Cu Ll Complexes

Asian Journal of Biochemical and Pharmaceutical Research Issue 1 (Vol. 1) 2011 ISSN: 2231-2560

Research Article

173

Asian Journal of Biochemical and Pharmaceutical Research

Synthesis, Characterization & Antimicrobial Activity of Metal Complexes Containing Azo Dye Ligand Of Sulfa Drugs

V. A. Modhavadiya

Dept. of Chemistry, M.M. Science College, MORBI-363642, Gujarat, India

Received: 30 December 2010; Revised: 31 December 2010; Accepted: 01 January 2011

Abstract: The azo dye ligand was synthesized by the coupling of diazonium salt of sulfadimidine with 2-ethyl-4-methyl phenol. The transition metal (II) complexes were formed by the refluxing of Fe(II) and Cu (II) sulphates with the azo dye ligands.The metal complexes were characterized by elemental analysis, metal contents, magnetic properties, molar conductance and spectral studies. The complexes are non-electrolytes in DMF and are all stable in air. The elemental analysis revealed that the azo dye ligands coordinated to the metal ions in 1:2 (metal-ligand) molar ratios. The infrared data indicates that the ligands are coordinated with metal ions through diazo (-N=N-) nitrogen and phenolic (-OH) oxygen. The spectral data suggest a tetragonal or distorted octahedral geometry as shown in the proposed structure. The ligand and their transition metal (II) complexes were screened for their invitro antibacterial activity against two Gram positive: Bacillus megaterium, Bacillus subtilis and Gram negative: Escherichia coli, Arobactor arogens bacterial strains by cup-plate method. The ligand and their transition metal (II) complexes were also screened for their invitro antifungal activity against Aspergillus awamori and Aspergillus niger by same method. The ligand was found to exhibit either low to moderate activity against one or more bacterial species and fungal species. However, the complexes exhibited varied activity against different bacteria and fungi.

Keywords: Azo dye ligand, transition metal complexes, spectral studies, Antimicrobial activity.

INTRODUCTION:

The azo dyes have the general structure R-N=N-R’, where R and R’ are alkyl, aryl or heterocyclic radicals. Most of them are prepared by the condensation of azo compounds with hydroxy aldehydes or ketones. Several bidentate azo dyes in which the phenolic –OH group and azo nitrogen are present in such a way that they form six membered ring with metal ions. Azo dyes have been investigated by many workers as chelating agent and their metal chelates and complexes have been extensively used in dyeing industry [1-5] and studied dyeing properties [6-7]. Azo dyes have been widely used in various fields and technologies like textiles,leather,plastics,paper,laser liquid crystalline displays and ink jet printers [8-10].They are also used in food [11],drug, cosmetic and photochemical production [12].

Metal complexes of biologically important ligands are sometimes more effective than the free ligands [13]. Azo dyes are well known for antiseptic activity [14-15] and some are useful as chemotherapeutic agents [16].Transition metals like Fe, Co, Ag, Au, Cu and Ni have long been used in medicine. A large number of metal sulphonamide complexes are found to be more potent than the parent sulphonamides [17-18].

Asian Journal of Biochemical and Pharmaceutical Research Issue 1 (Vol. 1) 2011

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Keeping in view of the importance of metal complexes of azo dyes in the dyeing industries and because of their special antimicrobial activity, present paper report the results of our studies on the synthesis, physicochemical and antimicrobial properties of Fe (II) and Cu (II) complexes of azo dye of sulfadimidine with 2-ethyl-4-methyl phenol.

EXPERIMENTAL:

MATERIALS AND METHODS:

Most of the special chemicals used were purchased from British Drug House (BDH) Ltd. And EMerk grade and were used without further purification. They are : p-cresol, acetic anhtdride,pyridine,anhydrous aluminum chloride, zinc dust,Hgcl2, Conc.HCl, NaNO2, CuSO4 and ferrous ammonium sulphate.The bacterial strains used are two Gram positive bacterial: Bacillus megaterium, Bacillus subtilis and Gram negative bacterials:Escherichia coli, Arobactor arogens.

The fungal strains used are Aspergillus awamori and Aspergillus niger.

Preparation of the ligand: Preparation of 3-ethyl-2-hydroxy-5-methyl-4’-(4”,6”-dimethyl pyrimidin-2”-yl)-aminosulphonyl azobenzene (Azo dye ligand, Fig.1). Sulfadimidine (0.025M) was taken in 10 ml HCl (0.055M) solution, and it was added to sodium nitrite solution 20ml (0.025M) and the mixture was cooled in ice bath. (Yields diazonium salt of sulfadimidine). In another flask 2-ethyl-4-methyl phenol (0.025M) dissolved in 10ml (0.025M) NaOH and cooled at 0oC. In situ diazonium salt of sulfadimidine was coupled with 2-ethyl-4-methyl phenol (in above solution) by adding drop wise at 0oC with constant stirring and keeping the PH of the solution neutral.

Earlier 2-ethyl-4-methyl phenol was prepared by clemmensen’s reduction [19-20] of 2-acetyl-4-methyl phenol. 2-acetyl-4-methyl phenol was prepared by Fries migration [21] of p-cresyl acetate. P-cresyl acetate was prepared by acetylation [22] of p-cresol.

Preparation of iron (II) complex: A mixture of ferrous ammonium sulphate solution (10.0ml, 0.1 M diluted to 50 ml), ammonium hydroxide followed with few drops of glacial acetic acid to get PH between 5.0 to 6.0 and excess of alcoholic solution of the ligand was refluxed on a water-bath for half an hour when a brown precipitates of iron complex was obtained. It was filtered, washed with distill water till free from sulphate ions and then dried at 1200C.

Preparation of copper (II) complex: Copper sulphate solution (10.0ml, 0.1M) diluted to 50 ml (solution become clear. If not clear then heat and cool.) Add liq. Ammonia till clear dark blue solution. This solution called copper hexamine. Heat it and excess of ligand solution in the rectified spirit was added. Add more ammonia for basic medium till PH become 10. Shake well and stand for 2 to 3 hour then filter it, dry it and recrystallised from absolute alcohol.

Physical Measurements: Elemental analysis for C and H were estimated n a cooleman C-H analyzer and N was estimated by Kjeldahl’s method. The percentages of metals were determined by EDTA complexometric [23] titration. Conductivity measurements in DMF were made using Toshniwal Conductivity Bridge using a dip type cell at room temperature. Magnetic moment was measured at room temperature on a Gouy balance using mercury (II) tetrathiocynate cobalt (II) as the calibrant. IR


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spectra were recorded using KBr disc on NICOLET MEGNA-IR550 SERIES II. Electronic spectra were recorded on Backman spectrometer using matched silica cells.

Antimicrobial studies: Antimicrobial studies was carried out by cup plate method [24-27] at a concentration of 50 µg, using DMF as a solvent against different strains of bacteria and fungi.

RESULT & DISCUSSION:

The prepared ligand and their metal (II) complexes gave poor yield. The conductivity values of the ligand and the complexes in DMF at concentration of 10-3 M are in the range 8.9-11.9 mohs.cm2 mole-1.This indicates that they are non electrolytes [28]. The results of conductivity measurements are presented in table I. In general, the complexes analyzed as ML2 where M = Cu (II) and ML2(H2O)2, where M=Fe (II).This shows that the copper (II) complexes is anhydrous while Iron (II) complex is hydrated.

The IR spectral analysis of ligand is in good arrangement with the synthesis ligand. The ligand shows bands at 3427cm-1 (OH) of the intramolecular hydrogen bonded group. This band is absent in the complexes indicating the breaking of the hydrogen bonding and consequent deportation and coordination of the metal ion. The band at 1620 and 1420 cm-1 (-N=N-) of the ligand undergoes a negative shift in the complexes indicating nitrogen coordination of the diazo moiety. The occurrence of medium intensity band at 3425cm-1 in iron complex and its absence in other complexes show that iron complex have coordinated water molecules unlike others.

The absorption spectra of the ligands in U.V. and visible region shows 3 bands at 230 to 240 nm, 320 to 370 nm and 400 to 440 nm wave length. The absorption corresponding to 230 to 240 nm and 320 to 370 nm are corresponding to n → π* and π→ π* and absorption corresponding to 400 to 500 nm is attributed to π→ π* transition due to presence of conjugation in the ligand molecule. The absorption spectra ligand peaks are obtained along with the absorption maxima due to d-d transition. The d-d transitions are La-Porte forbidden transitions therefore they are weak in intensity. The position of ligand bands are shifted which may be due to interaction of ligand with metal ion [29].The spectra of Cu(II) complex only two absorption bands are obtained at λmax 629 nm and 765 nm and are attributed to the transition 2B1g → 2Eg and 2B1g → 2B2g ,respectively. The spectra of Fe (II) complex show a very diffused band at 671 nm it is a weak band which is probably due to the transition 2A1g → 2T1g. The positions of these bands in the spectra of metal complexes are consistent with the expected distorted octahedral or square geometry.

The antibacterial activity of azo dye ligand and their corresponding metal(II) complexes were determined against two Gram positive ( Bacillus megaterium, Bacillus subtilis ) and Gram negative ( Escherichia coli, Arobactor arogens ) bacterial strains. The antifungi activities were determined against (Aspergillus awamori and Aspergillus niger) fungal strains. The ligand was found to exhibit either low to moderate activity against one or more bacterial species and fungal species. However, the complexes exhibited varied activity against different bacteria and fungi. The Cu ( II ) complexes have much toxicity. This is expected because the copper salts are mostly used as fungicides.


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The observed magnetic moments of the resulting complexes are given in Table-I. These values show that Fe (II) complex is diamagnetic nature while Cu (II) complex are paramagnetic nature with one unpaired [30, 31, 32].

CONCLUSION:

The ratios of metal to ligand are 1:2 in all the metal complexes as confirmed by their elemental analysis. The complexes are non-electrolytes as confirmed by their conductivity measurements. The electronic spectral data suggest possible distorted octahedral or square planner geometry around the metal ions as shown in the proposed structure (Fig. II & III).

The in vitro antimicrobial screening of the complexes confirmed their potency against most of the microorganisms used in this study. The proposed structures of the ligand and metal (II) complexes are as shown below:

ACKNOWLEDGEMENT:

The authors are thankful to Late Dr.G.K.Joshi for valuable guidance and Head, Department of chemistry, Saurashtra University, Rajkot India For providing the necessary laboratory facilities.

Table-1 :- Elemental analysis , conductance and magnetic measurements.

Compound

Mol. Formula

Mol. Wt.

Found/ Req.

% Found/ Calc. Cond. Mhos.cm2

/mole

µeff

B.M M C H N

Azo Dye Ligand

C21H2303N5S 416 - 59.29 5.41 16.47 - -- 425 - 59.35 5.46 16.51

Fe (II) complex

Fe(C21H223N5S)2

(H2O)2 929.27 5.94 53.63 5.11 14.90 11.9 Diamag. 939.85 5.99 53.67 5.14 14.95

Cu(II) Complex

Cu(C21H223N5S)2

902.44 6.97 55.29 4.83 15.36 8.9 2.13 911.54 6.99 55.32 4.87 15.40


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Table -2 Antimicrobial activity of Azodye Ligand and Metal(II) Complexes.

S

O

O

NHNN

OH

N

N

Fig. - 1 3-Ethyl-2-Hydroxy-5-methyl-4’-(4”,6”- dimethylpyrimidine-2”-yl) Aminosulphonyl

azobenzene (AZODYE LIGAND )

O

SO2NH

NNO

O2SHN

N N

M+2

N

N

N

N

O

SO2NH

NNO

O2SHN

N N

M+2

N

N

N

N

H2O

H2O

Fig.-2 CuII) Complex Fig.- 3 Fe(II) Complex

Sample Zone of Inhibition (mm) Antibacterial Acivity

anti fungal activity

Gram Positive Gram Negative A.awamori A.Niger B.

Mega. B.Subti. E.

Coli. A.Arogens

Azodye ligand 17 17 16 22 21 20 Fe(II) Complex 14 14 17 20 19 21 Cu(II) Complex 15 14 16 19 21 19 SulphaDiazine 22 21 24 22 24 23

Sulphamethoxazole 23 23 26 26 22 23


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*Correspondence Author: V.A.Modhavadiya, Dept. of Chemistry, M.M. Science College, MORBI-363642, Gujarat, INDIA

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