# Synthesis, Characterization, and Antibacterial Activity of Co(II), Ni(II), Cu(II), Zn(II), Cd(II), and Hg(II) Complexes of Schiff's Base Type Ligands Containing Benzofuran Moiety

Authors: N. Shashidhar Reddy; B. S. Shankara; P. Murali Krishana; C. Basavaraj; B. Mahesh
Journal: International Journal of Inorganic Chemistry
 (2013)

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## Abstract

Six new complexes of Co(II), Ni(II), Cu(II), Zn(II), Cd(II), and Hg(II) with substituted benzofuran derivatives have been synthesized and characterized by elemental analysis, magnetic moments, conductance measurements, spectral characterization, and so forth. Elemental data coincide with the general formulaMLC1n, where L = (E)-7-Methoxy-N1-(2,4,5-trimethoxy benzylidene) benzofuran-2-carbohydrazide (L1) or (E)-N1-(2,6-dichloro benzylidene)-7-methoxy benzofuran-2-carbohydrazide (L2), of the complexes. The ligands coordinate to the metal ions through the oxygen of the carbonyl group and the nitrogen of the hydrazine group. Electronic spectral data of the complexes suggests the probable geometry is octahedral in nature. All the complexes and ligands were screened for their antibacterial activity. Among them, Co, Ni, and Cu complexes of L2 showed good activity against all microbes.


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## Body

## 1. Introduction

Schiff’s bases are the most widely studied chelating ligands in coordination chemistry [1]. They are useful in catalysis in organic synthesis and in medicine as antibiotics, antiallergic, and antitumor agents [2]. Recently metal complexes of Schiff’s bases particularly derived from carbonyl compounds based on heterocyclic rings have been the centre of attraction in many areas [3–7]. Among them, benzofuran based fused heterocycles have been of great interest as they are abundant in nature and have wide pharmacological activities [8]. Benzofuran based compounds have been reported to show activities as anti-infective agents, like antifungal [9–12], antiprotozoal, and antitubercular [13–15], and also in the treatment of antiarrhythmic [16] and cardiovascular [17] diseases. According to the literature survey in the recent years, there has been an increased interest investigation of anti-microbacterial activities on benzofuran derivatives, especially 2-substituted [18] or 2,3-disubstituted benzofurans derivatives [19]. It is due to the presence of benzofuran derivatives in natural compounds. For example, the seed oil of the Egonoki plant, which contains a benzofuran derivative called egonal (Figure 1(a)), is an effective synergist for rotenone and pyrethrum against house flies, mosquitoes, aphides, and many other insects [20]. Similarly, Baker’s yeast contains a benzofuran derivative (Figure 1(b)) that acts as an antioxidant preventing hemorrhagic liver necrosis in rats and hemolysis of red cells in Vitamin-E deficient rats [21].Structures of the benzofuran derivatives in (a) Egonoki plant and (b) Baker’s yeast.
(a)
(b)Therefore we thought it is worthwhile to synthesis and characterize the benzofuran based ligands and their transition metal complexes and investigate their antimicrobial properties.As a part of our ongoing study on benzofuran derivatives [6, 7, 22–24], we report herein the synthesis, characterization, and antibacterial activity of (E)-7-Methoxy-N1-(2,4,5-trimethoxy benzylidene) benzofuran-2-carbohydrazide (L1) and (E)-N1-(2,6-dichloro benzylidene)-7-methoxy benzofuran-2-carbohydrazide (L2) and their metal complexes such as Co(II), Ni(II), Cu(II), Zn(II), Cd(II), and Hg(II) as shown in Scheme 1.Scheme 1
Synthesis of ligandsL1 and L2.


## 2. Experimental

2,4,5-Trimethoxybenzaldehyde, 2,6-dichlorobenzaldehyde, and 2-hydroxy-3-methoxybenzaldehyde were of reagent grade purchased from Sigma-Aldrich. All other chemicals were of AR grade and used as supplied. The solvents were dried and distilled before use. The starting material, 7-methoxy-1-benzofuran-2-carbohydrazide, was prepared according to the literature method [25].


### 2.1. Preparation of (E)-7-Methoxy-N1-(2,4,5-trimethoxybenzylidene)benzofuran-2-carbohydrazide (L1)

To a solution (25 mL) of 7-methoxy-1-benzofuran-2-carbohydrazide (2.5 g, 0.01 mol) dry ethanol (25 mL), a solution of 2,4,5-trimethoxybenzaldehyde (2.378 g, 0.01 mol) in dry ethanol (10 mL) was added. The reaction mixture was refluxed on a water bath. A light yellow crystalline product formed during 7-8 hrs; the reaction mass was cooled and collected by filtration. The solid was washed several times with hot water (10 mL × 5) and then with diethyl ether (10 mL × 3) and finally driedin vacuo. The obtained ligand (L1) was recrystallized from dry ethanol. Mol. Formula, C20H20N2O6: Mol. Wt. 383.378, M.P. 252°C, Yield: 75%.


### 2.2. Preparation of (E)-N1-(2,6-Dichlorobenzylidene)-7-methoxybenzofuran-2-carbohydrazide (L2)

To an ethanolic solution (25 mL) of 7-methoxy-1-benzofuran-2-carbohydrazide (2.5 g, 0.01 mol), 2,6-dichlorobenzaldehyde (2.122 g, 0.01 mol) in dry ethanol (10 mL) was added. The reaction mixture was refluxed on a water bath for 7-8 hrs. A light yellow crystalline solid formed. The reaction mixture was cooled and the solid was collected by filtration. This solid was washed with hot water (2×10 mL) and then with diethyl ether and then dried in vacuo. A crystalline solid was obtained by recrystallization from ethanol. Mol. Formula, C17H12N2O3: Mol. Wt. 363.198, M.P. 130°C, Yield: 80%.


### 2.3. Preparation of Complexes

Co(II), Ni(II), Cu(II), Zn(II), Cd(II), and Hg(II) complexes, were prepared by mixing calculated quantity ofL1 and L2 in ethanol and an aqueous solution of the corresponding metal chlorides in 2 : 1 molar ratio. The reaction mixture was refluxed on a water bath for 3-4 hrs. The completion of the reaction was monitored by thin layer chromatography. Once the reaction was completed, the solvent was removed approximately 50%, from hot solution. Then the residue was cooled to room temperature. The solid complexes formed were filtered, washed with hot water (10 mL, 4-5 times) and ethyl alcohol (10 mL, 3-4 times), and finally dried in vacuum desiccators over anhydrous CaCl2. The formation of the complexes may be represented by the following equations:
(1)nCoCl2·6H2O+nL(L=(L1)/(L2))→Alcohol,reflux,2hrs{[CoLCl2]·H2O}n+5H2O,nNiCl2·6H2O+nL→Alcohol,reflux,2hrs{[NiLCl2]}n+6H2O,nCuCl2·2H2O+nL→Alcohol,reflux,2hrs{[CuLCl2]}n+2H2O,nCdCl2+nL→Alcohol,reflux,2hrs[CdLCl2]n,MCl2+LM=ZnorHg→Alcohol,reflux,2hrs[MLCl2].


## 2.1. Preparation of (E)-7-Methoxy-N1-(2,4,5-trimethoxybenzylidene)benzofuran-2-carbohydrazide (L1)

To a solution (25 mL) of 7-methoxy-1-benzofuran-2-carbohydrazide (2.5 g, 0.01 mol) dry ethanol (25 mL), a solution of 2,4,5-trimethoxybenzaldehyde (2.378 g, 0.01 mol) in dry ethanol (10 mL) was added. The reaction mixture was refluxed on a water bath. A light yellow crystalline product formed during 7-8 hrs; the reaction mass was cooled and collected by filtration. The solid was washed several times with hot water (10 mL × 5) and then with diethyl ether (10 mL × 3) and finally driedin vacuo. The obtained ligand (L1) was recrystallized from dry ethanol. Mol. Formula, C20H20N2O6: Mol. Wt. 383.378, M.P. 252°C, Yield: 75%.


## 2.2. Preparation of (E)-N1-(2,6-Dichlorobenzylidene)-7-methoxybenzofuran-2-carbohydrazide (L2)

To an ethanolic solution (25 mL) of 7-methoxy-1-benzofuran-2-carbohydrazide (2.5 g, 0.01 mol), 2,6-dichlorobenzaldehyde (2.122 g, 0.01 mol) in dry ethanol (10 mL) was added. The reaction mixture was refluxed on a water bath for 7-8 hrs. A light yellow crystalline solid formed. The reaction mixture was cooled and the solid was collected by filtration. This solid was washed with hot water (2×10 mL) and then with diethyl ether and then dried in vacuo. A crystalline solid was obtained by recrystallization from ethanol. Mol. Formula, C17H12N2O3: Mol. Wt. 363.198, M.P. 130°C, Yield: 80%.


## 2.3. Preparation of Complexes

Co(II), Ni(II), Cu(II), Zn(II), Cd(II), and Hg(II) complexes, were prepared by mixing calculated quantity ofL1 and L2 in ethanol and an aqueous solution of the corresponding metal chlorides in 2 : 1 molar ratio. The reaction mixture was refluxed on a water bath for 3-4 hrs. The completion of the reaction was monitored by thin layer chromatography. Once the reaction was completed, the solvent was removed approximately 50%, from hot solution. Then the residue was cooled to room temperature. The solid complexes formed were filtered, washed with hot water (10 mL, 4-5 times) and ethyl alcohol (10 mL, 3-4 times), and finally dried in vacuum desiccators over anhydrous CaCl2. The formation of the complexes may be represented by the following equations:
(1)nCoCl2·6H2O+nL(L=(L1)/(L2))→Alcohol,reflux,2hrs{[CoLCl2]·H2O}n+5H2O,nNiCl2·6H2O+nL→Alcohol,reflux,2hrs{[NiLCl2]}n+6H2O,nCuCl2·2H2O+nL→Alcohol,reflux,2hrs{[CuLCl2]}n+2H2O,nCdCl2+nL→Alcohol,reflux,2hrs[CdLCl2]n,MCl2+LM=ZnorHg→Alcohol,reflux,2hrs[MLCl2].


## 3. Physical Measurements

Elemental analyses were carried out using Vario EL CHNS analyzer. Magnetic susceptibility measurements were carried out on a magnetic susceptibility balance (Sherwood scientific, Cambridge, England). Molar conductance measurements were made on an Elico CM-82 conductivity bridge in DMF (10−3 M) using a dip-type conductivity cell fitted with a platinum electrode having cell constant 0.1 Scm−1. The ESR spectra of complexes were recorded on a Varian E-122 X-band spectrophotometer at liquid nitrogen temperature in DMSO. The FT-IR spectra of ligands and their complexes were recorded as KBr discs in the range 4000–350 cm−1 on Shimadzu FT-IR spectrophotometer. 1H NMR spectra were recorded in DMSO-d6 on a Bruker 300 MHz spectrophotometer using TMS as an internal standard. The electronic spectra were recorded on an Elico-SL-159 single beam UV-Vis. spectrophotometer in the range of 200–1100 nm in N, N-dimethyl formamide (DMF) (10−3M) solution. FAB mass spectra were recorded on a JEOL SX 102/DA-6000 mass spectrophotometer from CDRI Lucknow, 6 KV, and 10 mA using argon as the FAB gas and m-nitro benzyl alcohol as the matrix.


## 4.  Antibacterial Activity

In vitro antibacterial activity of the newly synthesized compounds were investigated against five Gram-positive bacteria species Staphylococcus aureus, Staphylococcus citreus, Bacillus polymyx, Bacillus cereus, and Lactobacillus and five Gram-negative species Proteus mirabilis,Klebsiella pneumonia, E. coli, Salmonella typhi, and Pseudomonas aeruginosa by the agar well diffusion method [26, 27]. Nutrient agar (Hi Media, India) was used as the bacteriological medium. The extracts were dissolved in 10% aqueous dimethylsulfoxide (DMSO) to a final concentration of 50 μg/μL. Pure DMSO was taken as the control. 100 μL of inoculums was aseptically introduced on to the surface of sterile agar plates and sterilized cotton swabs were used for even distribution of the inoculums. Wells were prepared in the agar plates using a sterile cork borer of 6.0 mm diameter. 50 μL of test and control compound was introduced in the well. The same procedure was used for all the strains. The plates were incubated aerobically at 35°C and examined after 24 hours. The diameter of the zone of inhibition produced by each agent was measured with a ruler.


## 5. Results and Discussion

### 5.1. Characterization of LigandsL1 and L2

The ligandsL1and L2 are air stable crystalline solids. The analytical data are given in Table 1. The FT-IR spectrum of ligands L1 and L2 showed strong bands at 3354 and 3185 cm-1 due to νasy(NH) and νsy(NH) stretching vibrations, respectively, of secondary amide. Strong bands observed at 1670 and 1702 cm−1 in free ligands are assigned to ν(C=O) of -CONH group which matches with the literature reports [22]. Medium to strong intense bands at 1606 and 1596 cm−1 in L1 and L2 were assigned to ν(C=N) of the azomethine group [28]. The medium bands at 942 and 958 cm−1 were assigned to ν(N–N) stretching vibrations of hydrazine and ν(C–O–C) stretching vibrations of furan was observed in the region of 1029–1125 cm−1 [29, 30]. 1H NMR spectra of ligands L1 and L2were recorded in DMSO-d6. The singlet at δ, 12.00–12.10 ppm was assigned to amide proton (–CONH–). The singlet at δ, 8.30–8.65 ppm were assigned to azomethine (-HC=N-) proton in both ligands. The aromatic ring protons were appeared as multiplet at δ, 7.0–7.7 ppm in the 1H NMR spectra. The 1H NMR spectrum of L1 is shown in Figure 2.Table 1
Analytical data of ligands and their metal complexes.
Ligand/complex
Molecular weight
Yield (%)
Colour
M.P°C
Elemental analysis found (cal)
μeff (BM)
AM   (ohm−1 cm2mol−1)
C
H
N
L
1
[
C
20
H
20
O
6
N
2
]
383.378
75
Yellow
252
62.62
(62.65)
5.2
(5.3)
7.45
(7.306)
—
—
[Cu(C20H20O6N2)Cl2]
517.858
80
Green
244
46.53(46.39)
3.95(3.89)
5.98(5.41)
1.74
18.452
[Co(C20H20O6N2)Cl2]
513.211
78
Dark brown
238
46.95(46.81)
3.84(3.93)
5.81(5.46)
4.68
15.951
[Ni(C20H20O6N2)Cl2]
512.968
72
Light brown
262
46.54(46.83)
3.68(3.93)
5.63(5.46)
2.85
14.274
[Cd(C20H20O6N2)Cl2]
566.689
75
Yellow
>300
42.45(42.39)
3.68(3.55)
4.85(4.94)
—
20.361
[Hg(C20H20O6N2)Cl2]
654.868
75
Light yellow
>300
36.67(36.68)
3.75(3.08)
4.58(4.27)
—
13.853
[Zn(C20H20O6N2)Cl2]
519.67
72
Yellow
265
46.25(46.23)
3.63(3.88)
5.52(5.39)
—
18.593
L
2
[
C
17
H
12
N
2
O
3
]
363.198
80
Brown
130
56.26
(56.22)
3.43
(3.33)
7.6
(7.7)
—
—
[Cu(C17H12N2O3)Cl2]
497.637
75
Green
>300
41.58(41.03)
3.56(3.44)
5.85(5.63)
1.79
16.653
[Co(C17H12N2O3)Cl2]
493.030
70
Light brown
123
41.65(41.41)
2.55(2.45)
5.75(5.68)
4.87
15.032
[Ni(C17H12N2O3)Cl2]
492.788
73
Light brown
>276
41.57(41.44)
2.82(2.45)
5.69(5.68)
2.92
15.965
[Cd(C17H12N2O3)Cl2]
546.508
72
Yellow
>300
37.46(37.36)
2.35(2.21)
5.25(5.12)
—
19.942
[Hg(C17H12N2O3)Cl2]
634.687
75
Yellow
162
32.25(32.17)
1.95(1.91)
4.25(4.42)
—
14.093
[Zn(C17H12N2O3)Cl2]
499.488
73
Yellow
168
41.08(40.88)
2.81(2.42)
5.74(5.61)
—
19.573Figure 2
1H NMR spectrum of the ligand L1.The mass spectrometric studies ofL1 and L2 were performed. The mass spectra of the ligands showed molecular ion peaks (M+) at 383 and 363, respectively, are the corresponding molecular weights of both L1 and L2.


### 5.2. Characterization of the Metal Complexes

The analytical data (Table1) of the complexes, 1–6 indicated that all the complexes were of stoichiometry, [M(L1/L2)Cln], where M = Co(II) [1], Ni(II) [2], Cu(II) [3], Zn(II) [4], Cd(II) [5], and Hg(II) [6]. The molar conductivity values of the complexes in DMF (10-3M) are in the range 13.8–20.3 Ω−1 cm2 mol−1 suggested non-electrolytic nature of the complexes [31]. All the complexes are partially or almost insoluble in common organic solvents, but soluble in DMF, DMSO, and pyridine. Room temperature magnetic susceptibility measurements indicated paramagnetic nature for Co, Cu, and Ni complexes. The six-coordinate Co(II) complexes exhibit magnetic moments of 4.68 and 4.87 B.M., suggesting octahedral geometry for Co(II) [32]. Ni(II) complexes showed magnetic moment values of 2.85 and 2.92 B.M., slightly higher than the spin only (2.83 B.M.) value, indicating an octahedral environment around Ni(II) ion [33]. The observed magnetic moments for Cu(II) complexes are 1.74 and 1.79 B.M., suggesting a distorted octahedral geometry around Cu(II). FT-IR spectra of ligands and their metal complexes are presented n Table 2. The FT-IR stretching frequencies of free ligands were compared with that of their metal complexes. The FT-IR spectrum of ligands showing a strong band at 3354 cm−1 and 3185 cm−1, respectively, is due to νasy(NH) and νsy(NH) stretching vibrations of secondary amide. According to Halli et al. [23] coordination of NH results in splitting or shifting of bands to lower frequency side or decrease in intensity. In the present study no such changes were observed, instead ν(NH) bands were observed at higher wave number indicating non-participation of the coordination of NH with metal ion. The shift of about 15–40 cm−1 of ν(C=O) band to lower region in complexes was observed indicating participation of the carbonyl oxygen in coordination [34]. In free ligands at ν(C=N) of the azomethine group is observed at 1606 cm−1 and 1596 cm−1, which was shifted to lower region by 20–52 cm−1 which indicated the involvement of the azomethine N in dative bonding with metal ions [35]. The medium bands in ligands due to ν(N–N) stretching vibrations are shifted to higher wave number region confirming the involvement of one of the nitrogens of -N–N- in bonding with metal ions. The stretching vibration due to ν(C–O–C) of furan remains unaltered in the metal complexes, indicating non-participation of the O-furan ring in bonding with metal ions.Table 2
Important IR spectral bands (cm−1) of ligands and their metal complexes.
Compounds
ν(NH)
ν(C=N)
ν(C=O)
ν(N–N)
ν(M–O)
ν(M–N)
ν(M–Cl)t
ν(M–Cl)b
ν(M–Cl)
L
1
[
C
20
H
20
O
6
N
2
]
3264
1606
1696
942
—
—
—
—
—
[Cu(C20H20O6N2)Cl2]
3265
1586
1659
961
546
475
354
342
—
[Co(C20H20O6N2)Cl2]
3267
1584
1653
978
532
462
372
368
—
[Ni(C20H20O6N2)Cl2]
3269
1568
1656
969
567
465
361
372
—
[Cd(C20H20O6N2)Cl2]
3265
1578
1650
985
575
463
—
—
345
[Hg (C20H20O6N2)Cl2]
3266
1581
1655
968
525
473
—
—
356
[Zn (C20H20O6N2)Cl2]
3268
1575
1662
972
549
461
—
—
330
L
2
[
C
17
H
12
N
2
O
3
]
3267
1596
1702
958
—
—
—
—
—
[Cu(C17H12N2O3)Cl2]
3269
1581
1655
974
515
448
358
355
—
[Co(C17H12N2O3)Cl2]
3268
1573
1672
968
545
453
375
361
—
[Ni(C17H12N2O3)Cl2]
3269
1568
1662
971
562
458
391
368
—
[Cd(C17H12N2O3)Cl2]
3269
1582
1669
973
573
425
—
—
347
[Hg(C17H12N2O3)Cl2]
3267
1583
1670
965
542
469
—
—
359
[Zn(C17H12N2O3)Cl2]
3272
1578
1668
969
564
459
—
—
330Metal-ligand vibrations are generally observed in the far-IR region and usually give valuable information regarding the bonding of ligands to the metal ions. The weak non-ligand bands observed in the spectrum in the regions 515–575 cm−1, 425–475 cm−1, and 376–410 cm−1 are assigned to ν(M–O), ν(M–N), and ν(M–Cl) stretching vibrations, respectively [36]. The electronic spectra of the Cu(II), Co(II), and Ni(II) complexes were recorded in DMF (10−3M) solution at room temperature and spectral data are shown in Table 3.Table 3
Electronic spectral bands and ligand field parameters of the Cu(II), Co(II), and Ni(II) complexes in DMF (10−3) solution.
Ligand
Complexes
Transition in cm−1
Dq (cm−1)
B (cm−1)
β
β (%)
ν
2
/
ν
1
LFSE(k.cal)
ν
1
a
ν
2
b
ν
3
b
L
1
[C20H20O6N2]
[Co(C20H20O6N2)Cl2]
7535
16628
21154
815.14
972.15
0.9606
1.42
2.206
14.88
[Ni(C20H20O6N2)Cl2]
9372
15342
25810
1237.5
869.06
0.6889
12.23
1.6370
31.33
[Cu(C20H20O6N2)Cl2]
16194
L
2
[C17H12N2O3]
[Co(C17H12N2O3)Cl2]
7340
15902
20752
799.39
975.60
0,9505
1.35
2.1665
14.92
[Ni(C17H12N2O3)Cl2]
9415
15530
25637
1218.05
975.33
0.9513
17.11
1.649
32.11
[Cu(C17H12N2O3)Cl2]
16205
aCalculated values. bMolar extension coefficient values are given in parenthesis (in units of L mol−1 cm−1).In  electronic spectra of Co(II) complexes appeared two absorption bands at 16628, 21154 cm−1   due to  L1   and 15902, 20752 cm−1 due to L2  respectively. These bands are assigned to T1g4(F)→A42g(F)(ν2) and T1g4(F)→T2g(F)4(ν3) transitions, respectively, in an octahedral environment. The band υ1 could not be observed; however, ν1 would be calculated using band fitting procedure [37]. The octahedral geometry is further supported by the values of ligand field parameters such as Racah inter-electronic repulsion parameter (B1), ligand field splitting energy (10Dq), covalency factor (β), and ligand field stabilization energy (LFSE).The six coordinate Ni(II) complexes exhibit bands at 15342, 25810 cm−1 and 15530, 25637 cm−1 assignable to A2g3→T1g3(F)(ν2) and A2g3→T1g3(P)(ν3) transition, respectively. The high energy band in the region 29000–30000 cm−1 is assigned to charge transfer in the case of Co(II) and Ni(II) complexes. The octahedral geometry is further supported by ligand field parameters like Dq, B1, β, β%, ν2/ν1 ratio, and LFSE value. The B1 values for the complexes were lower than the free ion values, which is an indication of the orbital overlap and delocalization of d-orbitals. The β values obtained were less than unity, suggesting a considerable amount of covalency for the metal-ligand bonds. The β value for the Ni(II) complex was less than that of the Co(II) complex, indicating the greater covalency of the M–L bond [24].For the Co(II) complex the Racah inter-electronic repulsion parameter (B1) is calculated using the following equation:
(2)B¹=1510[7(ν3-2ν2)+3{81ν32-16ν2(ν2-ν3)}1/2],
while for Ni(II) complexes Dq and B are calculated from
(3)Dq=18(ν2+ν3)+[18(ν2+ν3)]2-4X340×ν2×ν32×340,B=ν2+ν3-3ν115.
The covalency factor (β) was obtained in the following manner:
(4)β=B1B,(whereBisfreeionvalue).The light green Cu(II) complexes exhibit a single broad asymmetric band in the region 18678–12345 cm−1. The broadness of the band indicates the three transitions, B1g2→A1g2(ν1), B1g2→B2g2(ν2), and B1g2→Eg2(ν3), which are similar in energy and give rise to only one broad band. The high intensity band observed in the region 33,000–28,000 cm−1 was assigned to charge transfer [38]. The broadness of the band may be due to dynamic John-Teller distortion. All of these data suggest a distorted octahedral geometry around Cu(II). Typical electronic spectrum of Cu(II) complex of L1 is shown in the Figure 3.Figure 3
A typical electronic spectrum of copper complex ofL1.ESR spectra of the copper (II) complexes were recorded at liquid nitrogen temperature in DMSO. Theg|| and g⊥ values were calculated from the spectrum using the tetracyanoethylene (TCNE) free radical as the “g” marker. Typical ESR spectrum of [Cu(L1)Cl2] is given in Figure 4. Neiman and Kivelson [39] have reported that g|| is less than 2.3 for covalent character and greater than 2.3 for ionic character of the metal-ligand bond in complexes. As seen in Table 4, g|| values for the present complexes are slightly higher than 2.3 suggesting a small amount of ionic character of the metal–ligand bond. The trend g||>g⊥>2.0023 suggests that the unpaired electron lies predominantly in the dx2-y2 orbital [40] characteristic of square planar or octahedral geometry in copper(II) complexes [41]. The gav value for these complexes is greater than 2 indicating the presence of covalent character [42]. The axial symmetry parameter (G) values of the complexes (greater than 4) suggest that there are no interactions between the copper centres in DMSO medium. The empirical factor f (=g||/A||) cm−1 is a measure of deviation from idealized geometry [43]. Values from 165 to 171 cm−1 for the present complexes suggest a moderate to considerable distortion in the geometry.Table 4
ESR-Spectral data of Cu(II) complexes of MBMePC and MBDPC bonding coefficient parameters.
Complex
g
∥
g
⊥
g
av
A
∥
×
10−4 (cm−1)
A
⊥
×
10−4 (cm−1)
A
av
×
10−4
g
∥/A∥
G
α
2
[Cu(C20H20O6N2)Cl2]
2.4596
2.0623
2.1947
144.19
27.91
66.672
170.57
7.62
0.1225
[Cu(C17H12O3N2)Cl2]
2.4675
2.0515
2.1901
147.91
37.67
74.42
166.82
9.45
0.1154Figure 4
X-Band ESR spectra of [Cu(L1)Cl2] at liquid nitrogen temperature (LNT) in DMSO.Based on the analytical data and spectral characterization of the compounds tentative structures of the complexes are shown in Figures5(a) and 5(b).(a)
Suggested structure of Co(II), Ni(II) and Cu(II) complexes of Schiff bases
(b)
Suggested structure of Zn(II), Cd(II) and Hg(II) complexes of Schiff bases


## 5.1. Characterization of LigandsL1 and L2

The ligandsL1and L2 are air stable crystalline solids. The analytical data are given in Table 1. The FT-IR spectrum of ligands L1 and L2 showed strong bands at 3354 and 3185 cm-1 due to νasy(NH) and νsy(NH) stretching vibrations, respectively, of secondary amide. Strong bands observed at 1670 and 1702 cm−1 in free ligands are assigned to ν(C=O) of -CONH group which matches with the literature reports [22]. Medium to strong intense bands at 1606 and 1596 cm−1 in L1 and L2 were assigned to ν(C=N) of the azomethine group [28]. The medium bands at 942 and 958 cm−1 were assigned to ν(N–N) stretching vibrations of hydrazine and ν(C–O–C) stretching vibrations of furan was observed in the region of 1029–1125 cm−1 [29, 30]. 1H NMR spectra of ligands L1 and L2were recorded in DMSO-d6. The singlet at δ, 12.00–12.10 ppm was assigned to amide proton (–CONH–). The singlet at δ, 8.30–8.65 ppm were assigned to azomethine (-HC=N-) proton in both ligands. The aromatic ring protons were appeared as multiplet at δ, 7.0–7.7 ppm in the 1H NMR spectra. The 1H NMR spectrum of L1 is shown in Figure 2.Table 1
Analytical data of ligands and their metal complexes.
Ligand/complex
Molecular weight
Yield (%)
Colour
M.P°C
Elemental analysis found (cal)
μeff (BM)
AM   (ohm−1 cm2mol−1)
C
H
N
L
1
[
C
20
H
20
O
6
N
2
]
383.378
75
Yellow
252
62.62
(62.65)
5.2
(5.3)
7.45
(7.306)
—
—
[Cu(C20H20O6N2)Cl2]
517.858
80
Green
244
46.53(46.39)
3.95(3.89)
5.98(5.41)
1.74
18.452
[Co(C20H20O6N2)Cl2]
513.211
78
Dark brown
238
46.95(46.81)
3.84(3.93)
5.81(5.46)
4.68
15.951
[Ni(C20H20O6N2)Cl2]
512.968
72
Light brown
262
46.54(46.83)
3.68(3.93)
5.63(5.46)
2.85
14.274
[Cd(C20H20O6N2)Cl2]
566.689
75
Yellow
>300
42.45(42.39)
3.68(3.55)
4.85(4.94)
—
20.361
[Hg(C20H20O6N2)Cl2]
654.868
75
Light yellow
>300
36.67(36.68)
3.75(3.08)
4.58(4.27)
—
13.853
[Zn(C20H20O6N2)Cl2]
519.67
72
Yellow
265
46.25(46.23)
3.63(3.88)
5.52(5.39)
—
18.593
L
2
[
C
17
H
12
N
2
O
3
]
363.198
80
Brown
130
56.26
(56.22)
3.43
(3.33)
7.6
(7.7)
—
—
[Cu(C17H12N2O3)Cl2]
497.637
75
Green
>300
41.58(41.03)
3.56(3.44)
5.85(5.63)
1.79
16.653
[Co(C17H12N2O3)Cl2]
493.030
70
Light brown
123
41.65(41.41)
2.55(2.45)
5.75(5.68)
4.87
15.032
[Ni(C17H12N2O3)Cl2]
492.788
73
Light brown
>276
41.57(41.44)
2.82(2.45)
5.69(5.68)
2.92
15.965
[Cd(C17H12N2O3)Cl2]
546.508
72
Yellow
>300
37.46(37.36)
2.35(2.21)
5.25(5.12)
—
19.942
[Hg(C17H12N2O3)Cl2]
634.687
75
Yellow
162
32.25(32.17)
1.95(1.91)
4.25(4.42)
—
14.093
[Zn(C17H12N2O3)Cl2]
499.488
73
Yellow
168
41.08(40.88)
2.81(2.42)
5.74(5.61)
—
19.573Figure 2
1H NMR spectrum of the ligand L1.The mass spectrometric studies ofL1 and L2 were performed. The mass spectra of the ligands showed molecular ion peaks (M+) at 383 and 363, respectively, are the corresponding molecular weights of both L1 and L2.


## 5.2. Characterization of the Metal Complexes

The analytical data (Table1) of the complexes, 1–6 indicated that all the complexes were of stoichiometry, [M(L1/L2)Cln], where M = Co(II) [1], Ni(II) [2], Cu(II) [3], Zn(II) [4], Cd(II) [5], and Hg(II) [6]. The molar conductivity values of the complexes in DMF (10-3M) are in the range 13.8–20.3 Ω−1 cm2 mol−1 suggested non-electrolytic nature of the complexes [31]. All the complexes are partially or almost insoluble in common organic solvents, but soluble in DMF, DMSO, and pyridine. Room temperature magnetic susceptibility measurements indicated paramagnetic nature for Co, Cu, and Ni complexes. The six-coordinate Co(II) complexes exhibit magnetic moments of 4.68 and 4.87 B.M., suggesting octahedral geometry for Co(II) [32]. Ni(II) complexes showed magnetic moment values of 2.85 and 2.92 B.M., slightly higher than the spin only (2.83 B.M.) value, indicating an octahedral environment around Ni(II) ion [33]. The observed magnetic moments for Cu(II) complexes are 1.74 and 1.79 B.M., suggesting a distorted octahedral geometry around Cu(II). FT-IR spectra of ligands and their metal complexes are presented n Table 2. The FT-IR stretching frequencies of free ligands were compared with that of their metal complexes. The FT-IR spectrum of ligands showing a strong band at 3354 cm−1 and 3185 cm−1, respectively, is due to νasy(NH) and νsy(NH) stretching vibrations of secondary amide. According to Halli et al. [23] coordination of NH results in splitting or shifting of bands to lower frequency side or decrease in intensity. In the present study no such changes were observed, instead ν(NH) bands were observed at higher wave number indicating non-participation of the coordination of NH with metal ion. The shift of about 15–40 cm−1 of ν(C=O) band to lower region in complexes was observed indicating participation of the carbonyl oxygen in coordination [34]. In free ligands at ν(C=N) of the azomethine group is observed at 1606 cm−1 and 1596 cm−1, which was shifted to lower region by 20–52 cm−1 which indicated the involvement of the azomethine N in dative bonding with metal ions [35]. The medium bands in ligands due to ν(N–N) stretching vibrations are shifted to higher wave number region confirming the involvement of one of the nitrogens of -N–N- in bonding with metal ions. The stretching vibration due to ν(C–O–C) of furan remains unaltered in the metal complexes, indicating non-participation of the O-furan ring in bonding with metal ions.Table 2
Important IR spectral bands (cm−1) of ligands and their metal complexes.
Compounds
ν(NH)
ν(C=N)
ν(C=O)
ν(N–N)
ν(M–O)
ν(M–N)
ν(M–Cl)t
ν(M–Cl)b
ν(M–Cl)
L
1
[
C
20
H
20
O
6
N
2
]
3264
1606
1696
942
—
—
—
—
—
[Cu(C20H20O6N2)Cl2]
3265
1586
1659
961
546
475
354
342
—
[Co(C20H20O6N2)Cl2]
3267
1584
1653
978
532
462
372
368
—
[Ni(C20H20O6N2)Cl2]
3269
1568
1656
969
567
465
361
372
—
[Cd(C20H20O6N2)Cl2]
3265
1578
1650
985
575
463
—
—
345
[Hg (C20H20O6N2)Cl2]
3266
1581
1655
968
525
473
—
—
356
[Zn (C20H20O6N2)Cl2]
3268
1575
1662
972
549
461
—
—
330
L
2
[
C
17
H
12
N
2
O
3
]
3267
1596
1702
958
—
—
—
—
—
[Cu(C17H12N2O3)Cl2]
3269
1581
1655
974
515
448
358
355
—
[Co(C17H12N2O3)Cl2]
3268
1573
1672
968
545
453
375
361
—
[Ni(C17H12N2O3)Cl2]
3269
1568
1662
971
562
458
391
368
—
[Cd(C17H12N2O3)Cl2]
3269
1582
1669
973
573
425
—
—
347
[Hg(C17H12N2O3)Cl2]
3267
1583
1670
965
542
469
—
—
359
[Zn(C17H12N2O3)Cl2]
3272
1578
1668
969
564
459
—
—
330Metal-ligand vibrations are generally observed in the far-IR region and usually give valuable information regarding the bonding of ligands to the metal ions. The weak non-ligand bands observed in the spectrum in the regions 515–575 cm−1, 425–475 cm−1, and 376–410 cm−1 are assigned to ν(M–O), ν(M–N), and ν(M–Cl) stretching vibrations, respectively [36]. The electronic spectra of the Cu(II), Co(II), and Ni(II) complexes were recorded in DMF (10−3M) solution at room temperature and spectral data are shown in Table 3.Table 3
Electronic spectral bands and ligand field parameters of the Cu(II), Co(II), and Ni(II) complexes in DMF (10−3) solution.
Ligand
Complexes
Transition in cm−1
Dq (cm−1)
B (cm−1)
β
β (%)
ν
2
/
ν
1
LFSE(k.cal)
ν
1
a
ν
2
b
ν
3
b
L
1
[C20H20O6N2]
[Co(C20H20O6N2)Cl2]
7535
16628
21154
815.14
972.15
0.9606
1.42
2.206
14.88
[Ni(C20H20O6N2)Cl2]
9372
15342
25810
1237.5
869.06
0.6889
12.23
1.6370
31.33
[Cu(C20H20O6N2)Cl2]
16194
L
2
[C17H12N2O3]
[Co(C17H12N2O3)Cl2]
7340
15902
20752
799.39
975.60
0,9505
1.35
2.1665
14.92
[Ni(C17H12N2O3)Cl2]
9415
15530
25637
1218.05
975.33
0.9513
17.11
1.649
32.11
[Cu(C17H12N2O3)Cl2]
16205
aCalculated values. bMolar extension coefficient values are given in parenthesis (in units of L mol−1 cm−1).In  electronic spectra of Co(II) complexes appeared two absorption bands at 16628, 21154 cm−1   due to  L1   and 15902, 20752 cm−1 due to L2  respectively. These bands are assigned to T1g4(F)→A42g(F)(ν2) and T1g4(F)→T2g(F)4(ν3) transitions, respectively, in an octahedral environment. The band υ1 could not be observed; however, ν1 would be calculated using band fitting procedure [37]. The octahedral geometry is further supported by the values of ligand field parameters such as Racah inter-electronic repulsion parameter (B1), ligand field splitting energy (10Dq), covalency factor (β), and ligand field stabilization energy (LFSE).The six coordinate Ni(II) complexes exhibit bands at 15342, 25810 cm−1 and 15530, 25637 cm−1 assignable to A2g3→T1g3(F)(ν2) and A2g3→T1g3(P)(ν3) transition, respectively. The high energy band in the region 29000–30000 cm−1 is assigned to charge transfer in the case of Co(II) and Ni(II) complexes. The octahedral geometry is further supported by ligand field parameters like Dq, B1, β, β%, ν2/ν1 ratio, and LFSE value. The B1 values for the complexes were lower than the free ion values, which is an indication of the orbital overlap and delocalization of d-orbitals. The β values obtained were less than unity, suggesting a considerable amount of covalency for the metal-ligand bonds. The β value for the Ni(II) complex was less than that of the Co(II) complex, indicating the greater covalency of the M–L bond [24].For the Co(II) complex the Racah inter-electronic repulsion parameter (B1) is calculated using the following equation:
(2)B¹=1510[7(ν3-2ν2)+3{81ν32-16ν2(ν2-ν3)}1/2],
while for Ni(II) complexes Dq and B are calculated from
(3)Dq=18(ν2+ν3)+[18(ν2+ν3)]2-4X340×ν2×ν32×340,B=ν2+ν3-3ν115.
The covalency factor (β) was obtained in the following manner:
(4)β=B1B,(whereBisfreeionvalue).The light green Cu(II) complexes exhibit a single broad asymmetric band in the region 18678–12345 cm−1. The broadness of the band indicates the three transitions, B1g2→A1g2(ν1), B1g2→B2g2(ν2), and B1g2→Eg2(ν3), which are similar in energy and give rise to only one broad band. The high intensity band observed in the region 33,000–28,000 cm−1 was assigned to charge transfer [38]. The broadness of the band may be due to dynamic John-Teller distortion. All of these data suggest a distorted octahedral geometry around Cu(II). Typical electronic spectrum of Cu(II) complex of L1 is shown in the Figure 3.Figure 3
A typical electronic spectrum of copper complex ofL1.ESR spectra of the copper (II) complexes were recorded at liquid nitrogen temperature in DMSO. Theg|| and g⊥ values were calculated from the spectrum using the tetracyanoethylene (TCNE) free radical as the “g” marker. Typical ESR spectrum of [Cu(L1)Cl2] is given in Figure 4. Neiman and Kivelson [39] have reported that g|| is less than 2.3 for covalent character and greater than 2.3 for ionic character of the metal-ligand bond in complexes. As seen in Table 4, g|| values for the present complexes are slightly higher than 2.3 suggesting a small amount of ionic character of the metal–ligand bond. The trend g||>g⊥>2.0023 suggests that the unpaired electron lies predominantly in the dx2-y2 orbital [40] characteristic of square planar or octahedral geometry in copper(II) complexes [41]. The gav value for these complexes is greater than 2 indicating the presence of covalent character [42]. The axial symmetry parameter (G) values of the complexes (greater than 4) suggest that there are no interactions between the copper centres in DMSO medium. The empirical factor f (=g||/A||) cm−1 is a measure of deviation from idealized geometry [43]. Values from 165 to 171 cm−1 for the present complexes suggest a moderate to considerable distortion in the geometry.Table 4
ESR-Spectral data of Cu(II) complexes of MBMePC and MBDPC bonding coefficient parameters.
Complex
g
∥
g
⊥
g
av
A
∥
×
10−4 (cm−1)
A
⊥
×
10−4 (cm−1)
A
av
×
10−4
g
∥/A∥
G
α
2
[Cu(C20H20O6N2)Cl2]
2.4596
2.0623
2.1947
144.19
27.91
66.672
170.57
7.62
0.1225
[Cu(C17H12O3N2)Cl2]
2.4675
2.0515
2.1901
147.91
37.67
74.42
166.82
9.45
0.1154Figure 4
X-Band ESR spectra of [Cu(L1)Cl2] at liquid nitrogen temperature (LNT) in DMSO.Based on the analytical data and spectral characterization of the compounds tentative structures of the complexes are shown in Figures5(a) and 5(b).(a)
Suggested structure of Co(II), Ni(II) and Cu(II) complexes of Schiff bases
(b)
Suggested structure of Zn(II), Cd(II) and Hg(II) complexes of Schiff bases


## 6.  Antibacterial Activities

Antibacterial activity of substituted benzofuran derivatives and their metal complexes were testedin vitro against representative Gram-positive bacteria species like “Staphylococcus aureus,”“Staphylococcus citreus,” “Bacillus polymyx,” “Bacillus cereus,” and “Lactobacillus” and Gram-negative bacteria species such as “Proteus mirabilis”,“Klebsiella pneumonia,” “E. coli,” “Salmonella typhi,”and “Pseudomonas aeruginosa” by agar well diffusion method. Compounds inhibiting growth of one or both microorganisms were further tested for their minimum inhibitory concentration (MIC) of the compound. Benzofuran ligands are more active against all most all microbes. Among all the complexes [Cu(L2)Cl2], [Ni(L2)Cl2], and [Co(L2)Cl2] complexes showed very good activity against all organisms (MIC = 25 μg/mL), whereas zinc and cadmium complexes are moderately active, but mercury complexes are least active. Least actitivity of mercury may be due to its toxic nature towards microbes. However, the synthesized compounds showed relatively higher or lower activ than the standard drug Streptomycin. It may be due the nature of the metal ion, the nature of the ligand, and orientation of the ligand around the metal ion. The results are summarized in Table 5.Table 5
Antibacterial activity of ligands and their metal complexes.
Ligands/complexes
Gram Positive
Gram Negative
Staphylococcus   aureus
Staphylococcus   citreus
Bacillus    polymyxa
Bacillus    cereus
Lactobacillus
Pseudomonas aeruginosa
Klebsiella pneumonia
Salmonella typhi
E.  coli
Proteus    mirabilis
L
1
(
C
20
H
20
O
6
N
2
)
23
20
22
21
21
18
20
22
21
18
[Cu(C20H20O6N2)Cl2]
20
15
18
19
16
13
19
17
14
16
[Ni(C20H20O6N2)Cl2]
17
15
12
12
12
12
10
12
20
14
[Co(C20H20O6N2)Cl2]
18
12
16
10
14
18
12
16
12
15
[Hg(C20H20O6N2)Cl2]
08
11
09
10
11
12
07
10
08
08
[Zn(C20H20O6N2)Cl2]
16
14
14
14
14
14
16
16
12
16
[Cd(C20H20O6N2)Cl2]
12
14
12
07
10
14
12
14
18
12
L
2
(
C
17
H
12
O
3
N
2
)
24
22
19
25
22
22
24
25
22
20
[Cu(C17H12O3N2)Cl2]
20
17
22
19
17
18
15
18
22
18
[Ni(C17H12O3N2)Cl2]
18
14
18
14
16
12
18
16
12
14
[Co(C17H12O3N2)Cl2]
16
17
14
10
18
15
19
16
20
19
[Hg(C17H12O3N2)Cl2]
10
12
11
10
11
08
13
09
13
08
[Cd(C17H12O3N2)Cl2]
14
12
13
16
14
14
14
12
11
14
[Zn(C17H12O3N2)Cl2]
15
16
14
14
15
15
17
17
13
17
Streptomycin
27
25
24
26
26
24
26
27
23
25


## 7.  Conclusion

Based on stoichiometries and analytical data of the ligands, (E)-7-Methoxy-N1-(2,4,5-trimethoxy benzylidene) benzofuran-2-carbohydrazide (L1) or (E)-N1-(2,6-dichloro benzylidene)-7-methoxy benzofuran-2-carbohydrazide (L2) are neutral, bidentate ligands coordinating through the “O” and “N” of the amide and azomethine group, respectively.All the complexes possess 1 : 1 (M : L) stoichiometry based on analytical and spectral data to chloride bridged polymeric octahedral structures of Cu(II), Co(II), and Ni(II) complexes (Figure5(a)) and monomer/dimeric tetrahedral structures to Zn(II), Cd(II), and Hg(II) complexes (Figure 5(b)). Benzofuran ligands are more active against almost all microbes. Hg complexes are less active; Zn and Cd complexes are moderately active Cu, Co, and Ni complexes showed very good activity against all bacteria.



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*Source: 614628-2013-04-24.xml*