SYNTHESIS, CHARACTERIZATION AND BIOLOGICAL STUDIES OF SOME METAL COMPLEXES DERIVED FROM BENZOFURAN...

www.wjpps.com Vol 3, Issue 7, 2014.

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Halli et al. World Journal of Pharmacy and Pharmaceutical Sciences

SYNTHESIS, CHARACTERIZATION AND BIOLOGICAL STUDIES

OF SOME METAL COMPLEXES DERIVED FROM BENZOFURAN

SCHIFF’S BASE.

M. B. Halli*1, K. Mallikarjun 1, S. S. Suryakanth1 and P. Vithal Reddy2

1Department of Post-Graduate Studies and Research in Chemistry, Gulbarga University,

Gulbarga, Karnataka (India) 585106. 2Department of Chemistry, B. V. Bhoomreddy College, Bidar.

ABSTRACT

Novel Schiff base and its metal complexes have been synthesized via

the condensation of Benzofuran-2-carbohydrazide and 2-hydroxy-3-

formylquinoline. The synthesized Schiff’s base and complexes were

characterized on the basis of elemental analysis, UV-Vis, IR, 1HNMR,

ESR and Mass spectral studies. All the complexes are soluble in DMF

and DMSO. The measured molar conductance values suggest that the

complexes are non-electrolytic in nature. We propose the octahedral

geometry for Co(II), Ni(II) and Cu(II) complexes, based on spectral

data, magnetic data and analytical data. The Cd(II), Zn(II) and Hg(II)

complexes show the tetrahedral geometry. The Schiff base and their metal complexes were

screened for their anti-bacterial, anti-fungal and DNA cleavage activity studies. The result

show that the biological activity of the ligand gets increased on complexation. DNA cleavage

studies shows the complexes have displayed complete cleavage of CT-DNA. In addition the

ligand and its complexes has been studied for their antioxidant activity.

Keywords: Benzofuran, Quinoline, Schiff base, Metal complexes, Spectral studies, DNA

cleavage. Antioxidant activity.

INTRODUCTION

Schiff’s bases have drawn considerable attention since such ligands dominates the area of

higher coordination number and from kinetic and thermodynamic point of view. The

chemistry of Schiff’s bases are it’s wide application in food industry and dyes industry,

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VVoolluummee 33,, IIssssuuee 77,, 11449999--11551122.. RReesseeaarrcchh AArrttiiccllee IISSSSNN 2278 – 4357

Article Received on 09 May 2014, Revised on 30 May 2014, Accepted on 23 June 2014

*Correspondence for Author

Dr. M. B. Halli,

Professor, Department of

Chemistry, Gulbarga

University, Gulbarga, INDIA.


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analytical chemistry, catalysis, fungicidal and agrochemical activities1 etc. Azomethine

complex ability have been enlightened in a considerable number of research articles2-3.

Abundance of information pouring into literature4-7 on metal complexes with ligands

containing O, N and S donor atoms, Schiff’s bases have claimed enormous portion of interest

because of their varied complexing ability.

Benzofuran compounds occur in nature in a variety of structural forms, which ranges from a

simple molecule such as 5-methoxybenzofuran to a highly complicated molecule like

morphine A and B and much more synthetic work has been carried out.

Quinolines are a class of nitrogen hetrocycles, Which are a part of a large number of natural

and synthetic compounds which play important roles in many biological systems. It has been

reported that some quinolines possess activities including antibacterial6, antifungal7, anti-

amoebic8, antitumor9 and antihypertensive10.

In view of the extensive use of Schiff bases derived from 2-hydroxy-3-formylquinoline and

its metal complexes in the area of coordination chemistry, we thought it is worthwhile to

prepare the benzofuran Schiff base and its metal complexes.

The current article describes synthesis of Co(II), Ni(II), Cu(II), Zn(II), Cd(II) and Hg(II)

complexes with Schiff base derived from condensation of 2-hydroxy-3-formylquinoline and

benzofuran-2-carbohydrazide (Figure 1). All the synthesized compounds are characterized

by spectroscopic ( 1HNMR, IR, UV-Vis, ESR, and Mass spectra) and physical data. Further

Schiff base complexes were subjected to antibacterial and antifungal activity screening. The

DNA cleavage activities of all the complexes were studied by the agarose gel electrophoresis

method.

Experimental

All the chemicals used are of AR grade with a highest purity available. Benzofuran-2-

carboxamide was synthesized according to the literature procedure11, the metal and the

chloride content are determined according reported procedure.

Synthesis of Schiff base N'-((2-hydroxyquinolin-3-yl)methylene)benzofuran-2-

carbohydrazide (L)

A mixture of benzofuran-2-carbohydrazide (0.1 mol) and 2-hydroxy-3-formylquinoline (0.1

mol) in ethanol (30 mL) were refluxed on water bath for about 8 h in presence of few drops


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of glacial acetic acid with occasional shaking. The product which was separated out as

crystalline solids on cooling was collected and recrystallized from ethanol.

O

C

O

NHNH2

N OH

CHO

+

Reflux 5-6 Hrs

Alcohol

OC

O

HN

N

HC

NOH

Fig. 1. Synthesis of ligand [L]

C19H13N3O3 [L] Molecular Weight = 331, mp = 238°C, Yield= 72%.

General procedure for preparation of metal complexes.

Metal chloride (0.01 mol) was mixed with Schiff base (0.01 mol) in an ethanolic medium 30

mL and reaction mixture was refluxed for about 4 h on water bath, then aqueous solution of

sodium acetate was added to the mixture to adjust the pH between 5-6 and further refluxed

for about an hour. The complexes separated were filtered off, washed with distilled water,

then with alcohol, and finally dried in vacuum over fused calcium chloride.

Physical measurements

All the experimental techniques used for the physical measurements were discussed in our

earlier paper12.

Antibacterial and antifungal assays

The antibacterial and antifungal activities of Schiff base (L) and Co(II), Ni(II), Cu(II), Zn(II),

Cd(II) and Hg(II) complexes have been studied by agar diffusion method using DMF as a

solvent against the bacteria Escheria coli, Staphylococus aures, Pseudomonas and Bacillus.

Aspergillus niger and A. Flavous fungal species Streptomycin and Fluconazole are used as a

standard antibacterial and antifungal drugs respectively, at four different concentrations.

Activity was determined by measuring the diameter of the zone showing complete inhibition.


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RESULTS AND DISCUSSION

Table 1: Elemental analysis, molar conductance, and magnetic susceptibility data for Schiff base (L) and its metal complexes.

Molecular formula Mol. wt

M.P. °C

Yield (%)

Elemental analysis (%) Found/(Calculated) eff

B.M.

Λ M

ohm-1 cm2

mole-1 C H N O M Cl

Ligand (L) [C19H13N3O3]

331.12 238 63 68.87 (68.78)

03.95 (4.00)

12.68 (12.70)

14.48 (14.45) ---- ---- ---- ----

[Cu(C19H12N3O3)2] 724.18 293 59 63.0 (63.02)

3.36 (3.34)

11.61 (11.60)

13.25 (13.26)

8.79 (8.77) ----- 1.93 15.76

[Ni(C19H12N3O3)2] 719.32 287 61 63.44 (63.46)

3.38 (3.36)

11.68 (11.67)

13.34 (13.35)

8.18 (8.16)

----- 3.01 16.56

[Co(C19H12N3O3)2] 719.6 >300 63 63.42 (63.43)

3.35 (3.36)

11.67 (11.68)

13.36 (13.34)

8.18 (8.19) ----- 4.98 15.87

[Zn(C19H12N3O3)Cl] 431.12 297 54 52.92 (52.93)

2.80 (2.81)

9.74 (9.75)

11.11 (11.13)

15.16 (15.17))

8.23 (8.22) ----- 15.59

[Cd(C19H12N3O3)Cl] 478.18 281 62 47.72 (47.72)

2.53 (2.52)

8.78 (8.79)

10.03 (10.04)

23.50 (23.51)

7.40 (7.41) ----- 14.52

[Hg(C19H12N3O3)Cl] 566.36 >300 68 40.29 (40.30)

2.13 (2.14)

7.41 (7.42)

8.46 (8.47)

35.41 (35.42)

6.25 (6.26) ----- 13.81


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All the complexes are light coloured, stable and non-hygroscopic in nature having high

melting points (>300 °C). Soluble in DMSO and DMF and sparingly soluble in common

organic solvents. Elemental analysis results (Table 1) show that the complexes of Cu(II),

Co(II) and Ni(II) have the 1:2 stoichiometry and the complexes of Zn(II), Cd(II) and Hg(II)

posses the 1:1 stoichiometry. The low molar conductance values (15.20 to 20.80 ohm-1 cm2

mol-1) indicate the non-electrolytic nature of the complexes.

Table 1. IR Studies

The IR spectra of synthesised Schiff base and its metal complexes Co (II), Ni (II), Cu (II),

Zn(II), Cd (II) and Hg(II) are listed in Table 2.

The IR spectra of ligand and metal(II) complexes have been taken in solid state and to find

out coordination of the ligand to metal ions, we observe the following changes

(i) The band observed at 3427 cm-1 in ligand moiety is disappeared in all the complexes

indicating deprotanation of phenolic –OH.

(ii) The strong band due to ν(C=O) stretch at 1653cm-1 in free ligand shifts to lower wave

number side in all the complexes.

(iii)The ν(C=N) stretch of azomethine13, 14 at 1567cm-1 in free ligand shifts to lower wave

number side in all the complexes. All these observation confirm that ligand acts as monobasic tridentate in all the complexes,

The coordination of oxygen of –CONH and azomethine nitrogen is further confirmed by

presence of non-ligand bands in IR spectra of complexes which are assigned to ν(M-O) and

ν(M-N) stretching modes.(table-2)

Table-2: The important Infrared frequencies (in cm-1) of Schiff base and their metal

complexes.

Compound ν(OH) ν(NH) ν(C=O) ν(C=N) ν(C-O-C) ν(M-N) ν(M-O) Ligand (L) [C19H13N3O3]

3427 3055 1653 1567 1184 ----- -----

[Cu(C19H12N3O3)2] ---- 3059 1611 1562 1185 433 502 [Ni(C19H12N3O3)2] ---- 3062 1639 1559 1184 438 527 [Co(C19H12N3O3)2] ---- 3056 1647 1559 1183 437 520 [Zn(C19H12N3O3)Cl] ---- 3059 1645 1561 1185 442 532 [Cd(C19H12N3O3)Cl] ---- 3059 1646 1557 1184 443 521

[Hg(C19H12N3O3)Cl] ---- 3058 1615 1558 1183 440 521


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Mass spectral studies

The LCMS mass spectra of the Schiff base (L) has showed a molecular ion peak at m/z

332.30, which is one mass unit more than that of the molecular weight of the Schiff base

suggesting the proposed structure. The LCMS mass spectrum of the Co(II) complex showed

a molecular ion peak at m/z 719.50 which is the molecular weight of the complex. Hence

supports the suggested structure of the complex.

Fig. 2. LCMS Spectra of the ligand (L)


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Fig. 3. LCMS Spectra of the Co(II) complex

1HNMR spectral studies

The 1HNMR spectrum of ligand (fig 4) shows a signal at δ 12.33(s, 1H) due to the presence

of –OH group, a signal at δ 12.04(s, 1H) due to the presence of amide (-CONH-) proton and a

signal at δ 8.792(s, 1H) due to the presence of azomethine (-CH=N-) proton. A signal at δ

(7.21-8.5) (m, 10H) due to the presence of aromatic protons. This confirms the structure of

Schiff’s base.


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Fig. 4: 1HNMR spectra of ligand

Magnetic Properties

Magnetic susceptibility measurements at the room temperature exhibits paramagnetism for

Co(II), Ni(II) and Cu(II) complexes are listed in Table-1. The cobalt complex exhibit

magnetic moment of 4.98 BM. suggesting octahedral geometry. The Ni(II) complex show

magnetic moment value of 3.01 BM. slightly higher than spin only value (2.83 BM),

indicating an octahedral environment. The observed magnetic moment values for the Cu(II)

complex is 1.93 BM suggesting a distorted octahedral geometry.

Electronic spectral studies

The electronic spectra of the Co(II) complex show the band at 16,524 cm-1 and 21,052 cm-1.

These two bands are assigned to 4T1g (F) →4A1g (ν2) and 4T1g (F) → 4T2g (ν3) transitions

respectively in an octahedral environment15. The Ni(II) complex exhibit two bands at 15,452

and 26,526 cm-1 assignable to 3A2g (F) → 3T1g(F)(ν2) and 3A2g (F) → 3T1g (F) (ν3) transitions

respectively in an octahedral environment. The lowest band ν1 could not be observed due to

limited range of the instrument used. However, it is calculated using band fitting procedure.

The copper complex exhibit broad asymmetric band in the region 12,820 – 17,094 cm-1. The

broadness of the band indicates the three transitions 2B1g (F) → 2A1g (ν1), 2B1g (F) → 2B2g (ν2)

and 2B1g (F) → 2Eg (ν3) which are similar in energy and gives rise to only one broad band.

The broadness of the bond may be due to Jahn-Teller distortion. All the data suggest the

distorted octahedral geometry around Cu(II)14. The octahedral structure is further supported

by the ligand field parameter (table-3)


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Table – 3: Electronic spectral bands and ligand field parameters of Co(II), Ni(II) and Cu(II) complexes in DMF (10-3 M) solution.

Complex

Transitions in cm-1 Dq (cm-1)

B (cm-1) β Β% ν2/ν1

LFSE (K.cal)

ν1a ν2 ν3

[Co(C19H12N3O3)2] 7418 16260 21252 880 950 0.9716 2.838 2.1820 15.10 [Ni(C19H12N3O3)2] 9403 15452 26526 940 918 0.8826 11.74 1.3421 32.2391 [Cu(C19H12N3O3)2] 12620-17362 1499 ------ ------ ------ ------ 25.698

aCalculated values.

Table-4: Minimum Inhibitory concentration, (MIC) of the complexes

Ligand/complexes Zone of inhibition ( in mm) Antibacterial activity

Concentrations E. Coli Bacillus Pseudomonas S.Aureus Concentrations 1000 500 250 125 1000 500 250 125 1000 500 250 125 1000 500 250 125

Ligand 15 10 14 12 12 15 17 13 15 14 16 13 13 22 12 17 Cu(II) complex 11 11 20 24 15 14 15 20 11 13 24 15 16 10 08 16 Zn(II) complex 15 22 14 13 25 22 25 18 17 20 17 21 15 22 18 11 Cd(II) Complex 10 15 17 18 25 20 23 21 24 22 24 25 26 15 16 21 Ni(II) Complex 10 11 7 14 12 20 13 20 10 11 15 20 12 10 17 14 Co(II) Complex 15 10 20 12 18 14 12 13 9 11 13 18 12 14 15 20 Hg(II) Complex 21 17 24 21 27 25 32 25 25 21 23 18 22 22 24 22 Streptomycin 25 25 28 26 30 35 36 30 34 30 31 29 34 25 28 25


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Table-5: Minimum Inhibitory concentration, (MIC) of the complexes

Ligand/complexes Zone of inhibition ( in mm) Antifungal activity A-Niger A-Flavous

Concentrations 1000 500 250 125 1000 500 250 125 Ligand 12 10 09 14 16 14 11 10 Cu(II) Complex 14 11 10 11 10 15 13 13 Zn(II) Complex 15 16 17 11 15 13 13 13 Cd(II) Complex 16 17 11 10 16 17 13 14 Ni(II) Complex 10 09 08 11 15 12 08 11 Co(II) Complex 10 09 07 14 12 10 12 13 Hg(II) Complex 20 20 20 20 12 13 10 14 Fluconazole 22 22 21 21 18 20 20 20


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ESR Spectra of Cu(II) complex

The ESR spectra of the Cu(II) complex in a polycrystalline state has been recorded at room

temperature. The values of g║ = 2.1847 and g = 2.0353 have been found. The gav was

calculated to be 2.0851. The spectrum showed bands with g║ > g > 2.00277, indicating the

unpaired electrons lay predominantly in the dx2-dy

2 orbital with possible mixing of dz2

because of low symmetry. The axial symmetry parameter ‘G’ found to be 5.2322 which is

more than 4 suggests that there is no interaction between the copper centers15 thus results

suggests that Cu(II) complex has distorted octahedral geometry.

Antibacterial and antifungal activities

The antibacterial activity of the Schiff base and its metal complexes were screened against

the bacteria Escheria coli , Staphylococcus aures, Pseudomonas and Bacillus and antifungal

activity of the synthesised compounds were screened against the Aspergillus niger, A

Flavous species by MIC method at 1000µg/mL, 500µg/mL, 250µg/mL and 125µg/mL

concentrations. The MIC values of the tested compounds are summarized in the Table-4 and

table-5. The results of the antibacterial and antifungal activities reveals that the values

obtained by MIC method of Schiff base and its metal complexes showed that the complexes

have higher growth inhibiting property than the Schiff base.

Antioxidant activity

The novel Schiff’s base and its complexes were screened for free radical scavenging activity

activity by DPPH method. Among the tested compounds Zn(II), Cd(II), Ni(II) and Hg(II)

complexes have exhibited good scavenging activity. Whereas the complexes Cu(II) and

Co(II) have shown moderate activity. While all the complexes have exhibited higher

scavenging activity than the Schiff’s base ligand because of incorporation of different metal

ions in to the ligand. Further, the compounds scavenged by the DPPH radical in a

concentration dependent manner. Results of percentage of free radical scavenging activity are

shown in (Figure 5).


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Fig. 5. Antioxidant results of Schiff’s base, metal complexes and Standard.

DNA Cleavage activity

The Ni(II), Cu(II), Co(II), Zn(II), Cd(II) and Hg(II) complexes were studied for there DNA

cleavage activity by agarose gel electrophoresis method against Calf-thyms DNA (figure 6).

Due to the molecular weight difference between the control and treated samples all the

complexes have acted on DNA. The difference was observed in bands of lanes 1-6 compared

to the control. The results indicated that all the samples have displayed the complete cleavage

of CT-DNA. It can be concluded that, the compound inhibits the growth of pathogenic

organism by cleaving the genome16.

Fig. 6. The DNA cleavage analysis

Note: In the photograph M- Standard DNA molecular weight marker (λ DNA EcoR1)

Hind-III double digest, Bangalore Genei, Bangalore (India))


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C- Control DNA (untreated CT-DNA)

M1-Ni(II), M2-Cu(II), M3-Co(II), M4-Zn(II), M5-Cd(II), M6-Hg(II) complex.

OC

O

HN

N

HC

NO

M

Cl Fig. 7 Proposed structure of complexes. Where M= Zn(II), Cd(II) and Hg(II).

O

C

O

HN

N

HC

NO

O

C

O

NH

N

CH

NO

M

Fig. 8 Proposed structure of complexes. Where M= Cu(II), Ni(II) and Co(II)

CONCLUSION

The synthesized Schiff base acts as a monobasic tridentate ligand, by coordinating through

the amide oxygen and nitrogen of azomethine group. The complexes possess higher

antibacterial and antifungal activity than the corresponding ligand. The DNA cleavage

experiment shows that complete cleavage of the DNA occurred in case of the Zn(II) and

Ni(II) complexes whereas Hg(II) and the Cu(II) shown the partial cleavage of DNA. Based

on the above results we proposed the probable structures for all the complexes as octahedral

to Cu(II), Co(II) and Ni(II) complexes and tetrahedral to Zn(II), Cd(II) and Hg(II) complexes.


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ACKNOWLEDGEMENT

Authors are thankful to the professor and Chairman, Department of Chemistry, Gulbarga

University, Gulbarga, for encouragement and facilities.

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SYNTHESIS, CHARACTERIZATION AND BIOLOGICAL STUDIES OF SOME METAL COMPLEXES DERIVED FROM BENZOFURAN...

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