Synthesis and Characterization of 4-Amino Antipyrine Based Schiff Base Complexes: Antimicrobial, Cytotoxicity and DNA Cleavage Studies

DOI : 10.17577/IJERTV6IS080005

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  • Volume & Issue : Volume 06, Issue 08 (August 2017)
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Synthesis and Characterization of 4-Amino Antipyrine Based Schiff Base Complexes: Antimicrobial, Cytotoxicity and DNA Cleavage Studies

R. Jayalakshmi 1

Research Scholar, Department of Chemistry,

Periyar University, Salem, India

D. Dhivya Priya 2

Assisstant Professor, Department of Chemistry,

Spectrum College of Technology, Salem, India

V. Jayakkumar2

M. Pil Research Scholar, Department of Chemistry

Periyar University , Salem, IndiaA

Dr. R. Rajavel 1* Assisstant Professor, Department of Chemistry

Periyar University, Salem, India

Abstract A series of novel Cu(II), Co(II), Ni(II) and Mn(II) complexes were synthesized from the Schiff base obtained by the condensation of 4-aminoantipyrine with furfuraldehyde and dl- cysteine. Their structural features and other properties were explored from the analytical and spectral methods. The measured low molar conductance values in DMF indicate that the complexes are non-electrolytes. The stoichiometry of the obtained complexes and the bonding modes of the ligand were found to depend on both nature of metal and ligand. The grain size of the complexes was calculated by Scherers formula using powder XRD. The bio-efficacy of the ligand and their complexes has been examined against the growth of bacteria and fungi in vitro to evaluate their anti-microbial potential. The Schiff base and their metal complexes were evaluated using neuroblastoma SH-SY5Y cell lines. DNA-cleavage studies with CT-DNA have shown that more obvious activity against both Schiff base and its metal complexes in the presence of H2O2.

KeywordsAntimicrobial, 4-aminoantipyrine,cytotoxicity, dl- cysteine, DNA Cleavage, Schiff base.


Coordination of an organic compound with metal, i.e., chelation causes a harsh change in the biological assets of the ligand and also their metal moiety (Sorenson, 1987; Macias et al., 2003; Chandra and Gupta, 2005). Biological actions of transition metal complexes derived from Schiff base ligand were one of the most exhaustively studied topics in coordination chemistry, due to their superior activities compared to non-Schiff base complexes [4-7]. The coordination chemistry of Schiff base complexes involving oxygen and nitrogen donor ligands has attracted considerable attention from the biochemists owing to their applications in catalysis and their relevance to bioinorganic systems (Shanker et al., 2009). There has been an enormous effort directed towards the development of novel chemical compounds able to arrest or reverse the development of cancer [9,10]. It has been reported that chelation was the cause and cure of many diseases including cancer. In recent

years, a great deal of interest in the synthesis and characterization of transition metal complexes of 4- aminoantipyrine derivatives has been extensively examined due to their wide applications in various fields corresponding biological, analytical and therapeutical. In additional, they have been probed due to their diverse biological possessions as antifungal, antibacterial, analgesic, sedative, antipyretic, anti-inflammatory agents (Chandra et al., 2009), anti-tumor and greater DNA binding ability (Raman et al., 2010). Schiff base metal complexes of amino acids have gained significance not only from the inorganic point of view, yet also because of their physiological and pharmacological activities[13,14]. On account of the importance of 4- aminoantipyrine Schiff base complexes, in this work we explore the synthesis of novel Schiff base metal complexes derived from 4-aminoantipyrine, furfuraldehyde, dl- cysteine and its metal complexes. They were characterized using analytical and spectral techniques. Furthermore, their biological studies like antimicrobial, cytotoxicity and DNA cleavage responses have been performed.

Experimental protocols

  1. Reagents and Instruments

    For the preparation of the Schiff base metal complexes, we were used analytical grade chemicals and were used without further purification. All reagents, 4- aminoantipyrine, furfuraldehyde, dl-cysteine and metal (II) chlorides were of Aldrich and Merck products. Commercial solvents were distilled and then used for the preparation of ligands and their complexes. Microanalyses (C, H and N) were performed using the Perkin Elmer elemental analyzer. Molar conductance measurements of the complexes (10-3 M) in DMF were carried out by using ELICO CM 185 conductivity Bridge. Infrared spectra were measured using KBr discs on a Jasco FT-IR-410spectrometer in the range 4000-400cm-1. The absorption spectra were recorded by using T80+double beam spectrophotometer at room temperature.

    The 1HNMR spectrum was recorded using a DMF-d6 on a BRUKER ADVANCED III 400 MHz instrument. Cyclic voltammetric measurements were performed using electrochemical analyzer CH instruments electrochemical work station (Model 680) using a tetrabutylammonium perchlorate as a supporting electrolyte. A mass spectrum was recorded on Agilent6330 Ion Trap mass spectrometer. X-ray powder patterns were obtained with a Rigaku Miniflex II diffractometer.

  2. Synthesis of Schiff base (L)

    A methanolic solution of 4-aminoantipyrine (0.20 g, 1mmol) was added to a methanolic solution of furfuraldehyde (0.82 g, 1mmol) and amino acid [dl-cysteine) (0.121 g, 1mmol)] which was dissolved in alcoholic potash. The resultant mixture was refluxed for 4 h. The orange color solid product formed was filtered and recrystallized from ethanol.

    L. Yield: 80%. Anal. Calc. for C19H20N4O3S: C, 59.30; H, 5.24; N, 14.57; O, 12.49; S, 8.33(%); Found: C, 59.30; H, 5.20; N, 14.57; O, 12.48; S, 8.34(%). IR (KBr pellet, cm- 1):1483(C=O); 1645 (HC=N); 2925 (S-H); 3431 (OH); 1NMR (): (furfurylidine Moiety) 6.67.8 (m); (-CH3) 2.4- 2.5(s); (N-CH3) 3.03-307 (s); (CH=N) 9.42 (s); (- SH)1.2(s).

  3. Synthesis of metal complexes

    The Schiff base metal(II) complexes were prepared by mixing the appropriate molar quantity of ligand and metal salt using the following procedure. A solution of metal(II) chloride in methanol (1 mmol) was mixed with a methanolic solution of the Schiff base (2 mmol), and the resultant mixture was refluxed for 3 h with constant stirring. The solid complexes was filtered off and washed systematically with ethanol and then dried in slow evaporation. Schematic diagram for the synthesis of ligand and metal complexes was given in Figure 1.

    (CuL) Yield: 80%. Anal. Calc. for C38H38CuN8O6S2: C, 54.96; H, 4.61; N, 13.49; O, 7.65; S, 7.71; Cu, 7.66 (%);

    Found: C, 54.91; H, 4.57; N, 13.48; O, 7.62; S, 7.70; Cu, 7.65(%). IR (KBr pellet, cm-1):1493 (C=O); 1632 (HC=N);

    2963 (S-H); 528 (M-O); 466 (M-N); µeff (BM): 1.93.

    (CoL) Yield: 78%. Anal. Calc. for C38H38CoN8O6S2: C, 55.27; H, 4.64; N, 13.57; O, 11.63; S, 7.75; Co, 7.14; Found:

    C, 55.21; H, 4.60; N, 13.05; O, 11.62; S, 7.74; Co, 7.15; IR (KBr pellet, cm-1):1485(C=O); 1644 (HC=N); 2962 (S-H); 556 (M-O); 504 (M-N); µeff (BM): 4.74.

    (NiL) Yield: 80%. Anal. Calc. for C38H38NiN8O6S2: C, 55.28; H, 4.64; N, 13.58; O, 11.63; S, 7.77; Ni, 7.11; Found: C,

    55.23; H, 4.60; N, 13.56; O, 11.62; S, 7.77; Ni, 7.10; IR (KBr

    pellet, cm-1):1488(C=O); 1627 (HC=N); 2964 (S-H); 543

    (M-O); 471 (M-N); µeff (BM): 3.17.

    (MnL) Yield: 80%. Anal.Calc. for C38H38MnN8O6S2: C, 55.54; H, 4.66; N, 13.63; O, 11.68; S, 7.80; Mn, 6.66; Found:

    C, 55.48; H, 4.62; N, 13.62; O, 11.68; S, 7.80; Mn, 6.69; IR (KBr pellet, cm-1):1486(C=O); 1630 (HC=N); 2958 (S-H); 538 (M-O); 495 (M-N); µeff (BM): 5.78.

    Figure 1. Synthetic route of Schiff base and its metal complxes

  4. Antibacterial activity

In a typical procedure [15], the antibacterial activities of the compounds were evaluated by the disc diffusion method against the bacterial microorganisms. Newly synthesized Schiff base and its metal complexes were tested against in vitro antibacterial strains such as S.aureus, Bacillus subtilis, K.pneumoniae and E.coli were separately inoculated into nutrient broth and incubated at 37ºC for 4-6 hours. Then broth culture of the test bacteria was seeded on Mueller-Hinton agar plates and spread evenly. Five wells of 6mm in diameter were cut on the seeded agar plates using a sterile cork borer. The different chemicals were poured into each well and the standard antibiotic disc (Ciprofloxcin) were placed on the center of the plate. The plates were incubated at 37ºC for 24hrs after which the zones of inhibition round the wells resolute the antibacterial bustle of the extracts. Zone diameter was recorded as the differences between.

5 Anti-fungal activity

Fungicidal activity of testing compound was assessed against Aspergillus Niger and Pencillium sp. by cup- plate method[16]. The 5 mm diameter and 1 mm thickness of the disc was filled with the test solution using a micropipette and the plates were incubated at 37 ºC for 72 h. During this period, the test solution was diffused and affected the growth of the vaccinated fungi. Later 36 h of incubation at 37 ºC, the diameter of the inhibition was measured. Compounds screening auspicious antifungal activity were selected for minimum inhibitory concentration studies. The minimum inhibitory concentration was determined by assaying at concentrations of compounds along with standards at the same concentration. Minimum inhibitory concentration (MIC) was the lowermost concentration of an antimicrobial compound, inhibiting the visible growth of microorganisms

Co mpo und s

Molecular Formula

Calculated (found)%

m (1c

m2m ol-1)







Liga nd











(8.34 )


C38H38CuN8 O6S2




(4.57 )








(7.65 )



C38H38CoN8 O6S2










(7.74 )


(7.15 )



C38H38NiN8 O6S2










(7.77 )


(7.10 )



C38H38MnN8 O6S2










(7.80 )




subsequent overnight incubation and are important in diagnostic laboratories endorsing resistance of

microorganisms to antimicrobial agents and also to monitor the activity of new antimicrobial agents.

6. Cytotoxicity effect

The SH-SY5Y cells (Human neuroblastoma) were grown in DMEM-F12 medium supplemented with 10% FCS (fetal calf serum). Incubation of cells were routinely trypsinized and plated at 2 X 105/5 cm2 flasks. Schiff base and its Schiff base metal complexes were dissolved in DMSO at a concentration of 10, 25 and 50 µM and the solutions were kept at humidified atmosphere at-20oC until used. In generally 1% of the solvent (DMSO) was used in the cell viability assays. After 24 h of incubation, the cell viability was evaluated by using the Trypan Blue exclusion method.

a. DNA Cleavage studies

The DNA cleavage activity of the Schiff base and its metal complexes was examined by agarose gel electrophoresis method. pUC19 plasmid was educated, insulated and used as DNA for the experiment. Test compounds were prepared in DMF (1 mg/ml). Further 25 µg of the test samples was added to the insulated plasmid and incubated for 2 h at 37oC. Afterward incubation, 30 µl of plasmid DNA sample assorted with bromophenol blue dye (1:1) was overloaded into the electrophoresis chamber along with the control DNA,5M FeSO4 (treated with DNA) and standard DNA marker having TAE buffer (4.84 g Tris base, pH 8.0, 0.5 MEDTA/1 L). To end with, it was loaded onto an agarose gel and electrophoresed at 50 V constant voltage up to 30 min. Subsequently the gel was detached and stained with 10 µg/ml ethidiumbromide and the image was taken in Versadoc (Biorad)imaging system. The fallouts were compared with standard DNA. Likewise the same system was followed in the presences of H2O2.


The Schiff base ligand and their Cu(II), Co(II), Ni(II) and Mn(II) complexes have been synthesized and characterized by spectral and elemental analytical data. They were found to be stable at room temperature. The ligand was soluble in common organic solvents and all the metal complexes were spontaneously soluble in DMF and DMSO.

  1. Elemental analysis and molar conductivity measurements

    The outcomes of elemental analysis for the metal complexes were in good agreement with the calculated values (Table1) showing that the complexes have 1:2 metalligand stoichiometry of the type ML2 where in L acts as a tridentate ligand. The Schiff base metal(II) complexes were dissolved in DMF and the molar conductivities (10-3 M) of their solution at room temperature were measured. The lower conductance values (3946 ohm-1 cm2 mol-1) of the complexes support their non-electrolytic nature.

    Table1.Analytical and Physical data of Schiff base ligand and their metal complexes.

  2. Infrared Spectra

    The coordination mode and sites of the ligand to the metal ions were investigated by comparing the infrared spectra of the free ligand with their metal complexes. The IR Spectra results were summarized in Table 2. The Schiff base ligand (L) show a band at 1645 cm-1 which was assigned to azomethine (CH=N) linkage and the band were shifted towards lower frequencies in the spectra of their metal complexes (16271644cm-1). The comparison of the IR spectra of the complexes with Schiff base indicates the involvement of the azomethine nitrogen in chelation with the metal ion[17]. The coordination of nitrogen to the metal ion could be expected to reduce the electron density of the azomethine link and thus causes a shift in the (CH=N) group. The intensity peak of absorption in the Schiff base ligand around 3431cm-1 due to the phenolic hydroxyl group of the Schiff base ligand and this peak of absorption disappears while chelation with metal ions. This confirms the coordination through phenolic OH and the central metal ion[18]. In addition, the ligand also exhibits a band at 2925 cm-1 due to two thionyl group (-SH) [19] originating from the amino acid which was shifted towards higher region at around 2958-2964 cm-1 on complexation. The bands are observed at 1483cm-1 for a free amino acid ligand (-C=O), for comparison, the display bands at 14861493 cm-1, respectively for all the metal complexes. These results reveal that the carbonyl group of the amino acid ligand was involved in the complex formation. The coordination through the nitrogen of azomethine and oxygen of (C-O) of ligand were further evidenced by the appearance of non-igand bands around 466-504 cm-1 and 528-556 cm-1 were due to M-N and M-O bonds respectively [20,21].


    * (nm)

    n-* (nm)

    L M (nm)

    d-d (nm)

    Magnetic moment

    value(µeff) BM














    635, 703






    712, 406






    683, 552

    and 528





    (, cm-1)


    (, cm-1)


    (, cm-1)


    (, cm-1)


    (, cm-1)


    (, cm-1)






    Cu- comple







    Co- comple








    comple x







    comple x






    Table.3. Electronic spectroscopic and magnetic moment for ligand and their complexes

    Table 2.IR spectra of ligand and metal complexes

  3. Electronic spectra

    The electronic spectra of the Schiff base ligand and its metal complexes were recorded in DMF solution at room temperature and values are shown in Table 3.The band appears at 327 nm were attributed to n-* transitions which are associated with the azomethine chromophore, which was shifted to longer wavelength (329-334 nm) for metal complexes[22,23]. All the complexes show the energy absorption bands in the region from 278-289 nm compare with ligand (263nm, which was confirmed by complexation (Figure 2). The electronic spectra of copper complex display the dd transition bands in the region 794 nm, which were due to 2Eg 2T2g (F) transition. This dd transition band strongly favors a distorted octahedral geometry around the metal ion [24]. Electronic spectra of cobalt complex display the dd transition bands in the region 635 and 703 nm, which were assigned to the 4T1g (F) 4A2g (F) and 4T1g (F) 4T2g(F) transitions, respectively. These transitions










    Cul CoL NiL MnL

    200 300 400 500 600 700 800


    correspondto the octahedral geometry and further supported by their magnetic susceptibility values (4.74 BM). The electronic spectra of Mn(II) complex display the absorption bands in the range 683, 552 and 528 nm. These absorption bands may be assigned to the 6A1g 4A1g, 6A1g 4A2g and 6A1g 4Eg, 4A1g transitions, respectively. These bands suggest that the complexes possess an octahedral geometry. The absorption spectra of nickel complex display two dd bands in the region of 712 and 406 nm respectively. This corresponds to 3A2g (F) 3T1g (F) and 3A2g (F) 3T1g

    (P) transitions, respectively, and existence the characteristic

    of an octahedral geometry. These were further supported by their magnetic susceptibility values 3.17 BM.

    Figure 2. Electronic spectrum of Schiff base metal complexes

  4. Cyclic Voltammetry

    The cyclic voltammogram of Cu(II) complex showed a redox active peak in the potential range from 200- 400 mV assigned to the Cu(II)/Cu(I) couple(Figure 3 & Table 4.1-4.2). A cyclic voltammogram displays a reduction peak at Epc= 0.84 V with an associated oxidation peak at Epa= 1.06 V and the peak separation value (Ep) was 220 mV. The different current intensity of cathodic and anodic peaks found to be the quasi reversible behavior of simple one electron transfer reaction. The redox potential of Cu(II)/Cu(I) couple shown that, it was dependent on coordination number, nature and bulkiness of Schiff base ligand [25-26]. The cobalt complex exhibit one electron quasi reversible transfer process with a peak at Epa= 0.86 V, Epc=0.97 V and Ep= 110 mV.This gives evidence for quasi reversible Co(II)/Co(I) couple. The cyclic voltammogram of Ni(II) complex shown the anodic peak at Epa= 0.37 and associated cathodic peak at Epc=0.51 V. This was corresponds to quasi-reversibility of Ni(II)/Ni(I) couple with Ep= 140mV [27]. The Manganese(II) complex exhibit one electron quasi reversible transfer process with a peak at Ep values falls in the range of 190 mV and the E1/2 values falls in the range of 0.47 V

    corresponds to the quasi reversible of Mn(II)/ Mn(I)


    Epc (V)

    Epa (V)

    E1/2 (V)

    Ep (mV)






















    Table.4.1. Electrochemical data of heterocyclic mononuclear Schiff base metal(II) complexes in DMF medium (Negative potential)


    Epc (V)

    Epa (V)

    E1/2 (V)

    Ep (mV)





















    Table 4.2. Electrochemical data of heterocyclic mononuclear Schiff base metal(II) complexes in DMF medium (Positive potential)

    Figure 3.Cyclic voltammogram of Cu(II) Complex

  5. 1H NMR spectrum

    The 1H NMR spectrum of ligand (L) was recorded in DMF and Spectrum was shown in Figure 4. 1H NMR spectrum of the Schiff base ligand shows peak singlet at 10.6 ppm due to-OH group present in free ligand. The peaks at

    9.42 ppm corresponds to azomethine (-C=N) group[29]. The signal formed in the region from 6.6-7.8 ppm showed the multiplet due to furfurylidine moiety. The ligand also shows the following signals: (-CH3 2.42.5 (s), (-N-CH3 3.033.07 (s); and (-SH 1.2) (s) respectively. All the protons were found to be in their expected region. The conclusions drawn from these studies offer additional support to the mode of bonding discussed in their IR spectra. The number of protons

    calculated from the integration curves and those attained from the values of the expected CHN analyses agree with each other.

    Figure 4.1H NMR Spectum of Schiff base ligand

  6. Mass spectra

    Mass spectra afford an energetic clue for elucidating the structure of compounds. The mass spectra of the ligand(C19H20N4O3S) were recorded and their stoichiometric compositions were compared (Figure 5).The molecular ion peak for the ligand (L) was observed at 384.45 m/z which confirm the stoichiometry of the ligand. Elemental analysis values were in good agreement with the values calculated from molecular formula which was further supported by the mass studies.

    Figure 5. Mass Spectrum of Schiff base ligand

  7. Powder XRD

    In the absence of single crystal, X-ray powder data were especially useful to deduce accurate cell parameters. The diffraction pattern reveals the crystalline nature of the complex. Powder XRD patterns of Ni(II) and Mn(II) complexes recorded in the range 1080º () at wavelength

    1.54 Aº were shown in Figure 6a & 6b. The XRD pattern of the metal complexes shows well demarcated crystalline peaks

    representing that the samples were crystalline in phase (Souaya et al., 2000). The metal complexes illustrated sharp crystalline XRD patterns, which differ considerably from that of the ligand. The appearance of crystallinity of the metal Schiff base complexes were due to the inherent crystalline nature of the metallic compounds.

    The calculated lattice parameter for Ni(II) and Mn(II) complexes was a=b=c= 8.2263 and 8.1925. The grain size of the metal Schiff base complexes, dxrd was calculated using Scherers formula (Cullity, 1978).

    dxrd= 0.9 / cos

    Where is the wavelength, is the full width at half maximum of prominent intensity peak and is the diffraction angle.

    The complexes have the average grain size values of 2.4-2.8 nm, suggesting that the complexes were in nanocrystalline regime.







    10 20 30 40 50 60 70 80 90

    2 Theta

    P-XRD for Mn(II) complex






    10 20 30 40 50 60 70 80 90

    2 Theta

    P-XRD for Ni(II) comple

    Figure 6(a). P-XRD for Ni(II) Complex

    Figure 6(b). P-XRD for Mn (II) Complex

  8. Anti-microbial Studies

    The bacteriological activity of the Schiff base and its metal complexes were resolute against two gram positive (Staphylococcus aureus, bacillus subtilis) and two gram negative bacteria (E.Coli, K.pneumoniae) under different concentration. The antibacterial activity of ligand and their complexes were shown in Figure 7. The agar well diffusion method was employed for the bacteria with respect to Ciprofloxacin as standard drug. The copper complex showed better activity than other metal complexes for microorganisms. The increased activity of the copper complexes can be explained on the basis of Tweedys theory.In addition, chelation may enhance or suppress the biochemical potential of bioactive organic species. It was suggested that chelation considerably reduces the charge of the metal ion mainly because of partial allocation of its positive charge with the donor groups and possible p-electron delocalization over the whole chelate ring which leads to increase in lipophilic character. Further, lipophilicity, which controls the rate of entry of molecules into the cell, was modified by coordination, so the metal complexes can become more active than the free ligand (Farrell, 2007). The higher activity of the metal complexes may be owing to the effect of metal ions on the normal cell membrane.

    Similarly, all the compounds screened for their antifungal activity, showed more than 60% inhibition of mycelial growth against Aspergillus Niger and Penicillium sp (Figure8).The antimicrobial studies suggested that all the Schiff bases were found to be biologically active and their metal complexes showed significantly enhanced antibacterial and antifungal activity against microbial strains in comparison to the free ligands.

    Figure 7. Antibacterial activity for schiff base ligand and its metal complexes

  9. Cytotoxic Activity

The cytotoxic activity of Schiff base and its metal complexes was treated on neuroblastoma SH-SY5Y cell lines in the concentration of 10, 25 and 50 µM. After 24 h of treatment, Cell viability performed by using the Trypan blue exclusion method shown in Figure 9. In our study revealed that the Schiff base and its metal complexes stimulate loss of cell proliferation on the increasing concentration for cell lines. From this observation, we noticed that the Schiff base and its complexes were non-toxic to the neuroblastoma SH- SY5Y cell lines [33]. Among the Schiff base and its metal complexes, we found that the Cu(II) complex act as a good antitumor agent on SH-SY5Y cell lines.

10 µM

25 µM

50 µM


Cell viability(%)















Aspergillus Niger

Ligand CuL coL NiL MnL




standard Ligand CuL CoL NiL MnL

Figure 9. Percentage of cell viability versus different









20 40 60 80 100


Penicillium Sp.

concentrations for SH-SY5Y cells exposed to the metal complexes after 24 h incubation.

10. DNA Cleavage Study

Ligand CuL CoL NiL MnL

The DNA cleavage study is one of the gel electrophoresis methods. It was subjected to the most of the anticancer and antimicrobial therapies for cleaving the cells. This method was conducted by using agarose gel and the system containing pUC19 DNA alone, hydrogen peroxide and the synthesized compounds [34-35]. Among the Schiff base ligand and the metal complexes, Cu(II) and Co(II) complexes have, the more potential cleavage compares with others were shown in Figure 10.








20 40 60 80 100


Figure 8. Anti-fungal activity of Schiff base ligand and their metal complexes

Figure 10 : Gel electrophoresis pattern of Schiff base and its metal complexes Lane 1: DNA alone; Lane 2: DNA+ H2O2+HL; Lane 3: DNA+ H2O2+CuHL; Lane 4: DNA+ H2O2+CoHL; Lane 5: DNA+ H2O2+NiHL; Lane 6: DNA+ H2O2+MnHL;


This work depicted the synthesis and characterization of 4-aminoantipyrine derived Schiff base and their metal(II) complexes. The Schiff base ligand were behaving as nitrogen and oxygen donor tridentate ligand. The bonding of ligand to metal ion was strengthened by elemental analyses, molar conductivities, cyclic voltammetry, IR spectra, UVVis., mass spectra,1H NMR spectra. All these studies predicted good evidence for the proposed structure. The Powder XRD data analyzed the nanocrystalline structure of Ni(II) and Mn(II) complexes. Antimicrobial study of the presently studied metal complexes showed that the general trend observed in inhibition potency against the bacterial and fungal strains. The result suggested that the antibacterial and antifungal activities of the ligand and their complexes exhibit high persuasive biocidal and fungicidal activity than the free ligand. Entire lines of cytotoxicity of Schiff base metal complexes possess a very distinct behavior in impacting the cell death. The Schiff base ligand and their metal complexes can excellently cleave the plasmid DNA in the presence of an oxidizing agent H2O2.


  1. Sorenson, John R.J.Biology of Copper Complexes.Clifton, NJ : Humana Press; 1987.

  2. Macias B, Garcia I, Villa M.V, Borras J, Gonzalez-A´ lvarez M, Casti~neiras A. Oxidative DNA damage of mixed copper(II) complexes with sulfonamides and 1,10-phenanthroline: Crystal structure of [Cu(N-quinolin-8-yl-p- toluene sulfonamidate)2 (1,10phenanthroline)]. J. Inorg. Biochem. 2003 : 96 ; 367 – 374.

  3. Chandra S, Gupta L.K.EPR, mass, IR, electronic, and magnetic studies on copper(II) complexes of semicarbazones and hiosemicarbazones.Spectrochim.Acta Part A. 2005:61 (12);269275.

  4. Refat M.S, El-Sayed M.Y, Adam A.M.A. Cu(II), Co(II) and Ni(II) complexes of new Schiff base ligand: Synthesis, thermal and spectroscopic characterizations. J. Mol. Struct. 2013:1038;62-72.

  5. Nejo A.A, Kolawole G.A, Nejo A.O. Synthesis, characterization, antibacterial, and thermal studies of unsymmetrical Schiff-base complexes of cobalt(II). J. Coord. Chem. 2010:63;4398-4410.

  6. Crans D.C, Woll K.A, Prusinskas K, Johnson M.D, Norkus E.Metal Speciation in Health and Medicine Represented by Iron and Vanadium. Inorg. Chem. 2013:52;12262- 12275.

  7. Nagesh G.Y, Mahendra Raj K, Mruthyunjayaswamy B.H.M.Synthesis, characterization, thermal study and biological evaluation of Cu(II),

    Co(II), Ni(II) and Zn(II) complexes of Schiff base ligand containing thiazole moiety.J. Mol. Struct. 2015:1079;423-432.

  8. Shanker K, Rohini R,Ravinder V, Muralidhar Reddy P, Yen-Peng Ho. Ru(II) complexes of N4 and N2O2 macrocyclic Schiff base ligands: Their antibacterial and antifungal studies. Spectrochim.Acta Part A. 2009:73 (1);205211.

  9. Airley R, Cancer Chemotherapy: Basic Science to the Clinic.Weinheim, Germany: Wiley-VCH;2009.

  10. Davis K.J, Richardson C, Beck J.L, Knowles B.M, Guedin A, Mergny J.L, Willis A.C, Ralph S.F. Synthesis and characterisation of nickel Schiff base complexes containing the meso-1,2- diphenylethylenediamine moiety: selective interactions with a tetramolecular DNA quadruplex.Dalton Trans. 2015:44;3136-3150.

  11. Chandra S, Jain D, Sharma A.K, Sharma P.Coordination Modes of a Schiff Base Pentadentate Derivative of 4-Aminoantipyrine with Cobalt(II), Nickel(II) and Copper(II) Metal Ions: Synthesis, Spectroscopic and Antimicrobial Studies.Molecules. 2009:14 (1);174 190.

  12. Raman N, Sobha S. Exploring the DNA binding mode of transition metal based biologically active compounds.Spectrochim. Acta. 2012:85A;223229.

  13. Tai A.E, Lien E.J, Lai M.M, Khawaja T.A. Novel N-hydroxyguanidine derivatives as anticancer and antiviral agents.J. Med. Chem. 1984:27(2);236-238.

  14. Wang P. H, Keck G.J, Lien E.J, Lai M.M.C. Design, Synthesis, Testing, and Quantitative Structure-Activity Relationship Analysis of Substituted Salicylaldehyde Schiff Bases of 1-Amino-3- hydroxyguanidine Tosylate as New Antiviral Agents against Coronavir us. J. Med.Chem. 1990:33;608-614.

  15. Marmur J. A procedure for the isolation of deoxyribonucleic acid from micro-organisms. J. Mol. Biol. 1961:3;208218.

  16. Seeley H.W and Van Denmark P.J. Microbes in Action; A Laboratory manual of microbiology, India; Taroporevala D.B Sons and Co. Pvt. Ltd:1975.

  17. Keypour H, Salehzadeh S and Parish R.V.Synthesis of Two Potentially Heptadentate (N4O3) Schiff-base Ligands Derived from Condensation of Tris(3-aminopropyl)-amine and Salicylaldehyde or 4- Hydroxysalicylaldehyde. Nickel(II) and Copper(II) Complexes of the Former Ligand.Molecules. 2002: 7;140-144.

  18. Ahmed AElS. Taha MAE.Synthesis, spectral characterization, solution equilibria, in vitro antibacterial and cytotoxic activities of Cu(II), Ni(II), Mn(II), Co(II) and Zn(II) complexes with Schiff base derived from 5- bromosalicylaldehydeand2aminomethylthiophene.Spectro Chim. Acta. 2011:79;1803-1814.

  19. Gehad G. Mohamed, M.M. Omar, Ahmed M.M. Hindy. Synthesis, characterization and biological activity of some transition metals with Schiff base derived from 2-thiophene carboxaldehyde and aminobenzoic acid.Spectrochim. Acta. Part A. 2005:62;1140-1150.

  20. Li C, Liu S.L, Guo L.H, Chen D.P.A new chemically amplified electrochemical system for DNA detection in solution.Electrochem. Commun. 2005:7;2328.

  21. Manonmani J, Kandaswamy M, Narayanan V, Thirumurugan R, ShanmugaSundura Raj S, Shanmugam G, Ponnuswamy M.N, Fun H.K.Synthesis of copper(II) and nickel(II) complexes using compartmental ligands: X-ray, electrochemical and magnetic studies.Polyhedron. 2001:20;30393048.

  22. Karaoglu K, Baran T, K. Serbest K. Two novel macroacyclic schiff bases containing bis-N2O2 donor set and their binuclear complexes: synthesis, spectroscopic and magnetic properties. J. Mol. Struct. 2009: 922;3945.

  23. Mustafa Dolaz, Vickie McKee, Ays egül Gölcü and Mehmet Tümer.Synthesis, structural characterization, thermal and electrochemical studies of the N,N-bis[(3,4- dichlorophenyl)methylidene]cyclohexane-1,4-diamine and its Cu(II), Co(II) and Ni(II) metal complexes.Spectrochim. Acta Part A. 2009:71;1648-1954.

  24. Natarajan Raman, ArunagiriSakthivel, Muthusamy Selvaganapathy, LiviuMitu.Effect of DNA interaction involving antioxidative 4- aminoantipyrine incorporating mixed ligand complexes having alpha-amino acid as co-ligand.J.Mol. Struct. 2014:1060;6374.

  25. Sengottuvelan N, Manonmani J, Kandaswamy M.Synthesis of unsymmetrical compartmental oxime nickel(II) and copper(II) complexes: spectral, electrochemical and magnetic studies.Polyhedron. 2002:21;2767-2772.

  26. Bard A. J, Izatt L. R, Electrochemical methods: Fundamentals and applications. 2nd ed. New York: Wiley;2001.

  27. Donzello M P, Dini D, Arcargelo G D, Ercolani C, Zhan R, Ou Z, Stuzhin PA, Kadish K M.Porphyrazines with Annulated Diazepine Rings. 2. Alternative Synthetic Route to Tetrakis-2,3-(5,7-diphenyl- 1,4-diazepino)porphyrazines: New Metal Complexes, General Physicochemical Data, UltravioletVisible Linear and Optical Limiting Behavior, and Electrochemical and Spectroelectrochemical Properties.J. Am. Chem. Soc. 2003:125(44);14190-14204.

  28. Raman N, Dhaveethu Raja J and Sakthivel A. Synthesis, spectral characterization of Schiff base transition metal complexes: DNA cleavage and antimicrobial activity studies. J.Chem. Sci. 2007:119(4);303-310.

  29. MalathyM&RajavelR. Binuclear Cu(II) Schiff base complexesas prescursors for the synthesis of CuOnanoparticles: anticancer activity against MCF-7cell line. Smart Science. 2016: 4(2);95-107.

  30. Souaya E.R, Hanna W.G, Ismail E.H, Milad N.E.Studies on some acid divalent-metal nitrilotriacetate complexes.Molecules. 2000:5;1121-1129.

  31. Cullity B.D, Elements of X-ray Diffraction, second ed. Philippines


  32. Farrell N.Biomedical uses and applications of inorganic chemistry. An overview.Coord. Chem.Rev. 2002: 232 (12);14.

  33. Lin, Y.C., Huang., Chen, S.C., Liaw C.C., Kuo, S.C., Huang, L.Y. and Gean, P.W.Neuroprotective Effecs of Ugonin K on Hydrogen Peroxide-Induced Cell Death in Human Neuroblastoma SH-SY5Y Cells. Neurochem Res. 2009:34;923-930.

  34. Raman N, Baskaran T and Selvan A.DNA interaction and antimicrobial studies of novel copper(II) complex having ternary Schiff base. J. Iran. Chem. Res. 2008:1(2);129-139.

  35. sThomas A.M, Naik A.D, Nethaji M and Chakravarty A. R.Photo- induced DNA cleavge activity of ternary (N-salicylidene-L- methioninato)copper(II) complexes of phenanthroline bases.Indian J Chem.2004: 43(A);691-700.

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