitz-Metzger methods. The synthesized Schiff base ligand and its complexes were also tested for their antimicrobial activity using various microorganisms.     

Pod razor (Ensis siliqua) shell powder as cost-effective biomineral for removal of nickel(II), copper(II) and zinc(II) from artificially contaminated industrial wastewater

The removal of Ni(II), Cu(II) and Zn(II) from aqueous model solutions and real wastewater samples by using pod razor (Ensis siliqua) shell powder has been investigated under several conditions such as heavy metal concentrations, pH, contact time, powder dosage. It was found that the removal of heavy metals was dependent on the dose of the biomineral and contact time. The results showed that this low-cost material can be fruitfully used for the removal of heavy metal ions such as Ni(II), Cu(II) and Zn(II) below concentration of 200 mg/L applying a shell powder dose of 1.2–4 g/L. The minimal dose for removal of Cu(II) and Zn(II) from industrial wastewater was found to be 1.2 g/L, while for Ni this value amounted to 1.6 g/L. The contact time necessary for quantitative removal was found to be 30–60 min and the optimum initial pH range was between 4 and 5.     

Effects of Ni(II), other divalent metal ions, and glucagon upon plasma glucose concentrations in normal, adrenalectomized and hypyphysectomized rats.

The effects of Ni(II), administered ip as NiCl₂ or NiSO₄, upon plasma glucose and serum insulin concentrations have been investigated in Fischer rats. In fasting rats, hyperglycemia occurred at 0.5 hr after injection of Ni(II) in dosages from 12 to 85 μmol/kg. At dosages ≥34 μmol/kg, hyperglycemia persisted for 4 hr after injection of Ni(II). In approximate order of decreasing magnitude and duration, the hyperglycemic responses to equimolar ip injections of divalent ions of selected first transition metals were: Ni ≥ Co ≥ Cu ≥ Zn > Cr > Fe > Mn. Concurrent administration of insulin antagonized the hyperglycemic response to Ni(II). Concentrations of endogenous immunoreactive insulin in serum were increased from 0.5 to 3 hr after injection of Ni(II) in dosage of 68 μmol/kg. Adrenergic blockade with phentolamine and propranolol did not affect the hyperglycemic response to Ni(II). The hyperglycemic responses to Ni(II), Co(II), and glucagon were greatly suppressed but were not completely prevented by adrenalectomy or by hypophysectomy. These findings are attributed to interruption of the permissive actions of glucocorticoids upon hepatic gluconeogenesis and glycogenolysis.     

Effect of derivatization of sulfamethoxazole and trimethoprim with copper and zinc on their medicinal value

Cu(II) and Zn(II) complexes of Schiff bases obtained by condensation of sulfamethoxazole with salicylaldehyde/pyridoxal were prepared and characterized by microanalytical, thermogravimetric, magnetic, and spectroscopic data. The Cu (II) and Zn (II) complexes of salicylidenesulfamethoxazole were found to be five coordinate while all others were six coordinate. The electron paramagnetic resonance spectral lines exhibited rhombic distortion from axial symmetry, with g _‖ > g _⊥ > g _e, in the case of the Cu (II) complexes. The geometry of the complexes appears to be square–pyramidal or octahedral. All the compounds under investigation possess antibacterial activity against the strains tested. The antibacterial activity showed the following trend: Cu (II) complexes > Zn (II) complexes > Schiff base ligands > parent drugs. All the copper complexes were found to be active against kaolin paw edema whereas the parent drugs were inactive.     

Antimicrobial and antioxidant activities of new metal complexes derived from (E)-3-((5-phenyl-1,3,4-oxadiazol-2-ylimino)methyl)naphthalen-2-ol

(E)-3-((5-phenyl-1,3,4-oxadiazol-2-ylimino)methyl)naphthalen-2-ol (LH) has been synthesized and used as a ligand for the formation of V(IV), Cr(III), Mn(II), Co(II), Ni(II), and Cu(II) complexes. The chemical structures were characterized using different spectroscopic methods. The elemental analyses revealed that the complexes have the general formula [ML₂(H₂O)₂] [where M?=?Mn(II), Co(II), and Cu(II)], while the Cr(III) complex has the formula [CrL₂(H₂O)₂]Cl, V(IV) complex has the formula [VO₂L₂], and Ni(II) complex has the formula [NiL₂]. The molar conductance data revealed that all the metal chelates except the Cr(III) are non-electrolytes. From the magnetic susceptibility measurement and UV–Visible spectra, it is found that the structures of Cr(III), Mn(II), Co(II), and Cu(II) complexes are octahedral, V(IV), complex is square pyramid and Ni(II) complex is square planar. The stability of the prepared complexes was studied theoretically using density function theory. The total energy for the complexes was calculated and it was shown that the copper complex is the most stable. Complexes were tested against selected types of microbial organisms and showed significant activities. The free radical scavenging activity of metal complexes have been determined by their interaction with the stable DPPH-free radicals. All the compounds have shown encouraging antioxidant activities.