Indian 10urnal of Chemistry Vol. 45A, February 2006, pp. 377-381

Synthesis, characterization, antibacterial and anthelmentic activities of copper(II) complexes with benzofuran Schiff bases

K Ramakrishna Reddy, K Madhusudan Reddy & K N Mahendra*

Department of Chemistry, Central College Campus, Bangalore University, Bangalore 560 001, India

Email : mahendrajadidal@yahoo.co.in

Received 8 July 2005; accepted 7 December 2005

Copper(H)chloride reacts with Schiff bases derived from benzaldehydes/acetophenone with 3-amino-2-benzofuran carboxamide/ethyl-3-amino-2-benzofuran carboxylate to yield polymeric complexes of general composition CuLCI2 (L = Schiff base). The authentici ty of the ligands and their complexes has been established by micro analysis, magnetic susceptibility, IR, electronic, ESR spectral studies and electrical conductance measurements. The ligands act as bidentate, with azomethane nitrogen and carbonyl oxygen atom as donor si tes. It is proposed that Cu(I1) complexes are polymeric with octahedral geometries. All the ligands and their metal complexes have been screened for antibacterial activity against two bacteria, viz. S.aureus and E.coli. The complexes of ligands lb, If, 19 and lh show promising results against S.aureus. Anthel'llentic activity of the li gands and t'1e complexes has been tested on earthworms. The activity is enhanced significantly on complexation.

IPC Code: InLCI.8 C07C25 1102; C07FI/08; C07D307/00

Transition metal ions are essential to many biological systems in nature l

. Metal ions are involved in a large number of chemical reactions by virtue of their ability to coordinate to simple or polymeric donor species. The compounds with benzofuran moiety have aroused much interest because they frequently occur in natural products and are biologically important2

. They have many applications both in qualitative and quantitative analysis3

.4. A little work has been carried out on the complexing behaviour of Schiff bases derived from substituted benzimidazoles with various metal ions, in particular Cu(Il). Keeping that in view, a series of Schiff bases have been synthesized derived from benzaldehydes/acetophenone with 3-amino-2-benzofuran carboxamide/ethyl-3-amino-2-benzofuran carboxylate and their complexing behaviour with Cu(TJ) has been studied. In addition to this, all the ligands and the complexes have been characterized and screened for their biological activity.

Materials and Methods The chemicals employed for the preparation of

Schiff bases were of AR or CP grade. All the solvents were purified by standard methods.

Preparation of ligands

3-Amino-2-benzofuran carboxamide and ethyl-3-amino-2-benzofuan carboxylate were synthesized by

known procedures5. A mixture of 3-amino-2-

benzofuran carboxamide/ethyl-3-amino-2-benzofuan carboxylate and corresponding benzaldehydesl acetophenone (1: 1) in an ethanolic medium containing few drops of glacial acetic acid was refluxed for about 3 h on a water bath. The resulting Schiff base (1) was separated upon concentration which was filtered, washed with ethanol and recrystallised from suitable solvent (Table 1).

N=C~--O-RII Co( -o R

(1)

Ligand R RI R

Ia CONH2 H H

lb CONH2 H CI

Ie CONH2 H OMe

ld CONH2 H N02

Ie CONH2 Me H

If COOEt H H

Ig COOEt H CI

lh COOEt H OMe

Ii COOEt H N02

Ij COOEt Me H

378 INDIAN J CHEM, SEC A, FEBRUARY 2006

Table I-Physical data of the ligands

Ligand R RI RII M.F.

la CONH2 H H CI6HI2N202

Ib CONHz H CI CI6HIINzOzCI

Ic CONHz H OCH3 C17HI4N203

Id CONHz H NOz CI6HIIN304

Ie CONH2 CH3 H C17HI4NzOz

If COOCzHs H H CisHISN03

Ig COOCzHs H CI ClsHI4N03C1

Ih COOCzHs H OCH3 C I9H 17N04

Ii COOCzHs H N02 CISHI4NzOs

lj COOCzHs CH3 H C I9H17NO)

Preparation of complexes

Copper(II) chloride (0.01 mole) was refluxed with Schiff base (0.01 mole) in ethanolic medium for 3-4 h. The complex that separated on partial evaporation was filtered, washed with ethanol and dried in vacuo.

Analysis and measurements

The micro analysis of the complexes was carried out at Micro Analytical Laboratory of Liquid Crystal Department, Raman Research Institute, Bangalore. The copper and chloride were estimated by standard methods6

. The conductivity measurements were made on ELiCO CL-82 Conductivity Bridge with a dip type conductivity cell. The magnetic susceptibility measurements were carried out at room temperature using Guoy balance. Electronic spectra were recorded in DMF (10-3

) in the range 900-350 nm in a Hitachi Model 200-20 spectrophotometer. ESR spectra of few Cu(II) complexes were obtained from Materials Research Centre, Indian Institute of Science, Bangalore. IR spectra of ligands and their complexes in Nujol mull were recorded in the region 4000-600 cm-' on a Perkin Elmer-297 and in the region 600-250 cm" on Hitachi 270-50 Infrared Spectrophotometer.

Results and Discussion All the complexes are amorphous in nature and

stable towards atmosphere with high melting points (>300°C). The molar conductivity values in DMF (10-3 M) varied between 69 and 85 ohm-I cm2 mor l

,

M.Pt. Yield,% % Found (Calculated) °C (Solvent of crystallization) C H N

212 88 72.71 4.50 10.60 (ethanol) (72.73) (4.54 (10.61 )

204 85 64.29 3.50 9.41 (benzene+pet.ether) (64.30) (3.68) (9.38)

194 90 69.37 4.80 9.53 (ethanol) (69.39) (4.76) (9.52)

230 92 62.11 3.61 13.58 (aq. DMF) (62.13) (3.56) (13.60)

208 83 73.31 5.00 10.00 (ethanol) (73.38) (5 .03) (10.07)

157 82 73.80 5.16 4.81 (ethanol) (73.75) (5.12) (4.78)

168 84 66.01 4.26 4.29 (aq. Ethanol) (65.95) (4.27) (4.27)

158 78 70.63 5.29 4.36 (benzene + pet. ether) (70.59) (5.26) (4.33)

167 81 64.02 4.11 8.31 (aq. DMF) (63.95) (4.14) (8.28)

160 87 74.20 5.50 4.51 (aq. Ethanol) (74.26) (5.53) (4.56)

indicating I: 1 electrolytic behaviour (Table 2). The complexes are soluble in DMF and DMSO and are insoluble in common organic solvents. Hence, the efforts for determining the molecular weight of complexes were not successful. The magnetic moments of the complexes fal ll in the range 1.88 - 2.10 B.M7.

Electr'onic spectra

The Cu(II) ion with £f configuration in a complex can be either distorted octahedral or tetrahedral or rarely square planar. The octahedrally coordinated Cu(II) ion has the ground state 2£g «(2g)6 (ei . The only excited state should then be 2T2g (t2i (e/, the energy difference being 10 Dq. The Cu(II) complexes under the present investigation exhibit a broad symmetric band in the region 16670-12820 cm-I with a maxima around 14900 cm-'. In the present case, broadness of the band may be due to dynamic John­Teller distortions. The studies on electronic spectra of CU(n) complexes indicate that the three transitions 2B,g ~ 2A 'g (y,), 2B'g ~ 2B2g(Y2) and 2B,£ ~ 2£g(Y3) are having similar energy and give rise to the single broad absorption envelope. The calculated value of 10 Dq (1429-1538 cm-') and LFSE (102.46-110.29 kllmole) indicate octahedral geometry around the central metal ion.

IR spectra

A broad band in the region 3485-3420 cm-' in Cuen) complexes of ligands If to Ij are attributed to

REDDY et al.: COPPER(II) COMPLEXES WITH BENZOFURAN SCHIFF BASES 379

Table 2 - Analytical. molar conductance and magnetic susceptibility of the complexes

Complex % Found (Calculated) AMohm-1cm2mol ·1 J.l elT

M CI C

CuCh(la) 15.37 17.97 48.12 (15.93) (17.81) (48.11)

CuCI2(lb) 14.06 24.47 44.29 (14.66) (24.39) (44.30)

CuCI2(lc) 14.78 16.85 47.55 (14.82) (16.56) (45.50)

CuCIz(ld) 14.32 16.02 43.24 (14.31) (16.00) (43.20)

CuCI2(le) 15.44 17.20 49.39 (15.39) (17.21 ) (49.42)

CuCI2(1f) 14.41 15.72 50.47 (14.25) ( 15.93) (50.61)

CuCI2(lg) 13.25 14.80 46.70 (13.22) (14.79) (46.68)

CuCI2(lh) 13.55 14.93 49.78 (13.35) (14.93) (49.69)

CuCh(li) 12.92 14.50 45.66 (12.94) (14.47) (45.65)

CuCI2(lj) 13.80 15.44 51.58 (13.81 ) (15.45) (51.60)

OH stretching frequency which may be due to hydrated or lattice held water molecule9

,1O. The bands in the region 3460-3140 cm" are assigned to NH2 vibrations of primary amide group in ligands practically remain unchanged in the spectra of the complexes suggesting non participation of NH2 group on chelation 10. The Schiff bases exhibit strong to medium intensity bands in the region 1590-1540 cm" (C=N stretching vibrations)", undergo a negative shift of 20-40 cm" on complexation suggesting the involvement in coordination of azomethane group. The bands in the region 1700-1620 cm" (C=O stretch of amide or ester group) undergo a negative shift in the complexes by 80-45 cm" indicates the bonding through carbonyl group" . The bands in the region 1200-1175 cm" are attributed to C-O-C stretch of furan ring in free k: ,lllds '2. These bands remain

.. !'¥

unchanged indicati'if ,'" 'll-participation of furan ring oxygen on coordination. In the far IR spectra of the complexes, the bands in the region 540-510 cm" and 485-400 cm" are assigned to M-O stretch '3, M-N stretch'4 and the bands at 336-315 cm" and 280-265cm" were assigned to and M-Cl'4 terminal and bridging stretching vibrations in all the complexes. It can be concluded that all the ligands act as bidentate, with azomethine nitrogen and carbonyl oxygen atom as donor sites.

H N BM

3.007 7.07 82.0 1.93 (3.01) (7.05)

2.75 6.46 85.0 1.88 (2.78) (6.50)

3.56 6.52 79.1 1.95 (3.54) (6.51)

2.47 9.46 76.2 1.92 (2.45) (9.48)

3.39 6.78 79.2 1.97 (3.40) (6.80)

3.50 3.27 71.3 2.10 (3.48) (3.30)

3.02 3.02 72.8 1.89 (3.04) (3.05)

3.71 3.05 70.4 1.89 (3.70) (3.07)

2.96 5.92 69.0 2.08 (2.91) (5.90)

3.85 3.16 84.0 2.05 (3.90) (3.18)

ESRspectra The ESR spectra do not show any hyperfine

splitting, which might be due to the weak coordination of the ligands. A sharp weak peak at 3240 G gives the position of DPPH (l,I-diphenyl-2-picrylhydrazyl free radical). The trend gll>gJ.>gDPPH observed for these complexes indicate that the unpaired electron lies predominantly in the d/ _/ orbital with the possibility of some mixing of d/ because of low symmetry '5. The EPR parameters (Table 3) computed from the spectra are indicative of octahedral geometry. In the present complexes, though the G values are less than 4, the interaction may be weak as the magnetic moments of these complexes are normal at room temperature '6. This is also confirmed by observing that there is no band corresponding to Ms = ±2 transitions in the spectrum ruling out any Cu-Cu interaction. The degree of covalency for the present complexes falls in the range 0.629-0.606. For the complexes under present investigation g,,, g.L, and gav are 2.178-2.182, 2.114-2.116 and 2.135-2.138, respectively. Based on this data, it is proposed that the Cu(lI) complexes are polymeric with octahedral geometries 17.

Anti-bacterial activity In view of the potential biological activity, all the

ligands and their copper complexes were tested

380 INDIAN J CHEM, SEC A, FEBRUARY 2006

Table 3 - Electronic spectral data and EPR data of Cu(ll) complexes

Complex

CuCI2Cla)

CuCI2(lb)

CuCI2(lc)

CuCI2(ld)

ClICI2(Ie)

CuCI2(lf)

CuCI2CIg)

CuCI2(Ih)

CuCI2(Ii)

CuClz(lj)

Band maxima (nm)

710

650

680

700

680

680

710

660

680

720

15380

15380

15380

14710

14710

14290

14930

14710

14710

14290

LFSE kl/mol

110.29

110.29

110.29

105.52

104.56

104.56

107.06

105.52

105.52

102.46

Table4 - Results of antibacterial activity of Schiff bases and their ClI(ll) complexes

Temp K

300

300

300

Ligand / Zone of inhibition Complex S. aureus E. coli

Ligand / Zone of inhibition Cornplex S. aureus E. coli

DMF(control)

Ligand Ia

CLI

Ligand lb

ClI

Ligand Ic

ClI

Ligand Id

ClI

Ligand Ie

ClI

7mm

13 mm

Ligand If

ClI 14 mrn Ligand Ig

ClI

Ligand Ih

8 rnm ClI

Ligand Ii

ClI

10 mm Ligand Ij 7 mm ClI

10m

11 mm

8mm

13mm

against two bacteria namely Staphylococcus aureus (S.aureus) and Escherichia coli (E.coli), which are representative type of gram positive and gram negative bacterial groups, respectively. The biological screemng was conducted by filter paper disc method l8

. The Schiff base ligands and some of its metal complexes did not show any activity (Table 4). However, the complexes of ligands 1b, If, 19 and 1h showed promising results against S.aureus. Thus, these compounds may prove to be good antibacterials against gram positive bacteria.

Anthelmentic activity (in vitro)

Anthelmentic activity was tested on earth worms (Pheretima Posthuma) using benzofuran Schiff bases and their Cu(II) complexes (Table 5) by reported method 19. Ligands Ie, 19 and Ij exhibited very high

g.L g <IV G

15380 2.178 2.114 2.135 1.56 0.629

[4710 2.182 2.116 2.138 1.57 0.615

14710 2.182 2.114 2.136 1.59 0.606

Table 5 - Results of anthelmentic activity of Schiff bases and their Cum) complexes

Ligand / Complex

Blank Normal saline Standard Piperzine citrate Ligand Ia

ClI

Li gand Ib

ClI

Li gand Ic

ClI

Ligand ld

ClI

Ligand Ie

ClI

Piperzine citrate

Ligand If

ClI

Ligand 19 ClI Ligand lh

ClI

Ligand Ii

Cu Ligand Ij

ClI

Concentration

5 mg/ml 5 mg/ml

5 mg/m!

5 mg/ml

5 mg/ml

5 mg/m!

5 mg/m!

5 mg/m!

5 mg/rnl

5 mg/ml

5 mg/ml

2 mg/ml 2 mg/ml

2 rng/ml 2 mg/ml

2 mg/ml 2 mg/ml

2 mg/ml

2 mg/ml

2 mg/ml

2 mg/ml

2 mg/ml

Til e taken foi' paralysi s and death of worms

Paralysis Death (min) (rnin)

No effect till ten hours

10 16 11

210 10 128 10

101 08 07 II 16 20 04

06 03 11 0

03 135 05 04

04

16 25 14

222 12

148

14 123 11

14

14 23 28 06 II 06 128 04

155 08

16 07

activity whereas ligands 1a and 1f exhibited moderate activity and the remaining ligands were inactive. The anthelmentic activity is enhanced significantly upon complexation with Cu(U).

REDDY et al.: COPPER(IJ) COMPLEXES WITH BENZOFURAN SCHIFF BASES 381

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